Levosimendan in rats decreases acute kidney injury after cardiopulmonary resuscitation by improving mitochondrial dysfunction

BackgroundAcute kidney injury (AKI), the most common complication after cardiac resuscitation, is highly prevalent and harmful. There is increasing evidence that levosimendan can improve cardiac output, increase renal blood flow, and prevent AKI. As a novel calcium sensitizer, levosimendan may exert its protective effect via mitochondria.MethodsRat models of asphyxia-induced cardiac arrest and cardiopulmonary resuscitation (CPR) were set up. Thirty healthy adult male SD rats were randomly divided into CPR group (CPR group, n=10), levosimendan-treated group (levo group, n=10), and sham-operated group (sham group, n=10). Twelve hours after CPR, serum renal function indicators were measured, the kidney injury and mitochondrial morphological changes were observed. Oxygen uptake of the mitochondria, mitochondrial adenosine triphosphate (ATP) and mitochondrial free Ca²⁺ concentration were measured. Oxidative stress-related indicator levels in rat kidney tissues were further detected to analyze the differences in apoptosis rates among these three groups. Mitochondrial optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1), and apoptosis-related proteins were detected using Western blotting.ResultsCompared with the sham group, the CPR group had a significant increase in renal tissue damage. PAS staining and HE stains confirmed that CPR led to renal histopathological damage and destruction of the mitochondrial structure. Levosimendan improved the histopathological and ultrastructural damages of kidneys. Further analysis revealed that mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (CSH-Px) decreased. Free Ca²⁺ concentration and malondialdehyde (MDA) significantly increased (all P<0.05) in the kidney tissues of rats in the CPR group. However, mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, SOD, CAT, and CSH-Px increased, whereas free Ca²⁺ concentration and MDA decreased (all P<0.05) in the levo group. The apoptosis rate increased in the CPR group. There were significantly increased levels of Drp1 protein levels, and significantly decreased Opa1 expression (all P<0.05). However, the levo group showed the opposite effects (all P<0.05).ConclusionsLevosimendan can alleviate AKI following CPR, which may be achieved by improving mitochondrial dysfunction and suppressing the mitochondrial apoptosis pathway.     

Inhibition of the proliferation,invasion, migration,and epithelial-mesenchymal transition of prostate cancer cells through the action of ATP1A2 on the TGF-β/Smad pathway

BackgroundProstate cancer (PC) is one of the major male malignancies worldwide. Because Na⁺-K⁺-ATPase is widely involved in various pathological processes, but the action of its α2 subtype (ATP1A2) in PC is unclear, we investigated the role of ATP1A2 in the invasion and migration of PC cells.MethodsWe measured the expression levels of ATP1A2 in human normal prostate epithelial cell line (RWPE-1) and PC cell lines (PC-3 and DU145) by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation, apoptosis, migration, and invasion of PC-3 and DU145 cells were investigated through clone formation assay, EdU assay, flow cytometry and transwell assay, respectively. The effect of ATP1A2 on a tumor-inhibitory pathway [transforming growth factor-β (TGF-β)/Smad] was assessed using western blot. In addition, tumor formation was detected using in vivo xenograft model in male BALB/c nude mice.ResultsThe Cancer Genome Atlas (TCGA) analysis showed that ATP1A2 expression was reduced in PC patients (P<0.05), and patients with low ATP1A2 expression had a lower survival rate (P<0.05). ATP1A2 levels were significantly reduced in PC-3 and DU145 cells, compared with RWPE-1 cells (P<0.01). We also demonstrated that overexpression of ATP1A2 significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of PC-3 and DU145 cells (P<0.01) and promoted apoptosis (P<0.01). However, silencing ATP1A2 had the opposite effect (P<0.01). In addition, overexpression of ATP1A2 significantly inhibited the TGF-β/Smad pathway (P<0.01), whereas silencing ATP1A2 activated the TGF-β/Smad pathway (P<0.01). Meanwhile, the effect of ATP1A2 silencing on the proliferation, apoptosis, migration and invasion was reversed by TGF-β/Smad pathway inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY364947","term_id":"1257906561","term_text":"LY364947"}}LY364947). Furthermore, ATP1A2 inhibited tumor growth in vivo.ConclusionsATP1A2 inhibited proliferation, apoptosis, migration, invasion, and EMT in PC by inhibiting the TGF-β/Smad pathway.     

