This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective To investigate the role of pulmonary neuroendocrine cells(PNEC)and γ-aminobutyric acid(GABA)in patients with pulmonary neuroendocrine tumors(PNET).Methods The pathological specimens of 29 cases of PNET treated in the eighth Medical Center of Chinese PLA General Hospital from October 2018 to January 2022 were collected.The morphological characteristics were observed by HE staining,and the expression levels of synaptophysin(Syn),chromogranin A(CgA),CD56,Ki-67,CD86 and CD163 were observed by immunohistochemical staining.Calcitonin gene-related peptide(CGRP)and glutamic acid decarboxylase(GAD)65/67 in different types of PNETs were detected by double antibody immunofluorescence co-staining,and the correlation between GAD65/67 positive PNEC and macrophage polarization was analyzed.Results The results of HE staining showed that all four types of PNET tissues had neuroendocrine(NE)characteristics:rosette structure and organ nesting or palisade pattern,but they were different,and the proportion of mitotic cells from low to high was typical carcinoid(TC),atypical carcinoid(AC),large cell neuroendocrine carcinoma(LCNEC)and small cell lung cancer(SCLC).The results of immunohistochemical staining showed that the positive expression rate of Syn and CgA and the positive degree of Syn,CgA and CD56 in carcinoid(TC and AC)were significantly higher than those in LCNEC and SCLC(P＜0.05).The Ki-67 indices of the four types of PNET are:TC＜5%,AC 5%-20%,LCNEC and SCLC＞75%respectively.The number of PNEC in carcinoid was significantly higher than that in LCNEC,SCLC and paratumoral tissues(P＜0.05),but there was no significant difference in the number of PNEC between LCNEC and SCLC and para-tumor tissues(P＞0.05).The results of immunofluorescence staining showed that the number of GAD65/67 positive cells co-expressing GAD65/67 in 95%PNEC was significantly higher than that in LCNEC,SCLC and para-tumor tissues(P＜0.05),but there was no significant difference between LCNEC and SCLC GAD65/67 positive cells and para-tumor tissues(P＞0.05).The results of immunohistochemical staining also showed that the number of CD86 positive M1 macrophages was significantly higher than that of CD163 positive M2 macrophages in para-tumor tissues(P＜0.05),while M2 macrophages were significantly more than M1 macrophages in AC,LCNEC and SCLC(P＜0.01).Correlation analysis showed that the number of GAD65/67 positive PNEC cells in PNET was negatively correlated with the number of CD163 positive M2 macrophages in tumor stroma(r=-0.6336,P=0.0174).Conclusions PNEC is the main source of GABA in lung tissue and plays an immunomodulatory role in the lung,which may be involved in the progression of PNET.

This article reports a single case of a patient with systemic lupus erythematosus(SLE)combined with pure red cell aplasia(PRCA),and reviews 51 additional cases of patients reported by domestic and overseas papers from 1974 to 2021.These 52(51+1)cases were analyzed to summarize the epidemiological features,clinical features,laboratory inspections,treatments and prognosis of the patients.The results indicated that among all the 52 cases,cases of SLE combined with PRCA were mostly seen in Asian childbearing age women.The median ages of patients diagnosed with SLE and diagnosed with PRCA were 31.5 years and 36.0 years,respectively.The time interval between the initial diagnosis of SLE and subsequent diagnosis of PRCA was significantly longer than the interval for the initial diagnosis of PRCA,suggesting a delayed onset of SLE in these patients(P=0.042).Various clinical features of the 52 patients were reported,including mostly fatigue,joint pains,Raynaud phenomena and rashes,and SLE maybe combined with autoimmune hemolytic anemia(AIHA),thymoma,hypothyroidism and myasthenia gravis(MG).In these reported cases,laboratory indicators showed higher proportions of antinuclear antibody(ANA),anti double stranded DNA antibody(anti-dsDNA antibody),positive urinary protein and low complement levels.Among the 52 patients,51 cases(98.08%)were treated with glucocorticoids,followed by blood transfusion,cyclosporin A,cyclophosphamide and high-dose intravenous immunoglobulin.Of the 50 patients whose prognoses were reported,44 showed improvement,while 3 treatments were not effective and 3 resulted in death.This article aims to enhance the understanding of SLE combined with PRCA among doctors.

