OBJECTIVES: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids. RESULTS: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05). CONCLUSIONS Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals ; Metformin/pharmacology* ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects* ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Fatty Acids, Volatile/metabolism* ; Fatty Acids/metabolism*

OBJECTIVE: Citri Reticulatae Pericarpium (Chenpi, CRP) is one of the most used traditional Chinese medicines with great medicinal, dietary and collection values, among which the Citrus reticulata cv. 'Chachi' (Citrus reticulata cv. Chachiensis) from Guangdong Xinhui is the geoherb of CRP. Xinhui CRP in the market was often counterfeited with other varieties or origins, molecular identification method can effectively distinguish different CRP varieties, but it's still a difficult problem to identify the same CRP variety from different origin. It is necessary to discover a new molecular marker to ensure the safe and effective application of Xinhui CRP. METHODS: We selected one of the most studied transcription factor families in Citrus genus, MYB, to design the specific candidate primers on the conserved region. The primers with good band repeatability and high polymorphism were screened for PCR amplification of the test materials, and the genetic similarity coefficient among different families, genera, species, and origins were calculated. The cluster analysis was performed by unweighted pair group method using arithmetic average (UPGMA). RESULTS: A total of ten MYB primers were screened out to identify Xinhui CRP from plants from different family (Panax ginseng and Morus alba), genus (Clausena lansium and Zanthoxylum schinifolium), and species (Citrus reticulata, C. sinensis and C. maxima). Furthermore, two from the ten primers, M1 and M10, were found to distinguish Xinhui CRP from other origins. There were 169, 113, 133 and 134 polymorphic bands in the identification of different families, genera, species, and origins respectively, and the accordingly polymorphism ration were 79.88%, 76.87%, 79.20% and 82.84%. Moreover, M1 was discovered to be the best primer to identify Xinhui CRP from other seven origins, the cluster analysis results based on the genetic similarity coefficients were consistent with the geographical distribution. CONCLUSION This study established a novel molecular identification method according to MYB transcription factor, which can analyze the potential parental relationship of CRP germplasm, as well as identify the quality and origins of Xinhui CPR.

This study was aimed atanalyzing the epidemic characteristics of dengue fever in Ruili City atthe China-Myanmar bor-der in late 2023,to provide evidence for local dengue fever prevention and control measures.Adult Aedes mosquitoes were collected from Ruili City with a backpack type mosquito sucking machine in October of 2023.Serum samples frompatients with suspected den-gue were collected in acutephase,in November of 2023.Detection ofdengue virus(DENV)nucleic acids in Aedesmosquitoes and acute phase serum samples from suspected dengue fever patients using reverse transcription-polymerase chain reaction,and nucleic acid positive samples were inoculated into Vero cells for viral culture.After three consecutive blind passage,samples with cytopathic effect(CPE)were collected for be sequencingand analysisof genetic and evolutionary information.Dengue case characteristics were analyzed through descriptive epidemiological methods.Among the 109 cases of dengue fever,the ratio of males to females was 1.27∶1.The youngest patient was 1 year old,the oldest patient was 84 years old,the age group of 20～59 years accounted for 73.39%,and the major-ity of occupations were freelancer(40.37%).A total of 827 female Aedes albopictus and 312 Aedes aegypti were collected,all of which tested negative for DENV nucleic acid.109 serum samples tested positive for DENV nucleic acid,including 49 DENV-1 and 60 DENV-2.Moreover,five DENV-1 and nine DENV-2 samples were obtainedthrough third-generation blind passaging with CPE.The E gene sequences of these five DENV-1 strains were detected,all were found to belong to DENV-1 genotype I,and had same evolu-tionary branch as the 2023 Guangzhou,China(PP563911),the 2019 Myanmar(MW793710),and 2019 Attapeu,Laos(MW559046).The nucleotide and amino acid sequence similarityamong the five DENV-1 genotype was 99.4%-99.9%and 99.8%-100.0%.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.5%-100.0%,99.4%-99.6%and 99.3%-99.5%,respec-tively,and amino acid similarity was 99.8%-100.0%.Nine DENV-2 E gene sequences were of Asian genotype I and belonged to the same evolutionary branch as the 2018 Myanmar(MW788982),2019 Hangzhou(OP684212)and 2019 Ruili(OQ928150).The nucleotide and amino acid similarities of the nine samples were 99.5%-100.0%and 99.8%-100.0%,respectively.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.7%-100.0%,99.3%-99.7%and 99.3%-99.7%,respectively,and the amino acid similarity was 99.8%-100%,99.8%-100.0%and 99.4%-99.6%,respectively.Two dengue vectors,Aedes albopictus and Aedes aegypti,were present in Ruili city,and the dengue outbreak was caused primarily by DENV-1 genotype I and DENV-2 Asian genotype I in later 2023.The sources of DENV-1 were probably the same as those of DENV-1 with Guangzhou(2023),and the sources of DENV-2 were probably from Myanmar.Dengue cases were found primarilyin the 20-59 year age group and freelancers,thus suggesting that relevant local departments should strengthen surveillance of dengue imported case and vector.

