Objective: To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation (FMT) in patients with type 2 diabetes mellitus (T2DM), and to preliminarily identify the traditional Chinese medicine (TCM) syndrome element characteristics of FMT in the treatment of T2DM. Methods: Between March 25, 2023 and September 30, 2024, T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. Participants received oral microbiota capsules as an adjunct to metformin therapy. Information obtained by four diagnostic methods of TCM, along with clinical and laboratory parameters, was collected before and after the intervention. Metagenomic sequencing was employed to analyze the gut microbiota, and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera. According to the post-treatment reduction in glycosylated hemoglobin (HbA1c), patients were categorized into a response (R) group and a non-response (NR) group. Treatment outcomes, safety indicators, gut microbiota changes, and TCM syndrome element features were compared between the two groups. Results: A total of 53 T2DM patients were included in the final analysis, and 30 patients were assigned to R group and 23 to NR group. After treatment, the R group exhibited significant reductions in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (2hPG) (P < 0.05 or P < 0.01). The NR group also showed significant decreases in HbA1c and FPG levels P < 0.01 or P < 0.05. Compared with the NR group, after treatment, FPG level in the R group demonstrated significant reductions (P < 0.01). As compared with before treatment, pancreatic islet function demonstrated enhancement in the R group, a significant increase in the 2-hour pastprandial C-peptide (2hC-P) levels in R group (P < 0.05), whereas no marked change was observed in the NR group. Regarding body composition indicators, the R group showed significantly lower waist-hip ratio (WHR), visceral fat (VF), and subcutaneous fat (SF) levels compared with the NR group (P < 0.01). After treatment, the NR group exhibited a significant elevation in aspartate aminotransferase (AST) levels (P < 0.05). Other safety-related indicators fluctuated within normal reference ranges, and no other adverse events, such as diarrhea, fever, or nausea, were reported. Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota, remodeling its overall structure. At the phylum level, the abundance of p_Firmicutes decreased significantly (P < 0.01), while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly (P < 0.01). At the family level, among the 125 identified taxa, the abundances of f_Bacteroidaceae, f_Lactobacillaceae, and f_Sutterellaceae were significantly elevated, whereas six families, including f_Lachnospiraceae, f_Ruminococcaceae, and f_Coriobacteriaceae, were significantly decreased (all P < 0.05). Among the 367 taxa at the genus level, the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella, and significantly decreased abundances in eight genera, including g_Faecalibacterium, g_Ruminococcus, g_Blautia, and g_Collinsella (all P < 0.05). Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters, g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide (FC-P) and 2hC-P (P < 0.05). HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger (P < 0.05) and a significantly negative correlation with g_Bacteroides and g_Collinsella (P > 0.05). Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness, phlegm, and Yang deficiency. Before treatment, statistically significant reductions in syndrome element scores were observed for dampness, Yang deficiency, spleen, phlegm, Qi deficiency, Qi stagnation, and Yin deficiency (P < 0.01), as well as for heat and liver (P < 0.05). The NR group was mainly featured with Qi deficiency and Yin deficiency. Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency (P < 0.01), and for spleen, Qi stagnation, liver, and blood deficiency (P < 0.05). In this group, the score changes for Yang deficiency, Yin deficiency, heat, and dampness were not statistically significant (P > 0.05). Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM. Patients with T2DM presented with specific TCM syndrome element characteristics, notably dampness, phlegm, and Yang deficiency, represent a highly responsive population to FMT therapy.

Objective To explore the mechanism of malignant behavior of cervical cancer(CC)cells based on AMP-activated protein kinase(AMPK)/rapamycin target protein(mTOR)signaling pathway mediated by nucleo-tide-binding oligomerization domain receptor 2(NOD2).Methods Bioinformatics analysis was performed to deter-mine the expression of NOD2 in CC tissue.Plasmids targeting NOD2(shNOD2)and shRNAs negative control(shNC),NOD2 overexpression(NOD2)and vectors(Vec)were transfected into CC cells.The effect of NOD2 on the growth of CC cells was determined by cell counting kit-8 assay,colony formation and Transwell cell invasion as-say.Transcriptome analysis was performed by high throughput RNA sequencing(RNA-Seq).Western blot was used to detect the expression of NOD2,AMPK/mTOR signaling pathway and autophagy protein in the cell line.24 female BALB/c nude mice were randomly divided into four groups,with 6 mice in each group:vector group(Vec group),NOD2 overexpression group(NOD2 group),shNC group and shNOD2 group.The distant metastasis mod-el was established in mice,and the fluorescence intensity of lung metastasis was monitored and the number of lung metastasis nodules was counted.Results On-line database analysis showed that the expression of NOD2 in CC tis-sues was significantly higher than that in normal tissues,and there were significant differences in the mRNA expres-sion of NOD2 in different stages of CC(P＜0.05).In addition,the high expression of NOD2 was associated with poor overall survival and disease-free survival(P＜0.05).NOD2 overexpression promoted the proliferation,colony formation,migration and invasion of CC cells,while NOD2 knock-down was the opposite.Consistent with the re-sults in vitro,the lung colonization and lung metastasis of CC cells in NOD2 group were significantly higher than those in Vec group(P＜0.05),while those in shNOD2 group were significantly lower than those in shNC group(P＜0.05).RNA-Seq results showed that the expression of NOD2 was significantly related to AMPK signal activa-tion,mTOR signal inhibition,autophagy regulation pathway activation and autophagy formation.Compared with shNC group,the expression of phosphorylated AMPK and LC3 protein decreased significantly in shNOD2 group(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein increased significantly(P＜0.05).Compared with Vec group,the expression levels of LC3 and AMPK protein in NOD2 group increased significantly(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein decreased significantly(P＜0.05).Compared with shNC group,the point accumulation of GFP-mRFP-LC3 in shNOD2 group decreased signifi-cantly(P＜0.05).Compared with Vec group,the point accumulation of GFP-mRFP-LC3 increased significantly(P＜0.05).Conclusion NOD2 may promote the proliferation,migration and invasion of CC through AMPK/mTOR signal,and its mechanism partly involves autophagy activation.

