Effect of Wuzi Yanzong Pills on Sertoli cells and blood–testis barrier in heat-stressed rats based on Akt signalling pathway

The blood–testis barrier (BTB) of Sertoli cells (SCs) is an important biological barrier that maintains spermatogenesis and provides a favourable microenvironment for spermatogenesis. However, heat stress can directly damage the BTB structural proteins of testicular SCs, leading to dyszoospermia. Wuzi Yanzong Pills (WYP) is a traditional Chinese medicine formula used to treat male reproductive diseases. However, whether WYP could ameliorate heat stress injury in primary SCs extracted from rat testes and BTB proteins remains unknown. Here, treatment with WYP (low, medium and high dose) increased the SC viability and the proliferation of cell antigen Ki67 significantly. Additionally, it promoted SC maturation, which presented in the form of increased androgen receptors (ARs) and decreased cytokeratin 18 (CK-18) in three WYP dose groups. WYP upregulated BTB proteins such as zonula occludens 1 (ZO-1) and occludin across all WYP groups and decreased phosphorylated Akt (p-Akt) in the middle and high-dose groups; however, ZO-1 and occludin recovery were reduced with the presence of Akt inhibitor in WYP groups. WYP improved SC viability and proliferation, and ameliorated dedifferentiation and BTB-proteins damaged by heat stress via Akt signalling. The findings present theoretical support for the effects of WYP in the management of dyszoospermia and male infertility.     

Research trends of prostatitis over past 20 years: A bibliometric analysis

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.     

Observation versus radiotherapy with or without temozolomide in postoperative WHO grade II high-risk low-grade glioma: a retrospective cohort study

The optimal adjuvant treatment of high-risk low-grade glioma (LGG) is controversial. We performed this retrospective cohort study to compare three treatments including observation, radiotherapy (RT) alone, and radiotherapy combined with concomitant and adjuvant temozolomide (TMZ) chemotherapy (STUPP regimen) in patients with high-risk LGG. Patients with high-risk (age > 40 or undergoing subtotal resection or biopsy) LGG treated with observation or radiotherapy alone or STUPP regimen after operation were retrospectively analyzed. Survival rates were evaluated by the Kaplan-Meier method; the log-rank test was applied to compare differences between groups. A total of 250 patients met the inclusion criteria. Median follow-up for living people was 70 months. Overall, patients who received radiotherapy with or without temozolomide had better progression-free survival (PFS) and overall survival (OS) when compared with observation (median PFS: observation, 59 months; RT, 82 months; STUPP, not reached; median OS: observation, 96 months; RT, not reached; STUPP, not reached), whereas STUPP regimen did not further prolong PFS or OS than RT alone (PFS, P = 0.203; OS, P = 0.146). In oligodendroglioma (IDH mutant and 1p/19q codeleted) subtype, only STUPP regimen brought longer PFS when compared with observation (P = 0.008). The incidence of grade 3 or 4 neutropenia (P < 0.001) and nausea or vomiting (P = 0.004) was higher in the STUPP group than the figure for the RT alone group. PFS and OS were similarly improved in patients with high-risk LGG receiving RT alone or STUPP regimen. However, only STUPP regimen was able to bring better PFS for oligodendroglioma (IDH mutant and 1p/19q codeleted) subgroup. Longer follow-up time is needed to determine an association with treatment effect in different histological and molecular subgroups.

     

Approach selection and outcomes of craniopharyngioma resection: a single-institute study

Neurosurgical Review - Since there are many approaches for successful craniopharyngioma resection, how to choose a suitable approach remains problematic. The aim of this study was to summarize...     

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson’s disease: a systematic review

Neurosurgical Review - Magnetic resonance imaging-guided focused ultrasound (MRgFUS) neurosurgery is a new option for medication-resistant Parkinson’s disease (PD), but its safety and...     

Inhibition of Smad3 promotes the healing of rotator cuff injury in a rat model

To investigate the effect of inhibiting transforming growth factor‐β (TGF‐β1)/Smad2/3 signaling on rotator cuff (RC) healing. A bilateral supraspinatus tendon detachment‐repair model of Sprague‐Dawley (SD) rats was utilized. A total of 120 SD rats were randomly assigned to six groups and each group received the subacromial injection of normal saline, empty vectors, or lentiviral vectors containing small interfering RNA against TGF‐β1, Smad2, Smad3 at the bone‐tendon junction. Biomechanical and histological analyses were performed to evaluate bone‐tendon junction healing quality at 8 weeks after repair. Histologically, scar healing was found in all surgical groups. Animals with inhibited Smad3 exhibited better bone‐tendon junction structures with higher density, parallel orientation, and collagen fiber continuity than other surgical group animals. Immunohistochemistry revealed that the protein expression level of collagen I in animals with inhibited Smad3 was more prominent compared with all other surgical groups. Biomechanically, Animals with inhibited Smad3 showed better results in the maximum load at 4, 6, and 8 weeks after surgery compared with other surgical groups. Besides, C3H10T1/2 (Smad3?) cells increased TT‐D6 cell migration and tendon‐associated genes expression (scleraxis, tenascin C, collagen I) in coculture system. We conclude that inhibition of Smad3 promotes RC tendon healing in the rat supraspinatus model.     

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus

AimsChronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear.MethodsThis retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis.ResultsAmong all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385–11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis.ConclusionsDKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.     

Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies

Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.