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 investigate the association between high normal blood pressure, hypertension and microalbuminuria (MAU), so as to provide the basis for early screening and prevention of renal injury caused by hypertension. Methods: A multi-stage cluster random sampling method was used to select permanent residents aged 18 to 75 years from six provinces including Hebei, Hunan, Sichuan, Heilongjiang, Qinghai and Jiangxi from September to October 2021. Basic information and lifestyle behaviors were collected through questionnaires. Indices including height, weight and blood pressure were measured. Urinary microalbumin and creatinine were measured in 24-hour urine samples. The associations between high normal blood pressure, hypertension, and MAU were analyzed by using a multivariable logistic regression model. Results: A total of 1 982 residents were surveyed, with 996 residents aged <50 years (50.25%) and 986 residents aged ≥50 years (49.75%). There were 958 males (48.34%) and 1 024 females (51.66%). Normal blood pressure was observed in 653 residents (32.95%), high normal blood pressure in 748 (37.74%) and hypertension in 581 (29.31%). MAU was detected in 164 participants, with a detection rate of 8.27%. The detection rates of MAU among residents with normal blood pressure, high normal blood pressure, and hypertension were 2.14%, 8.16% and 15.32%, respectively, and the difference was statistically significant (P<0.05). Multivariable logistic regression analysis showed that after adjusting for gender, age, educational level, smoking, alcohol consumption, regular exercise and body mass index, the residents with high normal blood pressure (OR=3.535, 95%CI: 1.898-6.585) and hypertension (OR=7.232, 95%CI: 3.808-13.732) had higher risks of MAU compared to those with normal blood pressure; the residents with hypertension (OR=1.914, 95%CI: 1.340-2.735) had a higher risk of MAU compared to those with high normal blood pressure. Conclusions High normal blood pressure and hypertension are associated with an increased risk of MAU.

Objective To evaluate the diagnostic value of cardiac magnetic resonance(CMR)in patients with severe connective tissue disease-associated pulmonary hypertension(CTD-PAH).Methods A total of 48 patients diagnosed with CTD-PAH by right heart catheterization(RHC)in Tianjin Medical University General Hospital from June 2018 to July 2021 were retrospectively included.The parameters of right ventricular(RV)morphology,function and ventricular septum(IVS)were obtained by manual delineation on CMR images and corrected by body surface area.The late gadolinium enhancement(LGE)myocardial mass(MM)and its percentage in left ventricular(LV)MM were manually sketched and calculated on LGE images.The patients were divided into the mild-moderate group and the severe group according to mean pulmonary arterial pressure(mPAP).CMR parameters were compared between the two groups.The diagnostic value of CMR for severe CTD-PAH was analyzed by receiver operating characteristic(ROC)curve.Results A total of 48 patients with CTD-PAH were included in this study.The curvature of interventricular septum(CIVS)and RV ejection fraction(EF)were lower in the severe group than those in the mild-moderate group,and the time proportion of IVS deformation,RV end-diastolic volume index(EDVI),RV end-systolic volume index(ESVI)and RV MM were higher than those in the mild-moderate group(P＜0.05).ROC curve analysis showed that RV MM,time proportion of IVS deformation and RV ESVI had better diagnostic efficacy in severe CTD-PAH patients(AUC was 0.792,0.766 and 0.731,respectively).The combined AUC of the three parameters was 0.840,specificity was 85.7%and sensitivity was 79.4%.Conclusion The parameters of RV and IVS measured by CMR can effectively evaluate patients with severe CTD-PAH and directly reflect serverity of cardiac impairment in patients with severe CTD-PAH from the morphological and functional perspective.