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia

BackgroundTo study the effects of L-carnitine (LC) combined with pancreatic kininogenase on thioredoxin 2 (Trx 2), thioredoxin reductase 1 (TrxR 1), and sperm quality in patients with oligoasthenospermia.MethodsA total of 300 male infertility patients with oligoasthenospermia who were treated in the andrology clinic of our hospital from December 2019 to December 2020 were randomly divided into an LC group and combined treatment group, and 50 males with normal semen were selected as a control group. The computer-assisted semen analysis system (CASA) was used to detect the total number, vitality, and forward motility of the sperm before and after treatment, and sperm morphology was detected by the Diff-Quik method of the sperm staining kit. Sperm chromatin dispersion (SCD) method was used to detect sperm DNA fragments, and Western-blot was used to detect the protein expression of Trx 2 and TrxR 1.ResultsThere were no significant differences in sperm density, motility rate, forward motile sperm rate, and DNA fragmentation rate in oligoasthenospermia patients before treatment (P>0.05). However, after 1 month of treatment, the sperm density, motility rate, and forward motile sperm rate were all higher than before treatment (P<0.05), while the DNA fragmentation rate was lower than before treatment. At the same time, each index of semen in the combination group was higher than that in the LC group (P<0.05), and the total effective rate in the combination group was significantly higher than in the LC group (P<0.01). The expression of Trx2 protein in oligoasthenospermia patients was significantly increased (P<0.05), while the expression of TrxR1 protein was significantly decreased (P<0.05). After 3 months of treatment, the expression of Trx2 protein was significantly decreased (P<0.05), while the expression of TrxR1 protein was significantly increased (P<0.05).ConclusionsThe results suggest Trx 2 and TrxR 1 may be candidate protein markers for oligoasthenospermia. LC combined with pancreatic kininogenase in the treatment of male oligoasthenospermia can effectively promote sperm maturation, enhance sperm motility, and improve semen quality, which has high application value.     

Efficacy evaluation of thickened condom in the treatment of premature ejaculation

BackgroundThis study aimed to evaluate the efficacy of thickened condoms in the treatment of premature ejaculation.MethodsFrom August to December 2021, patients with premature ejaculation treated in the Urology and Andrology Center of the First Affiliated Hospital of Medical College of Zhejiang University were selected for a clinical controlled study. A total of 100 patients with premature ejaculation were enrolled as the premature ejaculation group and 30 normal men as the control (normal married men, age <30 years, normal sexual life). Each patient’s ejaculation latency, contraceptive safety, comfort, glans sensitivity, dorsal nerve conduction velocity, serum reproductive hormone level, penile hardness, and penile erection were measured in the premature ejaculation and normal control groups.ResultsThe comfortability associated with thickened condoms in the premature ejaculation group was poor (P<0.05). After using a thickened condom, the time to ejaculate of the premature ejaculation group was significantly prolonged (P<0.05). Meanwhile, the penis vibration threshold increased significantly, indicating that the nerve sensitivity decreased (P<0.05). In the premature ejaculation group, the total erection time and the average hardness of coronary sulcus in the thickened condom group were significantly higher than those in the ordinary condom group (P<0.05), and the serum androgen level could be significantly increased after using the thickened condom (P<0.05).ConclusionsThe thickened condom can effectively maintain and prolong the hyperemia state of the penis and enhance the intensity of penile erection. Thickened condoms physically preserve and extend the time of penile erection, resist and overcome premature ejaculation, and improve the ejaculation condition to improve the quality of sexual intercourse.     

