Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

【Objective】 To explore the surgical treatments and therapeutic outcomes for benign testicular tumor. 【Methods】 Clinical data of 53 patients with benign testicular tumor treated with surgery during May 2004 and Jul.2021 were retrospectively analyzed. 【Results】 The postoperative pathological diagnosis of 53 patients included 33 patients with epidermal cysts, 12 with mature teratomas, 2 with bilateral testicular tumors (one of them was epidermal cysts in the left and mature teratoma in the right, and the other was bilateral leiomyomas), and 6 benign cases. Testis sparing surgery (TSS) group had 23 patients and radical orchiectomy (RO) group had 30 patients. There were no significant differences in patients’ age, tumor location, disease course, and ultrasound examination results between the two groups (P>0.05). The tumor size of the RO group was (2.60±0.94) cm, which was larger than that of the TSS group (1.55±0.52) cm (P<0.001). There were no statistically significant differences in surgical time and postoperative hospital stay between the two groups (P>0.05). A total of 15 patients (13 with TSS and 2 with RO) underwent intraoperative frozen rapid pathological examination (FSA), which was consistent with post-operative paraffin pathological results. Durign the follow up of 2-219 months,median 38 months, there was no recurrence in either groups. 【Conclusion】 Testis sparing surgery is a reliable treatment modality for benign testicular tumor, which may also decrease the level of androgen and incidence of asthenozoospermia. It can be considered for tumors less than 2 cm with benign tendency or uncertain nature.

Objective To investigate the value of echocardiography in assessing right ventricular function of primary light-chain amyloidosis(AL)-cardiac amyloidosis(CA)patients.Methods A total of 25 patients biopsy diagnosed as AL-CA,who were admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to December 2021,were enrolled in this study as amyloidosis group.And 25 heathy volunteers were set as control group.The routine right ventricular morphology and functional parameters were acquired by standard echocardiography.Right ventricular global longitudinal strain(RVGLS)and right ventricular free wall longitudinal strain(RVfwLS)were obtained by two-dimensional speckle tracking imagine.Tricuspid annular plane systolic excursion(TAPSE)/pulmonary artery systolic pressure(PASP),RVGLS/PASP,RVfwLS/PASP ratio were calculated as the noninvasively parameters of right ventricular-pulmonary artery coupling.Results ①Compared with control group,patients in amyloidosis group showed significantly larger right heart size,and significantly thicker right ventricular free wall[(7.16±1.84)mm vs.(3.76±0.66)mm],the difference was statistically significant(P<0.001).②Compared with control group,RVGLS[(17.43±2.45)%vs.(23.22±3.73)%]and RVfwLS[(18.44±2.10)%vs.(22.62±3.64)%]were significantly impaired in amyloidosis group,the difference was statistically significant(P<0.001).The ratios of TAPSE/PASP,RVGLS/PASP,RVfwLS/PASP were found to be lower in amyloidosis group,the difference was statistically significant(P<0.001).③TAPSE/PASP showed mild correlations with N-terminal brain natriuretic peptide precursor(NT-proBNP),highly sensitive T cardiac troponin(hs-TNT)(r=0.45 and 0.40)there were statistically significant(P<0.05).Conclusion Echocardiography can effectively evaluate the right heart function impairment in AL-CA patients,providing valuable information for a deeper understanding of the pathological and physiological mechanisms of the disease.

Objective:To evaluate the clinical and echocardiographic characteristics of valvular involvement in SLE patients and its predictive value for valvular outcome.Methods:A retrospective study included 58 adult SLE patients with valvular involvement diagnosed for the first time by echocardiography in the First Affiliated Hospital of Wenzhou Medical University. According to gender and age, 1∶2 SLE patients without valvular involvement were selected as the control group. Clinical and echocardiographic data within 24 hours after initial admission were collected. The predictive factors were analyzed using cox parametric regression analysis.Results:①Among 58 patients,significant valve lesions were detected by echocardiography in 50 and presented as valve thickening with regurgitation. The mitral valve was the most commonly affected, followed by the aortic valves. ②Compared with the non-valvular involvement group, the percent of CRP, SLC-R, IgA、aCL-IgG were higher in the valvular involvement group [CRP:60.3% vs 30.4%, χ2=10.54, P=0.001; SLC-R: 63.8% vs 19.8%, χ2=33.08, P<0.001; IgA:27.6% vs 22.4%, χ2=16.04, P<0.001; aCL-IgG: 27.6% vs 2.6%, χ2=24.84, P<0.001]. ③Cox parametric regression analysis showed that CRP [ HR (95% CI)=2.641(1.499, 4.654), P=0.001,SLC-R HR(95% CI)=3.234(11.776, 5.888), P<0.001], and aCL-IgG[ HR(95% CI)=2.166 (1.148, 4.087) , P=0.017] were independent predictors of valvular involvement. Conclusion:SLE patients with increased levels of CRP、SLC-R、IgA and aCL-IgG have a high risk of valvular involvement. CRP、SLC-R and aCL-IgG are independent predictors of valvular involvement.

Objective:To study the teaching effect of traditional teaching combined with virtual simulation teaching in pharmaceutical content analysis using high performance liquid chromatography (HPLC).Methods:The students in two parallel classes of grade 2016 were divided into experimental group (44 students) and control group (38 students). Taking the content analysis and its related analytical methodology of Metronidazole by HPLC as an example, the experimental group adopted the traditional offline teaching combines with virtual simulation teaching, and the control group adopted the traditional offline teaching. The teaching effects of the two groups were compared. SPSS 22.0 was used to conduct independent-samples t-test. Results:According to the mid-term test results, the experimental group was superior to the control group in practical operation assessment [(17.98±6.75) vs. (14.03±5.92)], and the difference was statistically significant ( P < 0.05). But there were no differences between the two groups in the scores of theory, discussion report and presentation. There was no significant difference in the final exam scores between the two groups. Conclusion:The ability of practical training and the teaching effect can be improved by the teaching method of traditional offline teaching combined with virtual simulation. Through the training of this project, students have mastered the operation of HPLC, the content determination of pharmaceutical preparations, the verification of analytical methods, data processing, and the writing of analytical reports, and have certain practical analysis ability.

