OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

OBJECTIVE: To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism. METHODS: Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+ Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS). RESULTS: In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P < 0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P < 0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P < 0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production. CONCLUSION Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS.
Animals ; Antioxidants/metabolism* ; Atrial Natriuretic Factor/pharmacology* ; Cardiomegaly ; Diabetes Mellitus, Experimental/metabolism* ; Fibrosis ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Metformin ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; RNA, Messenger/metabolism* ; Rats ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase-1/pharmacology* ; Xanthophylls

OBJECTIVE: To analyze the effect of Chinese medicine (CM) on mortality and quality of life (QOL) of acquired immunodefificiency syndrome (AIDS) patients treated with combined antiretroviral therapy (cART). METHODS: A random sample of AIDS patients enrolled in the National Chinese Medicine Treatment Trial Program (NCMTP) that met the inclusion criteria was included in this study. NCMTP patients were included as the CM+cART group, and those not in the NCMTP were included as the cART group. Survival from September 2004 to September 2012 was analyzed by retrospective cohort study. QOL was analyzed by cross-sectional study. RESULTS: The retrospective cohort study included 528 AIDS patients, 322 in the CM+cART group and 206 in the cART group. After 8 years, the mortality in the CM+cART group was 3.3/100 person-years, which was lower than the cART group of 5.3/100 person-years (P<0.05). The hazard ratio (HR) for mortality in the cART group was 1.6 times that of the CM+cART group by Cox proportional hazard model analysis. After controlling for gender, age, marital status, education, and CD4 T-cell count, the HR was 1.9 times higher in the cART group compared with the CM+cART group (P<0.05). The cross-sectional study investigated 275 AIDS patients. The mean scores of all QOL domains except spirituality/personal beliefs were higher in the CM+cART group than in the cART group (P<0.05). CONCLUSIONS For AIDS patients, CM could help to prolong life, decrease mortality, and improve QOL. However, there were limitations in the study, so prospective studies should be carried out to confifirm our primary results.
Acquired Immunodeficiency Syndrome ; drug therapy ; mortality ; Adult ; China ; epidemiology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Quality of Life ; Rural Population

Objective:To explore the abnormal gray matter volume regions of brain and the developmental characteristic of abnormal regions in patients with high functioning autism during 6-18 years old.Methods:The study enrolled 19 patients and 16 age,sex and intelligent quotient matched normal controls.The patients met the diagnostic criteria of autism in the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition.The full scale intelligence quotients of patients and normal controls were greater than or equal to 70.The magnetic resonance imaging (MRI) was used to collected brain images.Voxel-based morphometry was used to process the MRI images and two sample t-test in Statistical Parametric Mapping-8 (SPM8) was used to analyze differences between the two groups in gray matter volume of brain.The results were controlled with false discovery rate (FDR) multiple comparison correction (P ＜ 0.05).Partial correlative analysis was performed to examine correlation between gray matter volume of abnormal brain region and age in two groups.Results:Compared with normal controls,patients with high functioning autism during 6-18 years old exhibited smaller gray matter volume at right inferior orbital frontal (P ＜ 0.05,FDR corrected).In patients with high functioning autism,the volume of right inferior orbital frontal was negatively correlated with age(r =0.70,P ＜0.01).The negative correlation between the volume of right inferior orbital frontal and age was also found in normal controls(r =-0.59,P ＜ 0.05).Conclusion:It suggests that right inferior orbital frontal of brain is abnormal in patients with high functioning autism during 6-18 years old.The fight inferior orbital frontal may be significant for pathological mechanism of autism.

