ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

OBJECTIVE: To elucidate the role and underlying mechanism of ubiquitin-specific protease 35 (USP35) in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS), thereby enhancing our comprehension of the pathogenesis of RA and identifying potential therapeutic targets for its treatment. METHODS: (1) RA-FLS were cultured in vitro and transduced with lentiviral vectors to establish stable cell lines: A USP35-knockdown line (short hairpin ribonucleic acid of USP35, shUSP35) and its control (negtive control of short hairpin ribonucleic acid, shNC), as well as a overexpression of USP35 line (USP35 OE) and its control (Vector). To investigate the role of USP35 in ferroptosis regulation, a ferroptosis model was induced in RA-FLS by treatment with 1 μmol/L Erastin. The cells were divided into six groups: shNC, shNC + Erastin, shUSP35 + Erastin, Vector, Vector + Erastin, and USP35 OE + Erastin. (2) Cell viability was detected using the cell counting kit-8 (CCK-8). (3) Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione/glutathione disulfide (GSH/GSSG) ratios, and Ferrous ion (Fe²⁺) levels were measured using specific assay kits to evaluate oxidative stress, lipid peroxidation, and glutathione redox status in the cells. (4) Protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected using Western blotting to investigate their potential involvement in USP35-mediated ferroptosis regulation. RESULTS: (1) Compared with the shNC +Erastin group, the cell viability of the shUSP35+Erastin group was significantly decreased (P < 0.001), while it was notably increased in the USP35 OE+Erastin group compared with the Vector+Erastin group (P < 0.001). These findings indicated that USP35 could alleviate the inhibitory effect of Erastin on RA-FLS cell viability. (2) In comparison to the shNC+Erastin group, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.001) were significantly elevated, and the GSH/GSSG ratio was increased (P < 0.05) in the shUSP35+Erastin group. Conversely, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.05) were significantly decreased, and the GSH/GSSG ratio was decreased (P < 0.05) in the USP35 OE+Erastin group compared with the Vector+Erastin group. These results suggested that USP35 could inhibit Erastin-induced oxidative stress and lipid peroxidation in RA-FLS. (3) In Erastin-induced RA-FLS, the expression of USP35 was positively correlated with the protein levels of SLC7A11 and GPX4, indicating a potential mechanism by which USP35 regulated ferroptosis in these cells. CONCLUSION USP35 inhibits ferroptosis in RA-FLS, potentially through the increased expression of SLC7A11 and GPX4.
Ferroptosis ; Humans ; Arthritis, Rheumatoid/metabolism* ; Synoviocytes/pathology* ; Reactive Oxygen Species/metabolism* ; Ubiquitin-Specific Proteases/metabolism* ; Fibroblasts/pathology* ; Cell Survival ; Piperazines/pharmacology* ; Endopeptidases/metabolism* ; Cells, Cultured ; Cell Line ; Amino Acid Transport System y+

BACKGROUND:For the treatment of osteochondral lesions of the talus,different treatment methods are adopted according to different types or clinical symptoms,including rehabilitation treatment,surgical treatment and biological agent treatment. Most of the rehabilitation treatment relieved the symptoms and delayed the disease in a short time. In recent years,arthroscopic microfractures,kirschner wire drilling,talus cartilage transplantation,autologous osteochondrocyte transplantation,stem cell transplantation,and biological preparation platelet-rich plasma can achieve good results.OBJECTIVE:To summarize the progress in the treatment of osteochondral lesions of the talus and provide a reference for their clinical treatment. METHODS:Using English search terms "talus,osteochondral lesions of the talus" and Chinese search terms "microfracture,transplantation,platelet-richplasma,stem cell," we searched the PubMed and CNKI databases for related articles published from January 2019 to January 2024. A total of 67 articles were included for comprehensive analysis.RESULTS AND CONCLUSION:(1) There are many ways to treat osteochondral lesions of the talus. Conservative rehabilitation and biological agents can alleviate the condition for Hepple type Ⅰ and Ⅱ lesions. Microfracture or Kirschner wire drilling bone marrow stimulation treatment is used for Hepple type Ⅲ and above and lesion diameter<15 mm,but the long-term efficacy is poor. Replacement and regeneration strategies are used for larger lesions,and transplant failure is the main risk. (2) Biological agent treatment is a new treatment method and is often used in combination therapy. (3) In view of the treatment of osteochondral lesions of the talus,many factors such as the area and location of cartilage injury should be taken into account. The selection of the treatment plan should also take into account the level of medical technology,patient acceptance,economic status and other factor. Personalized combination treatment of various schemes is recommended to achieve good results.

