EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes,by Activating AMPK-Dependent Pathway

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.     

Radiotherapy of granulomatosis with polyangiitis occurring in the eyelid: A case report and literature review

Introduction:Granulomatosis with polyangiitis (GPA) is a chronic systemic vasculitis characterized by necrotizing granulomatous vasculitis. The disease mainly affects the middle and small blood vessels and mainly occurs in the upper respiratory tract (nose and paranasal sinuses), lower respiratory tract (lungs), and kidneys. Disease occurrence in the eyelid area is relatively rare. The standard GPA treatment is combination therapy with adrenocortical hormone and immunosuppressants. Radiotherapy as a treatment option for GPA has not been widely investigated.Patient concerns:A 29-year-old man presented with a 1.0 × 1.0 cm mass without exophthalmos and decreased vision in the left lower eyelid. Computed tomography revealed a mass-like high-density shadow below the left eye with a computed tomography value of 80-108 U.Diagnosis:The laboratory investigations revealed positive cytoplasmic antineutrophil cytoplasmic antibodies (titer = 1:40). Biopsy of the lower left eyelid mass revealed necrosis and granulomatous reaction with a large number of inflammatory cell infiltration. After consultation with the pathology department, the diagnosis was determined as left lower eyelid GPA.Interventions:The patient received 9MeV electron beam radiation therapy in the area of the left lower eyelid lesion.Outcomes:The lesion in the patient was significantly reduced and the symptom relieved obviously. No symptom recurrence or significant toxicity occurred during or after the treatment. The patient remains under routine follow-up.Conclusion:We present a case of a male patient with GPA located exclusively in the eyelid area, who underwent successful radiotherapy and achieved a complete response. The lesson we learned from this case study is that for GPA patients, when the standard treatment model fails to achieve good results, novel treatments such as radiotherapy should be considered according to the situation.     

The meta-analysis of the effect of 68Ga-PSMA-PET/CT diagnosis of prostatic cancer compared with bone scan

Background:⁶⁸Ga-PSMA-PET/CT (positron emission tomography/computed tomography) is a promising method for prostate cancer (PC) detection. However, the ability of ⁶⁸Ga-PSMA-PET/CT to detect malignant bone lesions, and whether this method is superior to the existing bone imaging methods are still lack of systematic analysis.Purpose:To evaluate the value of ⁶⁸Ga-PSMA-PET/CT and bone scan in clinical diagnosis of prostatic cancer from the perspective of evidence-based medicine.Methods:PubMed, The Cochrane Library, EMBASE, Springer Link, Sinomed, CNKI, Wanfang database, and CQVIP database were searched to find the satisfactory studies that needed systematic review of trials and compared the value of 68Ga-PSMA-PET/CT and bone scan. All studies published from inception to March 31, 2020. According to the inclusion and exclusion criteria, 2 reviewers independently evaluated and extracted the literature. Review Manager 5.3 was applied to evaluate the included literature quality. The heterogeneity of the included literature was tested by Meta Disc 1.4, and the effect model was selected according to the heterogeneity test results, and the sensitivity (SEN), specificity (SPE), PLR, NLR and diagnostic odds ratio (DOR) were analyzed. After testing the heterogeneity results of literature by using the 95% confidence interval and the forest map.Results:A total of 4 studies were eligible for inclusion in the meta-analysis, which included 318 patients, 120 cases with bone metastasis and 198 cases without bone metastasis. The results of summary evaluation for ⁶⁸Ga-PSMA-PET/CT and bone scan in diagnosis of prostatic cancer as follow respectively: The SEN were 0.97 and 0.86; the SPE were 1.00 and 0.87; the DOR were 1468.33 and 36.23; PLR were 88.45 and 6.67; NLR were 0.05 and 0.19; and the area under curve (AUC) and 95% CI were 0.9973 (1.0000–0.9927) and 0.8838 (0.9584–0.8092).Conclusion:By comparing the diagnostic results of ⁶⁸Ga-PSMA-PET/CT and bone scan imaging diagnosis methods, the ⁶⁸Ga-PSMA-PET/CT has a higher SEN and SPE than bone scan, and it has a higher diagnostic efficiency for prostate cancer bone metastasis, which is worthy of clinical application.     

The safety and effectiveness of salvianolate in preventing perioperative venous thromboembolism in China: A PRISMA-compliant meta-analysis based on RCTs

Background:Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China.Objective:This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients.Methods:Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis.Results:A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05).Conclusion:Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.     

