Subclinical hypothyroidism (SCH) is a subclinical state of mild hypothyroidism. In recent years, the impact of SCH on multiple systems of the body has gradually attracted attention. Although SCH patients usually do not have obvious clinical symptoms, studies have shown that SCH may be associated with a variety of chronic diseases, such as cardiovascular disease and metabolic syndrome. Due to the complex interrelationship between diabetes mellitus and thyroid disease, researchers have begun to pay attention to the potential impact of SCH on diabetic retinopathy (diabetic retinopathy, DR). This article aims to comprehensively review the current research progress on the impact of SCH on DR, and explore in depth the pathophysiological mechanisms, clinical manifestations, and treatment strategies, providing clinicians with more comprehensive diagnostic and treatment ideas.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective To investigate the inhibitory effect of Scutellaria baicalensis combined with 5-Fu on Lewis tumor bearing mouse lung cancer based on the JAK2/STAT3 signaling pathway.Methods To detect the changes in body mass,food intake and tumor volume of Lewis tumor-bearing mice after intervention of Scutellaria baicalensis(20 mg/kg)combined with 5-Fu.Pathological changes in tumor tissue were observed by HE staining,expression levels of proliferation related protein Ki67 were observed by immunohistochemical staining,changes in cell apoptosis levels in tumor tissue were observed by TUNEL staining,and changes in expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 proteins in tumor tissue were observed by immunohistochemical staining.Results Compared with the model group,the tumor volume of mice after combined intervention significantly decreased(P＜0.01)and body mass increased(P＜0.05),but there was no significant change food intake.The expression of proliferation related protein Ki67 in tumor tissue was significantly reduced,and the number of apoptotic cells labeled with TUNEL was significantly increased;The expression of p-JAK2 and p-STAT3 proteins is elevated.Conclusions Scutellaria baicalensis decoction can inhibit the JAK2/STAT3 signaling pathway and increase the inhibitory effect of 5-Fu on mouse lung cancer.

Objective To investigate the prevalence of hyperuricemia among ethnic groups in Gongshan county,Yunnan province through a cross-sectional study.Methods A total of 229 residents aged ≥ 18 years from Dulong,Nu,Tibetan,Bai and Lisu ethnic groups were randomly selected in Gongshan County of Yunnan Province for questionnaire survey,physical examinations and laboratory tests.SPSS 22.0 was used for t test,Chi-square test,correlation analysis,and multivariate logistic regression analysis.Results A total of 107 cases of hyperuricemia were identified,with a detection rate of 46.7％,among which the prevalence was 43.9％in males,52.63％in female,48％in the Dulong,51％in the Lisu,47％in the Nu,37.5％in the Bai,52％in the Tibetan and 50％in the Han.There were no statistically significant differences in prevalence among all nationalities(P＞0.05).The proportion of individuals with a history of diabetes,as well as levels of urea nitrogen and serum creatinine,were significantly higher in the hyperuricemia group compared to the non-hyperuricemia group(P＜0.05).Correlation analysis showed a positive correlation between hyperuricemia and diabetes,urea nitrogen and serum creatinine.(P＜0.05).Multivariate regression analysis showed that diabetes and elevated serum creatinine were independent risk factors for the onset of hyperuricemia(P＜0.05).Conclusion The detection rate of hyperuricemia is relatively high in Gongshan County,Yunnan Province,and there is no significant differences in prevalence among ethnic groups.Diabetes and elevated serum creatinine are associated with hyperuricemia,which increase the risk of developing hyperuricemia.