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 pathogenesis and prognostic factors of brain metastasis of hepatocellular carcinoma(HCC)after liver transplantation(LT).Methods:Retrospective review was performed for 17 HCC cases with brain metastasis after liver transplantation from 2000 to 2020.All cases were diagnosed as hepatitis B cirrhosis complicated with HCC.All of them were beyond the Milan Criteria.The immunosuppressive regimen consisted of baliximab + mycophenolate mofetil + calcineurin inhibitors(CNIs)+ corticosteroids in early postoperative period with a gradual tapering of corticosteroids and mycophenolate mofetil.Three patients received sirolimus immunotherapy after tumor recurrence and withdrew CNIs.One of three cases received sorafenib.Results:Other organ involvements included lung metastasis( n=16, 94.1%), bone metastasis( n=5, 29.4%)and liver metastasis( n=6, 35.3%). The median survival time after brain metastasis was 7 months and the 1-year cumulative survival rate 29.4%.The median survival time post-LT was 14 months and the 1-year cumulative survival rate 64.7%.Among 7 patients with a resection of brain metastasis, two deaths at Month 1 post-operation were due to cerebral hemorrhage.The longest survival time was 214 months and the median survival time 9 months. Conclusions:The prognosis of brain metastasis post-LT remains poor.However, early detection and reasonable treatment can prolong patient survival time and even achieve long-term survival.Most brain metastases are accompanied by lung metastases.And the finding of lung metastatic tumor hints at a presence of intracranial lesions.

Objective:To explore the efficacy of single-plane bi-parameter magnetic resonance imaging (bpMRI) in the diagnosis of prostate cancer.Methods:The clinical data of 343 patients who underwent transperineal template prostate magnetic resonance-transrectal ultrasound (MRI-TRUS) cognitive fusion biopsy at the First Affiliated Hospital of Nanjing Medical University from January 2020 to July 2021 were retrospectively analyzed, with median age of [65.0(59.0, 72.0)] years, median body mass index (BMI) of [24.1(22.2, 25.6)]kg/m 2, median prostate volume (PV) of [41.7(29.1, 53.3)]ml, median PSA[6.9 (5.5, 8.4) ng/ml], median PSAD of[0.17(0.12, 0.22) ng/ml 2], and abnormal rate of digital rectal examination (DRE) [6.4%(22/343)]. All patients underwent initial biopsy and bi-parameter magnetic resonance imaging (bpMRI) examination before biopsy, and the images were interpreted using prostate image reporting and data system version 2.1 (PI-RADS v2.1). The detection rates of prostate cancer and clinically significant prostate cancer (csPCa) were compared between single-plane bpMRI and bpMRI. When PI-RADS≥3 score, MRI results were positive; when PI-RADS ≤2 score, MRI results were negative. Results:In the single-plane bpMRI group, 121 MRI results were negative and 222 were positive. Positive patients included 95 with PI-RADS 3 score, 94 with PI-RADS 4 score, and 33 with PI-RADS 5 score. In bpMRI group, 141 MRI results were negative and 202 were positive. Among the positive patients, 67 patients with PI-RADS 3 score, 102 patients with PI-RADS 4 score, and 33 patients with PI-RADS 5 score. The detection rates of single-plane bpMRI and bpMRI for prostate cancer were 22.3% (27/121) and 15.6% (22/141) in MRI negative cases[22.3% (27/121) and 15.6% (22/141), P=0.17], and PI-RADS scores with 3 points [35.8% (34/95) vs. 44.8% (30/67), P=0.25], 4 points [89.4% (84/94)vs. 90.2% (92/102), P=0.85] and 5 points [90.9% (30/33) vs. 93.9% (31/33), P=1.00] showed no significant difference in stratification. The detection rate of csPCa in the single-plane bpMRI group and bpMRI group was significantly different in the MRI negative cases [7.4% (9/121) and 2.1% (3/141), P=0.04]. PI-RADS scores with 3 points [22.1% (21/95) vs. 29.9% (20/67), P=0.27], 4 points [80.9% (76/94) vs. 79.4% (81/102), P=0.80] and 5 points [84.9% (28/33) vs. 90.9% (30/33), P=0.71] showed no significant difference in stratification. Conclusions:For those suspected of prostate cancer patients with PSA 4-10 ng/ml and PI-RADS score ≥3, single-plane bpMRI or bpMRI examination has the same efficacy in term of the detection rate of prostate cancer and csPCa.

