Objective To screen the differentially expressed proteins in glomeruli during the treatment of lupus nephritis(LN)with hydroxychloroquine sulfate(HCQ).Methods Sixty female NZB/WF1 mice were used.At the age of 28 weeks,40 mice with proteinuria of 3+to 4+were divided into HCQ and control groups.After feeding for 36 weeks,the glomerular proteins were extracted by magnetic beads and analyzed by two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry(MALDI-TOF-MS).The expression of the candidate proteins in the glomeruli of the LN mice was exa-mined by immunohistochemistry.Results A total of 31 differentially expressed proteins were identified between the two groups,including 24 upregulated and seven downregulated proteins.Conclusion The expression of proteins like RI and ENOA in the glomeruli of LN mice was significantly different during HCQ treatment.These proteins may be involved in the pathogenesis of LN and are therefore potential targets of HCQ in the treatment of LN.

Objective To investigate the expression level and clinical significance of WW domain-containing E3 ubiquitin protein ligase 1(WWP1)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in patients with heart failure with preserved ejection fraction(HFpEF).Methods A total of 153 patients with HFpEF admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to September 2022 were collected as the observation group.According to the New York Heart Association(NYHA)cardiac function grading of patients,they were grouped into cardiac function grading Ⅰ～Ⅱ group(n=64)and cardiac function grading Ⅲ～Ⅳ group(n=89),while 148 healthy volunteers were collected as the control group.The correlation between serum WWP1 and NLRP3 levels and cardiac function indexes of patients was explored by Pearson analysis.The diagnostic value of serum WWP1 and NLRP3 levels on the severity of heart failure in HFpEF patients was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression levels of WWP1(1.68±0.35 vs 1.04±0.19)and NLRP3(6.72±1.26 ng/ml vs 4.57±0.84 ng/ml)in the observation group were significantly increased,and the differences were statistically significant(t=19.623,17.359,all P<0.05).Compared with grade Ⅰ to Ⅱ groups,WWP1(1.87±0.39 vs 1.42±0.32)and NLRP3(7.53±1.40 ng/ml vs 5.59±1.18 ng/ml)expression levels in grade Ⅲ to Ⅳ groups were significantly increased and the differences were statistically significant(t=7.744,9.017,all P<0.05).The differences of heart rate,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic diameter(LVEDD),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVPWT),left ventricular ejection fraction(LVEF),peak mitral early diastolic velocity(E)/peak late diastolic velocity(A)and the incidence of atrial fibrillation between the cardiac function grade Ⅰ to Ⅱ groups and the grade Ⅲ to Ⅳ groups were significant(t/χ2=2.757～7.069,all P<0.05).Serum WWP1 level in HFpEF patients was positively correlated with LAD,LVEDD and LVPWT(r=0.547,0.471,0.536,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.485,-0.417,all P<0.05).Serum NLRP3 level was positively correlated with LAD,LVEDD and LVPWT(r=0.534,0.494,0.520,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.462,-0.523,all P<0.05).ROC results showed that the area under the curve(AUC)of serum WWP1 and NLRP3 levels alone for diagnosing the severity of heart failure in HFpEF patients was 0.825 and 0.855,respectively,and the AUC(0.924)diagnosed by the combination of the two was significantly greater than that diagnosed by the serum WWP1 alone and the AUC diagnosed by the NLRP3 alone(Z=3.600,P<0.001;Z=3.053,P=0.002).Conclusion The levels of serum WWP1 and NLRP3 were increased in patients with HFpEF,which were closely related to the cardiac function of patients.Serum WWP1 and NLRP3 have certain diagnostic value for the severity of heart failure in patients with HFpEF.

