Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.

Objective To determine the neurotoxic effects of amyloid beta 42(Aβ42)oligomers and investigate the mechanism of their induction of Alzheimer's disease(AD)-like pathogenesis in neuronal cells.Methods Western blotting and transmission electron microscopy were used to identify the synthesized Aβ42 oligomers.In order to assess the impact of the oligomers,MTT assay was employed to measure cell viability in neuroblastoma cell line SH-SY5Y treated with 10μmol/L Aβ42 oligomers for 12 or 24 h,glutamatergic neurons derived from human embryonic stem cells(hESC)exposed to Aβ42 oligomers for 24,48,or 96 h,and corresponding control cells.TUNEL assay was utilized to assess the apoptosis of glutamatergic neurons.Additionally,immu-nofluorescence assay was applied to detect the changes in Aβ plaques and p-tau pathology.Results Western blotting displayed monomers and small-molecule aggregation(＜30 000)in our synthe-sized Aβ42 oligomers,and transmission electron microscopy showed that the synthesized oligomers were mainly in a shape of spherical particles.Treatment of 10 μmol/L Aβ42 oligomers for 12 and 24 h in SH-SY5Y cells significantly decreased cell viability when compared with the control cells[(70.89±2.54)％vs(100.00±2.02)％,(52.63±3.37)％vs(100.00±2.80)％,P＜0.05].The 10μmol/L oligomers treatment for 24,48 and 96 h also decreased cell viability in glutamatergic neu-rons(P＜0.05).The apoptotic rates was significantly higher in glutamatergic neurons after treat-ment for 48 and 96 h when compared to the control cells[(1.44±0.31)％vs(1.00±0.38)％,(1.75±0.64)％vs(1.00±0.31)％,P＜0.05].Furthermore,circular granular Aβ-positive plaque signals were observed in the glutamatergic neurons after treated with the oligomers for 24,48,and 96 h,but no such plaque signals were seen in the control cells.Additionally,glutamatergic neurons incu-bation with 10 μmol/L oligomers for 24 h resulted in tau hyperphosphorylation at the Thr231 site,with the average fluorescence intensity significantly higher than that in control cells(P＜0.05).Conclusion Aβ42 oligomers show toxic effects to both SH-SY5Y cells and glutamatergic neurons,and they can also induce glutamatergic neurons to produce AD pathology.

Objective:Bibliometric analysis of SCI papers in Shanghai tertiary obstetrics and gynecology specialized hospitals from 2017 to 2021 was conducted to provide reference for further improving management measures and optimizing the quality of SCI papers in specialized hospitals.Methods:The Web of Science database was used to retrieve SCI papers published by tertiary obstetrics and gynecology specialized hospitals in Shanghai from 2017 to 2021. Based on bibliometric methods VOSviwer 1.6.17 and Scimago Graphica 1.0.23 was adopted to analyze the number, journals, domestic and international cooperation, and hot research areas.Results:2 721 papers were published by Shanghai Tertiary A obstetrics and Gynecology hospitals from 2017 to 2021. These papers published in 765 journals. The number of papers published and publication journals increased year by year. The number of papers and journals with an impact factor of 3~5 is the largest, accounting for 37.96% and 35.95% of the total number of papers and journals respectively. However, papers and journals with more than 10 points accounted for only 7.98% and 10.20% respectively. Scientific Reports, a comprehensive journal, published the largest number of papers. International cooperation is concentrated in the United States. Domestic cooperation is concentrated in universities and research institutions in Jiangsu, Zhejiang and Shanghai. The hot research areas focused on Oncology, Obstetrics & Gynecology, Genetics, Reproductive Biology and other basic medical fields.Conclusions:The number of papers published by Shanghai's tertiary obstetrics and gynecology specialized hospitals has increased year by year, but there are fewer highly influential journals. Domestic and international scientific research cooperation is limited to several institutions. The achievements in the field of basic research are far more than those in clinical research.