Acupuncture combined with moxibustion promote the recovery of spinal cord injury in correlation with Shh/Gli-1 signaling pathway

Objective: Acupuncture combined with moxibustion (AM) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The present study aimed to confirm the effect and mechanism of AM treatment on the recovery of SCI.Design: Male Sprague–Dawley rats were used to establish the SCI model by impact method. SCI rat models were subjected to AM treatment at Dazhui (GV14) and Jiaji points (T7-T12), Yaoyangguan (GV3), Zusanli (ST36) and Ciliao (BL32).Outcome measures: Motor function and cell apoptosis in rats after SCI. The mRNA and protein expression levels of Shh and Gli-1 were determined by real-time quantitative polymerase chain reaction, western blot and immunohistochemistry.Results: After AM treatment, the hindlimb motor function of SCI rats was significantly increased than the SCI group at 7, 9, 11, 14 days (P < 0.05). AM treatment 7 d and 14 d significantly preserved the nissl-stained positive neurons and significantly decreased number of apoptotic cells, compared to that of SCI 7 and 14 d groups (P < 0.05). AM treatment improved the mRNA protein levels of Shh and Gli-1 after 7 and 14 days treatment compared to the SCI group (P < 0.05).Conclusion: AM could improve the expression of Shh and Gli-1 in injured spinal cord of rats. That could be part of underlying mechanisms of AM treatment including recover motor function and preserve the neuron cells and alleviate the apoptosis of nerve cells in rats after SCI.     

Devazepide suppresses cell proliferation and migration,and induces apoptosis in bladder carcinoma

BackgroundThis study aimed to examine the effects of devazepide on the proliferation, migration, and apoptosis of human bladder cancer (BC) 5637 cells, and its mechanism.MethodsA cell counting kit-8 (CCK-8) for cell viability assays, a colony formation assay, and immunofluorescence were applied to detect the effects of devazepide on the proliferation of 5637 cells. Cell cycle assay, cell apoptosis assay and wound healing assay were performed to detect the effects of devazepide on the cell cycle, apoptosis, and migration of 5637 cells. The protein expression of CyclinD1, Bcl-2-associated X protein (Bax), poly ADP-ribose polymerase 1 (PARP1), and Cleaved Caspase-3 in 5637 cells was detected by a western blot assay.ResultsThe proliferation of 5637 cells was significantly inhibited (P<0.001) after incubation with 12, 25, and 50 µM devazepide for 48 and 72 h. A treatment of 25 µM devazepide for 48 h induced G1–S cell cycle arrest and apoptosis (P<0.01), and inhibited cell migration (P<0.05). By western blot assay, we found that devazepide can down-regulate CyclinD1 expression, and up-regulate Bax, PARP1, and Cleaved Caspase-3 expression.ConclusionsDevazepide inhibits the migration and proliferation of human BC 5637 cells by arresting the G1–S cell cycle, and induces cell apoptosis.     

Comprehensive Interventions Including Vitamin D Effectively Reduce the Risk of Falls in Elderly Osteoporotic Patients

ObjectiveTo evaluate the effects of different intervention measures to prevent falls in elderly osteoporotic patients.MethodsA randomized controlled trial was conducted in our outpatient ward from August 2014 to September 2015. A total of 420 patients over 60 years of age were assigned to four groups. NA VitD group took 800 mg calcium and 800 IU non‐active vitamin D. P‐NA VitD group took 800 mg calcium, 800 IU non‐active vitamin D, and received physical exercise. A VitD group took 800 mg calcium and 0.5 μg active vitamin D. P‐A VitD took 800 mg calcium, 0.5 μg active vitamin D, and received physical exercise. Physical exercise includes guidance in improving muscle strength and balance ability. Short physical performance battery (SPPB), grip strength, modified falls efficacy scale (MFES), blood calcium, and 25‐hydroxyl vitamin D were measured before interventions and at 3, 6, and 12 months after interventions. Bone mineral density (BMD) was detected before interventions and at 12 months after interventions. The incidence of falls and fractures, adverse events, and drug reactions were recorded for 12 months.ResultsA total of 420 patients were allocated in the four groups: 98 cases into the NA VitD group (11 males, 87 females), 97 cases into the P‐NA VitD group (13 males, 84 females), 99 cases in the A VitD group (15 males, 84 females), and 98 cases into the P‐A VitD group (11 males, 87 females). At 6 months after interventions, the SPPB of A VitD group significantly increased from 6.9 ± 1.9 to 8.0 ± 2.4 (P < 0.05), and the SPPB of A VitD group significantly increased from 7.2 ± 2.1 to 8.6 ± 1.7 (P < 0.05). At 6 months after interventions, MFES of P‐NA VitD group 7.0 ± 1.6 to 7.6 ± 1.6 (P < 0.05), and MFES of P‐A VitD group significantly increased from 6.7 ± 1.6 to 7.5 ± 1.6 (P < 0.05). At 12 months after interventions, SPPB of all groups, grip strength, and MFES of P‐NA VitD group, A VitD group, P‐A VitD group were significantly improved (P < 0.05). The BMD of lumbar vertebrae of A VitD group significantly increased from 0.742 ± 0.042 to 0.776 ± 0.039, and P‐A VitD group significantly increased from 0.743 ± 0.048 to 0.783 ± 0.042 (P < 0.05). No serious adverse events occurred during the 12 months of follow‐up.ConclusionActive vitamin D is better than non‐active vitamin D to improve physical ability and the BMD of lumbar vertebrae and reduce the risk of falls.     