Objective To observe the clinical efficacy and safety of alteplase withdifferent doses and thrombolysis time in the treatment of acute ischemic stroke.Methods A total of 220 patients with acute ischemic stroke were randomly divided into A group(n =90 cases),B group(n =90 cases) and C group (n =40 cases).A group was given 0.6 mg· kg-1 alteplase,the thrombolysis timewas less than 30 minutes;B group wasgiyen 0.6 mg · kg-1 alteplase,the thrombolysis time was about 60 min;C group was given 0.9 mg · kg-1 alteplase,the thrombolysis time was about 60 min.1 d after thrombolysis treatment,all patients were given oral aspirin 100 mg qd for 3 months.The national institutes of health stroke scale (NIHSS) score and adverse drug reactions were compared between three groups.Resnlts 1 h after treatment,the NIHSS in A,B,C groups were (7.11 ±0.83),(8.24 ±0.96),(8.32 ± 1.38) points;1 d after treatment,the NIHSS in A,B,C groups were (7.92 ± 0.93),(8.92 ± 1.03),(9.09 ± 1.17) points;7 d after treatment,the NIHSS in A,B,C groups were (6.63 ± 0.77),(7.31 ± 0.83),(7.36 ± 0.88) points;30 d after treatment,the NIHSS in A,B,C groups were (4.89 ± 0.62),(5.62 ± 0.76),(5.78 ± 0.87) points;90 d after treatment,the NIHSS in A,B,C groups were (3.53 ± 0.58),(4.77 ± 0.55),(4.69 ± 0.61) points.90 d after treatment,the modified rankin scale scores in A,B,C groups were 72.22％ (65/90 cases),54.44％ (49/90 cases),55.00％ (22/40 eases).The differences were statistically significant between A group and B,C groups (P ＜ 0.05),which was not signi-ficant between B group and C group (P ＞ 0.05).The adverse drug reactions were based on gingival bleeding,the incidences of adverse drug reactions in A,B,C groups were 8.89％,12.22％,17.50％ without significant difference (P ＞ 0.05).ConclusionAlteplasehasa definitive clinical efficacy in the treatment of acute ischemie strokewith the dose of 0.6 mg· kg-1 and intravenous thrombolysis time ＜ 30 min,which can reduce the financial burden,without increasing the incidence of adverse drug reactions.

Objective To explore the role of Rho-kinase in glioma cell proliferation induced by connective tissue growth factor ( CTGF ) and effects of triptolide/tripterine.Methods A subculture growth of glioma cells were got to take the experiment, the normal control group was not give any drug intervention .CTGF group was given CTGF 2.5 μg? L-1 and incubation for 24 h.Triptolide group was given CTGF 2.5 μg? L-1 and triptolide 0.5 ng? mL-1 and incubation for 24 h.Tripterine group were given CTGF 2.5 μg? L-1 and tripterine 0.5 ng? mL-1 and incuba-tion for 24 h.Y27632 ( group specificity of Rho kinase inhibitor ) cells after 30 min to give CTGF 2.5 μg? L -1 and Y27632 1 μmol? L-1 pre-treatment.The expressions of Rho -kinase protein were detected by ELISA.Glioma cell proliferation was measured by 3 H -TdR assay. Results CTGF could induce the proliferation of glioma cell .Triptolide, tripterine and Y27632 ( Rho kinase inhibitor ) could significantly reverse these effects ( P<0.05 ).In addition, CTGF could induce the activation of Rho-kinase ( P<0.01 ) , while triptolide and tripterine could significantly reverse these effects ( P<0.05 ) , indica-ting the activation of Rho -kinase pathway participates in glioma cell proliferation induced by CTGF . Conclusion CTGF could induce the proliferation of glioma cell , while triptolide , tripterine and Y27632 could significantly reverse these effects.Rho-kinase pathway participates in glioma cell proliferation induced by CTGF .

This paper collected the traditional Chinese medicine (TCM) prescriptions of osteoporosis and osteoarthritis from CNKI to set up database and used TCM inheritance system to analyze the composing principles in prescriptions. We collected 103 and 106 prescriptions for osteoporosis and osteoarthritis respectively, then analyzed inherent principles between herbs in prescriptions by using the TCM inheritance system, and obtained the frequency of each herb, and drug combinations of two diseases' prescriptions. The result showed that the principles in TCM prescriptions of osteoporosis and osteoarthritis are similarities, buch as tonifying kidney and invigorating the circulation of blood, but differences of the specific drugs. That is to say, tonifying kidney is the main method of osteoporosis treatment, however, invigorating the circulation of blood is the main method of osteoarthritis treatment.
Blood Circulation ; drug effects ; Databases, Factual ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoarthritis ; drug therapy ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology