In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective　To analyze the current situation and influencing factors of health-care seeking delay of tuberculosis patients registered in Changsha from 2019 to 2023, and to understand the current status of health-care seeking delay after the transformation of the tuberculosis prevention and treatment service model in Changsha, so as to provide reference bases for improving the patient discovery strategy and optimizing tuberculosis control and prevention measures. Methods　The case data of 23 371 tuberculosis patients registered in Changsha City from 2019 to 2023 were collected, and the time of health-care seeking delay and the rate of health-care seeking delay were calculated. Comparison of differences between groups with different characteristics using rank sum test and chi-square test, and the Cochran-Armitage method was used to analyze the trend of health-care seeking delay rate, and multifactorial analysis was carried out with the help of logistic regression model. Results　The median health-care seeking time of tuberculosis patients in Changsha City from 2019-2023 was 16 (5, 44) days, and the overall health-care seeking delay rate was 53.5%, with an overall increasing trend (Z=-7.256, P<0.001). Between-group comparisons revealed differences in health-care seeking delay time and health-care seeking delay rate between groups of patients with different gender, age group, occupation, current address, types of household registration, medical history, complication, diagnostic triage, pathogenic results and geographic accessibility (P<0.05). The results of multifactorial analysis showed that compared to the<25 years age group, the 25-<65 years age group (OR=1.579, 95%CI: 1.490-1.669) and the ≥65 years age group (OR=2.016，95%CI: 1.918-2.113) had a higher risk of health-care seeking delay, presence of complication (OR=1.213，95%CI:1.141-1.285), positive pathology (OR=1.503, 95%CI: 1.449-1.556), and average geographic accessibility of healthcare services (OR=1.073, 95%CI:1.017-1.129) were risk factors for health-care seeking delay, and the risk was relatively lower in the migrating population (OR=0.920, 95%CI: 0.815-0.989). Conclusion　The rate of delayed health-care seeking for tuberculosis patients in Changsha City in 2019-2023 is at a moderate level in the surrounding areas, and the overall trend is increasing. It suggests that proactive screening strategies for key populations should be optimized to improve the accessibility of healthcare services and reduce the rate of health-care seeking delay.

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans ; Hypertension/complications* ; Low Back Pain/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/drug effects* ; Medicine, Chinese Traditional ; Chronic Pain/drug therapy*

Astragalus membranaceus(A. membranaceus), a traditional tonic, contains flavonoids as one of its main bioactive components and key indicators for quality standard detection. These compounds predominantly exist in glycosylated forms after glycosylation modification within the plant. The catalytic products of flavonoid glycosyltransferases in A. membranaceus have been reported to be mostly monoglycosides, and only AmUGT28 catalyzes luteolin to form diglycosides. In this study, we cloned a glycosyltransferase gene, AmGT90, from A. membranaceus, with an ORF length of 1 335 bp, encoding 444 amino acids, and the protein had a relative molecular mass of 50.5 kDa. Phylogenetic tree analysis indicated that AmGT90 belongs to the UGT74 family. In vitro enzymatic reaction showed that AmGT90 had broad substrate specificity and could catalyze the glycosylation of various flavonoids, including isoflavones, flavones, flavanones, and chalcones. AmGT90 not only catalyzed the formation of monoglycosides but also diglycosides. In addition, the mechanism of AmGT90 catalyzing the formation of diglycosides from luteolin was preliminarily explored. The experimental results showed that AmGT90 may preferentially recognize C4'-OH of luteolin and then recognize C7-OH to form diglycosides. This study reported a glycosyltransferase from A. membranaceus capable of converting flavonoids into monoglycosides and diglycosides. This finding not only enhances our understanding of the biosynthetic pathways of flavonoid glycosides in A. membranaceus but also introduces a new component for glycoside production through synthetic biology.
Glycosyltransferases/chemistry* ; Flavonoids/chemistry* ; Astragalus propinquus/classification* ; Phylogeny ; Glycosylation ; Plant Proteins/chemistry* ; Substrate Specificity ; Cloning, Molecular ; Amino Acid Sequence

Osteoporosis(OP) is a metabolic bone disorder characterized by reduced bone mass and degenerative bone tissue. Osteoporotic pain(OPP) is its most common clinical symptom, significantly affecting the quality of life of patients. With the limitations of modern medical treatments and the intensification of aging, it is imperative to explore more cost-effective interventions for OPP. This paper, based on databases such as China National Knowledge Infrastructure(CNKI), VIP, Wanfang, BioMed, and Web of Science, uncovered the connection between the pathogenesis of OPP in traditional Chinese medicine(TCM) and modern medical mechanisms and retrospectively summarized the basic and clinical research methods and evidence of TCM prescriptions in the treatment of OP and related pain diseases. Studies have shown that TCM prescriptions, focusing on treatments such as nourishing the kidney, strengthening the spleen, and activating blood circulation to remove blood stasis, can significantly improve pain symptoms, increase bone mineral density(BMD), and adjust bone metabolic indicators such as C-terminal telopeptide of type Ⅰ collagen(CTX), serum bone Gla-protein(S-BGP), and alkaline phosphatase(ALP). The mechanisms of action of TCM prescriptions in treating OP and improving OPP symptoms were related to signaling pathways such as Wnt/β-catenin, nuclear factor kappa-B(NF-κB), mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and the osteoprotegerin(OPG)/receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand(RANKL) axis. Further strengthening the accumulation and analysis of clinical data, rigorously designing and conducting randomized controlled trials of TCM treatments for OPP with large sample sizes, standardizing outcome measures in basic and clinical research by using methods such as the core outcome set(COS), and incorporating mass spectrometry and omics approaches to uncover more potential active components and mechanisms may contribute to a deeper exploration of the advantages and essence of TCM prescriptions in the treatment of OPP.
Humans ; Osteoporosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Retrospective Studies ; Bone Density/drug effects* ; Medicine, Chinese Traditional ; Pain/metabolism* ; Animals

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.

