Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective To analyze the correlation of copper death inducer ferredoxin 1(FDX1)and lipoic acid(LA)with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease(CHD).Methods We analyzed the data of 226 patients undergoing coronary artery angiography(CAG)in our hospital between October,2021 and October,2022,including 47 patients with normal CAG findings(control group)and 179 patients with mild,moderate or severe coronary artery stenosis(CHD group).Serum FDX1 and LA levels were determined with ELISA for all the patients.We also examined pathological changes in the aorta of normal and ApoE-/-mice using HE staining and observed collagen fiber deposition with Sirius red staining.Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta,and RT-PCR was performed to detect the expressions of FDX1,LIAS and ACO2 mRNAs in the myocardial tissues.Results Compared with the control patients,CHD patients had significantly lower serum FDX1 and LA levels,which decreased progressively as coronary artery stenosis worsened(P<0.01)and as the number of involved coronary artery branches increased(P<0.05).Serum FDX1 and LA levels were positively correlated(r=0.451,P<0.01)and they both negatively correlated with the Gensini score(r=-0.241 and-0.273,respectively;P<0.01).Compared with normal mice,ApoE-/-mice showed significantly increased lipid levels(P<0.01)and atherosclerosis index,obvious thickening,lipid aggregation,and collagen fiber hyperplasia in the aorta,and significantly reduced expressions of FDX1,LA,LIAS,and ACO2(P<0.05).Conclusion Serum FDX1 and LA levels decrease with worsening of coronary artery lesions,and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

Objective To analyze the correlation of copper death inducer ferredoxin 1(FDX1)and lipoic acid(LA)with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease(CHD).Methods We analyzed the data of 226 patients undergoing coronary artery angiography(CAG)in our hospital between October,2021 and October,2022,including 47 patients with normal CAG findings(control group)and 179 patients with mild,moderate or severe coronary artery stenosis(CHD group).Serum FDX1 and LA levels were determined with ELISA for all the patients.We also examined pathological changes in the aorta of normal and ApoE-/-mice using HE staining and observed collagen fiber deposition with Sirius red staining.Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta,and RT-PCR was performed to detect the expressions of FDX1,LIAS and ACO2 mRNAs in the myocardial tissues.Results Compared with the control patients,CHD patients had significantly lower serum FDX1 and LA levels,which decreased progressively as coronary artery stenosis worsened(P<0.01)and as the number of involved coronary artery branches increased(P<0.05).Serum FDX1 and LA levels were positively correlated(r=0.451,P<0.01)and they both negatively correlated with the Gensini score(r=-0.241 and-0.273,respectively;P<0.01).Compared with normal mice,ApoE-/-mice showed significantly increased lipid levels(P<0.01)and atherosclerosis index,obvious thickening,lipid aggregation,and collagen fiber hyperplasia in the aorta,and significantly reduced expressions of FDX1,LA,LIAS,and ACO2(P<0.05).Conclusion Serum FDX1 and LA levels decrease with worsening of coronary artery lesions,and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

Objective To study the effect of curcumin on osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)in high glucose condition and its mechanism.Methods The cultured hBMSCs were divided into the normal group,high glucose group,and high glucose+curcumin group.The early osteogenic differentiation level of the cells in each group was assessed by detecting alkaline phosphatase(ALP)activity.Alizarin red staining was used to evaluate the formation of mineralized nodules in the late stage of osteo-genic differentiation.The expression of osteogenic-related genes,including Runt-related transcription factor 2(Runx2),osteocalcin(OCN),and type Ⅰ collagen(COL-1),was detected by RT-PCR after 21 days of osteogenic induction.Western blot was used to detect the expression of heme oxygenase-1(HO-1)in each group.Furthermore,an HO-1 small interfering RNA(siRNA)model was constructed and its interference efficiency was assessed.The expression levels of osteogenesis-related proteins(Runx2,OCN,and COL-1)between the high glucose+curcumin group and high glucose+curcumin+siHO-1 group were compared.Results Compared with the normal group,the high glucose group showed decreased ALP activity,reduced formation of mineralized nodules,decreased expression of osteogenic-related genes(Runx2,OCN,and COL-1),and inhibited expression of HO-1(P＜0.05).Compared with the empty vector group,the siHO-1 group showed significantly reduced expression of HO-1 in cells,indicating successful siRNA interference(P＜0.01).Compared with the high glucose+curcumin group,the expression levels of osteogenesis-related proteins(OCN,COL-1,and Runx2)were all decreased in the high glucose+curcumin+siHO-1 group(P＜0.05).Conclusion Curcumin can promote osteogenic differentiation of hBMSCs under high glucose environment,which is related to the expression of HO-1.