Endoscopically assisted transoral resection of a Bailey type IV second branchial cleft cyst: A case report

Rationale:The diagnosis of type IV branchial cleft cyst (BCC) according to the Bailey classification is very challenging due to lack of specific clinical manifestations in the early stage of the disease. Here, we present the transoral surgical route of endoscopic resection of second BCC in the parapharyngeal space (PPS) with good outcomes.Patient concerns:A 21-year-old man with a 1-year history of snoring complained about sore throat for 1 month and a fever that lasted for 3 days.Diagnoses:On admission, physical examination revealed a temperature of 39°C, pain when swallowing accompanied with a lump sensation in the throat, and inability to open mouth more than 3 cm. Blood testing revealed 19.29 × 10⁹ white blood cells (WBCs)/L and 14.94 × 10⁹ neutrophils/L. A cervical computed tomography (CT) examination revealed a mass with liquid density of 6.2 × 4.0 × 7.7 cm³ in the left parapharyngeal space (PPS) and pharyngeal cavity stenosis. Postoperative pathology showed the existence of lymphoepithelial cysts (left PPS), which was in accordance with the diagnosis of BCC.Interventions:The patient was administered 1.5 g ceftazidime every 12 hours, anti-inflammatory drugs, and incision drainage was performed subsequently. Then, endoscopy-assisted resection of the left PPS was performed via the transoral route. We used low-temperature plasma and an 8-Fr Foley catheter with a water capsule during the surgery.Outcomes:After resection of the mass, the patient''s blood results returned to within the normal range and his symptoms improved. Five days postoperatively, the incision made in the palatine arch of the pharynx opened up by 1 cm, and eventually the wound and laceration healed. Normal oral eating was restored, and no complications were observed.Lessons:Magnetic resonance imaging (MRI), and color Doppler ultrasound can be useful to diagnose BCC in PPS, which rarely occurs in the clinical setting. Extended endoscopy provides a satisfactory surgical field for trans-oral resection allowing complete resection of the BCC without serious postoperative complications.     

The efficiency and safety of manual therapy for cervicogenic cephalic syndrome (CCS): A systematic review and meta-analysis

Background:Manual therapy is a common technique for the treatment of (CCS) cervicogenic cephalic syndrome, but the efficiency is various. The aim of the study is to evaluate the evidence pertaining to the efficiency and safety of using manual therapy to treat patients with CCS.Methods:We searched the electronic databases including PubMed, ScienceDirect, and the Cochrane Library. Only randomized controlled trials (RCTs) were enrolled in this systematic review and cumulative meta-analysis.Results:A total of 8 RCTs with 395 patients were included for meta-analysis. Patients who underwent manual therapy showed lower scores of visual analog scale (VAS) (weighted mean difference) WMD = 1.7, 95% confidence interval CI = 0.74–2.65, P = .0005); dizziness handicap inventory (DHI) (WMD = 0.66, 95%CI = 0.31–1, P = .0002); and neck disability index (NDI) (WMD = 0.59, 95%CI = 0.23–0.96, P = .002) and better rotation range of motion (ROM) of the cervical spine (WMD = −6.54, 95%CI = −7.60 to −5.48, P < .0001). However, these patients did not show much benefit from manual therapy with respect to the frequency of CCS episodes and head repositioning accuracy (HRA). No serious adverse effects were reported in our included studies lasting longer than 24 hours.Conclusions:Manual therapy offers an effective and safe approach to treat CCS with lower VAS, DHI, and NDI scores and better cervical spinal movement. Further high-quality RCTs are required to provide more conclusive evidence.Systematic review registration number:PROSPERO172740.     

Exploration of simulation-based medical education for undergraduate students

Over the past decades, extensive studies have underscored the growing importance of simulation-based medical education (SBME) for medical students. However, the underlying influence of SBME on undergraduate students is yet to be investigated. This work is a single-center cohort study involving 1178 undergraduate students who were divided into a control group and an SBME group. All participants gave their written informed consent. We compared the theoretical and practical achievements of these 2 groups and distributed a feedback questionnaire. Results show that SBME significantly improves the practical or theoretical achievements of students (P < .001). The humanistic care (improvement rate: 69.2%) and doctor–patient communication (improvement rate: 56.3%) performances of these studies were vastly improved. The students in the SBME group tend to allocate more time to communicating with others. SBME is an effective teaching method that can improve the reflective capacity and communication skills of undergraduate medical students, thereby resulting in their relatively improved performance.     

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Aim:

Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.

Methods:

Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg⁻¹·d⁻¹) or PEG-CDs (size: 8.3 nm, 5 mg·kg⁻¹·d⁻¹) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos'' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf.

Results:

Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments.

Conclusion:

CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.     

Current treatment and outcome of esophageal perforation: A single-center experience and a pooled analysis

Background:Esophageal perforation has been one of the serious clinical emergencies, because of the high mortality and complication rates. However, the current prognosis of esophageal perforation and the outcomes of available treatment methods are not well defined. This study attempted to pool the immediate outcomes of esophageal perforation in the past 2 decades.Methods:The clinical data of 22 consecutive adult patients with esophageal perforation in our center were analyzed. A pooled analysis was also conducted to summarize results from the literatures published between 1999 and 2020. Studies that met the inclusion criteria were assessed, and their methodological quality was examined.Results:The mortality and complication rates in our center were 4.55% and 31.82%, separately. The pooled analysis included 45 studies published between 1999 and 2019, which highlighted an overall immediate mortality rate of 9.86%. Surgical treatments were associated with a pooled immediate mortality of 10.01%, and for conservative treatments of 6.49%. Besides, in the past decade, the mortality and complication rates decreased by 27.12% and 46.75%, respectively.Conclusions:In the past 2 decades, the overall immediate mortality rate of esophageal perforation was about 10% in the worldwide, and the outcomes of esophageal perforation treatment are getting better in the last 10 years.Ethics Registration Information:LW2020011.