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.

This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans ; Apoptosis/drug effects* ; Hep G2 Cells ; Glycyrrhetinic Acid/pharmacology* ; Doxorubicin/pharmacology* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/physiopathology* ; Mitochondria/metabolism* ; Endoplasmic Reticulum/metabolism* ; Cell Survival/drug effects* ; Membrane Proteins/genetics*

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

Objective To observe the clinical efficacy of adjuvant PD-1 inhibitor in the treatment of patients with hepatocellular carcinoma after microwave ablation and the changes of lymphocyte subsets before and after treatment.Methods A total of 56 patients with hepatocellular carcinoma who underwent microwave ablation in our hospital were randomly divided into two groups according to different treatments,with 28 cases in each group.Patients in the group A received adjuvant treatment with PD-1 inhibitors after microwave ablation,while patients in the group B received microwave ablation alone.The local efficacy of microwave ablation,the survival of patients after adjuvant treatment of PD-1 inhibitor and the occurrence of related adverse reactions were observed.Peripheral venous blood was collected to detect the number of T lymphocyte subsets before microwave ablation in the two groups,after microwave ablation in the group B,and after six cycles of immunotherapy in the group A.Results There was no significant difference in the complete ablation rate of cases between group A and group B(89.3% vs.85.7%,P=0.69),and there was no significant difference in the complete ablation rate of lesions between group A and group B(91.7% vs.85.3%,P=0.40).The median progression-free survival(mPFS)of the group A was not yet reached,the mPFS of group B was 12.6 months,and there was a statistically significant difference in the mPFS between the two groups(P=0.03).The median overall survival(mOS)of the two group were not yet reached.The proportion of CD4+T lymphocytes after treatment in the group A significantly increased compared with that in the group B[(37.05±2.22)% vs.(29.23±2.88)%,P=0.03],while the proportion of CD8+T lymphocytes[(21.08±2.23)% vs.(27.18±1.75)%,P=0.04)]and the proportion of Treg cells[(4.26±0.31)% vs.(5.22±0.34)%,P=0.04]significantly decreased.There was no serious adverse reactions in all patients after microwave ablation,and 28 patients in the group A had no adverse reactions above grade 3 after PD-1 inhibitor treatment.Conclusion Adjuvant PD-1 inhibitor therapy after microwave ablation can prolong the progression-free survival of patients,enhance the function of T lymphocytes,and weaken the role of immunosuppressive cells,which may be an effective strategy to delay the recurrence of liver cancer after microwave ablation.

Aesculus chinensis is an important medicinal and horticultural plant. Its dried mature seeds, known as "Suoluozi", are a well-known traditional Chinese medicine. Aescins are its main active components, possessing multiple pharmacological activities such as anti-inflammatory and anti-exudative effects. They are widely used in the treatment of diseases such as lumbar disc herniation, postoperative edema, and sports injuries, leading to a continuous increase in market demand in recent years. The DNA binding with one finger(Dof) family is a unique transcription factor family found in the plant kingdom. It plays a crucial role in plant growth, development, stress responses, and regulation of secondary metabolism. However, research on the Dof gene family in A. chinensis is relatively scarce. In this study, we identified 36 AcDof genes from the genome of A. chinensis and analyzed their physicochemical properties, chromosomal localization, phylogenetic relationships, gene structures, cis-acting elements, and expression patterns in different tissues. The results showed that AcDof proteins ranged from 81 to 493 amino acids in length, with molecular weights ranging from 9 270.38 to 55 015.68 and isoelectric points ranging from 4.84 to 10.2. The subcellular localization analysis revealed that 34 AcDof proteins were located in the nucleus, while the remaining two AcDof proteins were located in the chloroplasts. Phylogenetic analysis divided AcDofs into nine subgroups, and gene structure analysis indicated that all AcDof genes possessed a C2-C2 type single zinc finger domain. Gene expression analysis using transcriptome data revealed tissue-specific expression patterns among AcDof family members. Specifically, AcDof04, AcDof02, and AcDof03 exhibited specific expression in seeds, suggesting their potential involvement in the regulation of aescin biosynthesis. This study not only enhances our understanding of the Dof gene family in A. chinensis but also provides important genetic resources for further investigation of the functions and regulatory mechanisms of Dof genes in this species.
Plant Proteins/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Gene Expression Profiling ; Multigene Family

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Liver ; Lipoproteins, LDL/metabolism* ; Signal Transduction ; Diet, High-Fat/adverse effects* ; RNA, Messenger/metabolism*

Abstract: Objective　To find out the existing problems and provide reference for further improving the quality of report information by analyzing the report cards of COVID-19 and the positive report cards of primary screening reported in Ningxia. Methods　All COVID-19 case cards from 2020 to 2021 and initial screening positive cards were derived from the Chinese Information System for Disease Control and Prevention according to final review date. The timeliness of case reporting, timeliness of case review, completeness and accuracy of the case cards were analyzed. Results　In Ningxia, the first case of COVID-19 was reported on January 20, 2020, and as of December 31, 2021, 122 confirmed cases and 4 symptomatic infected cases were reported. In 2021, the timely reporting rate of COVID-19 was 98.00%, which increased by 8.24% compared with 2020 (90.54%). Compared with 2020, the average time limit for diagnosis to reporting of COVID-19 in 2021 was shortened by 83.12%; in 2021, the timely review rate of COVID-19 was 100.00%, which increased by 13.84% compared with 2020 (87.84%). Compared with 2020, the time from reporting to final review was shortened by 98.91%. In 2021, the timely rate of positive reports in COVID-19 in Ningxia was 90.00%, among which the timely rate of reports by county (district) nucleic acid detection institutions was the highest (92.31%), followed by municipal (91.67%) and autonomous region (81.82%). Conclusions　At the beginning of the epidemic in 2020, the timeliness of COVID-19 in Ningxia was poor, and through the implementation of measures such as technical training, supervision and inspection to continuously optimize the staffing of medical institutions and disease control institutions, the timeliness of reporting COVID-19 in Ningxia in 2021 was substantially improved, but there were still some weak links. In the future work, technical guidance and training should be carried out for weak links, and efforts should be made to improve the quality of reports.

Aim To explore the material basis of anti-tumor effect of Compound Muji Granules. Methods The anti-tumor pharmacodynamics of Compound Muji Granules in vitro was studied by microfluidic chip technology. The fingerprint of Compound Muji Granules was established by HPLC. The "Spectrum-Material-Effect" of Compound Muji Granules was analyzed by grey correlation analysis,partial least squares regression analysis and network pharmacology approach. Results Seven batches of Compound Muji Granules with different extraction methods were successfully established. The results of grey correlation analysis showed that there was a positive correlation between Compound Muji Granules and 7 of the 14 components with pharmacodynamic correlation coefficient >0.80. The contribution of anti liver tumor was peak number 48(luteolin)>6(gallic acid)>19(chlorogenic acid)>59(quercetin)>67(kaempferol)>65(naringin)>38(ellagic acid),in that order. Conclusions Through the establishment of "Spectrum-Material-Effect" research method,it is clear that the above seven active monomers may be the anti-tumor material basis of Compound Muji Granules.