COX4I2 is a novel biomarker of blood supply in adrenal tumors

BackgroundPrevious study has been reported that COX4I2 expression level demonstrated a positive correlation with microvessel density in pheochromocytomas (PCC) samples, suggesting that the expression of COX4I2 maybe related to blood supply level in other adrenal tumors as well. The aim of this study is to clarify the correlation of COX4I2 expression and blood supply in adrenal tumors.MethodsA total of 84 patients were recruited, among which 46 was diagnosed as adrenocortical adenoma (ACA) and 38 was diagnosed as PCC. Contrast-enhanced CT values were used to evaluate the blood supply levels in those patients. The expression of mRNA was examined by quantitative real-time polymerase chain reaction (qPCR) and protein was detected by immunohistochemistry (IHC).ResultsThe COX4I2 expression level in PCC group is significantly higher than that in ACA group (P<0.01). The expression of angiogenesis-related genes EPAS1, VEGFA and KDR mRNA in PCC group is higher than that of ACA group (P<0.05). Correlation analysis shows COX4I2 expression level is correlated with CT values (P<0.001), intraoperative blood loss (P<0.05) and operation time (P<0.05), and the expression of COX4I2 mRNA is correlated with EPAS1, VEGFA and KDR mRNA (P<0.01).ConclusionsThe results displayed a distinct expression level of COX4I2 between ACA and PCC, suggesting that COX4I2 is a novel biomarker of blood supply in adrenal tumors. This research also opens the possibility for further research on COX4I2 as a novel target for anti-tumor angiogenesis.     

Access and engagement with places in the community,and the quality of life among people with spinal cord damage

ObjectivesThis study aims to investigate the association between self-reported accessibility and engagement with health services and places in the community, and quality of life (QOL) for people with spinal cord damage (SCD).DesignCross-sectional survey.SettingCommunity.ParticipantsTwo-hundred and sixty-six people with a SCD residing in Australia (M_age = 62.34, SD_age = 15.95).Outcome MeasureThe International Spinal Cord Injury Quality of Life Basic Data Set.ResultsUnivariate regressions demonstrated that accessing a higher number of places in the community was significantly associated with favorable self-reported psychological health (β = .160, P < .01), physical health (β = .144, P < .01), overall well-being (β = .206, P < .01), and QOL (β = .187, P < .01). In contrast, reporting a higher number of inaccessible places was significantly associated with unfavorable self-reported psychological health (β = −.171, P < .01), physical health (β = −.270, P < .001), overall well-being (β = −.238, P < .001), and QOL (β = −.244, P < .001). Being older and living with injury or onset of damage longer were significantly associated with favorable scores across all outcomes (P < .01) except physical health.ConclusionsCommunity engagement can have a considerable impact on the self-reported health and QOL of people with SCD. Interventions aimed at increasing community engagement, particularly for people who have recently experienced SCD are warranted.     

Impact of preoperative body mass index on perioperative outcomes is optimized by enhanced recovery protocols in laparoscopic radical cystectomy with intracorporeal urinary diversion