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To investigate the influencing mechanism of micro ribonucleic acid(miR)-375 targeting phos-phatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway on high glucose-induced proliferation and angiogenesis in human retinal endothelial cells(hRECs).Methods The hRECs were cultured in vitro,and transfection and dual lucifer-ase assay were performed on them.These hRECs were divided into the control group,high glucose group,high glucose+miR-375 group,and high glucose+miR-375+LM22B-10 group.The Cell Counting Kit-8 was used to detect the cell prolifera-tion ability,the angiogenesis assay was used to detect the vascular formation ability,real-time quantitative PCR was used to detect the miR-375 and PI3K mRNA expressions in hRECs,and Western blot was used to detect the PI3K and p-AKT/AKT protein expressions in hRECs.Results At 48 h and 72 h after the cultivation,compared with the control group,the pro-liferation viability,PI3K and p-AKT/AKT protein expressions,vascular formation ability,and PI3K mRNA expression in hRECs significantly increased,and the miR-375 expression in hRECs significantly decreased in the high glucose group,high glucose+miR-375 group and high glucose+miR-375+LM22B-10 group(all P＜0.05).Compared with the high glucose group,the proliferation viability,PI3K mRNA and protein expressions,p-AKT/AKT protein expression and vascular forma-tion ability in hRECs were significantly reduced,and miR-375 expression significantly increased in the high glucose+miR-375 group(all P＜0.05).Compared with the high glucose+miR-375 group,the proliferation viability,vascular formation a-bility and p-AKT/AKT protein expression in hRECs significantly increased in the high glucose+miR-375+LM22B-10 group(all P＜0.05);there was no significant difference in the miR-375 and PI3K mRNA(all P＞0.05).After transfected with miR-375 mimic and wt-PI3K-pGL4,the relative luciferase activity in hRECs significantly decreased compared with transfec-tion with miR-375 NC and mut-PI3K-pGL4(all P＜0.05).Conclusion The targeted inhibition of the PI3K/AKT pathway by miR-375 can suppress the high glucose-induced proliferation and angiogenesis of hRECs,alleviating DR.

OBJECTIVE To explore the antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.

Objective To investigate the role of PPARγ/GluT4 axis in insulin resistance(IR),cell proliferation and apoptosis of granulosa cells.Methods A total of 45 married women with PCOS who received routine IVF-ET assisted pregnancy treatment in Center of Reproductive Medicine,Qinghai Provincial People's Hospital were enrolled in this study from August 2018 to August 2020.All the patients were divided into IR group(PCOS-IR group,HOMA-IR≥2.57,n=23)and non-IR group(PCOS-NIR group,HOMA-IR<2.57,n=22)according to HOMA-IR.Meanwhile,21 married patients with infertility due to male or fallopian tube factors were enrolled as control group(Con).miR-27a mimics,miR-27a inhibitors(miR-27a inhibitor)and corresponding controls(mimics NC and inhibitor NC)transfected PCOS-IR granulosa cells,which were then divided into miR-27a mimics group,miR-27a inhibitor group,mimics-NC group and inhibitor-NC group.Double luciferase report test confirmed that miR-27a binded to PPARγ.Cell proliferation and apoptosis were detected by CCK-8 method and Annexinv-FITC/PI method.The expression of miR-27a,GluT4,PPARγ,Bax related to B lymphomas-2,Cleaved caspase-3 and B lymphomas-2(Bcl-2)were detected by RT-qPCR and Western blot respectively.Results Compared with Con group,the expression of miR-27a increased(P<0.01),while the expression of PPARγ mRNA and protein decreased in PCOS-NIR and PCOS-IR groups(P<0.01).Compared with PCOS-NIR group,the expression of miR-27a increased(P<0.05),while the expression of PPARγ mRNA and protein decreased in PCOS-IR group(P<0.01).The double luciferase report showed that there was a targeted binding site between PPARγ and miR-27a.Compared with inhibitor-NC group,the cell activity increased at 24 h,48 h,72 h and 96 h in miR-27a inhibitor group(P<0.05 or P<0.01),while the apoptosis rate decreased inmiR-27a inhibitor and mimics-NC group(P<0.05 or P<0.01).Compared with miR-27a inhibitor group,the apoptosis rate increased,and the cell activity decreased at 24,48,72 and 96 h in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Compared with the inhibitor-NC group,the expression of miR-27a,Bax and Cleaved caspase-3 increased(P<0.05 or P<0.01),while the expression of GluT4,PPARγ and Bcl-2 decreased in miR-27a mimics group(P<0.01).In miR-27a inhibitor group,the protein expressions of GluT4,PPARγ and Bcl-2 increased(P<0.05 or P<0.01),while miR-27a,Bax and Cleaved caspase-3 decreased(P<0.01).Compared with miR-27a inhibitor group,the expressions of miR-27a,Bax and Cleaved caspase-3 increased(P<0.01),while the expressions of GluT4,PPARγ and Bcl-2 decreased in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Conclusion The expression level of miRNA-27a is related to IR,cell proliferation,and apoptosis of granulosa cells,which may be related to PPARγ signal path.