This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Objective To investigate the relationship between the expression of serum solute carrier family member 11 (SLC7A11) and acyl CoA synthase long-chain family member 4 (ACSL4) and the degree of neurological impairment and prognosis in patients with acute cerebral infarction (ACI). Methods 60 ACI patients admitted to the Department of Neurology,Suzhou Jiulong Hospital,School of Medicine,Shanghai Jiaotong University from October 2019 to December 2022 were selected as the ACI group,and 60 healthy people in the same period were taken as a control group. Serum SLC7A11 and ACSL4 levels were detected by enzyme-linked immunosorbent assay(ELISA). According to the degree of neurological impairment[assessed by the National Institutes of Health Stroke Scale (NIHSS)],60 patients with ACI were divided into a mild group(n=41) and a severe group (n=19). According to the prognosis of patients 3 months after discharge[assessed by the modified Rankin scale (mRS) score],60 patients with ACI were divided into good group(n=47) and bad group(n=13),and the serum SLC7A11 and ACSL4 levels of ACI patients in different groups were compared. Pearson correlation was used to analyze the correlation between serum SLC7A11 and ACSL4 levels and the degree of neurological impairment and prognosis,and receiver operating characteristic(ROC) curve was used to analyze the value of serum SLC7A11 and ACSL4 levels in predicting poor prognosis of ACI patients.Results The serum SLC7A11 (16.88±3.19ng/ml)level in ACI group was lower than that in the control group(25.13±5.61ng/ml),and the ACSL4(40.01±4.23ng/ml)level was higher than that in the control group(23.29±5.72ng/ml),with statistical significance (t=9.902,18.205,all P<0.05).Serum SLC7A11(15.16±3.91ng/ml)level in ACI patients in the severe group was lower than that in the mild group(17.68±2.41ng/ml),and ACSL4 (42.08±5.02ng/ml) level was higher than that in a mild group(39.05±3.40ng/ml),the serum SLC7A11(14.25±2.95 ng/ml)level of ACI patients in the bad group was lower than that in the good group(17.61±2.85 ng/ml),and the ACSL4 (43.54±3.87 ng/ml)level was higher than that in the good group(39.03±3.78 ng/ml),and the differences were statistical significance (t=3.070,2.747;3.735,3.789,all P<0.05). Pearson correlation analysis showed that serum SLC7A11 level was negatively correlated with NISS and mRS scores of ACI patients (r=-0.416,-0.378,all P<0.05). The serum ACSL4 level was positively correlated with NISS and mRS scores (r=0.351,0.415,all P<0.05). The AUC (95％ CI) of serum SLC7A11 and ACSL4 in predicting the poor prognosis of ACI patients was 0.810 (0.688～0.900),and the sensitivity and specificity were 68.09％ and 92.31％,respectively,which were better than those of individual detection (Z=2.176,1.977,P=0.030,0.048). Conclusion The combination of serum SLC7A11 and ACSL4 has a high predictive efficiency for the poor prognosis of ACI patients.

The development of breast cancer is closely related to the information transfer in its microenvironment.As a novel information communication tool,exosomes present non-coding RNAs that are involved in breast cancer cell proliferation,migration,invasion,tumour-associated fibroblasts ogenesis,cell cycle,degradation of oncogenes,etc.This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.

AIM To evaluate the quality of benchmark sample of Zexie Decoction.METHODS HPLC fingerprints were established,after which the content determination of epoxy alisma ene,23-acetyl alisol B,23-acetyl alisol C,alisol A,alisol B,atractylenolide Ⅰ,atractylenolide Ⅱ and atractylenolide Ⅲ was performed,and the transfer rate and paste yield were calculated.RESULTS There were 20 common peaks in the fingerprints for 15 batches of benchmark samples with the similarities of more than 0.95.The average contents of various effective constituents were 180.86 μg/g for alisol B 23-acetate,18.65 μg/g for alisol C 23-acetate,34.74 μg/g for alismoxide,17.65 μg/g for alisol A,238.19 μg/g for alisol B,2.85 μg/g for atractylenolide Ⅰ,6.38 μg/g for atractylenolide Ⅱ,and 15.42 μg/g for atractylenolide Ⅲ,respectively.In the decoction piece-benchmark sample,alisol B 23-acetate,alisol C 23-acetate,atractylenolide Ⅰ,atractylenolide Ⅱ and atractylenolide Ⅲ demonstrated the average transfer rates of 12.09％,16.45％,3.93％,12.17％and 34.37％respectively.The paste yields in various batches of benchmark samples were 15.2％-20.2％.CONCLUSION HPLC fingerprints combined with content determination can be used for the quality control of benchmark sample of Zexie Decoction,thus provides a reference for the development of its compound preparations.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective To investigate the relationship between the expression of serum solute carrier family member 11 (SLC7A11) and acyl CoA synthase long-chain family member 4 (ACSL4) and the degree of neurological impairment and prognosis in patients with acute cerebral infarction (ACI). Methods 60 ACI patients admitted to the Department of Neurology,Suzhou Jiulong Hospital,School of Medicine,Shanghai Jiaotong University from October 2019 to December 2022 were selected as the ACI group,and 60 healthy people in the same period were taken as a control group. Serum SLC7A11 and ACSL4 levels were detected by enzyme-linked immunosorbent assay(ELISA). According to the degree of neurological impairment[assessed by the National Institutes of Health Stroke Scale (NIHSS)],60 patients with ACI were divided into a mild group(n=41) and a severe group (n=19). According to the prognosis of patients 3 months after discharge[assessed by the modified Rankin scale (mRS) score],60 patients with ACI were divided into good group(n=47) and bad group(n=13),and the serum SLC7A11 and ACSL4 levels of ACI patients in different groups were compared. Pearson correlation was used to analyze the correlation between serum SLC7A11 and ACSL4 levels and the degree of neurological impairment and prognosis,and receiver operating characteristic(ROC) curve was used to analyze the value of serum SLC7A11 and ACSL4 levels in predicting poor prognosis of ACI patients.Results The serum SLC7A11 (16.88±3.19ng/ml)level in ACI group was lower than that in the control group(25.13±5.61ng/ml),and the ACSL4(40.01±4.23ng/ml)level was higher than that in the control group(23.29±5.72ng/ml),with statistical significance (t=9.902,18.205,all P<0.05).Serum SLC7A11(15.16±3.91ng/ml)level in ACI patients in the severe group was lower than that in the mild group(17.68±2.41ng/ml),and ACSL4 (42.08±5.02ng/ml) level was higher than that in a mild group(39.05±3.40ng/ml),the serum SLC7A11(14.25±2.95 ng/ml)level of ACI patients in the bad group was lower than that in the good group(17.61±2.85 ng/ml),and the ACSL4 (43.54±3.87 ng/ml)level was higher than that in the good group(39.03±3.78 ng/ml),and the differences were statistical significance (t=3.070,2.747;3.735,3.789,all P<0.05). Pearson correlation analysis showed that serum SLC7A11 level was negatively correlated with NISS and mRS scores of ACI patients (r=-0.416,-0.378,all P<0.05). The serum ACSL4 level was positively correlated with NISS and mRS scores (r=0.351,0.415,all P<0.05). The AUC (95％ CI) of serum SLC7A11 and ACSL4 in predicting the poor prognosis of ACI patients was 0.810 (0.688～0.900),and the sensitivity and specificity were 68.09％ and 92.31％,respectively,which were better than those of individual detection (Z=2.176,1.977,P=0.030,0.048). Conclusion The combination of serum SLC7A11 and ACSL4 has a high predictive efficiency for the poor prognosis of ACI patients.