ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

ObjectiveTo analyze the detected results of CD4⁺T lymphocytes and viral load in newly identified human immunodeficiency virus (HIV) infected patients in Huangpu District of Shanghai in 2023, to explore the correlation between them, so as to provide a scientific basis for the development of targeted prevention and control measures and antiviral treatment programs. MethodsThe data of CD4 cell count, viral load and demographic characteristics of the newly infected patients living with HIV in Huangpu District, Shanghai in 2023 were collected and analyzed by using descriptive epidemiological method. ResultsThe mean CD4 cell count of the 67 newly identified HIV infected patients in Huangpu District was (301.22±235.19) cells·µL^-1, with a mean viral load of (5.15±1.28) ×10⁵ copies·mL^-1.There were statistically significant differences in CD4 cell count and viral load among different age groups (P<0.05), but there were no statistically significant differences by gender and marital status (both P>0.05). The CD4 cell count and CD4/CD8 ratio both were negatively correlated with the lg value of viral load (r=-0.290, -0.378; P=0.027, 0.002). ConclusionThe CD4 cell counts of the newly identified HIV infected patients in Huangpu District in 2023 were generally low, the proportion of patients with high viral load was high, but the risk for elderly infected with HIV was high. The elderly have gradually become the key population for AIDS prevention and control in Huangpu District. It is recommended to expand HIV screening in the elderly to reduce the risk of HIV transmission and increase the rate of early detection and treatment.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

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*

Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

BACKGROUND: Stroke is the leading cause of death and long-term disability worldwide, including China. This study aimed to provide timely updates on stroke burden and stroke-related risk factors to help improve population-based prevention and control strategies. METHODS: Based on the Global Burden of Disease study 2021, incidence rate, prevalence rate, mortality rate, and disability-adjusted life-year (DALY) rate were used to estimate stroke burden trend from 1990 to 2021. RESULTS: In 2021, China had 4.1 million incident stroke cases, 26.3 million prevalent stroke cases, 2.6 million stroke related deaths, and 53.2 million stroke related DALYs, compared to 11.9 million incident stroke cases, 93.8 million prevalent stroke cases, 7.3 million stroke related deaths, and 160.5 million stroke-related DALYs worldwide. In 2021, the top six risk factors contributing to stroke burden were high blood pressure, air pollution, tobacco consumption, dietary risk factors, high low-density lipoprotein cholesterol, and high fasting plasma glucose, both in China and worldwide. From 1990 to 2021, China had significant increases of incidence rate, prevalence rate, mortality rate, and DALY rate for stroke, with estimates of 100.6 (95% uncertainty intervals [UI]: 87.2, 114.1)%, 102.9 (95% UI: 95.5, 110.9)%, 40.0 (95% UI: 14.9, 72.3)% and 15.7 (95% UI: -4.6, 41.2)%, respectively, while global incidence rate, prevalence rate, mortality rate and DALY rate for total stroke showed relatively moderate increases or even decreases, with estimates of 15.0 (95% UI: 12.1,18.0)%, 25.8 (95% UI: 23.7, 28.0)%, -2.6 (95% UI: -10.6, 5.5)%, and -10.7 (95% UI: -17.7, -3.6)%, respectively. CONCLUSION Stroke remains a huge disease burden worldwide and in China, and compared to the worldwide China has a significantly higher burden of stroke.
Humans ; Stroke/etiology* ; China/epidemiology* ; Risk Factors ; Global Burden of Disease ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Female ; Quality-Adjusted Life Years ; Male

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*