Objective To investigate the protective effect of mitochondrial fission inhibitor 1(Mdivi-1),on organ function in rats with explosive blast injury combined with hemorrhagic shock.Methods A total of 192 SD rats(half male and half female,12 weeks old,weighing about 220 g)were randomly divided into 6 groups:Sham group(only surgical incision along the midline of the abdomen),model group(ESH group,thermal radiation and shock wave injury followed by femoral artery hemorrhage),lactated Ringer's solution resuscitation group(ESH+LR group,LR solution infusion in the femoral vein for resuscitation),and low-,middle-and high-dose Mdivi-1 groups(0.1,0.5 and 1.0 mg/kg Mdivi-1 intervention after infusion of LR solution).Fluorescent protein tracing was used to determine the leakage amount of fluorescent protein in the lung and kidney tissues to evaluate the vascular permeability.Evans blue dye staining was employed to observe the intestinal permeability and pulmonary vascular permeability.Laser Doppler flowmetry was applied to monitor the tissue blood perfusion in the liver,kidneys,and intestine.Serum levels of cardiac injury marker troponin I(TNI),liver function markers aspartate aminotransferase(AST)and alanine aminotransferase(ALT),and renal function markers serum creatinine(Scr)and blood urea nitrogen(BUN)were detected to evaluate the functions of corresponding organs.The water contents of the lungs and brain were calculated by measuring wet weight and dry weight of the lung and brain tissues.Blood pressure,heart rate,and respiratory rate were monitored.The survival time and 72-hour survival rate were recorded and calculated.Results Compared with the Sham group,the ESH group exhibited significantly increased vascular permeability in the lungs and kidneys as well as intestinal tissue(P<0.05),along with obviously elevated water contents in the lungs and brain(P<0.05),and decreased blood perfusion in the liver,kidneys,and intestine by 57.1%,39.2%,and 43.2%of the Sham group,respectively(P<0.05),elevated levels of TNI,AST,ALT,Scr and BUN(P<0.05),mean survival time of 3.8±1.1 h,and a 72-hour survival rate of 0(P<0.05).Although LR solution resuscitation reduced vascular permeability and alleviated organ injury in rats with explosive injury combined with hemorrhagic shock,there were no significant differences compared to the ESH group(P>0.05).Mdivi-1 treatment notably decreased vascular permeability in the lungs and kidneys and intestine,and water contents in the lungs and brain when compared with the LR group(P<0.05),with the dose of 0.5 mg/kg demonstrating the most significant effect.Additionally,Mdivi-1 treatment also significantly enhanced organ perfusion,improved organ functions,prolonged survival time,and increased survival rate.The 0.5 mg/kg treatment resulted in a 72-hour average survival time 55.64 h and a survival rate of 62.5%.Conclusion Mitochondrial fission inhibitor Mdivi-1 can reduce the permeabilities in the lungs,kidneys and intestine,improve tissue blood perfusion,protect the organ functions of the heart,liver and kidneys,and finally prolong survival time and increase survival rate in rats with concomitant explosive blast injury and hemorrhagic shock.

