Alzheimer's disease （AD）， a degenerative disease of the central nervous system， is characterized by progressive degradation of learning， memory， and cognitive functions. Currently， few drugs are available for treating AD， and their effects are limited. Berberine （BBR） is a natural isoquinoline （quaternary ammonium-like） with a wide range of pharmacological effects. Studies have proven that BBR has good potential in the treatment of AD. Specifically， BBR can inhibit the generation， aggregation， and neurotoxicity of amyloid-β and the hyperphosphorylation of Tau protein， promote the clearance of phosphorylated Tau protein， reduce the cholinesterase activity， neuroinflammation， and oxidative stress， regulate neuronal apoptosis， improve the mitochondrial function and glucose and lipid metabolism， suppress the monoamine oxidase activity， and modulate gut microbiota. In addition， researchers have ameliorated the low bioavailability of BBR. Probing into the potential targets is hoped to provide a reference for further research on the prevention and treatment of AD by BBR.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To explore the value of dual-phase enhanced CT radiomics in predicting post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A total of 145 patients with acute pancreatitis(AP)were retrospectively collected,including 62 patients in PPDM-A group and 83 patients in non-PPDM-A group.The patients were randomly divided into training set and test set at a ratio of 7︰3,the pancreatic parenchyma in arterial phase and venous phase was delineated and the radiomics features were extracted.Vari-ance threshold method,univariate selection method and least absolute shrinkage and selection operator(LASSO)were used to screen radiomics features.The prediction performance of the model was evaluated by the area under the curve(AUC).The DeLong test was used to compare the prediction efficiency between the models,and the calibration curve and decision curve were used to evaluate the prediction efficiency of the model.Results The AUC of arterial phase model,venous phase model,combined arterial venous phase model,clinical model and radiomics combined clinical model in the training set were 0.845,0.792,0.829,0.656 and 0.862,respec-tively.The DeLong test results showed that only the difference between the radiomics combined clinical model and the clinical model in the training set and the test set was statistically significant(P<0.05).The decision curve showed that the radiomics combined clinical model had high clinical practicability in a certain range,and the calibration curve showed that the radiomics combined clinical model had the best fitting degree with the actual observation value.Conclusion Based on the dual-phase enhanced CT radiomics combined clinical model,PPDM-A can be predicted more accurately,and it can provide a certain reference value for the clinical development of per-sonalized treatment programs.

Objective:To explore the association between the variability of triglyceride glucose index (TyG) and the risk of type 2 diabetes mellitus(T2DM).Methods:This study was a retrospective cohort study. A total of 22 929 community-dwelling elderly (aged≥60 years) who received annual health check-ups in Kunshan city of Suzhou Municipality during 2014 to 2021 were enrolled in the study. Fasting triglycerides and blood glucose were measured during annual physical check-ups and the TyG was calculated, the standard deviation of TyG measurements in three consecutive physical check-ups was used as the indicatior of TyG long-term variability. According to the quartile of TyG long-term variability, the study subjects were divided into four groups, namely Q 1 (0-0.14), Q 2 (>0.14-0.22), Q 3 (>0.22-0.33), Q 4 (>0.33-1.90). The outcome variable was the occurrence of T2DM. The relationship between TyG variability and T2DM incidence was analyzed by multivariate Cox regression. Results:In the study cohort 11 518 (50.2%) were females and the mean age was (67.42±5.35) years. By the end of follow-up, 2 934 cases of new T2DM were diagnosed, with an oveall incidence rate of 12.8%. After adjusting for multiple confounders and average TyG, long-term variability of TyG was significantly associated with T2DM risk ( HR=1.83, 95% CI: 1.51-2.20). The risk of T2DM in Q 4 group was significantly higher than that in Q 1 group ( HR=1.33, 95% CI: 1.19-1.47). Kaplan-Meier survival curve showed that long-term variability of TyG was significantly correlated with the cumulative risk of T2DM incidence ( P<0.001). Conclusions:TyG variability is an independent risk factor for T2DM, suggesting that attention should be paid not only to specific time-point TyG levels but also to TyG fluctuation for early identification of T2DM risk.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Objective To investigate the association between clonal hematopoiesis of indeterminate potential(CHIP)and the severity of coronary artery lesions in coronary heart disease(CHD)patients with renal insufficiency.Methods A case-control trial was conducted on 70 CHD patients with renal insufficiency admitted in Chongqing Emergency Medical Center(Affiliated Central Hospital of Chongqing University)and Department of Cardiovascular Diseases of the First Affiliated Hospital of Chongqing Medical University from December 2023 to July 2024.According to the median Gensini score,they were classified into the Gensini score＜44 group(n=34)and ≥44 group(n=36),and based on carrying CHIP mutation or not,they were divided into CHIP group(n=23)and non-CHIP group(n=47).The differences in clinical data were compared between the above 2 pair groups respectively.Binary logistic regression analysis was used to assess the relationship between CHIP status and the severity of coronary artery lesions.Results Compared with the Gensini score＜44 group,the Gensini score ≥44 group had a higher CHIP carriage rate(17.2％vs 47.6％,P=0.008)as well as NT-proBNP level(767 vs 3 480 ng/L,P=0.039).Binary logistic regression analysis showed that CHIP status was still associated with higher Gensini scores after adjustment of NT-proBNP(OR=3.935,95％CI=1.153～13.435,P=0.029).Further CHIP grouping results suggested that the patients in the CHIP group had higher Gensini score(48 vs 38,P=0.004),larger proportion of 3-vessle disease(52.2％vs 25.5％,P=0.040),and lower left ventricular ejection fraction(55.0％vs 58.0％,P=0.042)than those in the non-CHIP group.Conclusion CHIP is an independent risk factor for severe coronary artery disease in CHD patients with renal insufficiency.

