Abstract Background The analgesic effects of erector spinae plane block in general anesthesia for cesarean section and recovery from puerperae remain unclear. Methods Sixty patients with contraindications for spinal anesthesia who required general anesthesia for cesarean section were enrolled and randomly divided into the erector spinal plane block (ESPB) combined with the general anesthesia group (group E) and general anesthesia group (group G). Group E received bilateral ESPB (20 ml of 0.25% ropivacaine on each side) under ultrasound guidance 30 min before general anesthesia. The primary outcomes were the number of patient-controlled intravenous analgesia (PCIA) boluses, and Bruggemann comfort scale (BCS) scores at 2 h, 6 h, 12 h, and 24 h after operation. The second outcome was intraoperative anesthesia dosage, fetal delivery time, puerperae emergence time, visual analog scale (VAS) at 2 h, 6 h, 12 h, and 24 h after operation, and incidence of nausea and vomiting. Heart rate (HR) and mean arterial pressure (MAP) were recorded 10 min before the start of anesthesia (T0), at the induction of anesthesia (T1), at skin incision (T2), and fetal delivery (T3), and immediately after surgery (T4). Results The number of PCIA boluses was lower in group E than in group G ( P < 0.001). The BCS score increased at 2 h and 6 h after the operation in group E ( P < 0.05), while the VAS score significantly decreased in group E at the same time ( P < 0.05). Compared with group G, the doses of propofol and remifentanil were significantly decreased in group E ( P < 0.001), the emergence time of puerperae was shortened ( P = 0.003), and the incidence of nausea and vomiting was significantly decreased ( P = 0.014). Conclusion Ultrasound-guided ESPB applied to general anesthesia for a cesarean section can significantly reduce the required dose of general anesthetic drugs, shorten the recovery time of the puerperae, and improve postoperative analgesia. Trial registration: www.clinicaltrials.gov under the number ChiCTR2200056337 (04–02-2022).
To test the efficacy of lansoprazole, bismuth, levofloxacin, and amoxicillin therapy compared to bismuth metronidazole tetracycline (BMT) quadruple therapy for second-line treatment of Helicobacter pylori infection.A total of 284 patients who failed prior H. pylori eradication were randomized to receive 14-day regimens containing lansoprazole 30 mg twice a day (b.i.d.), bismuth subcitrate 240 mg b.i.d., and either amoxcillin, 1 g b.i.d. and levofloxacin 500 mg once daily (qd) (levofloxacin/bismuth therapy) or metronidazole 400 mg four times daily (q.i.d.) and tetracycline, 500 mg q.i.d. (BMT quadruple therapy). Endoscopy and culture were performed before treatment. Antimicrobial susceptibility was by agar dilution. H. pylori status was determined 6 weeks after the end of therapy using a (13)C-urea breath test.The metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates were 85.3%, 40.2%, 1.1%, and 0.5%, respectively. The intention-to-treat and per-protocol (PP) eradication rates were 83% (95% confidence interval [CI]: 75.9-88.3%) and 88.1% (95% CI: 81.2-92.4%) (p = 0.22) for levofloxacin-bismuth (levo-bismuth) versus BMT quadruple, respectively, and PP rates were 85.4% (95% CI: 78.5-90.3%) and 90.6% (95% CI: 84.6-94.5%) (p = 0.18). Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth (22.4% vs. 5%, p < 0.001) and higher in women (28.4%) than men (10.4%) in BMT quadruple therapy group (p = 0.015).Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection. However, compliance was significantly higher with levo-bismuth quadruple therapy, especially among women.
The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell-based myocardial therapy are needed.The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation.MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications.Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted.
Objective
To investigate the prognostic significance of the lymphovascular invasion (LVI) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).
Methods
A retrospective review was performed on 812 patients who underwent radical nephroureterectomy for UTUC in our hospital from January 1998 to March 2016. Among all the patients, 534 were male and 278 female, with median age 67 years old(ranged 25 to 89 years). Three hundred and three patients had hypertension and 119 patients had diabetes. Hydronephrosis was present in 393 patients. 445 patients had tumor in left side and the remaining 367 in right side. The tumor was located in the renal pelvis in 422 patients and was ureteric in 319 patients and multifocal in 71 patients. Low pathological grade and high pathological grade was diagnosed in 239 and 573, respectively. The χ2 test was used to detect the association between lymphovascular invasion (LVI) and several clinicopathological features. Kaplan-Meier method with the log-rank test was used to assess overall survival (OS) and cancer-specific survival (CSS). Multivariate analysis was conducted using Cox proportional-hazards regression model.
Results
There were 396 cases with pathological stage Tis+ Ta+ T1, 135 cases T2, 257 cases T3 and 24 cases T4. Of all patients, 52 had lymph node metastasis. The median follow-up time was 41 months (ranged 2 to 206 months). Of all 812 patients included, 110 patients (13.5%) had LVI, while 702 patients (86.5%) were LVI negative. The 5-year OS and CSS was 44.8% and 48.9% for LVI positive group while 70.1% and 76.0% for LVI negative group (P<0.001). Furthermore, there were statistically significant differences between LVI positive group and LVI negative group in hydronephrosis, tumor grade, tumor stage, muscle invasion and lymph node metastasis (P<0.05). Cox regression showed LVI, advanced age (≥65 year), higher tumor grade, advanced tumor stage (≥pT2), lymph node metastasis and multifocal tumor were significant prognostic factors in patients with UTUC after RUN.