This study was aimed atanalyzing the epidemic characteristics of dengue fever in Ruili City atthe China-Myanmar bor-der in late 2023,to provide evidence for local dengue fever prevention and control measures.Adult Aedes mosquitoes were collected from Ruili City with a backpack type mosquito sucking machine in October of 2023.Serum samples frompatients with suspected den-gue were collected in acutephase,in November of 2023.Detection ofdengue virus(DENV)nucleic acids in Aedesmosquitoes and acute phase serum samples from suspected dengue fever patients using reverse transcription-polymerase chain reaction,and nucleic acid positive samples were inoculated into Vero cells for viral culture.After three consecutive blind passage,samples with cytopathic effect(CPE)were collected for be sequencingand analysisof genetic and evolutionary information.Dengue case characteristics were analyzed through descriptive epidemiological methods.Among the 109 cases of dengue fever,the ratio of males to females was 1.27∶1.The youngest patient was 1 year old,the oldest patient was 84 years old,the age group of 20～59 years accounted for 73.39%,and the major-ity of occupations were freelancer(40.37%).A total of 827 female Aedes albopictus and 312 Aedes aegypti were collected,all of which tested negative for DENV nucleic acid.109 serum samples tested positive for DENV nucleic acid,including 49 DENV-1 and 60 DENV-2.Moreover,five DENV-1 and nine DENV-2 samples were obtainedthrough third-generation blind passaging with CPE.The E gene sequences of these five DENV-1 strains were detected,all were found to belong to DENV-1 genotype I,and had same evolu-tionary branch as the 2023 Guangzhou,China(PP563911),the 2019 Myanmar(MW793710),and 2019 Attapeu,Laos(MW559046).The nucleotide and amino acid sequence similarityamong the five DENV-1 genotype was 99.4%-99.9%and 99.8%-100.0%.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.5%-100.0%,99.4%-99.6%and 99.3%-99.5%,respec-tively,and amino acid similarity was 99.8%-100.0%.Nine DENV-2 E gene sequences were of Asian genotype I and belonged to the same evolutionary branch as the 2018 Myanmar(MW788982),2019 Hangzhou(OP684212)and 2019 Ruili(OQ928150).The nucleotide and amino acid similarities of the nine samples were 99.5%-100.0%and 99.8%-100.0%,respectively.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.7%-100.0%,99.3%-99.7%and 99.3%-99.7%,respectively,and the amino acid similarity was 99.8%-100%,99.8%-100.0%and 99.4%-99.6%,respectively.Two dengue vectors,Aedes albopictus and Aedes aegypti,were present in Ruili city,and the dengue outbreak was caused primarily by DENV-1 genotype I and DENV-2 Asian genotype I in later 2023.The sources of DENV-1 were probably the same as those of DENV-1 with Guangzhou(2023),and the sources of DENV-2 were probably from Myanmar.Dengue cases were found primarilyin the 20-59 year age group and freelancers,thus suggesting that relevant local departments should strengthen surveillance of dengue imported case and vector.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Objective] To explore the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou, and to investigate the correlation between donation frequency and these factors. [Methods] A cross-sectional study was conducted among 13 042 whole blood donors from 17 street blood donation sites of Guangzhou Blood Center from May to August 2020. Descriptive analysis was used to describe the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou. Ordinal multinomial logistic regression model was used to analyze the correlation between donation frequency and these factors. [Results] It was found that some of 13 042 blood donors had unhealthy habits, such as 6.8% (698/10 214，2 828 missing values) had severe tobacco dependence, 30.6% (3 997/13 042) had low exercise levels, 38.8%（5 056/13 042）had poor sleep quality, and 2.2% (271/12 159，883 missing values) had alcohol dependence. In addition, 2.8% (364/13 042) and 1.3% (172/13 042) of the donors may have moderate to severe depression and anxiety symptoms, respectively. The results of the ordinal multinomial logistic regression model showed that exercise level was significantly negatively correlated with the degree of depression and anxiety among blood donors. With the decrease in exercise level, the possibility of depression and anxiety among donors increased significantly. BMI, household income, education level, marital status, donation frequency, alcohol consumption and smoking had no significant correlation with the mental health status of donors. [Conclusion] Improving the exercise habits of blood donors may help enhance their mental health level. It is recommended that blood station staff strengthen the content of exercise when providing health education to blood donors to maintain a healthy lifestyle. It also suggests that there may be a certain degree of under-diagnosis of mental health problems in the process of health consultation before blood donation, and conducting more comprehensive and effective mental health assessments for blood donors is recommended.