Objective To investigate the longitudinal changes in left ventricular(LV)structure and function after bariatric surgery in obese individuals and their relationship with preoperative left ventricular ejection fraction(LVEF)by cardiac magnetic resonance(CMR)imaging.Methods We prospectively enrolled 75 obese subjects scheduled for laparoscopic sleeve gastrectomy and 46 age and sex-matched healthy controls(the control group).All subjects underwent CMR examination to obtain LV structural parameters,LVEF,and strain parameters.According to their preoperative LVEF,the obese subjects were divided into two obesity groups,including the group of patients with LVEF≥60％(n=43)and the group of patients with 50％≤LVEF＜60％(n=32).LV structural and functional differences between the control group and the two obesity groups were compared.Eventually,38 obese subjects completed the CMR follow-up at 1 month and 12 months after bariatric surgery.The longitudinal changes in LV structure and function after surgery in the LVEF ≥ 60％(n=20)group and the 50％≤LVEF＜60％group(n=18)were compared.Results Before bariatric surgery,the global longitudinal strain was significantly lower in the LVEF ≥ 60％group than that in the control group([-18.36±1.86]％vs.[-19.50±1.53]％,P＜0.05).The global radial([27.70±3.52]％vs.[34.44±4.11]％,P＜0.05),circumferential([-17.35±1.46]％vs.[-19.85±1.42]％,P＜0.05),and longitudinal([-16.22±1.81]％vs.[-19.50±1.53]％,P＜0.05)strain in the 50％≤ LVEF＜60％group was significantly lower than that in the control group.At 12 months after bariatric surgery,the global radial([32.52±7.84]％vs.[30.92±4.27]％,P＞0.05),circumferential([-19.02±2.42]％vs.[-18.63±1.49]％,P＞0.05),and longitudinal([-18.18±2.06]％vs.[-17.78±1.66]％,P＞0.05)strain in the LVEF≥60％group showed no significant difference compared with the baseline findings.In the 50％≤ LVEF＜60％group,the global radial([32.73±5.86]％vs.[26.83±4.85]％,P＜0.05)and circumferential([-19.10±2.00]％vs.[-16.91±2.09]％,P＜0.05)strain was significantly higher than that before surgery.Conclusion LV remodeling is reversed after bariatric surgery in obese subjects,and the longitudinal changes in LV structure and function vary with the preoperative LVEF.

Systematic research on the quality evaluation methods of Chinese medicinal materials is an intrinsic requirement,which is beneficial to the clinical application of traditional Chinese medicine and the sound development of traditional Chinese medicinal industry.The intrinsic quality evaluation methods of Chinese medicinal materials have developed from chemical fingerprint to quality marker of Chinese medicinal materials,and it represents that the evaluation mode has developed from chemical component as research index to the combination of chemical component and pharmacodynamic components,chemical component and biological activity.The extrinsic character evaluation method of Chinese medicinal materials from"Quality Evaluation Through Morphological Identification"to the application of intelligent sensory technology make up for the accumulation of objective data.The trend of quality evaluation of the intrinsic quality and extrinsic traits of Chinese herbal medicines conform to the innovation strategy called integrated quality control of TCMs.This paper reviews the development and evolution of the research on the intrinsic quality and extrinsic traits of Chinese herbal medicines,systematically expounds the research status and development trend of"intrinsic and extrinsic combination",and facilitate the establishment of quality evaluation system of Chinese herbal medicines with standardization and informatization characteristics in accordance with the theory of traditional Chinese medicine.

Objective This study proposes to visually review the current situation and progress of standards sets by the International Organization for Standardization/Technical Committee on Traditional Chinese Medicine (ISO/TC 249). The review aims to explore the development strategies of the standards, which will exhibit the considerable impact on the economy, trade and exchanges, and cooperation in the area of traditional Chinese medicine (TCM). Methods ISO/TC 249 standards were searched on the ISO website, and their title, proposed time, current stage, scope, and classification were obtained for further summarization. Gephi was utilized to portray the co-occurrence network graph of the ISO/TC 249 standards subject. Results In ISO/TC 249, there were 116 standards, including 81 published standards and 35 developing standards by April 30, 2022. Two withdrawal standards were published after revision, which were not counted in the total standards. The number of published standards has been increasing since the first standard was published in 2014, whose title was “Sterile acupuncture needles for single use”. Among these standards, 17.24% (20/116) standards were in review, 56.03% (65/116) in publication, 3.45% (4/116) in approval, 5.17% (6/116) in enquiry, 3.45% (4/116) in committee, and 14.66% (17/116) in preparation, respectively. With 116 standards, most of the research focused on the medicament, as its classification of the International Classification for Standards (ICS) showed the proportion reaching 49.54%. The network analysis data revealed that the top five most frequent words were “materials” “root” “requirements” “products” and “system”, after removing the noise data, such as prepositions, conjunctions, and pronouns. Additionally, the word “system” co-exists with the terms “computerized” “coding” “image” “tongue” and “analysis”; the word “requirement” co-exists with “manufacturing” “decoction” “process” and “materials”; whereas the word “devices” co-exists with “pulse” “electric” “skin” and “measurement”. Conclusion With the increased diversification and complexity of problems, the development of standards is also oriented to multidisciplinary fields to cultivate the interdisciplinary talents, and especially the international standardization talents of compound TCM. Multi-angle analysis, formulation, and demonstration of standards, in line with industry needs in different disciplines, enhance the availability of standards and the ability to serve the industry.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.