BackgroundWe aimed to examine whether body mass index (BMI) had an impact on clinical outcomes of laparoscopic radical cystectomy with intracorporeal urinary diversion. Furthermore, we analyzed the optimization of enhanced recovery protocols (ERPs) on the impact of BMI on clinical outcomes.MethodsBy searching our database, data of 83 consecutive patients were retrospectively collected, including 37 patients with a BMI <24 kg/m² (group A) and 46 patients with a BMI ≥24 kg/m² (group B). The baseline and peri-operative variables of the two groups were compared. Subgroup analysis was conducted for ERPs (11 patients in group A₁, 18 patients in group B₁) and conventional recovery protocols (CRPs; 26 patients in group A₂, 28 patients in group B₂). The primary outcomes were 30-day overall complication rate and ΔALB_min (reduction proportion of minimum albumin). The secondary outcomes were operative time and length of stay.ResultsThe baseline variables were similar between the two groups (P>0.05). The 30-day overall complication rate, operative time, and length of stay were similar between the two groups (P>0.05). But post-operative nausea and vomiting (PONV) was higher in group A than in group B (32.4% vs. 8.7%, P=0.014). Group A was associated with lower serum albumin level pre-operatively and on post-operative days 1–3. ΔALB_min was higher in group A than in group B (33.08%±9.88% vs. 27.92%±8.52%, P<0.05). In the subgroup analysis, the CRPs group presented similar results, with group A₂ showing higher PONV rate, lower albumin level pre- and post-operatively, and higher level of reduction proportion (P<0.05). For the ERPs group, the PONV rate, pre-operative albumin level, and reduction proportion were similar between group A₁ and B₁ (P>0.05). Multivariable analysis showed that PONV and CRPs were independently associated with ΔALB_min ≥34% (P<0.05).ConclusionsBMI had no impact on the 30-day overall complication rate, operative time, and length of stay of patients who underwent laparoscopic radical cystectomy with intracorporeal urinary diversion. BMI <24 kg/m² was associated with higher PONV rate and more albumin loss, both of which could be optimized by ERPs.     

Efficacy of anastrozole in the treatment of hypogonadal,subfertile men with body mass index ≥25 kg/m2

BackgroundAnastrozole is a non-steroidal fourth generation aromatase inhibitor that stops the conversion of testosterone to estradiol and has been used as empiric medical therapy for the treatment of male infertility in men with an abnormal testosterone-to-estradiol ratio <10 in order to increase endogenous testosterone levels. This study sought to evaluate the efficacy of anastrozole in the treatment of hypogonadal, subfertile men with body mass index greater than 25 mg/kg² with respect to hormonal profile, semen parameters and overall fertility status.MethodsRetrospective chart review was performed of hypogonadal, subfertile men with body mass index ≥25 kg/m² who were treated with anastrozole (1 mg daily). Hormonal measurements and semen analysis prior to and after treatment was analyzed in 30 men. Total motile count was calculated from semen analysis. Clinical pregnancy rates were recorded.ResultsMen treated with anastrozole had increases in follicle stimulating hormone (4.8 versus 7.6 IU/L, P<0.0001), luteinizing hormone (3.4 versus 5.4 IU/L, P<0.0001), testosterone (270.6 versus 412 ng/dL, P<0.0001) and testosterone-to-estradiol ratio (9 versus 26.5, P<0.0001) and decrease in estradiol level (32 versus 15.9 pg/mL, P<0.01) after 5 months of therapy. Increases in sperm concentration (7.8 versus 14.2 million/mL, P<0.001), total motile count (12.6 versus 17.7 million, P<0.01) and strict morphology (3.0% versus 3.5%, P<0.05) was appreciated. Clinical pregnancy rate for our cohort was 46.6% (14 of 30), with 71.4% (10 of 14) conceiving through in vitro fertilization, 14.2% (2 of 14) through intrauterine insemination and 14.2% (2 of 14) through natural intercourse.ConclusionsAnastrozole improves hormonal profiles and semen parameters in hypogonadal, subfertile men with body mass index over 25 kg/m² and may aid in achieving pregnancy especially in conjunction with assisted reproductive techniques.     

