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.

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.

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.

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.

This experiment aims to investigate the effects of a dietary supplement of herbal tea resi-due on white feather broilers in the prospectives of growth performance,serum indexes and intesti-nal immune indexes.A total of 280 1-day-old white feather broilers with similar body mass and good health were randomly divided into 4 groups with 5 replicates per group and 14 birds per repli-cate.Group Ⅰ(control group)was fed a basal diet.Groups Ⅱ,Ⅲ and Ⅳ were fed a diet supple-mented with 2％,4％and 6％herbal tea residue powder,respectively.The feeding lasted for 49 days,and was divided into 2 phases from 1 to 21 days of age and 22 to 49 days of age.Blood,tissue and mucosa of the duodenum and jejunum were collected on 21 d and 49 d.Total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and the activities of aspartate aminotransferase(AST)and alanine amin-otransferase(ALT)in the serum were examined.The villus height and crypt depth of the jejunum were observed and measured by morphology.The mRNA expression levels of intestinal interleukin-1β(IL-1β),interleukin-2(IL-2),interleukin-4(IL-4),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were determined by qPCR.The results showed that compared with group Ⅰ,the mass of group Ⅲ on 21 d and 49 d significantly increased(P＜0.05).The average daily feed intake of 22-49 d and 1-49 d significantly increased(P＜0.05).The average daily mass gain of 1-21 d,22-49 d and 1-49 d significantly increased(P＜0.05).In the serum of 21 d,compared with group Ⅰ,T-CHO in group Ⅱ significantly decreased(P＜0.05).TG in groups Ⅱ,m and Ⅳ significantly de-creased(P＜0.05).LDL-C and AST activity in group Ⅳ significantly decreased(P＜0.05).In the serum of 49 d,T-CHO in group Ⅲ,LDL-C in group Ⅳ,HDL-C of groups Ⅲ and Ⅳ significantly increased(P＜0.05),and the ALT activity of these two groups decreased(P＜0.05).AST activity in group Ⅱ significantly decreased(P＜0.05).In the duodenum of 21 d,compared with group Ⅰ,the expressions of TNF-α in group Ⅱ was significantly decreased(P＜0.05).In the duodenum of 49 d,the expression of IL-10 in group Ⅱ was significantly increased(P＜0.05),and the expression of IL-2 in groups Ⅲ and Ⅳ was significantly decreased(P＜0.05).In the jejunum of 49 d,the ex-pression of IL-10 in group Ⅱ was increased(P＜0.05),and the expression of IL-2 in groups Ⅲand Ⅳ was significantly decreased(P＜0.05).In conclusion,dietary herbal tea residue can regulate circulating lipid level and enhance intestinal immunity of white feather broilers without affecting their normal growth performance.This experiment also suggested that the a 2％-4％supplementa-tion of herbal tea residues to white feather broilers was of good effect.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.