Objective: To investigate the characteristics of rabies-exposed population in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide insights into the prevention and control of rabies. Methods: Data of rabies-exposed population in Wenzhou City from 2014 to 2023 were collected through Wenzhou Rabies-Exposed Population Summary Sheet reported by dog injury clinics. The species of animals causing injuries, exposure time, exposure grade, exposure site, and post-exposure treatment were descriptively analyzed. Results: Totally 709 900 patients were admitted to dog injury clinics in Wenzhou City from 2014 to 2023, and the exposure rate showed an increasing trend (Z=7.238, P<0.001), with an average annual exposure rate of 750.75/105. The number of cases with exposure to rabies peaked in July (79 230 cases, 11.16%) and August (78 570 cases, 11.07%). Dogs were predominant animals causing injuries (448 900 cases, 63.23%), and the exposure rate showed a downward trend (Z=-5.921, P<0.001); cats were the second (175 142 cases, 24.67%), and the exposure rate showed an upward trend (Z=23.314, P<0.001). The upper (379 695 cases, 53.49%) and lower limbs (287 521 cases, 40.50%) were the main exposure sites. There were 21 034 cases (2.96%) exposed to head and face, and the exposure rate of head and face showed an upward trend (Z=3.549, P<0.001). Grade II exposure was the most common (403 881 cases, 56.89%), and the exposure rate showed an upward trend (Z=8.769, P<0.001). The proportion of using human rabies immune globulin was 23.13% in Grade III exposed population, showing a downward trend (Z=-12.848, P<0.001). Conclusions The exposure rate of rabies in Wenzhou City showed an upward trend from 2014 to 2023, with July and August as the peak months of exposure. Injuries mainly caused by dogs, while the exposure rate of cat bites showed an upward trend. The proportion of using human rabies immune globulin needs to be improved.

In 2022, Chinese Medical Doctor Association issued the model of physician competency that includes six core competencies. Workplace-based formative assessment is an important method for the implementation of competency-based medical education, among which direct observation assessment, such as mini-clinical evaluation exercise and direct observation of procedural skills, together with multi-source assessment (i.e., 360-degree assessment), widely covers competency assessment, and entrustable professional activities (EPAs) are also worth exploring. Design of a comprehensive assessment system, establishment of a clinical competency committee, and enhancement of the external conditions of medical education may help with the implementation of competency assessment. Extending competency-based medical education to the stage of undergraduate education is an important measure to improve the quality of medical education.

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

Objective:To investigate the role and related mechanisms of Musashi RNA binding protein 2 (MSI2) in hepatocellular carcinoma (HCC).Methods:The mRNA expression data of HCC patients from the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEX) as well as the corresponding clinical information were obtained, and the expression level of MSI2 was evaluated in 50 pairs of matched tumor/normal HCC samples. Furthermore, the protein-protein interaction (PPI) network, the Kyoto encyclopedia of genes and genomes (KEGG) and the encyclopedia of RNA interactions (ENCORI) databases were used to explore how MSI2 affects the progression of HCC. Three pairs of short hairpin RNA (shRNA) sequences targeting MSI2 and β-catenin were designed and cloned into lentiviral vectors and transfected into HepG2, MHCC97H and MHCC97L cells as knockdown plasmids for the construction of MSI2 knockdown group cells (HepG2 sh-MSI2 group, MHCC97H sh-MSI2 group) and β-catenin knockdown group cells (MHCC97L sh-β-catenin group) and their respective negative control cells (HepG2 sh-Ctrl group, MHCC97H sh-Ctrl group, and MHCC97L sh-Ctrl group). The overexpression level of MSI2 was detected by Western blotting. CCK-8 and colony formation assay were used to detect the proliferation of hepatocellular carcinoma cells. Cell suspensions of HepG2 sh-Ctrl group, HepG2 sh-MSI2 group, MHCC97L sh-Ctrl group and MHCC97L sh-β-catenin group were injected subcutaneously into the front thighs of the nude mice in each group. Nude mice were sacrificed after 4 weeks, and tumors were removed for volume measurement. Results:The analysis based on TCGA and GTEX databases showed that the expression of MSI2 in 50 pairs of matched tumors was higher than that in normal samples (2.073±0.767 vs. 1.256±0.260), and the difference was statistically different ( P<0.001). The results showed that MSI2 was positively correlated with β-catenin ( r=0.455, P<0.001), transcription factor 7 (TCF7) ( r=0.142, P=0.006) and lymphatic enhancement factor 1 (LEF1) ( r=0.246, P<0.001) in HCC. Compared with the HepG2 sh-Ctrl group, the expressions of MSI2, β-catenin, TCF7 and LEF1 in the HepG2 sh-MSI2 group were down-regulated, and the expressions of MSI2, β-catenin, TCF7 and LEF1 in the MHCC97H sh-MSI2 group were down-regulated compared with the MHCC97H sh-Ctrl group, and the differences were statistically significant (all P<0.001). Compared with the MHCC97L sh-Ctrl group, the expression of β-catenin in the MHCC97L sh-β-catenin group decreased statistically significant ( P<0.001). The results of CCK-8 proliferation assay showed that the activity of HCC cells in the HepG2 sh-MSI2 group was reduced compared with the HepG2 sh-Ctrl group, in the MHCC97H sh-MSI2 group was decreased compared with the MHCC97H sh-Ctrl group, and compared with the MHCC97L sh-Ctrl group, the activity of HCC cells in the MHCC97L sh-β-catenin group was decreased (all P<0.001). The results of colony formation experiments showed that the ability of HCC cells to form colonies in the HepG2 sh-MSI2 group was reduced compared with the HepG2 sh-Ctrl group, and in the MHCC97H sh-MSI2 group was reduced compared with the MHCC97H sh-Ctrl group, furthermore, compared with the MHCC97L sh-Ctrl group, the ability in the MHCC97L sh-β-catenin group was significantly lower (all P<0.001). Compared with the HepG2 sh-Ctrl group, the tumor volume of nude mice in the HepG2 sh-MSI2 group decreased [(160.19±60.22) mm 3 vs. (480.46±65.28) mm 3], compared with the MHCC97L sh-Ctrl group, the tumor volume in the MHCC97L sh-β-catenin group also decreased [(456.48±38.23) mm 3 vs. (845.67±33.19) mm 3], and the differences were statistically significant (both P<0.05). Conclusion:Up-regulation of MSI2 expression promotes the proliferation of HCC cells through the Wnt/β-catenin signaling pathway.