Objective:To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS).Methods:A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry.Results:Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years ( Z=-2.45, P=0.014) and those involving multiple glands ( Z=-2.04, P=0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions:IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient′s age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65^f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Objective:To investigate the clinical effect of peroneal fracture line in the treatment of posterior Pilon fracture.Methods:The data of 26 patients treated with fibular fracture line from January 2017 to July 2019 were analyzed retrospectively, including 11 males and 15 females; the age ranged from 28 to 69 years, with an average of 42.2 years. There were 10 cases of falling injury, 9 cases of falling injury and 7 cases of traffic injury; all of them were fresh closed fibular fractures;According to Yu Guangrong's classification, there were 11 cases of type I, 8 cases of type II and 7 cases of type III; AGH was divided into 10 cases of type I, 5 cases of type IIa, 2 cases of type IIb, 5 cases of type IIIa and 4 cases of type IIIb. All cases were treated by opening the fibular fracture line through the posterolateral approach, the quality of fracture reduction was evaluated by Burwell Charnley radiological evaluation standard after operation; At the last follow-up, ankle function was evaluated by American Association of Foot and Ankle surgery (AOFAS) ankle and hindfoot scores.Results:All 26 patients were followed up for 12-23 months, with an average of 14.9 months; Bone healing was achieved in all fractures. The healing time was 3-6 months, with an average of 4.0 months. The quality of fracture reduction was evaluated according to the Burwell Charnley radiology evaluation standard after operation, including anatomical reduction in 23 cases and acceptable reduction in 3 cases. The anatomical reduction rate was 88% (23/26). At the last follow-up, AOFAS ankle and hindfoot scores ranged from 80 to 100, with an average of 89.9 points, of which 17 cases were excellent and 9 cases were good, and the excellent and good rate was 100%. At the last follow-up, no patient had complications such as reduction loss, skin necrosis, infection, internal fixation loosening or ankle stiffness.Conclusion:After the treatment of Pilon fractures via peroneal fracture line, the distal tibial articular surface and posterior ankle fracture gap can be fully exposed, which can be repositioned and fixed under direct vision, with high anatomical repositioning rate and good and safe clinical results.

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT < 150×10 9 /L) who received the DAA treatment regimen without interferon for 12-24 weeks in Tianjin Third Central Hospital from April 2018 to March 2019, and the changes in virologic response, liver function parameters, PLT, and liver stiffness measurement (LSM) were evaluated at the end of treatment (EOT) and at week 12 after EOT. Quantitative data accord with normal distribution were compared by repeated measures ANOVA. Normal transformation was performed before the comparison between skewed data, then repeated measures ANOVA was carried out. A logistic regression analysis was used to investigate the predictive factors for PLT elevation, and the receiver operating characteristic (ROC) curve was plotted to analyze the value of LSM in predicting PLT elevation after treatment. Results Among the 83 CHC patients with thrombocytopenia, 61.4% had liver cirrhosis, and the rate of sustained virologic response at week 12 after the end of treatment (SVR12) was 98.8%. From baseline to EOT and SVR12, the patients had significant reductions in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and globin, a significant increase in the serum level of albumin, and a significant reduction in LSM (all P < 0.05). For all patients, PLT at EOT and SVR12 was significantly higher than that at baseline [EOT vs baseline: (110.4±44.6)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01; SVR12 vs baseline: (109.0±47.7)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01]. At SVR12, there were significant differences in the proportion of patients with liver cirrhosis, baseline LSM, and baseline white blood cell count between the PLT elevation group and the non-PLT elevation group (all P < 0.05). The multivariate logistic regression analysis showed that LSM was an independent predictive factor for significant PLT elevation after DAA treatment (odds ratio=0.929, 95% confidence interval: 0.864-0.999, P < 0.05). Baseline LSM had an area under the ROC curve of 0.644 in predicting PLT elevation, with a sensitivity of 81.0% and a specificity of 48.6% at a cut-off value of 20.15 kPa. The patients with PLT > 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