Objective:To investigate the clinical characteristics of hospital-acquired pulmonary embolism(HA-PE) and identify the risk factors associated with in-hospital mortality.Methods:The retrospective cohort study was used. The clinical and follow-up data were collected of 60 patients with primary diseases who were admitted to the General Surgery Ward of Beijing Friendship Hospital affiliated to Capital Medical University from January 2015 to December 2021. These patients were planned for surgical treatment and were diagnosed with HA-PE during their hospitalization. A total of 60 patients were included in the study, comprising 18 males and 42 females.The age was (69.7±10.9)years, ranging from 45 to 91 years. Baseline clinical parameters were collected and recorded. Measurement data with normal distribution were expressed as mean ± standard deviation ( ± s), measurement data with skewed distribution were expressed as M( Q1, Q3), and count data were expressed as examples and percentages(%). Univariate Logistic regression analysis was used to screen out the risk factors related to in-hospital PE mortality, and multivariate logistic regression model was used to analyze the independent risk factors related to death of HA-PE patients. Results:Fourteen patients did not undergo surgery for primary disease due to HA-PE, the time from admission to HA-PE diagnosis was 7.0(4.0, 10.0) days. 20 patients were underwent implantation of an inferior vena cava filter, all filters used were retrievable. Successful removal of filters was achieved in 10 patients, the duration of filter placement was recorded as (19.6±3.4) days. All patients had high-risk sPESI scores, and 6 patients died from HA-PE during their hospitalization period. Multivariate analysis revealed that symptoms such as chest tightness and dyspnea ( OR=1.83, 95% CI: 1.45-10.15, P=0.039); Elevated TNI levels( OR=1.75, 95% CI: 1.46-7.78, P=0.036) and severe thrombocytopenia ( OR=3.6, 95% CI: 2.46-6.06, P=0.009) were independently correlated with in-hospital PE mortality. Conclusions:The in-hospital mortality rate of HA-PE patients is comparable to primary pulmonary embolism. Following standardized treatment, both the recurrence and mortality rates of pulmonary embolism within one year are significantly reduced. Notably, chest tightness and dyspnea, elevated TNI levels, and severe thrombocytopenia are independent risk factors for in-hospital mortality in HA-PE patients.

ObjectiveTo evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.MethodsThis was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control (n = 40) and intervention (n = 40) groups. The control group received conventional orthopedic treatment, whereas the intervention group received TEAS and conventional treatment. The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks. The primary outcomes were muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and gastrocnemius muscles, whereas the secondary outcome measure was echo intensity (EI). Data were collected before the fixation operations (baseline assessment) and 4 and 8 weeks after intervention.ResultsCompared with baseline, the MT and CSA were reduced in both groups by the end of treatment, whereas EI increased in both groups. At week 4, the reduction in the rectus femoris CSA in the intervention group was significantly lower than that in the control group (P = .02); however, the between-group differences in the MT and EI (all P .05) were not significant. No serious adverse events were observed in either group.ConclusionOur study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA. Because this was only a pilot trial, subsequent studies will need longer follow-ups and larger sample sizes.

Objective To compare the efficacy of artificial intelligence(AI)diagnostic group and artificial reading group in the diagnosis for osteoporotic vertebral compression fractures.Methods From January 2023 to December 2023,80 patients with osteoporotic vertebral compression fractures and 20 patients without fractures but with nonspecific low back pain were included in the study.According to the patient's computed tomography(CT)image,the AI software diagnosis and physicians of different seniority(one senior physician,one intermediate physician and one junior physician)diagnosis were performed.The diagnostic efficacy of different detection methods was compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and area under the receiver operating characteristic(ROC)curve(AUC)and Kappa value of each group were as follows:AI image interpretation:0.975,0.900,0.975,0.900,0.938,0.875;senior physician:0.950,0.900,0.974,0.818,0.925,0.819;intermediate physician:0.825,0.850,0.957,0.548,0.837,0.560;and junior physician:0.750,0.750,0.923,0.429,0.751,0.390.Conclusion The diagnostic performance of AI was comparable to that of senior physician,and significantly higher than that of intermediate and primary physicians.

Agenesis of the dorsal pancreas(ADP)is an extremely rare congenital pancreatic malformation characterized by the absence or hypoplasia of the pancreatic body and tail.Its pathogenesis is closely related to abnormal embryonic development of the ventral and dorsal pancreatic buds,governed by a complex network of transcription factors,including HLXB9,HNF1B,PDX1,PTF1A,GATA4,and GATA6.The clinical spectrum of ADP is highly variable,ranging from asymptomatic cases to manifestations such as abdominal pain,diabetes mellitus,or pancreatitis.Imaging modalities-including ultrasonography,CT,magnetic resonance cholangiopancreatography,and endoscopic retrograde cholangio-pancreatography-serve as the main diagnostic tools,with characteristic findings of absent pancreatic body and tail accompanied by compensatory enlargement of the pancreatic head.ADP is frequently associated with congenital anomalies of the kidney,biliary tract,cardiovascular system,or genital organs.Management is primarily symptomatic,with insulin replacement for diabetes and pancreatic enzyme supplementation for exocrine insufficiency.Advances in genetic sequencing and stem cell research have deepened understanding of the pathogenesis,genetic background,and potential therapeutic strategies of ADP.This review summarizes current progress in embryology,genetics,clinical features,diagnosis,and treatment of ADP,aiming to improve clinical recognition and guide future investigations.