Objective:To investigate the life expectancy of antiretroviral treatment (ART) HIV-infected patients and its trends in Taizhou City, Zhejiang Province from 2014 to 2023.Methods:The data were obtained from the China Information System for Disease Control and Prevention , and the study subjects were HIV-infected patients received ART in Taizhou City. An abbreviated life expectancy table was prepared based on Chiang's method to analyze the differences in life expectancy of HIV-infected patients receiving ART in Taizhou City with different characteristics in 2023 and to compare the trends in life expectancy of patients with different CD4 +T lymphocytes (CD4) counts at the time of initiation of ART from 2014 to 2023. Results:A total of 4 825 patients were enrolled in this study, with a cumulative follow-up of 276 648.56 person-years, and a case-fatality rate of 18.07 (95% CI: 16.48-19.65) /1 000 person-years. In 2023, male patients had lower life expectancy than females in all age groups, and those who were married had higher life expectancy than those who were unmarried and those who were divorced or widowed; patients who had been transmitted heterosexually had lower life expectancy than those who had been transmitted through homosexual transmission. Patients with different CD4 counts at the time of initiating ART had different life expectancies in all age groups. The life expectancy of patients with CD4 counts ≥350 cells/μl when initiating the treatment was higher than that of patients with CD4 counts <200 cells/μl in all age groups. The life expectancy of HIV-infected patients on ART at age 20 and 50 increased from 39.0 years and 19.1 years in 2014 to 46.0 years and 24.1 years in 2023, respectively, with an average annual percentage change of 2.43% (95% CI: 0.81%-4.07%) and 3.34% (95% CI: 1.17%-5.56%). The change in life expectancy was similar for patients with CD4 counts ≥350 cells/μl and 200-349 cells/μl at the time of initiating treatment in 2016-2023, and was higher than that for patients with CD4 counts <200 cells/μl. The rate of increase in life expectancy for patients at age 50 was higher than that at age 20 for all CD4 counts. Conclusions:The rising trend of life expectancy among HIV-infected patients on ART in Taizhou City is obvious. But the disparity between patients with different characteristics is obvious, especially among patients with baseline CD4 counts <200 cells/μl, suggesting the importance of expanded testing, early diagnosis and timely initiation of ART to improve the life expectancy of HIV-infected patients.

N6-methyladenosine(m6A)is the most common mRNA modification in eukaryotes,and fat mass and obesity-related protein(FTO),are its demethylases,which efficiently remove the modification of m6A mRNA,and is strongly associated with obesity.Atherosclerosis is a chronic inflammatory lesion of the blood vessel wall driven by lipids.It was found that FTO-mediated m6A may influence the process of atherosclerosis through lipid metabolism,oxidative stress,mitochondrial dysfunction,and macrophage foaminess.

Objective To evaluate the clinical value of non-invasive ultrasound hemodynamic monito-ring in critically ill neonates in plateau area(altitude＞2 500 m).Methods A total of 205 critically ill neo-nates admitted to the NICU of Qamdo People's Hospital from September 2023 to December 2024 were ran-domly divided into the control group(n=105)and the observation group(n=100)using a random number table.There was no statistically significant difference in the baseline data between the two groups(P＞0.05).The observation group underwent noninvasive ultrasonic hemodynamic monitoring within 12 hours of admis-sion,measuring corrected flow time(FTC),stroke volume(SV),cardiac index,systemic vascular resistance index(SVRI),and myocardial contractility index(SMII).The control group received conventional monito-ring.The treatment was adjusted based on the results.The above parameters were remeasured 4-8 hours af-ter treatment adjustment.Hospital stay and 28 d survival rate were compared between the two groups.Multi-ple linear regression and binary logistic regression were used to analyze the factors influencing hospital stay and 28 d survival rate,respectively.Results Compared to pre-treatment levels,the observation group showed significant post-treatment decreases in FTC[(364.03±47.70)ms vs.(414.09±52.20)ms]and SVRI[(1 521.00±186.93)dyn·s·(cm5)-1·(m2)-1 vs.(1 720.00±347.31)dyn·s·(cm5)-1·(m2)-1].Con-versely,significant increases were observed in SV[(5.23±0.66)mL vs.(5.09±0.88)mL],cardiac index[(3.35±1.17)L·min-1·(m2)-1 vs.(3.19±0.99)L·min-1·(m2)-1],and SMII[(0.56±0.10)W/m2 vs.(0.51±0.14)W/m2](P＜0.05).The observation group had a significantly shorter hospital stay than the control group[(11.53±3.61)d vs.(13.83±2.56)d,P＜0.05].The 28 d survival rate was higher in the ob-servation group(100.0％vs.98.1％),although the difference was not statistically significant(P＞0.05).Multiple linear regression analysis revealed that both gestational age and cardiac index were negatively correla-ted with the duration of hospital stay.Binary logistic regression analysis indicated that birth weight was a sig-nificant factor influencing the 28 d survival rate(OR=4.600,95％CI:2.465-10.654,P=0.001).Conclusion Non-invasive ultrasonic hemodynamic monitoring can facilitate early identification of hemodynamic alterations in critically ill neonates in platean area,which could guide treatment and potentially reducing hospital stay.