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.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.

Placental diseases may affect the outcome of pregnancy and long-term health of the mother and fetus. Fetal fraction is a key indicator for the success of non-invasive prenatal testing, and has been associated with gestational age, body mass index and fetal chromosomal aneuploidies. Many studies have found that fetal fraction is also related to placenta-derived diseases and may become a new predictor for such diseases. This article has summarized the association between the two, with an aim to provide new ideas for the prediction of placental diseases.

Unplanned readmission is one of the adverse outcomes of patients after left ventricular assist device implantation,which seriously affects the prognosis of patients.This article reviews the incidence,causes,influencing factors and intervention measures of unplanned readmission of patients after left ventricular assist device implantation,in order to improve the attention of nursing staff,early identify high-risk groups of unplanned readmission of patients after left ventricular assist device implantation and provide references for formulating personalized intervention measures.

OBJECTIVE To establish the fingerprint of Shenfukang Ⅱ capsule(SC-Ⅱ), and to screen out its indicative compounds for quality control combined with chemometrics methods and network pharmacology. METHODS The HPLC fingerprint of 10 batches of SC-Ⅱ was established, and similarity evaluation was analyzed by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 A Edition) to determine common peaks; common peaks were identified through standard comparison. Chemometrics methods was used to evaluate quality of 10 batches of SC-Ⅱ, and network pharmacology was used to screen out core targets and pathways of SC-Ⅱ. Combined with the above results, indicative compounds for quality control of SC-Ⅱ were screened out. RESULTS A total of 37 common peaks were obtained in the HPLC fingerprint, the similarity of samples was greater than 0.97. Twenty compounds were identified as morroniside, loganin, paeoniflorin and et al. The samples were divided into two categories by chemical pattern recognition, salvianolic acid B, morroniside, salvianolic acid A and paeoniflorin were differential marker compounds for SC-Ⅱ. Network pharmacology predicted that active compounds such as salvianolic acid B, paeoniflorin and morroniside might exert pharmacological effects through 45 core targets and 15 main pathways. The research preliminary preliminarily predicted that morroniside, paeoniflorin and salvianolic acid B were quality control index components for SC-II. CONCLUSION The established HPLC fingerprint method is simple and good repeatability. The quality control indicative compounds of SC-Ⅱ can provide a basis for its quality control.

Objective:To develop a list of basic and expanded medical laboratory tests in community health service centers in Shanghai.Methods:The status quo of human and equipment resource allocation, the test items and quality control currently performed, the perspectives of various stakeholders, the capacity building of community clinical laboratory in community health service centers in Shanghai were investigated by quantitative survey and qualitative interview; and the rating scores of each test item were assessed by expert consultation using Delphi method. The expert focus discussion was conducted, and each test item was rated and classified. Finally a list of the basic tests and expanded tests in clinical laboratories of community health service center was developed.Results:A total of 247 questionnaires were distributed and 192 (77.7%) were answered. A list of 94 laboratory test items was screened out based on the questionnaire survey of the laboratories of the community health centers. Thirty one experts in the relevant areas were invited to rate the test items, the average authority coefficient of experts was 0.90, with which the weighted average of the expert ratings was made. There were 45 (47.9%) items scored 7 or higher, 38 (40.4%) scored between 5 and 7, and 11 (11.7%) scored less than 5. Based on the results of the expert focus discussion, 48 items were recommended as the basic tests and 46 items as the extended tests.Conclusion:In this study a list of tests recommended to clinical laboratories in Shanghai community health service centers has been developed, which contains 48 basic tests and 46 extended tests.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

This article reported a survived case of amniotic band syndrome (ABS) following fetal reduction by radiofrequency ablation. The woman conceived monochorionic diamniotic twin pregnancy spontaneously. Prenatal ultrasound at 24 weeks of gestation indicated twin-twin transfusion syndrome (stage Ⅲ), and radiofrequency ablation for fetal reduction was successfully performed after formal consent. At 28 +6 weeks, ultrasound reexamination revealed significant edema in the left foot of the fetus, with banding around the ankle, as well as the strangulation mark and narrowing rings. Fetal ABS (ⅡB stage) was diagnosed after multidisciplinary consultation. An immediate emergency cesarean section was performed and a live male baby was born. A thin amniotic band could be seen wrapping around the left ankle of the newborn for several rounds, with obvious strangulation marks about 1 cm deep into the skin, and significant edema on the dorsum and sole of the foot, and the submalleolus area. The amniotic band was released at once, and the edema faded gradually after surgery. After a follow-up of 28 days, the lower limbs of the newborn became normal.

Objective:To investigate the infection rate in close contacts of COVID-19 patients before and after the last negative nucleic acid test, evaluate the effect of dynamic nucleic acid test in determining the infectivity of COVID-19 patients.Methods:Dynamic nucleic acid test results of COVID-19 cases were collected in a retrospective cohort study. COVID-19 cases with negative nucleic acid test results before their first positive nucleic acid tests were selected as study subjects. Close contacts of the index cases and the secondary close contacts were kept isolation for medical observation to assess their risk of infection.Results:This study included 89 confirmed cases from two local COVID-19 epidemics in Ningbo. A total of 5 609 close contacts were surveyed, the overall infection rate was 0.20%. No close contacts of the COVID-19 cases before the last negative nucleic acid test were infected, and the infection rate in the close contacts of the COVID-19 cases after the last negative nucleic acid test was 1.33%, all of these close contacts lived together with the index cases. No secondary close contacts were infected.Conclusion:COVID-19 patient becomes infectious after the last nucleic acid is negative, and has no infectivity before the last nucleic acid negative.