BACKGROUND:For the treatment of osteochondral lesions of the talus,different treatment methods are adopted according to different types or clinical symptoms,including rehabilitation treatment,surgical treatment and biological agent treatment. Most of the rehabilitation treatment relieved the symptoms and delayed the disease in a short time. In recent years,arthroscopic microfractures,kirschner wire drilling,talus cartilage transplantation,autologous osteochondrocyte transplantation,stem cell transplantation,and biological preparation platelet-rich plasma can achieve good results.OBJECTIVE:To summarize the progress in the treatment of osteochondral lesions of the talus and provide a reference for their clinical treatment. METHODS:Using English search terms "talus,osteochondral lesions of the talus" and Chinese search terms "microfracture,transplantation,platelet-richplasma,stem cell," we searched the PubMed and CNKI databases for related articles published from January 2019 to January 2024. A total of 67 articles were included for comprehensive analysis.RESULTS AND CONCLUSION:(1) There are many ways to treat osteochondral lesions of the talus. Conservative rehabilitation and biological agents can alleviate the condition for Hepple type Ⅰ and Ⅱ lesions. Microfracture or Kirschner wire drilling bone marrow stimulation treatment is used for Hepple type Ⅲ and above and lesion diameter<15 mm,but the long-term efficacy is poor. Replacement and regeneration strategies are used for larger lesions,and transplant failure is the main risk. (2) Biological agent treatment is a new treatment method and is often used in combination therapy. (3) In view of the treatment of osteochondral lesions of the talus,many factors such as the area and location of cartilage injury should be taken into account. The selection of the treatment plan should also take into account the level of medical technology,patient acceptance,economic status and other factor. Personalized combination treatment of various schemes is recommended to achieve good results.

Objective To compare the efficacy of artificial intelligence(AI)diagnostic group and artificial reading group in the diagnosis for osteoporotic vertebral compression fractures.Methods From January 2023 to December 2023,80 patients with osteoporotic vertebral compression fractures and 20 patients without fractures but with nonspecific low back pain were included in the study.According to the patient's computed tomography(CT)image,the AI software diagnosis and physicians of different seniority(one senior physician,one intermediate physician and one junior physician)diagnosis were performed.The diagnostic efficacy of different detection methods was compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and area under the receiver operating characteristic(ROC)curve(AUC)and Kappa value of each group were as follows:AI image interpretation:0.975,0.900,0.975,0.900,0.938,0.875;senior physician:0.950,0.900,0.974,0.818,0.925,0.819;intermediate physician:0.825,0.850,0.957,0.548,0.837,0.560;and junior physician:0.750,0.750,0.923,0.429,0.751,0.390.Conclusion The diagnostic performance of AI was comparable to that of senior physician,and significantly higher than that of intermediate and primary physicians.

Agenesis of the dorsal pancreas(ADP)is an extremely rare congenital pancreatic malformation characterized by the absence or hypoplasia of the pancreatic body and tail.Its pathogenesis is closely related to abnormal embryonic development of the ventral and dorsal pancreatic buds,governed by a complex network of transcription factors,including HLXB9,HNF1B,PDX1,PTF1A,GATA4,and GATA6.The clinical spectrum of ADP is highly variable,ranging from asymptomatic cases to manifestations such as abdominal pain,diabetes mellitus,or pancreatitis.Imaging modalities-including ultrasonography,CT,magnetic resonance cholangiopancreatography,and endoscopic retrograde cholangio-pancreatography-serve as the main diagnostic tools,with characteristic findings of absent pancreatic body and tail accompanied by compensatory enlargement of the pancreatic head.ADP is frequently associated with congenital anomalies of the kidney,biliary tract,cardiovascular system,or genital organs.Management is primarily symptomatic,with insulin replacement for diabetes and pancreatic enzyme supplementation for exocrine insufficiency.Advances in genetic sequencing and stem cell research have deepened understanding of the pathogenesis,genetic background,and potential therapeutic strategies of ADP.This review summarizes current progress in embryology,genetics,clinical features,diagnosis,and treatment of ADP,aiming to improve clinical recognition and guide future investigations.