Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Objective:To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction.Methods:This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language.Results:Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI: 0.625-0.876). Conclusions:Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.

ObjectiveTo study the mechanism of Mahuang Xixin Fuzitang （MXFT） against migraine. MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SiwssTargetPrediction and other databases were used to screen the active components and action targets of MXFT as well as migraine-related targets. The potential protein-protein interaction （PPI） network diagram was plotted for the intersection targets of MXFT and migraine using STRING 11.5. Metascape was used for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of potential intersection targets. The component-target-pathway network of MXFT was constructed by Cytoscape 3.7.1 to screen core targets with high degree value. Finally， the binding strength between core target and its mapping components was verified by molecular docking， and the core targets with desirable docking results were verified by animal experiments in vivo. Forty eight SD rats were selected， and except the blank group， the other rats were subcutaneously injected with nitroglycerin to prepare the migraine rat model. The modeled rats were randomly divided into model group， positive drug group and MXFT high-， medium- and low-dose groups. The positive drug group was given zolmitriptan tablets， and the MXFT high-， medium- and low-dose groups were given high， medium and low doses of MXFT， respectively. The changes of behavior and pain threshold of rats in each group were observed every other day after modeling. The levels of calcitonin gene-related peptide （CGRP）， extracellular signal-regulated kinase 2 （ERK2） and c-fos proto-oncogene （FOS） protein in plasma were detected by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical technique and Western blot were employed to determine the levels of extracellular signal-regulated kinase 1/2 （ERK1/2， also known as MAPK1/3） and protein kinase B 1 （Akt1）， protein kinase C α （PRKCA） in trigeminal nerve of SD rats. ResultThe network pharmacology showed that the core targets of MXFT in the treatment of migraine were MAPK1， MAPK3， Akt1， PRKCA， etc.， mainly involving neuroactive ligand-receptor interaction signaling pathway， calcium signaling pathway， MAPK signaling pathway， etc. The molecular docking demonstrated that MAPK1， MAPK3， Akt1， PRKCA， PRKCB and PRKCG had good binding ability with their mapping components. The animal experiments indicated that compared with the conditions in the blank group， the number of head scratching in the model group was increased （P<0.01）， and the pain threshold was decreased （P<0.01）. Compared with the conditions in the model group， the number of head scratching in each administration group was reduced （P<0.01）， and the pain threshold was increased （P<0.01）. In addition， the levels of CGRP， ERK2 and FOS proteins in plasma， and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of the model group were higher than those of the blank group （P<0.05， P<0.01）. The levels of CGRP， ERK2 and FOS proteins in plasma and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of each administration group were lower than those of the model group （P<0.05， P<0.01）. ConclusionMXFT had multi-component， multi-target and multi-pathway characteristics in the treatment of migraine， and the mechanism might be related to inhibiting vasodilation， reducing the release of inflammatory factors and inhibiting neuronal hyperactivity.

Male accessory nipple is a special manifestation of accessory breast with or without presenting areola and mammary tissues. It has been recognized as a rare disease with a low prevalence. Male accessory nipples might result in embarrassing circumstances, psychological concerns, and even potential malignancy. The present study reports a case of male accessory nipples in chest wall and was treated with radical surgical resection in outpatient center at the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in November 2019. Pathology revealed pilosebaceous units in lesions without mammary tissue. 13 months after surgery, surgical areas were observed minimal cicatrix with slight pigmentation. No relapse was filed. Patient was satisfied with the cosmetic result.

Male accessory nipple is a special manifestation of accessory breast with or without presenting areola and mammary tissues. It has been recognized as a rare disease with a low prevalence. Male accessory nipples might result in embarrassing circumstances, psychological concerns, and even potential malignancy. The present study reports a case of male accessory nipples in chest wall and was treated with radical surgical resection in outpatient center at the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in November 2019. Pathology revealed pilosebaceous units in lesions without mammary tissue. 13 months after surgery, surgical areas were observed minimal cicatrix with slight pigmentation. No relapse was filed. Patient was satisfied with the cosmetic result.