Purpose To explore the CT features of solid components between benign and malignant mixed ground-glass nodules(mGGO),and between minimally invasive adenocarcinoma(MIA)and invasive adenocarcinoma(IAC),and to improve the accuracy of preoperative diagnosis of mGGO.Materials and Methods The clinical and imaging data of 313 patients with mGGO admitted to the First Affiliated Hospital of Chongqing Medical University from January 2016 to July 2022 were retrospectively analyzed,and all patients were divided into benign group(95 cases)and malignant group(218 cases)according to follow-up or pathological results.All patients in malignant group were further divided into MIA(118 cases)and IAC(100 cases)groups.Logistic regression analysis models were established using the statistically significant CT features above,and the area under the curve(AUC)was calculated to evaluate the effectiveness of the model.Results ① Comparison of clinical characteristics between benign and malignant groups:malignant mGGO were more common in older people,females and nonsmokers,without smoking history,and the differences between two groups were significantly different(Z=-3.776,χ2=13.587,19.257;all P<0.001).②Comparison of CT features between benign and malignant groups:benign group existed a higher proportion of single solid component(84.21%vs.55.50%),while malignant group existed a higher proportion of multiple solid components(44.50%vs.15.79%),and the difference between two groups was significantly different(χ2=23.728,P<0.001).As for patients with single solid component,the solid components in malignant group were more likely to be irregular,mostly with eccentric distribution,and the proportion of solid components connected with blood vessels and pleura were higher than the benign group,the differences between two groups were significant(χ2=23.785,5.025,7.264;all P<0.05).Meanwhile,the benign group also had higher CT value[-153.00(-254.00,-80.50)Hu vs.-265.00(-363.25,-122.00)Hu],while lower relative CT value(0.30±0.16 vs.0.41±0.22),the differences between two groups were significant(all P<0.001).Logistic regression analysis:irregular morphology of the solid component(OR=0.236,P<0.001)and higher CT value(OR=1.009,P<0.05)were independent predictors of malignant mGGO.Receiver operator characteristic(ROC)curve analysis showed that the AUC was 0.772,and its accuracy,sensitivity and specificity was 70.65%,74.40%and 65.00%,respectively.③Comparison of CT features between MIA and IAC groups:MIA group existed a higher proportion of single solid component(74.58%vs.33.00%),while IAC group existed a higher proportion of multiple solid components(67.00%vs.25.42%),and the difference between two groups was significantly different(χ2=37.885,P<0.001).As for patients with single solid component,the solid components in IAC group were more likely to be irregular,it also had higher area,area proportion,and CT value,while lower relative CT value than the MIA group,the differences between two groups were significant(χ2=7.563,Z=-4.388,-3.923,-3.996;all P<0.05).Logistic regression analysis:eccentric distribution of the solid component(OR=0.083,P<0.05)and large area(OR=1.063,P<0.05)were independent predictors of IAC.ROC curve analysis showed that the AUC was 0.865,and its accuracy,sensitivity and specificity was 83.47%,87.90%and 68.20%,respectively.Conclusion The solid components between benign and malignant nodules as well as between MIA and IAC show different CT features.Based on these different features,it's helpful to improve the preoperative diagnostic accuracy of mGGO and guide the clinical treatment plans.