This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Objective To analyze the influencing factors of death in the elderly with coronavirus disease 2019(COVID-19).Methods The case data of death caused by COVID-19 in West China Fourth Hospital from January 1 to July 8,2023 were collected,and surviving cases from the West China Elderly Health Cohort infected with COVID-19 during the same period were selected as the control.LASSO-Logistic regression was adopted to analyze the data after propensity score matching and the validity of the model was verified by drawing the receiver operating characteristic curve.Results A total of 3 239 COVID-19 survivors and 142 deaths with COVID-19 were included.The results of LASSO-Logistic regression showed that smoking(OR=3.33,95%CI=1.46-7.59,P=0.004),stroke(OR=3.55,95%CI=1.15-10.30,P=0.022),malignant tumors(OR=19.93, 95%CI=8.52-49.23, P<0.001),coronary heart disease(OR=7.68, 95%CI=3.52-17.07, P<0.001),fever(OR=0.51, 95%CI=0.26-0.96, P=0.042),difficulty breathing or asthma symptoms(OR=21.48, 95%CI=9.44-51.95, P<0.001),and vomiting(OR=8.19,95%CI=2.87-23.58, P<0.001)increased the risk of death with COVID-19.The prediction model constructed based on the influencing factors achieved an area under the curve of 0.889 in the test set.Conclusions Smoking,stroke,malignant tumors,coronary heart disease,fever,breathing difficulty or asthma symptoms,and vomiting were identified as key factors influencing the death risk in COVID-19.
Humans ; COVID-19/mortality* ; Aged ; Propensity Score ; China/epidemiology* ; Risk Factors ; Logistic Models ; Smoking ; SARS-CoV-2 ; Male ; Female ; Stroke ; Neoplasms

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.
Humans ; Carcinoma, Renal Cell/genetics* ; Immunotherapy ; Kidney ; Kidney Neoplasms/genetics* ; Prognosis ; Copper ; Apoptosis

Many therapies are effective in treating varicoceles, including dilation of the pampiniform plexus in males. The most common method of treatment is varicocelectomy. We aimed to assess an alternative technique (microsurgical spermatic [distal end]-superficial or inferior epigastric vein anastomosis) that preserves the normal blood flow pattern for varicocele treatment. We retrospectively analyzed 27 men with varicocele between October 2019 and July 2020. All patients underwent microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The prognosis was reviewed retrospectively with an additional survey conducted 3 months after surgery. The mean ± standard deviation of the age was 26.1 ± 7.3 years in patients with microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The maximum diameter of the varicocele vein, perineal pain score, sperm density, and forward movement of sperm improved over 3 months after surgery. Microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis is a safe and efficient surgical treatment for varicoceles.
Humans ; Male ; Adolescent ; Young Adult ; Adult ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery/methods* ; Semen ; Anastomosis, Surgical/methods* ; Spermatozoa ; Pain/surgery*

Objective: Using two measuring tools to examine the prevalence and correlates of neurocognitive impairment (NCI) as well as characteristics of neurocognitive performance among people with HIV (PWH) on antiretroviral treatment (ART). Methods: A total of 2 250 treated PWH from the Comparative HIV and Aging Research in Taizhou (CHART) were recruited in Taizhou, Zhejiang province. The Chinese version of the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) were used to evaluate their neurocognitive performance. Cluster analysis was conducted on the seven cognitive domains in the scale. Results: Among 2 250 treated PWH, 48.0% (1 080/2 250) were aged 45 to 89, 79.2% (1 782/2 250) were male, and 37.8% (852/2 250) had primary school education or below. The prevalence of neurocognitive impairment judged by MMSE and IHDS among HIV-infected people was 14.3% (321/2 250) and 31.8% (716/2 250), respectively. Aged 60 to 89 (aOR=2.63, 95%CI:1.52-4.56), depressive symptoms (aOR=5.58, 95%CI:4.20-7.40) and treatment with EFV (aOR=2.86, 95%CI:1.89-4.34) were main risk factors of NCI diagnosed by MMSE. Male (aOR=0.71, 95%CI:0.51-1.00), overweight (aOR=0.63, 95%CI:0.44-0.89), and high education level (aOR=0.11, 95%CI:0.05-0.25) were protective factors of NCI diagnosed by MMSE. Aged 60 to 89 (aOR=3.10, 95%CI:2.09-4.59), depressive symptoms (aOR=1.78, 95%CI:1.44-2.20) and treatment with EFV (aOR=1.79, 95%CI:1.41-2.29) were risk factors of NCI diagnosed by IHDS. Male (aOR=0.75, 95%CI:0.58-0.97), underweight (aOR=0.67, 95%CI:0.47-0.96), baseline CD4⁺ T lymphocyte (CD4) counts ≥350 cells/μl (aOR=0.69, 95%CI:0.53-0.91) and high education level (aOR=0.23, 95%CI:0.14-0.39) were protective factors of NCI diagnosed by IHDS. The neurocognitive performance of HIV-infected people can be divided into four main types. Among four types, age, gender, education level, alcohol drinking, depressive symptoms, waist-to-hip ratio, hypertension, diabetes, baseline CD4 counts and treatment with EFV were different statistically (all P<0.05). Conclusions: There are four main types of neurocognitive performance in treated PWH. The prevalence of NCI is high among this population, underscoring the need for tailored prevention and intervention.
Male ; Humans ; Female ; Anti-Retroviral Agents ; Educational Status ; CD4 Lymphocyte Count ; Protective Factors ; HIV Infections/drug therapy*