Objective:To explore the independent risk factors of preoperative CT findings affecting the overall survival of patients with clear cell renal cell carcinoma (ccRCC) and to draw a nomogram.Methods:The retrospective study was performed on 238 patients with ccRCC who underwent preoperative CT scan and were pathologically confirmed in First Affiliated Hospital of Air Force Medical University from October 2011 to December 2015. CT findings of each patient were evaluated by two radiologists, and general information, renal function examination, and World Health Organization/International Society for Urology and Pathology (WHO/ISUP) grading were collected. The Kaplan-Meier survival curve was plotted, and survival rates were compared using log-rank test. Cox proportional hazard regression was used for univariate and multivariate analysis, and the nomogram was drawn according to the results of multivariate analysis, and the C-index was calculated after internal validation by Bootstrap 1000.Results:After 3-74 months of follow-up for 238 patients, 32 cases were in the death group and 206 cases were in the censored group. The tumor diameter of the death group [(65.70±27.29) mm] was larger than that of the censored group [(46.25±26.16) mm], with a statistically significant difference ( t=-3.889, P<0.001). The incidence rate of tumor necrosis ( χ2=45.716, P<0.001), regional lymph node enlargement ( χ2=43.342, P<0.001) and perirenal fat invasion ( χ2=19.324, P<0.001) in the death group were higher than those in the censored group. Survival rates were different in patients with different tumor diameter of ccRCC, with a statistically significant difference ( χ2=17.108, P<0.001). The survival rate of patients with tumor necrosis was lower than those without necrosis ( χ2=48.195, P<0.001). The survival rate of patients with regional lymph node enlargement was lower than those without regional lymph node enlargement ( χ2=47.232, P<0.001). The survival rate of patients with perirenal fat invasion was lower than those without perirenal fat invasion ( χ2=19.964, P<0.001). Survival rates were also different in ccRCC patients with different WHO/ISUP grades, with a statistically significant difference ( χ2=27.765, P<0.001). In Cox multivariate analysis, tumor diameter ( HR=2.90, 95% CI: 1.37-6.14, P=0.006), necrosis ( HR=8.88, 95% CI: 3.33-23.69, P<0.001) and regional lymph node enlargement ( HR=4.48, 95% CI: 2.04-9.86, P<0.001) in CT findings were independent risk factors for death in patients with ccRCC. The C-index of nomogram was 0.870. Conclusion:Preoperative CT findings are correlated with survival rate of patients with ccRCC, in which tumor diameter, tumor necrosis and regional lymph node enlargement are independent risk factors for death, and the nomograms has high accuracy.

Objective:To observe the clinical effect of pelvic floor ultrasound in the diagnosis and rehabilitation training of postpartum stress urinary incontinence(SUI).Methods:From May 2017 to May 2019, 200 SUI patients and 200 healthy pregnant women in the same period admitted to the First People's Hospital of Huzhou were selected in this study.All the subjects were tested by perineum and pelvic floor ultrasound, and the patients with SUI were instructed to carry out pelvic floor muscle rehabilitation training, the level of rehabilitation training effect was evaluated, and to statistically analyze the difference of pelvic floor ultrasound parameters between the patients with SUI and the healthy women, and the patients with different levels of efficacy.Results:The results of pelvic floor ultrasound in SUI patients were significantly higher than those in healthy women( t=6.536-14.925, all P<0.05). The rate of urinary leakage in SUI patients [88.50%(177/200)] was significantly higher than that in healthy women [10.50%(21/200)](χ 2=243.384, P<0.05). The total effective rate of rehabilitation training was 79.50%(159/200). The bladder neck moving distance, urethra rotation angle, posterior angle of bladder urethra in resting state and posterior angle of bladder urethra in Valsalva state in SUI patients with ineffective rehabilitation training were significantly higher than those in SUI patients with general effective rehabilitation training( t=4.662-12.537, all P<0.05). The formation rate of urethra infundibulum in SUI patients with ineffective rehabilitation training [70.73%(29/41)] was significantly higher than that in SUI patients with effective rehabilitation training [19.50%(31/159)](χ 2=40.744, P<0.05). Conclusion:The rehabilitation training of discoid muscles can effectively relieve the related clinical symptoms of postnatal SUI patients.The detection of pelvic ultrasound has a certain clinical value in the diagnosis of postpartum SUI and evaluation of rehabilitation training effect.