ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases （NCDs） and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS （aged≥45 years） in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University， and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version （EQ-5D-3L） were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants， 29（7.9%） had cardiovascular disease， 45（12.3%） had hypertension， 122（33.3%） had hyperglycemia， 151（41.3%）had hyperlipidemia，7（1.9%） had cancer， 17 （4.6%） had chronic kidney disease， 38 （10.4%） had chronic liver disease， 21（5.7%） had musculoskeletal disorders， and 253（69.1%） suffered from at least one type of chronic diseases. The median （lower and upper quartiles） of EQ-5D utility index was 1.000（0.964~1.000）. Multivariate Tobit regression results of the total population showed that cancer ［b_a=-0.08，95%CI （-0.15，-0.01），P=0.036］， chronic kidney disease ［b_a=-0.07， 95%CI （-0.12，-0.02），P=0.006］， musculoskeletal disease ［b_a=-0.09， 95%CI （-0.13， -0.05），P<0.001］， and ≥3 types of chronic diseases［b_a=-0.05， 95%CI（-0.08，-0.01），P=0.013］ were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension ［b_a=-0.07， 95%CI （-0.12， -0.02）， P=0.007］， chronic kidney disease ［b_a=-0.10，95%CI （-0.18，-0.03）， P=0.006］， musculoskeletal disease ［b_a=-0.15， 95%CI （-0.22，-0.07）， P<0.001］ and ≥3 types of chronic diseases ［b_a=-0.09， 95%CI （-0.09， -0.01）， P<0.001］ were negatively correlated with EQ-5D utility index in the group with CD4≤500 （cells/μL）， whereas cancer［b_a=-0.11， 95%CI （-0.20，-0.01）， P=0.031］ was negatively correlated with EQ-5D utility index in the group with CD4＞500（cells/μL）. ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However，this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage， strengthen linkages and integration of health services for AIDS and chronic NCDs， and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

Objective:To analyze the clinical characteristics，laboratory tests，endoscopic features，treatment，and follow-up of peptic ulcers caused by eosinophilic gastrointestinal disorders（EGIDs）in children，with the aim of improving the level of understanding，diagnosis and treatment of EGIDs in children with the onset of peptic ulcers.Methods:A retrospective analysis was conducted on children admitted to the Department of Gastroenterology，Capital Center for Children's Health，Capital Medical University from January 1st，2019 to October 31st，2023，who underwent complete endoscopic examination. The first examination showed the presence of peptic ulcers（gastric or duodenal ulcers）under the endoscope，and were ultimately diagnosed with peptic ulcers caused by EGIDs through examination and follow-up. The clinical characteristics，laboratory tests，endoscopic results，and treatment follow-up were analyzed.Results:Thirty-five children were EGIDs，22 males and 13 females.Twenty-two cases（62.9%）had abdominal pain as the main symptom.Laboratory tests：17 cases（48.6%）showed a decrease in hemoglobin，15 cases（42.9%）showed an increase in eosinophil count，20 cases（57.1%）tested gastro positive for food allergen specific IgE，and 17 cases（48.6%）showed thickening of the intestinal wall on gastrointestinal ultrasound. Endoscopic features：8 cases（22.9%）showed gastric antral ulcers，including 7 cases（20.0%）with multiple gastric antral ulcers，and 25 cases（71.4%）showed duodenal bulb ulcers.There were 15 cases（42.9%）showed huge ulcers，and 14 cases（40.0%）were located in the duodenal bulb. Comparison of clinical characteristics between children with EGIDs（EGIDs group）and those with peptic ulcers caused by Helicobacter pylori infection（Hp group）：the first clinical symptom in both groups was mainly abdominal pain，but the incidence rate in the EGIDs group was lower（62.9% vs 93.5%），and the weigth for length Z score in the EGIDs group was lower［0（-1.6，0.8）vs 1.1（0，1.9）］，with statistical significance（all P<0.05）. Comparison of laboratory tests：the EGIDs group showed a statistically significant difference in hemoglobin levels［120（101，124）g/L vs 130（100，138）g/L］，eosinophil count［0.28（0.13，0.71）× 10 9/L vs 0.16（0.08，0.22）×10 9/L］，a positive rate of food allergen specific IgE detection（57.1% vs 32.3%），and a positive rate of intestinal wall thickening detected by gastrointestinal ultrasound（48.6% vs 16.1%）compared with the Hp group（all P<0.05）. Comparison of endoscopic examinations：multiple ulcers in the gastric antrum were more common in the EGIDs group than in the Hp group（20.0% vs 0），and the difference was statistically significant（ P<0.05）. Conclusion:For children with peptic ulcers with onset of abdominal pain，with anemia or malnutrition，or multiple ulcers in the gastric antrum and huge ulcers in the duodenal bulb detected by endoscopy，it is recommended to perform multi site biopsies to help diagnose EGIDs early.

Objective To investigate the characteristics of epilepsy onset based on the theory of five circuits and six qi in traditional Chinese medicine(TCM).Methods A total of 8 389 epilepsy patients from a community-based natural population cohort study from UK Biobank were included.Frequency and constituent ratio analyses were performed to describe the distribution of epilepsy onset in relation to the five circuits and six qi elements,and statistical inferences were made using chi-square tests.Results The analysis revealed statistically significant differences existed in epilepsy onset across different heavenly stems,earthly branches,recombinant yearly circuit,celestial control and terrestrial effect,and dominant qi(all P＜0.05).From the perspective of circuits,the highest incidence occurred in years corresponding to the"Ji"and"Hai"years,while the lowest incidence was observed in"Bing"and"Mao"years.Years dominated by wood circuit and wind manifestations exhibited the highest incidence,whereas years with cold manifestations showed the lowest incidence,suggesting the liver as the primary pathological site in epilepsy.From the perspective of qi,the third dominant qi was most frequently associated with onset.Regarding presiding and subordinate qi,years with taiyin damp earth presiding and taiyang cold water subordinate had the highest incidence,while years with yangming dry metal presiding and shaoyang monarch fire subordinate had the lowest incidence,indicating that cold-damp years and midsummer periods are potential triggers for epilepsy.Conclusion There is a certain regularity in the epilepsy onset correlated with the features of five circuits and six qi,which can guide prevention and clinical diagnosis and treatment of epilepsy.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*