Aim To investigate the protective poten-tial of paeoniflorin 6-oxy-benzenesulfonate(CP-25)in preserving knee cartilage integrity in osteoarthritis mice through inhibition of GRK2 activity.Methods The posttraumatic osteoarthritis model was established fol-lowing DMM surgery.The experiment consisted of a sham operation group,a model group,a CP-25 admin-istration group,and a paroxetine positive control group.Intragastric administration commenced after the surgery.After 12 weeks of administration,the animals were euthanized.Micro-CT imaging was used to ob-serve the knee cartilage degeneration and abnormal bone remodeling,and the joint histopathology of mice was observed by staining with ferrubens solid green.Immunohistochemistry and immunofluorescence were used to detect the expression level of related molecules in cartilage tissue.Furthermore,Western blot was em-ployed to determine GRK2 and EP4 membrane protein expression levels as well as total protein levels of GRK2 and MMP13 following CP-25 treatment.Results Compared with the sham operation group,the articular cartilage in the model group was significantly degrad-ed,with the cartilage surface calcifying and osteo-phytes forming.CP-25 could significantly reduce the number of osteophytes and the thickness of the sub-chondral plate of articular cartilage,promote the regen-eration of the cartilage matrix,reduce the expression of cartilage matrix degradation protein,and have a signifi-cant protective effect on knee cartilage.Immunohisto-chemical and immunofluorescence results showed that compared with the model group,CP-25 treatment sig-nificantly decreased the expressions of GRK2,AD-AMTS5 and MMP13 in knee tissue and increased the expressions of Col Ⅱ and Aggrecan in knee tissue.The results of in vitro experiments showed that CP-25 ad-ministration could significantly reduce the expression levels of GRK2 membrane protein and total protein,in-crease the level of EP4 membrane protein,and de-crease the level of MMP13.Conclusions The ad-ministration of CP-25 can significantly promote the re-generation of articular cartilage matrix in OA mice,re-duce the degradation of cartilage matrix,and exhibit therapeutic effects on OA.The mechanism behind this is related to the inhibition of GRK2-mediated cartilage matrix metabolism.

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.
Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Objective: To analyze the changes in tobacco use and exposure in primary school students in Shandong province in 2012 and 2019. Methods: A multi-stage stratified cluster random sampling method was used in the survey. In 2012 and 2019, 5 861 and 4 021 students from 3 different cities of Shandong province were selected as the study population. The questionnaire was filled anonymously by the subjects. χ² test was conducted to compare the difference of groups. Results: In 2012 and 2019, the rate of attempting smoking among pupils under this study in Shandong province were 6.0％and 6.3%, respectively, while the current smoking rate were 1.2％and 2.3%, respectively. The sex ratio of male and female students attempting to smoke was 2.56∶1 in 2012 and 1.31∶1 in 2019. The sex ratio of current smoking rate was 2.43∶1 and 2.00∶1, respectively in 2012 and in 2019. The rate of tobacco exposure in the public places was 50.5％and 41.4%, respectively. The rate of tobacco exposure in family was 49.7% and 46.4%, respectively. Two rates of tobacco exposure decreased, but the reduction in family (3.3%) was far less than that in public places (9.1%). In 2019, the rate of tobacco exposure in family was higher than that in public places. Conclusions: The tobacco exposure rate declined in senior pupils in Shandong province. However, the situation is still grim for the current smoking rate, growth trend of girls tobacco use, and tobacco exposure in family.
Cities ; Environment ; Female ; Humans ; Male ; Prevalence ; Students ; Surveys and Questionnaires ; Tobacco Smoke Pollution ; Tobacco Use/epidemiology*

Objective:To identify the risk factors of cognitive dysfunction in patients with atrial fibrillation and to establish a risk prediction model.Methods:The convenience sampling method was used to evaluate 260 patients with atrial fibrillation who were hospitalized in the Department of Cardiology of the Affiliated Hospital of Jining Medical College from January to December 2020. The cognitive function of the patients was evaluated with the Montreal Cognitive Function Assessment Scale (MoCA). Univariate analysis was used to screen the independent variables that had influence on the occurrence of cognitive dysfunction, and the statistically significant variables were included in the multivariate Logistic regression model. According to the regression coefficients of statistically significant variables, a line map was drawn to construct the risk prediction model of cognitive dysfunction in patients with atrial fibrillation.Results:There were 209 cases with cognitive impairment and 51 cases without cognitive impairment. Univariate analysis showed that sex, age, smoking history, drinking history, education level, free thyroxine, hemoglobin, D-dimer and BMI ( χ2 values were 4.08-18.83, t values were -6.04-2.94, Z=-2.76) were significantly different between the patients with or without cognitive dysfunction. The results of multivariate Logistic regression analysis showed that age ( OR values were 1.13), education level ( OR=0.01-0.05), quit smoking history ( OR=0.36), drinking history ( OR=0.35) and free thyroxine( OR=1.14) had significantly statistical significance ( P<0.05). The area under ROC curve (AUC) = 0.878 and AUC>0.8, this model had good clinical prediction ability. Conclusions:The construction of cognitive dysfunction risk prediction model for patients with atrial fibrillation can prevent or intervene high risk factors in advance, facilitate clinical use, and provide data support for the improvement of cognitive function in patients with atrial fibrillation.