Three-dimensional measurement and analysis of benign prostatic hyperplasia

BackgroundThe volume and thickness of intravesical prostatic protrusion and other characteristics of benign prostatic hyperplasia have not been investigated. We determine the effects of age and prostate volume on anatomical features of benign prostatic hyperplasia using three-dimensional measurement in this study.MethodsThis retrospective study included a total of 98 patients with benign prostatic hyperplasia. Three-dimensional models of prostate, central gland, peripheral zone, intravesical prostatic protrusion, prostatic urethra and bladder were reconstructed according to pelvic T2-weighted magnetic resonance imaging of these patients. The models were used to measure the intravesical prostatic protrusion volume, intravesical prostatic protrusion thickness, intravesical prostatic protrusion index, intravesical prostatic protrusion, prostate volume, peripheral zone volume, peripheral zone thickness, peripheral zone index, prostatic urethra thickness, the angle and distance of distal prostatic urethra with regard to coronal plane and sagittal plane and so on.ResultsIntravesical prostatic protrusion volume, intravesical prostatic protrusion thickness and peripheral zone volume of prostate volume >80 mL group were significantly higher than these in prostate volume <80 mL group (P<0.001, 0.01, 0.01, respectively). These parameters significantly increased with age (P<0.001, 0.01, 0.05, respectively). Peripheral zone index was significantly lower of prostate volume >80 mL group than these in prostate volume <80 mL group (P<0.05). Peripheral zone index significantly decreased with age (P<0.01). Intravesical prostatic protrusion index had no significant difference in all age groups. Peripheral zone thickness and prostatic urethra thickness had no significant difference in all groups. The distance and angle of distal prostatic urethra prostatic urethra with regard to coronal plane were significantly higher than these with regard to sagittal plane (both P<0.001).ConclusionsThe rearward slope of the prostatic urethra is greater than the left or right offset during the process of benign prostatic hyperplasia. Three-dimensional measurement provides good supports for further clinical and scientific research.     

Bionic Tiger‐Bone Powder Improves Bone Microstructure and Bone Biomechanical Strength of Ovariectomized Rats

ObjectiveTo study the curative effect of bionic tiger‐bone powder on osteoporosis in ovariectomized rats and investigate its mechanism.MethodsOverall, a 120 female Wistar rats were randomly divided into Sham (sham‐operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger‐bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger‐bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L₆ vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three‐point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson''s trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting.ResultsCompared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P < 0.05), while the CTX level was lower (P < 0.05). Bone collagen fiber structures in the TB and TB + VD groups were repaired, and the collagen content was significantly higher than that in the OVX group (P < 0.05). In the TB group, BMP‐2, P‐SMAD1/5, RUNX2 and OPG levels were increased in bone tissue (P < 0.01), RANKL levels were decreased (P < 0.01), and the bone microstructure and biomechanical strength were improved.ConclusionBionic tiger‐bone powder promotes osteogenesis by activating the BMP2/SMAD/RUNX2 signaling pathway, suppresses osteoclasts by downregulating the OPG/RANK/RANKL signaling pathway, increases bone collagen content, and improves bone microstructure and bone biomechanical strength.     

Prognostic significance of preoperative Naples prognostic score on short- and long-term outcomes after pancreatoduodenectomy for ampullary carcinoma

BackgroundThe Naples prognostic score (NPS) is an effective and objective tool to assess the immune–nutritional status of patients with malignant tumors. The aim of this study was to investigate the clinical significance of preoperative NPS on short- and long-term outcomes after pancreatoduodenectomy (PD) for ampullary carcinoma.MethodsWe retrospectively analyzed 404 consecutive patients with ampullary carcinoma who underwent PD between January 2012 and June 2018. Preoperative NPS was calculated from serum albumin and total cholesterol concentrations, and the neutrophil–lymphocyte ratio and lymphocyte-monocyte ratio (LMR). Patients were then divided into three groups according to their NPS. Clinicopathological variables, postoperative outcomes, and survival data were compared between the three groups. Univariate and multivariate Cox analysis of overall survival (OS) and recurrence-free survival (RFS) were also conducted, and time-dependent receiver operating characteristic (ROC) curves were created to evaluate the discriminatory ability of the prognostic scoring systems.ResultsPatients with higher NPS had worse prognosis, and significant OS difference (group 0 vs. 1, P=0.02; group 1 vs. 2, P<0.001; group 0 vs. 2, P<0.001) and RFS difference (group 0 vs. 1, P=0.088; group 1 vs. 2, P<0.001; group 0 vs. 2, P<0.001). Multivariate analysis revealed that NPS was an independent significant predictor of OS (grade 2 vs. grade 1 or 0, hazard ratio: 3.067; P<0.001) and RFS (grade 2 vs. grade 1 or 0, hazard ratio: 2.732; P<0.001). The time-dependent receiver operating curve analysis showed that NPS had better prognostic performance for OS and RFS than other prognostic models. Additionally, significant differences in the incidence of postoperative morbidity were observed between the three groups, and the NPS was an independent risk factor of overall postoperative complications (grade 2 vs. grade 1 or 0, odds ratio: 1.692; P=0.02).ConclusionsThe NPS was an independent predictor of overall- and RFS in patients undergoing PD for ampullary carcinoma, and was independently associated with the incidence of postoperative complications.     