Objective:A novel anatomic posterior malleolus locking plate for Chinese people was designed, researched, developed, and tested biomechanically.Methods:An anatomic parameter database of posterior malleolus of Chinese people was established by collecting CT images of ankle joints from 100 healthy volunteers in Shanghai Tongji hospital from June 2022 to May 2023. Combined with relevant computer-aided technologies, a novel anatomic posterior malleolus locking plate for Chinese people was designed and produced. In addition, model verification and biomechanical test were carried out on vertical displacements under different fixation modes and different axial loads (500, 1 000, and 1 500 N). Failure loads at a displacement of 2 mm and maximum failure loads at the complete failure of internal fixation were also tested and recorded.Results:Based on the imaging anatomic measurement, the width quartile of posterior malleolus was 19.4, 26.6, 35.0 mm. The 3D reconstruction models of ankle joint CT corresponded to small, medium, and large basic posterior malleolus plates. Height of the screw safety zone was 5.5(5.3, 5.7) mm. The tip-back angle was 153.0°(148.5°, 157.5°) and tip-back height was 20.0(19.7, 20.9) mm. The novel anatomic posterior malleolus locking plate based on tibiofibular and ankle joint CT scan and relevant computer-aided technologies fit well with posterior malleolus of tibia, showing anatomic fitting. Based on the associate biomechanical test, the novel plate fixation had smaller vertical displacements of posterior malleolus fragment under axial loads of 500, 1 000, and 1 500 N compared with the control plate, but greater failure loads when the vertical displacement of the posterior malleolus fragment was 2 mm and greater maximum failure loads at complete failure of the internal fixation. At an axial load of 500 N, the vertical displacements of the posterior malleolus fragment after posterior malleolus fixation with a control plate, a 6-hole anatomical locking plate, and a 5-hole anatomical locking plate were 0.60±0.02, 0.45±0.04, and 0.52±0.04 mm, respectively with significant difference ( F=88.287, P<0.001); at an axial load of 1 000 N, the vertical displacements were 2.22±0.03, 1.10±0.03, and 1.15±0.03 mm for the three fixation modes, respectively, and the difference was statistically significant ( F=10 061.890, P<0.001); At an axial load of 1 500 N, the vertical displacements were 2.81±0.04, 1.50±0.03 and 1.67±0.03 mm for the three fixation modes, respectively with significant difference ( F=9 774.019, P<0.001). When the vertical displacement of the posterior malleolus fragment was 2 mm, the failure loads for the three fixation modes were 0.80(0.73, 0.80)、2.00(1.93, 2.00) and 1.70(1.70, 1.70) kN, respectively with significant differences ( H=54.245, P<0.001). The maximum failure loads at complete failure of the internal fixation for the three fixation modes were 1.90(1.90, 1.98)、4.30(4.30, 4.30) and 3.70(3.63, 3.70) kN, respectively with significant differences ( H=53.863, P<0.001). Conclusions:The novel anatomic posterior malleolus locking plate for Chinese people was well matched to the posterior malleolus with high mechanical strength and good stability, showing a promising future for clinical application.