Objective:To analyze the feasibility and advantages of gastric triangle suspension technique in laparoscopic radical anterograde modular pancreatiplenectomy (L-RAMPS) for patients of pancreatic body and tail malignant tumor.Methods:The clinical data of 29 patients with L-RAMPS in Li Huili Hospital of Ningbo Medical Center from January 2019 to October 2023 were retrospectively analyzed, including 14 males and 15 females, aged (67.6±7.5) years. According to whether gastric triangle suspension was used during operation, 29 patients were divided into suspension group ( n=14) and control group ( n=15). The two groups were compared with several indexes of body mass index, tumor length, postoperative pathological type, operation time, intraoperative blood loss, intraoperative incision margin, intraoperative blood transfusion, pancreatic fistula, postoperative massive bleeding, postoperative gastroparesis, length of hospital stay and so on. Results:There were no significant differences in age, sex, body mass index, tumor length and pathological type between the two groups (all P>0.05). Postoperative pathologic findings of the 29 patients included 21 cases of pancreatic adenocarcinoma (72.4%), 2 cases of intraductal papillary mucinous tumors (6.9%), 2 cases of pancreatic neuroendocrine tumors (6.9%), 1 case of pancreatic adenosquamous carcinoma (3.4%), and 3 cases of mucinous cystadenocarcinoma (10.3%). There was no significant difference in the proportion of positive first incision margin, intraoperative blood transfusion, postoperative B/C pancreatic fistula, postoperative massive hemorrhage and postoperative gastroparesis between the two groups (all P>0.05). The operative time and intraoperative blood loss in the suspension group were (200.3±13.5) min and (148.6±42.2) ml respectively, less than that in the control group (223.5±36.3) min and (205.3±63.3) ml, and the hospital stay in the suspension group was 14 (12, 17) d, shorter than that in the control group 26 (17, 32) d. The differences were statistically significant (all P<0.05). Conclusion:Gastric triangle suspension in L-RAMPS for patients of pancreatic body and tail malignant tumor can reduce the amount of intraoperative bleeding, shorten the operation time and hospital stay, is a reliable and simple suspension method.

Aim To observe the behavioral effects of exogenous allopregnanolone(ALLO)and its inhibitor finasteride on the receptive period(R)and non-recep-tive period(NR)of PMDD liver-qi inversion model rats and the expression of GABAARα4,GABAARδ mR-NA and protein effects to explore its pathogenesis.Methods The PMDD liver-qi reverse syndrome rat model was prepared.The rats were divided into the normal group R and NR(control-R,control-NR),model group R and NR(Model-R,Model-NR),nor-mal group R+ALLO and NR+ALLO(Control+A-R,Control+A-NR),and model group R+ALLO and NR+ALLO(Model+A-R,Model+A-NR),model group R+finasteride and NR+finasteride(Model+F-R,Model+F-NR).The elevated cross labyrinth ex-periment and social interaction experiment were used to detect the behaviors of rats;fluorescence quantitative PCR and immunofluorescence were used to detect the expression of GABAARα4 and 8 mRNA and protein in rat amygdala and hippocampus.Results In the be-havioral evaluation,in the NR period,in the elevated cross maze test and in the social interaction test,the rats in the model group had anxiety behavior and de-creased social communication ability(P＜0.05),while the rats in the Model+A group could effectively relieve anxiety symptoms and improve their social com-munication ability(P＜0.05),and the rats in the Model+F group had increased anxiety behavior and social disorder(P＜0.05).In fluorescence quantita-tive PCR and immunofluorescence experiments,the ex-pression of GABAARα4 subunit in the model group was up-regulated in the hippocampus(P＜0.01),and the expression of δ subunit was down-regulated(P＜0.01);the expression of GABAARα4 subunit in the a-mygdala and hippocampus of the Model+A group de-creased(P＜0.01),and the expression of δ subunit increased in the hippocampus(P＜0.01).Conclu-sions The abnormal expression of GABAARα4 and 8 subunits mediated by ALLO improves the anxiety symptoms and social interaction ability of PMDD,which is the pathogenesis of PMDD liver-qi reverse syndrome,and provides basis and support for subse-quent exploration of the pathogenesis of PMDD liver-qi reverse syndrome.