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

Effect of high-BDNF microenvironment stem cells therapy on neurogenic bladder model in rats

BackgroundThe purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism.MethodsMale Sprague-Dawley rat (12-week-old, weighing about 370–400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis.ResultsMSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01).ConclusionsIn a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF.     

Single Posterior Surgery Versus Combined Posterior–Anterior Surgery for Lumbar Tuberculosis Patients

ObjectivePosterior approach of debridement, interbody graft, and instrumentation, and combined posterior–anterior approach of posterior instrumentation and anterior debridement and interbody graft are two essential surgeries for the surgical treatment of spinal tuberculosis (TB), and, until now, which one should be chosen is still controversial. This study aimed to compare the therapeutic efficacy between the single posterior surgery and combined posterior–anterior surgery for lumbar tuberculosis (LTB) patients to elucidate the role of debridement and the effects that result from posterior structure resection.MethodsOne hundred and nineteen LTB patients managed with single posterior debridement, interbody graft, and instrumentation surgery (Group P, 73 cases), or combined posterior–anterior surgery of posterior instrumentation and anterior debridement and interbody graft (Group P‐A, 46 cases) from January 2008 to December 2016 were retrospectively analyzed. Different indexes were compared between the two groups to evaluate the curative effect and explore the role of debridement and the effects that result from posterior structure resection: operation time, blood loss, visual analog scale (VAS), Japanese Orthopaedic Association (JOA), Erythrocyte Sedimentation Rate (ESR), C‐reactive Protein (CRP), surgical complication type and rate, spinopelvic sagittal parameters (local kyphosis [LK], pelvic incidence [PI] and pelvic tilt [PT], lumbar lordosis [LL], and sacral slope [SS]), drainage retention duration, hospital stay, time of abscess disappearance, time of activity recovery, and time of bone graft fusion by t‐test or χ² test.ResultsThe follow‐up period ranged from 24 to 60 months. No significant variations were detected between the two groups for age, sex ratio, BMI, disease duration, indication, and the preoperative values of VAS, JOA, ESR, CRP, and LK (p > 0.05). The VAS, JOA, ESR, and CRP significantly improved in both groups after the operation (p < 0.05), along with the LK and LL (p < 0.05). Meanwhile, the SS, PI, and PT showed minor improvement after the operation (p > 0.05). Compared to the P‐A group, the P group had shorter operation time and less blood loss and hospital stay (p < 0.05). However, both groups presented similar VAS, JOA, ESR, CRP, and LK improvements (p > 0.05). Additionally, the surgical complication type and rate, postoperative spinopelvic sagittal parameters, and bone graft fusion time did not differ between the two groups (p > 0.05). On the other hand, the patients in the P‐A group had a shorter time of abscess disappearance and activity recovery (p < 0.05) but a similar time of drainage retention (p > 0.05) compared to the P group.ConclusionBoth single posterior and combined posterior–anterior surgeries presented a good therapeutic effect for LTB patients with a low surgical complication rate and good quality of LK correction and LL reconstruction and maintenance. Moreover, single posterior surgery was less traumatic than combined posterior–anterior surgery but with slower TB lesion healing and activity recovery. Compared to debridement, stability seems to be more vital for STB healing, posterior structure resection does not affect the effect of spinopelvic realignment.     

Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats

BackgroundThe role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP).MethodsA total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC.ResultsThe rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected.ConclusionsP2X3 receptors in dorsal root ganglion (DRG) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.     