Conclusion
UTUC may have a poor prognosis and LVI could be an independent predictor of both OS and CSS.
Key words:
Upper tract urothelial carcinoma; Radical nephroureterectomy; Lymphovascular invasion; Prognosis
Abstract The vesicular monoamine transporter (VMAT2) plays a crucial role in maintaining dopamine (DA) homeostasis through packaged DA into vesicles, which has been suggested to being an excellent marker for presynaptic dopaminergic nerve terminals in the nigrostriatal of Parkinson's disease. Gastrodin (GTD), the major bioactive compound of Gastrodia elata , has shown neuroprotective in animal models for many neurological disorders. However, it is unclear whether GTD confers neuroprotection via activating VMAT2 to maintain DA homeostasis in an animal model of Parkinson's disease (PD) using the DA neuron-specific toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we first identified that GTD could ameliorate cell damage and the dysfunction of DA homeostasis in PC12 cells induced by MPTP via up-regulating VMAT2 expression. Moreover, GTD could enhance VMAT2 protein expression, increase striatal vesicle volume, and ameliorate DA dysregulation in MPTP-induced PD mice. Furthermore, we found that the DA homeostasis and therapeutic effect of GTD could be reversed by the VMAT2 inhibitor in vitro and in vivo. Finally, we confirmed that GTD could increase VMAT2 expression by activating MEK/ERK pathway. In summary, our data showed that GTD attenuated MPTP neurotoxicity through activating of the MEK/ERK/VMAT2 signaling pathway maintained DA homeostasis, suggesting that the manipulation of VMAT2 by GTD may provide a potential therapeutic strategy for PD.
The cultivation of general practitioner is a key to improve China ’s community-based medical and health care system. Zunyi Medical University, in the process of cultivating tuition-free students with the mode of serving and staying in the countryside after their graduation, always upholds the principles of being oriented by post competence, being led by medical humanities, optimizing featured courses about general practitioner, carrying out students-centered teaching methodology, focusing on training students' autonomous learning ability, and fully building the practical teaching system, so as to strive to cultivate high-quality talents in the field of general medicine to make them better serve the rural community-based medical institutions.
Key words:
Post competency; General medicine; Cultivation
Summary Background Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. Aim To test the effectiveness of susceptibility‐guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first‐line H pylori treatment in a region with high antimicrobial resistance . Methods We compared 14‐day susceptibility‐guided with empiric therapy using a multicentre superiority‐design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility‐guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple‐resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylori eradication. Results Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility‐guided and the empiric regimens were highly successful with per‐protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent‐to‐treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility‐guided therapy was not superior to empiric therapy with 0.1% per‐protocol (95% CI −3.1% to 3.2%) and 6.2% intent‐to‐treat (−0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. Conclusions Both susceptibility‐guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.
Background: The prognostic risk of non-metastatic clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is variable among individual patients following radical nephrectomy and thrombectomy. We sought to develop and validate a prognostic model for the risk-stratification of these patients by evaluating comprehensive pathological characteristics of VTT, especially the pathological grading of VTT.Methods: A nationwide cohort of non-metastatic ccRCC patients with VTT from China were subdivided into training (n=664) and internal validation (n=517) cohorts, followed by an external validation cohort from Poland (n=82). Independent predictors from multivariable Cox regression analysis were developed into a prognostic model that was assessed by Harrell's concordance index (c-index), area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA).Findings: Using a multi-cohort of 1263 patients, we identified that VTT grading represents an unheeded and powerful independent prognostic factor of adverse outcomes across all cohorts in multivariate analysis for overall survival (OS) and disease-free survival (DFS) (P < .001; P < .001; P = 0.014 in China-Training, China-Validation, and Poland-Validation cohorts, respectively). A risk positioning model, named the TT-GPS score, was constructed based on the four independent predictors: VTT height, WHO/ISUP Grading in VTT, Perinephric fat invasion, and Sarcomatoid differentiation in primary tumor. The TT-GPS score (OS, c-index: 0.736 and 0.746, AUC: 0.828 and 0.815; DFS, c-index: 0.705 and 0.710, AUC: 0.797 and 0.787 in China-Training and China-Validation cohorts, respectively) displayed better accuracy and discriminatory ability than previously reported models in risk assessment. Poland-Validation cohort established the superiority of the TT-GPS score (OS, c-index: 0.840, AUC: 0.874).Interpretation: VTT grading displayed superior accuracy in prediction of survival risk. By incorporating VTT grading, the TT-GPS score is a powerful predictor of adverse outcomes in non-metastatic ccRCC patients with VTT beyond previously reported models. As it is based on routinely available clinical and pathologic characteristics, it can be readily applied in routine practice.Funding Information: This work was supported by the National Natural Science Foundation of China (No. 81772740 and 82173345 to Le Qu, No. 81972333 to Cheng Chen, No. 81730073 and 81872074 to Linhui Wang), Foundation for Distinguished Youths of Jiangsu Province (No. BK20200006 to Le Qu).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the institutional review board of each participating site (ID Number: 2021NZKY-004-01).