Objective:To compare the effect of interlocking intramedullary nail and locking plate in the treatment of varus proximal humeral fractures in the elderly.Method:A retrospective case-control study was conducted to analyze the clinical data of 46 elderly patients with varus proximal humeral fractures treated in Central Theater General Hospital of PLA from June 2016 to January 2019, including 27 males and 19 females, at age of 60-84 years［（71.9±5.7）years］. All fractures were fresh. Overall 25 patients were treated with interlocking intramedullary nail（intramedullary nail group）, and 21 patients were treated with locking plate（bone plate group）. The incision length, operation time, intraoperative bleeding and fracture healing time were compared between the two groups. Visual analogue scale（VAS）was used to evaluate the degree of pain relief at 1 week and 1 month after operation, and Constant-Murley score was used to evaluate the recovery of shoulder function at 1 month, 3 months and 1 year after operation. The cervical trunk angle was recorded at 2 days and 1 year after operation to judge whether there was a loss of cervical trunk angle. Postoperative complications were observed.Results:All patients were followed up for 12-32 months［（19.7±6.6）months］. The incision length［（7.1±0.6）cm］, operation time［（60.8±5.2）minutes］, intraoperative bleeding［（64.4±8.4）ml］and fracture healing time［（10.0±1.0）weeks］in intramedullary nail group were significantly less than those in bone plate group［（13.6±0.9）cm,（80.2±8.1）minutes,（151.0±15.2）ml,（11.0±1.5）weeks］（ P<0.05）. In both groups, the VAS decreased significantly over time, and markedly increased Constant-Murley score was detected as well（ P<0.05）. The VAS in intramedullary nail group［（2.8±0.2）points,（1.1±0.2）points］was significantly lower than that in bone plate group［（4.0±0.2）points,（1.5±0.1）points］at 1 week and 1 month after operation（ P<0.05）. The Constant-Murley score in intramedullary nail group［（59.9±6.9）points,（79.1±6.8）points］was higher than that in bone plate group［（50.1±8.5）points,（73.6±8.4）points］at 1 month and 3 months after operation（ P<0.05）, but the score showed no significant difference between intramedullary nail group［（89.1±5.3）points］and bone plate group［（86.4±6.4）points］at 1 year after operation（ P>0.05）. According to Constant-Murley score, 10 patients were evaluated as excellent and 15 patients as good in intramedullary nail group at 1 year after operation, with the excellent and good rate of 100%, while 8 patients were evaluated as excellent, 11 patients as good and 2 patients as fair in bone plate group at 1 year after operation, with the excellent and good rate of 91%（ P>0.05）. The cervical trunk angle in intramedullary nail group［（140.2±2.9）°,（139.6±2.3）°］had significant difference from that in bone plate group［（139.6±3.2）°,（138.8±3.3）°］at 2 days and 1 year after operation（ P<0.05）. In both groups, the cervical trunk angle had slight lost at 1 year after operation compared with that at 2 days after operation, but the difference was not statistically significant（ P>0.05）. In intramedullary nail group, 1 patient had subacromial impact. In bone plate group, 1 patient had screw cutting, 2 patients subacromial impact, and 2 patients delayed fracture healing. The incidence of complications in intramedullary nail group was 4%（1/25）, lower than 24%（5/21）in bone plate group（ P<0.05）. Conclusion:Compared with locking nail plate, interlocking intramedullary nail in the treatment of senile varus proximal humeral fracture has the advantages of small trauma, early fracture healing, less pain, early function recovery and less complications.

Objective: Based on the KAP and Prospect theory, to explore, construct and verify the theoretical model and formation mechanism of driving factors of primary care doctors′ willingness to carry out the primary diagnosis. Methods: Using the random cluster sampling method, from April to May 2019, a questionnaire survey was conducted among doctors at 20 primary medical and health service institutions in Hangzhou. The survey covered the primary care doctors′ cognition level of primary diagnosis, their self-evaluation of primary medical care capabilities, evaluation of policies and systems, expectation of primary medical care, and their job satisfaction. Descriptive statistic, multiple linear regression and structural equation model were used to analyze and explore the driving factors and formation mechanism of their willingness to carry out the primary diagnosis. Results: Primary care doctors′ willingness rate for primary diagnosis was 76.4%(308/403). Positive expectation(beta=0.309), cognition level(beta=0.216), evaluation of policies and systems(beta=0.184), and self-evaluation of primary diagnosis capability(beta=0.170), all of which directly affect the said willingness. The total effect of the five types of driving factors on the willingness of the primary diagnosis was as follows: cognitive level of the primary diagnosis(0.536), evaluation of the policy system(0.494), self-evaluation of the primary diagnosis capability(0.436), positive expectations of the primary diagnosis work(0.186), job satisfaction(0.146). Conclusions The cognition of the primary diagnosis, the capability of the primary diagnosis, the policy system and the positive expectation are the important premises, key driving forces, and a strong guarantee and motivation to drive primary care doctors to carry out the primary diagnosis. It is suggested that the government and medical institutions should further improve the cognition level of primary care doctors, focusing on systematically improving the service capability of primary care doctors′ primary consultation, coordinating to improve policy guidance measures such as financial input, medical insurance reimbursement and referral system, establishing and improving incentive measures such as career development, performance appraisal, salary and welfare of primary care doctors.

Objective:Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery.Methods:A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery.Results:A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ 2=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ 2=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions:The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.