In the era of artificial intelligence based on big data， data acquisition， storage and processing are more convenient， which provides a guarantee for accelerating the development of traditional Chinese medicine （TCM）， but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM， combined with the current development trend of artificial intelligence， this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template"， in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template"， the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM， in which the self-recognition， self-assembly， self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes：the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM， and store the memory information database in the meridian and collateral organs in the form of "imprinting template"， and then pass the "imprinting template". The comparison， analysis， and judgment of imprinting templates guide the self-assembly， self-organization and self-replication among "molecular society"， synthesize biological machines， produce biological functions， repair or strengthen biological supramolecular bodies， and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence"， while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world， artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world， suggesting the development direction of "intelligence" functionalization of drug innovation mode.

The application of modern scientific theories and technologies to explore the mechanism of Chinese medicine and its compounds is one of the key issues in realizing the modernization of traditional Chinese medicine （TCM） research. Chinese medicine and its compounds produce comprehensive pharmacodynamics through multiple components acting on multiple targets， the core of clarifying the mechanism is to solve the key scientific problems of static correlation and dynamic integration verification between the components and the target network topology. At present， the effective method to clarify the mechanism of Chinese medicine and its compounds is to statically correlate the topological network of in vitro components and targets through network pharmacology. Although there are also component-target verification studies， they often learn from research idea of single component-single target， it is urgent to establish a quantitative integration and overall verification method that conforms to the characteristics of TCM. According to supramolecular Qi chromatography theory of TCM， the microscopic mechanism of interaction between Chinese medicine and human body is actually the two supramolecular host and object groups （the active ingredient group of Chinese medicine and the target group of human body） based on imprinted template， which shows the macroscopic properties and pharmacodynamics. Based on this， the author proposes to use supramolecular Qi chromatography theory as the guidance， combined with supramolecular chemistry， network dynamics， quantitative pharmacology and other methods to quantitatively integrate and verify the compositions and the target groups with imprinted template as the core predicted by network pharmacology， looking for the optimal quality markers， greatly reducing the difficulty of multi-component-multi-target experimental verification of Chinese medicine and its compounds.

Objective:To construct the targeting evaluation method of traditional Chinese medicine （TCM） preparations based on supramolecular Qi chromatography theory， and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index （MCI） was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang， and combined with target dynamics and total statistical moment principle， aimed at the independent action characteristics of multi-component imprinted template of TCM， a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group， Bupleuri Radix group， Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted， the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8， Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2， so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established， including relative total uptake efficiency （RUE_T）， relative total concentration （RC_T）， relative imprinted tendency （RIT_T） and relative imprinted variance （RIV_T）. The RUE_T and RC_T of liver were the highest in all tissues （RUE_T=1.88>1，RC_T=2.30>1）， and the corresponding values of other tissues were all <1， indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma， the RIT_T and RIV_T of other tissues fluctuated around 1.0， indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory， a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters， so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

Objective: To investigate the influencing factors for myopia among primary and secondary school students in Suzhou, so as to provide basis for myopia prevention and control. Methods: The students in Grade 4-12 were recruited by stratified cluster random sampling method. Gender, grade, parents＇ myopia history, outdoor activity time and video display terminal time were collected through the questionnaire of National Surveillance Program of Influencing Factors for Common Diseases and Health in Students. Uncorrected visual acuity and cycloplegic refraction were tested. Multivariate logistic regression analysis was performed to explore myopia-related factors. Results: A total of 990 questionnaires were distributed, and 882 valid questionnaires were recovered, with an effective rate of 89.09%. The prevalence rate of myopia was 78.23% ( 690 cases ). Multivariate logistic regression analysis showed that females ( OR=1.703, 95%CI: 1.173-2.474 ) , middle school students ( OR:5.597-11.949, 95%CI: 3.573-28.349 ) , both parents＇myopia ( OR=2.445, 95%CI: 1.597-3.742 ) , video display terminal time over 3 hours per day ( OR=2.026, 95%CI: 1.235-3.325 ) were risk factors for myopia; outdoor activity time over 2 hours per day ( OR: 0.493-0.510, 95%CI: 0.273-0.943 ) was a protective factor for myopia. Conclusion The prevalence of myopia among primary and secondary school students in Suzhou is 78.23%. Gender, grade, parents＇ myopia history, outdoor activity time and video display terminal time are influencing factors for myopia.