The influence of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on the N- and M-staging and subsequent clinical management of intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly metastatic cancer. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) enables sensitive tumor and metastasis detection. Our aim is to evaluate the influence of pre-treatment PET/CT on the N- and M-staging and subsequent clinical management in ICC patients.MethodsBetween August 2010 and August 2018, 660 consecutive ICC patients, without prior anti-tumor treatments nor other malignancies, were enrolled. The diagnostic performance of PET/CT on the N- and M-staging was compared with conventional imaging, and the preoperative staging accuracy and treatment re-allocation by PET/CT were retrospectively calculated. Survival difference was compared between patients receiving PET/CT or not after propensity score matching.ResultsPatients were divided into group A (n=291) and group B (n=369) according to whether PET/CT was performed. Among 291 patients with both PET/CT and conventional imaging for staging in group A, PET/CT showed significantly higher sensitivity (83.0% vs. 70.5%, P=0.001), specificity (88.3% vs. 74.9%, P<0.001) and accuracy (86.3% vs. 73.2%, P<0.001) than conventional imaging in diagnosing regional lymph node metastasis, as well as higher sensitivity (87.8% vs. 67.6%, P<0.001) and accuracy (93.5% vs. 89.3%, P=0.023) in diagnosing distant metastasis. Overall, PET/CT improved the accuracy of preoperative staging from 60.1% to 71.8% (P<0.001), and modified clinical treatment strategy in 5.8% (17/291) of ICC patients, with unique roles in different tumor-node-metastasis (TNM) stages. High tumor-to-non-tumor ratio (TNR) predicted poor overall survival [hazard ratio (HR) = 2.17; 95% confidence interval (CI): 1.49–3.15; P<0.001]. Furthermore, patients performing PET/CT had longer overall survival compared with those without PET/CT (HR =0.74; 95% CI: 0.58–0.93; P=0.011) after propensity score matching.ConclusionsPET/CT was valuable for diagnosing regional lymph node metastasis and distant metastasis in ICC patients, and facilitated accurate tumor staging and optimal treatment allocation.     

Ki-67, topoisomerase IIα and miR-221 have a limited prostate cancer risk stratification ability on a medium-term follow-up: results of a high-risk radical prostatectomy cohort

BackgroundCurrently, no biomarkers are able to differentiate lethal from relatively indolent prostate cancer (PCa) within high-risk diseases. Nonetheless, several molecules are under investigation. Amongst them, topoisomerase-II-alpha (TOPIIA), Ki67 and miR-221 showed promising results. Our aim was to investigate their prognostic role in the context of biochemical recurrence (BCR), clinical recurrence (CR) and PCa-related death (PcD).MethodsWe included 64 consecutive cM0 high-risk PCa [prostate specific antigen (PSA) >20 ng/mL or Gleason Score (GS) >7 or cT >2] undergoing radical prostatectomy (RP). Changes in miR-221 expression and alternative splicing were determined using microarrays. Immunohistochemical determination of Ki67 and TOPIIa were performed using monoclonal antibody MIB-1 and 3F6 respectively. Cox proportional-hazards regression models were used to predict BCR and CR as multivariate analysis. BCR and CR were defined as three consecutive rises in PSA and PSA >0.2 ng/mL and histologically-proven local recurrence or imaging positive for distant metastasis respectively.ResultsWe included 64 men. Mean pre-operative PSA was 26.53 (range, 1.3–135); all GSs were ≥7 and pT was ≥ T3 in 78.13%. Positive margins and lymph-nodes were present in 42.19% and 32.81% respectively. At a mean follow-up of 5.7 years (range, 1.8–12.5), 42.18% experienced BCR (n=27), 29.68% CR (n=19) and 7.81% PcD (n=5). On univariate analysis positive nodes (<0.01), seminal vesicle invasion (0.02) and miR-221 downregulation (P=0.03), but not Ki67 and TOPIIA (both P>0.5) were associated with BCR whereas only PSA (P<0.01), seminal vesicle invasion (P<0.01) and positive nodes (both P<0.01) were linked to CR. No parameters predicted PcD (all P>0.05) or BCR and CR on multivariate analysis (all P>0.05 - miR-221 HR 0.776; 95% CI: 0.503–1.196 for BCR and HR 0.673; 95% CI: 0.412–1.099 for CR). Limitation of the study include its small sample size and limited follow-up.ConclusionsTOPIIA, Ki-67 and miR-221 may not predict BCR, CR or PcD in high-risk PCa patients who underwent RP at a medium-term follow-up. Longer follow-up and larger cohorts are needed to confirm our findings.