Objective:To compare the efficacy of staged versus elective operation for treating acute closed fracture-dislocation of tarsometatarsal joint complex.Methods:A retrospective cohort study was used to analyze the clinical data of 26 patients with acute closed fracture-dislocation of tarsometatarsal joint complex admitted to Tongji Hospital of Tongji University from January 2017 to January 2021, of whom 18 were males and 8 were females, aged 32-52 years [(44.3±5.2)years]. According to the time from injury to admission, 14 patients admitted within 8 hours after injury underwent staged surgical treatment (staged group), and 12 patients admitted more than 8 hours after injury underwent elective surgery (elective group). In the staged group, emergency reduction and temporary internal fixation with K-wire were done under the supervision of a C-arm X-ray machine in the first stage, while after the swelling subsided, open reduction and internal fixation were done for tarsometatarsal joint fracture-dislocation in the second stage. In the elective group, open reduction and internal fixation were performed for tarsometatarsal joint fracture-dislocation on a scheduled basis after the swelling subsided. The operation time, hospitalization time and fracture healing time were recorded. The visual analogue score (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) midfoot score were evaluated before operation, at 1, 6, 12 months after operation and at the final follow-up. The rate of complications was observed after operation.Results:All patients were followed up for 12-24 months [(18.5±3.8)months]. The operation time, hospitalization time and fracture healing time in the staged group were (77.3±5.6)minutes, (14.3±2.2)days and (12.3±1.2)weeks, respectively, significantly shorter than those in the elective group [(101.5±7.5)minutes, (20.3±5.2)days and (14.3±2.2)weeks] (all P<0.01). VAS significantly decreased and AOFAS midfoot score significantly increased in both groups as postoperative time increased (all P<0.05). There were no significant differences in VAS between the two groups before operation, at 12 months after operation or at the final follow-up (all P>0.05). The VAS at 1, 6 months after operation was (4.4±0.8)points and (2.1±0.4)points in the staged group, significantly lower than those in the elective group [(6.0±1.0)points and (3.5±0.6)points] (all P<0.01). There was no significant difference in preoperative AOFAS midfoot score between the two groups ( P>0.05). The AOFAS midfoot score at 1, 6, 12 months after operation and at the final follow-up was (67.6±4.5)points, (75.7±5.2)points, (83.6±2.2)points and (85.9±4.3)points in the staged group, significantly higher than those in the elective group [(60.2±3.9)points, (70.2±3.4)points, (75.4±3.3)points and (78.7±4.4)points] (all P<0.01). The rate of complications was 14.3% (2/14) in the staged group, significantly lower than that in the elective group [33.3% (4/12)] ( P<0.05). Conclusion:Compared to traditional elective surgery, staged surgery for acute closed fracture-dislocation of tarsometatarsal joint complex has the advantages of shortened operation time, hospitalization time and fracture healing time, eary pain relief, improved functional recovery of the foot and reduced postoperative complications.

Objective:To summarize the best evidence for early enteral nutrition support in postoperative patients with gastric cancer and evaluate its effectiveness.Methods:From March to August 2021, 108 postoperative patients with gastric cancer admitted to the Gastrointestinal Surgery of the First Affiliated Hospital of Ningbo University were selected. We applied evidence-based nursing methods to summarize the best evidence for early enteral nutrition support in postoperative gastric cancer patients, and constructed and implemented the best evidence application strategy through baseline review, evaluation of evidence application clinical scenarios and barriers. We compared the various indicators of two groups of patients before the application of evidence (March to May 2021, n=55) and after the application of evidence (June to August 2021, n=53) . Results:No adverse events occurred during the application of evidence. After applying evidence, the correct nutritional assessment rate increased from 41.82% (23/55) at baseline review to 90.57% (48/53), the implementation rate of early postoperative enteral nutrition increased from 0 to 45.28% (24/53), the start time of postoperative enteral nutrition shortened from (3.75±2.33) days to (2.06±1.38) days, and the implementation rate of postoperative priority oral nutrition increased from 63.64% (35/55) to 86.79% (46/53), nutritional related complications decreased from 40.00% (22/55) to 20.75% (11/53), and the differences were all statistically significant ( P<0.05) . Conclusions:The application of the best evidence for early enteral nutrition support in postoperative gastric cancer patients can shorten the start time of postoperative enteral nutrition, reduce postoperative nutrition related complications, and promote early recovery of patients.

OBJECTIVE: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. METHODS: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. RESULTS: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. CONCLUSION With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.
Humans ; Female ; Tibia/surgery* ; Finite Element Analysis ; Ankle ; Arthritis ; Fibula/surgery* ; Ankle Joint/surgery*