Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Objective:To study the clinical characteristics and death risk factors of the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020.Methods:The clinical data were retrospectively analyzed of the 894 patients with fall-related injuries who had been admitted to Department of Trauma Center, The First People's Hospital of Kashgar Prefecture, Xinjiang Uygur Autonomous Region from January 2019 to December 2020. Recorded were the patient's gender, age, location of fall, month of fall, fall height, major injury site, injury severity score (ISS) and Glasgow score (GCS). The clinical characteristics and death risk factors of the fall patients were analyzed.Results:Of the 894 patients, 72.3%(646/894) were male and 86.9%(777/894) fell from a height from 1 to 6 meters. Their ages ranged mainly from 15 to 59 years old (74.3%, 664/894). Home was the most frequent site for falls (60.2%, 538/894) and the patients who fell in summer months (from June to August) were the most (32.3%, 289/894). Twenty-one patients (2.3%, 21/894) died. There were significant differences in the major injury site, blood transfusion, ISS score and GCS score between the dead and survival patients ( P<0.05). The multivariate logistic regression analysis showed that the injury to the head, face and neck [ OR=10.936, 95% CI: 1.177 to 101.627, P=0.035] and GCS score ≤12 [ OR=5.640, 95% CI: 2.658 to 11.968, P< 0.001] were the death risk factors for the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020. Conclusions:In the patients with fall-related injuries in parts of Kashgar Prefecture during 2019-2020, males aged from 15 to 59 years old were the high-risk group of falls. Months with a high incidence of falls were from June to August. The fall patients with injuries to the head, face and neck and with a GCS score of ≤12 were at a high risk of death.

To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli. In the adjuvant-induced arthritis (AIA) mice model, BsDb showed selective accumulation and retention in the inflamed paws but rapid clearance from blood, resulting in high arthritic paw to blood ratios. These data indicate that BsDb is endowed with high specificity to inflamed site and low toxicity to normal tissues and holds great potential for in vivo application for the targeted therapy of RA and other chronic inflammatory diseases.
Animals ; Antibodies, Bispecific ; biosynthesis ; immunology ; Antibodies, Neutralizing ; biosynthesis ; immunology ; Escherichia coli ; Fibronectins ; chemistry ; immunology ; Humans ; Mice ; Single-Chain Antibodies ; biosynthesis ; immunology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVE: To detect the expression of miR-126 in different tissues and organs and the change of peripheral blood glucose in microRNA-126 knock down (miR-126 KD) mouse, and to explore the pathological significance. METHODS: Total RNAs were isolated from twelve kinds of tissues and organs in wild-type mouse (WT) and miR-126 KD mouse respectively. Th en, the expression level of miR-126 was detected by real-time PCR assay. Th e levels of peripheral blood glucose and body weight of miR-126 KD mice were measured. Th e pathologic changes of pancreas and lung tissue were observed by HE staining. RESULTS: Compared with the WT mice, the relative expression of miR-126 in spleen, liver, muscle and lung from the miR-126 KD mice were dramatically decreased respectively (P<0.05). The level of peripheral blood glucose in the miR-126 KD mouse increased significantly at seven week and sixteen week after the birth (P<0.05). HE staining showed that the pathological structure of pancreas and liver were abnormal. The body weight of miR-126 KD mice was increased obviously from thirteen week after birth (P<0.05). CONCLUSION Peripheral blood glucose levels in the miR-126 KD mouse were dramatically elevated, which might be related to the pathological changes in the structure of pancreas and liver. These results suggest that miR-126 may play an important role in the metabolism of blood glucose and the development of type 2 diabetes mellitus.
Animals ; Blood Glucose ; analysis ; Body Weight ; Diabetes Mellitus, Type 2 ; Gene Knockdown Techniques ; Liver ; pathology ; Mice ; MicroRNAs ; genetics ; Pancreas ; pathology ; Real-Time Polymerase Chain Reaction

Background Researchers are paying increasing attention to the effect of cellular senescence in vascular dysfunctional diseases,and it is hypothesized that cellular senescence may also be involved in the development of diabetes related vascular complications.The outstanding feature of cellular senescence is the upregulation of beta-galactosidase.Objective This study was to investigate the effects of high glucose on cell senescent in vitro and in vivo on bovine retinal endothelial cells (BRVECs) and mouse retina.Methods BRVECs were cultured and passaged,and the seventh generation of cells were employed in this study.The cells were divided into the control group and the high glucose culture group and cultivated using M199 medium containing 5.5 mmol/L or 25.0 mmol/L glucose,respectively.5-bromine-chlorine-4-3-indole-beta D galactose glucoside (X-Gal) staining was used to examine the expression of beta-galactosidase in the cells.Diabetic models were established in the SPF male C57BL/6J mice aged 8-10 weeks by intraperitoneal injection of streptozotocin (STZ),and the age-and gendermatched normal mice served as controls.The mouse retinas were collected and starched in the 48-well plates 3 months later.X-Gal staining was employed to calculate the positive cells.Results BRVECs grew well 24 hours after culture but showed irregular arrangement.Forty-eight hours later,the cells reached confluence with a tight connect.The ratios of positive BRVECs and total cells were (51.4±5.4) ％ and (36.6-±3.8) ％ in the high glucose culture group and the control group,with a significant difference between the two groups (t =-3.204,P =0.033).The number of positive cells for X-Gal in mouse retinas was (94.0± 15.1) /field in the diabetic group,which was higher than that in the control group ([60.0 ± 5.7]/field) (t =-2.974,P =0.041).Conclusions High glucose environment accelerates senescence of retinal cells,and high glucose induces premature cell senescence,which likely plays an important role in the pathogenesis of diabetic retinopathy.

Objective To analyze factors contributing to the quality of life of earthquake victims with nonunion fracture in limbs after medical rehabilitation and to provide a clinical reference for future disasters.Methods Thirty-one wounded who sustained their injuries in the Sichuan earthquake completed the short form-36(SF-36)questionnaire 2 weeks before their amputation,and after 3,6 and 12 months of medical rehabilitation.The SF-36scores were compared with Sichuan population norms.Stepwise multiple linear regression was used to highlight variables which influenced their functional recovery and their physical and mental health.Results The physical and mental health composite scores of the 31 victims were significantly lower than Sichuan population norms before medical rehabilitation,but they had a significant increasing trend after 3,6 and 12 months of treatment.Their scores on all the domains remained significantly lower than Sichuan population norms at a later follow-up.Smoking,external fixations and chronic diseases were related to their recovery of physical function.Age,permanent housing,family income and casualties among family members were related to their mental health recovery.Conclusion The quality of life of patients with nonunion fracture caused by earthquake can be improved significantly through medical rehabilitation.But social factors should be considered in addition to medical rehabilitation after an earthquake.