ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective The long-term epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) in Huai’an, Jiangsu were analyzed to provide scientific evidence for the prevention of HFMD. Methods The data of HFMD reports, etiological diagnosis and in Huai’an from 2009 to 2022 were described and analyzed. Results A total of 78 535 cases were reported from 2009 to 2022 , with 14-year average annual incidence rate of 114.71/100 000. Before 2020, the incidence rate of HFMD in Huai’an showed the epidemic intensity increased every other year on the whole, and the average annual incidence rate during the COVID-19 pandemic (2020-2022) (55.69/100 000) was significantly lower than that in previous years (2009-2019) (129.95/100 000). The joinpoint regression analysis showed that the best fitting model from 2009 to 2022 had no joinpoints, APC=AAPC=-1.24%. The overall trend showed a monotonously decreasing trend, but the trend was not statistically significant. The male-to-female distribution ratio was 1.53:1, and the age distribution was mainly under 5 years old, especially in scattered children. The epidemic season was from April to July. The results of etiological surveillance showed that the co-epidemic of Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) during the early stages had changed to the co-epidemic of CV-A16 and CV-A6 in the current period. Conclusion The burden of HFMD in Huai’an was large, and the epidemic intensity increased every other year was affected by the COVID-19 pandemic. The epidemiological features after the COVID-19 pandemic should be further monitored.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To compare the changes of the medical animal resources(MAR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2020-2022).Methods After field investigation and identification of the photos of the animals,the data of the MAR in Sichuan found in the 4th CMMRI were analyzed and compared with the data of 3rd CMMRI.Results 745 species of MAR were found in Sichuan during the 4th CMMRI,including 212 families and 468 genera.Compared with the 108 species found in 3rd CMMRI,the number of MAR in Sichuan had greatly increased,The Aves was found to have 243 species of MAR,which is the most plenty one among the 7 classes.There were 14 families which have more than 10 species of MAR.The family,Cyprinidae had 48 species of MAR.There were 33 common Chinese medicinal herbs and 3 genuine medicinal materials including Cordyceps sinensis,musk and Venenum bufonis were found in this investigation.The new distributions of Liangshan Cordyceps and Cordyceps gunnii were found in the investigation,and the new resources of Atypus heterothecus was found in Mountain Emei.There were 140 species of key protection of wild medicinal animals,including 44 species of animals under first-class protection and 96 species of animals under second-class protection.There were 230 species of animals which had important ecological,scientific,and social values,too.Conclusion Sichuan was plenty of medical animal resources and the protection of the forest musk deer,the Cordyceps sinensis and the pangolin was need to be strengthened.

Objective To evaluate the efficacy of transurethral resection of bladder tumor(TURBT)in treating cystitis glandularis(CG),and to explore the influencing factors.Methods A retrospective analysis was conducted on 243 CG patients treated with TURBT during Jan.2013 and Dec.2020 in our hospitals.Postoperative efficacy was assessed using global response assessment(GRA).The correlation between GRA score and the demographic characteristics,comorbidities,initial complaints,and postoperative recurrence was determined with logistic regression analysis.Results Among the 243 patients,3.70％(9/243)had dysplasia,2.47％(6/243)had exuberant hyperplasia of Brinell's nest,and 2.06％(5/243)had intestinal metaplasia.The mean GRA score was(2.02±0.72)after a follow-up of(47.10±28.53)months.Re-operation was performed in 10.29％(25/243)of the patients due to recurrence,and the improvement of hydronephrosis and dysuria was 70.59％(12/17)and 50.00％(15/30),respectively.Pelvic fat increase developed in 1 patient(0.41％)after surgery.Logistic regression analysis showed that postoperative GRA score was not significantly correlated with demographic characteristics,body mass index,comorbidities,alcoholism and postoperative recurrence(P＞0.05).Conclusion TURBT is an effective method in the treatment of CG,which can significantly improve patients'hydronephrosis and dysuria.However,approximately 10％of the patients experience recurrence,necessitating further surgery,which suggests the need for vigilance regarding potential recurrence during treatment.

Objective To analyze the clinical manifestations of delayed serological transfusion reactions(DSTR)after platelet transfusion in tumor patients,and to explore the transfusion strategy.Methods Clinical data and laboratory test re-sults of patients with positive antibody screening were analyzed after platelet transfusion in our hospital from January 1,2015 to June 30,2023,and the incidence rate,clinical characteristics and transfusion strategy of patients with DSTR were ana-lyzed.Results A total of 2 553 patients with 6 057 platelet transfusions were reviewed.Eight patients developed DSTR and received a total of 21 therapeutic amounts of platelets,and 5 patients were subsequently transfused with red blood cells.Rh system antibodies were detected in 7 cases(4 anti-E,1 anti-c/E,1 anti-C and 1 anti-c)and Kell system antibodies in 1 case.Conclusion Tumor patients may also develop DSTR after platelet transfusion.It is necessary to pay close attention to the antibody situation and perform matched transfusion when transfusing blood again.

Objective To investigate the mechanism of the interaction between Wnt/β-catenin signaling and the epithelial mesenchymal transition(EMT)pathway in mediating sunitinib-resistance in renal cancer cells.Methods The sunitinib-resistant kidney cancer cell lines were constructed by stepwise increase in drug concentrations method with sunitinib,and were divided into resistance group,lv-NC group and lv-Twist group,and human kidney cancer cell lines were selected as normal group.The normal and drug-resistant groups were treated with conventional culture;the lv-NC group was treated with 40 μL of lv-NC lentivirus supernatant containing 2.25 × 108 TU·mL-1 for 72 h,and the lv-Twist group was treated with 50 μL of Twist lentivirus supernatant containing 1.64 × 108 TU·mL-1 for 72 h.The apoptosis ability was detected by flow cytometry;the cell migration ability was detected by cell scratch assay;the cell invasion ability was detected by Transwell assay;and the protein expression levels of Wnt1,β-catenin and Twist were detected by Western blotting assay.Results The apoptosis rates of control,resistant,lv-NC and lv-Twist groups were(17.60±0.59)％,(8.61±0.34)％,(8.60±0.40)％and(3.10±0.34)％;the migration rates were(14.10±0.12)％,(27.64±0.41)％,(14.24±0.45)％and(32.74±2.53)％;the number of invading cells was 27.33±1.15,53.33±1.53,46.00±2.65 and 99.33±2.52;the relative expression levels of Wnt1 protein were 0.10±0.01,0.96±0.06,0.39±0.03 and 3.09±0.31;the relative expression levels of β-catenin protein were 0.39±0.01,1.48±0.16,0.81±0.05 and 1.24±0.14;the relative expression levels of Twist protein were 0.10±0.02,0.91±0.04,0.39±0.03 and 3.09±0.31,respectively.The differences of above indexes were statistically significant between the resistant group and the normal group,and between the lv-Twist group and the lv-NC group(all P＜0.05).Conclusion Twist(EMT related protein)mediates sunitinib resistance in renal cell carcinoma by interacting with Wnt/β-catenin signaling pathway.