Objective:To explore health utility value, evaluate health-related quality-of-life(QOL)of pediatric liver transplantation(LT)recipients and examine its influencing factors to provide rationales for related health economic evaluations.Methods:This cross-sectional QOL was conducted through a questionnaire in pediatric LT recipients aged 5-17 years.The interviewees undergoing initial LT from June 2013 to September 2021 were reviewed regularly.Those children and their parents unwilling to participate or failing to understand the contents of questionnaire were excluded.The questionnaire was designed on the basis of Child Health Utility 9D Instrument(CHU9D)and answered online by one of primary caregiver.Chinese score system of CHU9D was employed for converting the responses into health utility values and the influencing factors were analyzed.Univariate analysis was performed by nonparametric tests and multivariate analysis by multiple linear regression model. P<0.05 was deemed as statistically significant. Results:A total of 140 valid questionnaires were obtained.Mean age of pediatric LT recipients was(7.95±2.74)years and mean postoperative time(4.90±2.17)years.Among them, 19 cases had experienced acute rejection and 101(72.1%)cases were living-related LT recipients.CHU9D scale indicated that average health utility value was(0.85±0.14)points.Univariate analysis revealed that age( P=0.008), education level( P<0.001)and primary disease( P=0.010)influenced the postoperative level of QOL.Multivariate analysis indicated that QOL was correlated with education level(behind schedule: 95% CI: -0.146, -0.034, P=0.002; leave of absence: 95% CI: -0.251, -0.068, P=0.001). Conclusions:Health utility of pediatric LT recipients is high with an excellent QOL.Poor QOL is associated with absence from school or dropping out of school.

AIM: To investigate the effects of hyperoside on traumatic brain injury (TBI) rats by regulating the Ras homolog gene family, member A (RhoA)/Rho-associated coiled coil-forming kinase (ROCK) signal pathway. METHODS: The TBI rat model was established by modified Feeney free fall hit method, and was randomly divided into model group, low-dose hyperoside (60 mg / kg) group, high-dose hyperoside (120 mg / kg) group, high-dose hyperoside (120 mg / kg) + no load group, and high-dose hyperoside (120 mg / kg) + RhoA overexpression group, with 10 rats in each group, another 10 healthy rats were set as sham operation group, after hyperoside and plasmid were grouped, the nerve injury was detected by modified neurological deficit score (mNSS) and dark avoidance test; Evans blue (EB) quantitative method was used to detect the permeability of blood brain barrier in rats; ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy; the levels of tumor necrosis factor- α (TNF- α), interleukin-8 (IL-8), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue of rats were measured with the kit; and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot. RESULTS: Compared with the sham operation group, the blood brain barrier structure of the model group rats was damaged, the step-through latency and SOD level decreased obviously (P<0.05), the mNSS score, the number of mistakes, the content of EB in brain tissue, the levels of TNF - α, IL-8, MDA in serum and brain tissue, and the expression of RhoA, ROCK1, ROCK2 proteins in brain tissue increased obviously (P<0.05). Compared with the model group, the damage of blood brain barrier structure of rats in the low - dose hyperoside group and the high-dose hyperoside group was alleviated, the step-through latency and SOD level increased (P<0.05), the mNSS score, the number of mistakes, the content of EB in brain tissue, the levels of TNF-α, IL-8, MDA in serum and brain tissue, and the expression of RhoA, ROCK1, ROCK2 proteins in brain tissue all decreased (P<0.05); high-dose hyperoside group has stronger effect. Overexpression of RhoA can reverse the effects of high-dose hyperoside on various indexes of TBI rats; there was no obvious change in all indexes in high-dose hyperoside+empty load group (P>0.05). CONCLUSION: Hyperoside can inhibit neuroinflammation and oxidative stress in TBI rats by down-regulating RhoA / ROCK signal pathway, thereby reducing the damage of blood brain barrier and repairing its neural function.

Objective: To explore the clinical efficacy of spine subtle adjusting manipulation for postpartum low back pain (PLBP). Methods: A total of 76 patients with PLBP were randomized into a control group and a treatment group, with 38 cases in each group. The control group was treated with core muscle strengthening exercises, and the treatment group was treated with spine subtle adjusting manipulation. After 3 weeks of treatment, the clinical efficacy was observed, and the visual analog scale (VAS) score and Oswestry disability index (ODI), and the changes of lumbar Cobb angle and pelvic rotation were compared between the two groups. Results: The total effective rate of the treatment group was 92.1％, and that of the control group was 78.9％. The difference between the two groups was statistically significant (P<0.05). After treatment, the VAS score and ODI in both groups decreased, and the intra-group differences were all statistically significant (P<0.05). There were no intra-group statistical differences in the lumbar Cobb angle or pelvic rotation in the two groups (P>0.05). After treatment, there were no statistical differences in the lumbar Cobb angle or pelvic rotation between the two groups (P>0.05); the VAS score and ODI in the treatment group were significantly lower than those in the control group (P<0.05). Conclusion: Spine subtle adjusting manipulation can effectively relieve the pain for patients with PLBP, and improve their daily activity function.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients' infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Models, Theoretical ; Pandemics ; SARS-CoV-2