OBJECTIVE To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase （JNK） activator Anisomycin 2 mg/kg ]， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected. RESULTS Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail：mcvi45@163.com p65 proteins were increased significantly （P＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （P＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （P＜0.05）， showing an obvious dose-effect relationship （P＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （P＜0.05）. CONCLUSIONS Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Ovulatory disorders are mainly characterized by abnormal follicular maturation or ovulation， with complex etiologies and a lack of effective prevention and treatment methods. Autophagy dysfunction is closely related to the generation and progression of ovulatory disorders. This article systematically elucidates the mechanisms of TCM on follicular development and ovulatory disorders from the perspective of autophagy. It also reviews relevant studies on how TCM regulates autophagy to influence follicular development and improve ovulatory disorders. The findings reveal that TCM monomers/active ingredients （leonurine， total flavonoids from Eucommia ulmoides， alpinetin， icariin， etc.） and compound formulas （including Cangfu daotan decoction， Guishen yugong decoction， Zhuluan decoction， Yishen yangluan formula， Guishen pill， etc.） improve the follicular microenvironment， regulate sex hormone levels， and reduce follicular atresia by regulating autophagy-related genes and signaling pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin and AMP-activated protein kinase. These actions thereby promote normal follicular development and ovulation， and delay ovarian aging. Most research in this field is based on cellular and animal experiments， often focusing on a single signaling pathway or factor. Some studies fail to fully reflect the individualized treatment characteristics of TCM that emphasize “syndrome differentiation and treatment”， highlighting the urgent need for further investigation.

Objective: To investigate the value of decreased carbohydrate antigen 19-9(CA19-9) kinetics in predicting short-term outcomes and determining prognosis among advanced biliary or pancreatic cancer patients receiving first-or second-line therapy in the real world. Methods : Eighty-nine patients were retrospectively collected with advanced biliary or pancreatic cancer, especially on the CA19-9 dynamics and decline rates at different time points. This study evaluated the association of CA19-9 changes with clinicopathological features, short-term response to antitumor therapy, and survival outcomes. Results : The enrolled patients recorded baseline CA19-9 levels ranging from 1.20 to 65 706.40 U/ml, with a median of 303.11 U/ml. There was no statistical correlation between baseline CA19-9 levels and gender, age, body mass index, primary tumor site, hepatic metastases, pulmonary metastases, lymph node metastases, peritoneal metastases, performance status, treatment lines, and combinations of drug types. Baseline CA19-9 levels were not associated with systemic immunoinflammatory index, prognostic nutritional index, and total bilirubin. A 25% or 50% decrease in CA19-9 after 2-3 therapy courses indicated short-term efficacy in reaching tumor objective remission or disease control. Both combinations of multiple drug types and a 25% decline in CA19-9 after one course of treatment were independent prognostic factors that affected the longer progression-free survival of patients receiving first or second line of treatment. Conclusion Decreased CA19-9 kinetics has specific values in predicting the efficacy and prognosis of advanced biliary or pancreatic cancer.