Objective:To analyze the epidemiological characteristics and transmission chain of an epidemic of COVID-19 in Haidian district, Beijing.Methods:Descriptive epidemiological method was used to analyze the epidemiological characteristics of the epidemic, and field investigation and big data technology were used to analyze the transmission chain of the epidemic.Results:From April 27 to May 13, 2022, an epidemic of COVID-19 occurred in Haidian district. The strains isolated from the cases were identified by whole genome sequencing as Omicron variant (BA.2.2 evolutionary branch). A total of 38 infection cases were detected, including 34 confirmed cases and 4 asymptomatic cases. Most cases were mild ones (88.2%), no severe, critical or death cases occurred. The early clinical symptoms were mainly sore throat (50.0%) and cough (29.4%). The epidemic lasted for 17 days, resulting in 7 generations of the cases and involving 3 community transmissions, 2 working place transmissions and 8 family transmissions; the main infection routes were co-residence (47.6%) and co-space exposure (31.6%). The intergenerational interval M( Q1, Q3)was 3 (1, 6) days. The overall secondary attack rate was 1.5% (37/2 482), and the family secondary attack rate was 36.7% (18/49). Conclusions:The cases in this COVID-19 epidemic caused by Omicron variant had mild clinical symptoms, but the case clustering in families and communities was obvious, the transmission was rapid, and the risk for co-space exposure was high. It is necessary to use information technology to identify close contacts in the local population for the rapid and effective blocking of the epidemic spread.

Objective To investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. Methods Surgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People's Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. Results All 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (18.18%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
China ; Humans ; Liver Transplantation

Objective To observe the indexes of liver injury and the expression of inflammation-related factor interleukin-10 (IL-10) in rats with severe acute pancreatitis (SAP), and to discuss the correlation between the expression of IL-10 and the related factors of liver injury in SAP rats at different altitudes. Methods 280 male Wistar rats with SPF grade aged 5 to 6 months were divided into four groups according to random number table with 70 rats in each group, and the rats were placed in different altitudes such as Xi'an (at an altitude of 1 027 m), Xining (at an altitude of 2 260 m), Xinghai (at an altitude of 3 300 m) and Wenquan (at an altitude of 3 950 m). The rats in each altitude were randomly divided into sham operation group (Sham group, n = 10) and SAP 1, 6, 12, 24 hours groups (all n = 15). SAP rat model was reproduced by injecting sodium cholate into the posterior membrane of pancreas, and the rats of Sham group were only turned pancreas over several times after opening the abdomen and then closed the abdomen. The rats were sacrificed at the corresponding time points after model reproduction in SAP groups, and rats in Sham group were sacrificed at 6 hours after sham operation. At the same time, the abdominal aorta blood was harvested, and the contents of serum amylase (AMY), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer. Liver tissues were harvested, and the expression level of IL-10 was determined by immunohistochemistry. Pancreatic tissues were harvested, and hematoxylin-eosin (HE) staining was performed to observe the pathological changes under light microscopy. The correlations among the indicators were analyzed by Pearson correlation. Results At different altitudes, no significant abnormality was found in the pancreas of Sham group, but significant pathological changes were found in the pancreas of all SAP groups, mainly manifested as pancreatic acinar swelling, inflammatory cell infiltration, vascular congestion and hemorrhage, acinar cell degeneration and dissolution, changes in glandular lobule structure, peri-pancreatic fat necrosis, and continuous aggravation with the increasing of time and altitude. At the same altitude, the pancreatic pathology score, the serum AMY, ALT and AST levels, and the hepatic IL-10 expression were all significantly increased in all the SAP groups as compared with those in Sham group, and they were continuously increased with time. In Sham group, there was no statistically significant difference in pancreatic pathology score, AMY, ALT, AST, or IL-10 level among different altitudes. At the corresponding time point after model reproduction, the pancreatic pathology score, AMY, ALT, AST and IL-10 levels in the SAP groups were also shown a continuous rising tendency with altitude increase, and the differences in above parameters of SAP 24 hours group in Wenquan area were statistically significant as compared with those of Sham group [pathology score: 11.06±0.94 vs. 0.23±0.15, AMY (mmol/L): 2 706.6±208.3 vs. 336.5±94.3, ALT (U/L): 267.00±5.37 vs. 52.00±4.84, AST (U/L): 465.88±11.02 vs. 139.00±11.61, IL-10 (A value): 0.579±0.006 vs. 0.281±0.006, all P < 0.05]. It was shown by correlation analysis that IL-10 of SAP rats at different altitudes was positively correlated with pancreatic pathology score, AMY, ALT and AST, the correlation coefficient (r value) between IL-10 and the above indicators in the Wenquan area with the highest altitude was 0.959, 0.928, 0.977, 0.983, respectively (all P < 0.01). Conclusions The severity of SAP rats was positively correlated with altitude. IL-10 was involved in the pathological expression process of SAP liver damage, and its expression level was positively correlated with altitude and the degree of SAP liver damage.