AIM:To observe the effect of Pingwei capsule on the precancerous lesions of gastric cancer(PLGC)cell model induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG),and to preliminarily explore its mecha-nism.METHODS:Blank serum and Pingwei capsule-containing serum were prepared for later use.A PLGC cell model was established by MNNG-induced human gastric mucosal epithelial cell line GES-1.To evaluate the model,cell morpho-logical changes were observed under inverted microscope,and the expression of proliferating cell-related antigen Ki67 was detected by immunofluorescence staining.CCK-8 assay was used to screen the optimal intervention concentration and time of serum containing drugs.Reactive oxygen species(ROS)content in cells was detected using a fluorescent probe DCFH-DA.Malondialdehyde(MDA)content was detected by ELISA,and the activity of superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)was detected using biochemical reagents.A novel fluorescent probe JC-10 was used to detect mitochondrial membrane potential.The mRNA expression levels of Ki67 and melanoma differentiation-associated gene-7(MDA-7)were detected by real-time fluorescence quantitative PCR.The protein expression levels of Ki67,interleukin-6(IL-6)and MDA-7 were detected by Western blot.RESULTS:Compared with normal group,the ROS and MDA levels in model group and blank serum group were significantly increased(P<0.01),while the activity of SOD and GSH-Px was significantly decreased(P<0.01).The mitochondrial membrane potential was significantly decreased(P<0.01).The protein expression levels of Ki67 and IL-6 were significantly increased(P<0.01),while the protein expression level of MDA-7 was significantly decreased(P<0.01).There were no significant differences of the above indicators between model group and blank serum group(P>0.05).Compared with blank serum group,the Pingwei capsule-containing serum group showed significantly decreased ROS and MDA levels(P<0.01),significantly increased activity of SOD and GSH-Px(P<0.05),significantly increased mitochondrial membrane potential(P<0.01),significantly decreased protein expres-sion levels of Ki67 and IL-6(P<0.01),and significantly increased protein and mRNA expression levels of MDA-7(P<0.01).CONCLUSION:Pingwei capsule can significantly alleviate MNNG-induced oxidative damage and inflammatory response,and regulate the expression of oncogenes and tumor suppressor genes,thereby playing a role in prevention and treatment of PLGC.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Macrophages have strong plasticity and heterogeneity,and can undergo functional transformation in response to different signal stimuli,such as classical activation of M1 type(M1 type polarization)and selective activation of M2 type(M2 type polarization).The pathways of macrophage M1/M2 polarization are quite extensive,involving nuclear factor-κB(NF-κB)/mitogen-activated protein kinase(MAPK)signaling pathway,interleukin-4(IL-4)/signal transduction and activator of transcription 6(STAT6)signaling pathway,Notch signaling pathway,Wnt/β-catenin signaling pathway,etc.At the same time,M1/M2 polarization of macrophages is also regulated by exosomes,metabolites,non-coding RNA,electrical stimulation,probiotics,etc.,and its imbalance is closely related to the occurrence and development of different types of liver disease.In this paper,the mechanism of its polarization was reviewed,and it was found that M1 polarization of macrophages played a promoting role in the process of liver tissue injury,inflammation and fibrosis,while M2 polarization of macrophages played the opposite role.Among them,hepatocellular carcinoma,as the advanced stage of chronic liver disease,was characterized by increased M2 polarization and impaired M1 polarization of macrophages.Therefore,this paper pays attention to the role of M1/M2 polarization of macrophages in different types of liver diseases,in order to better establish the targeted therapy of macrophage subsets.

[Objective]To discuss the causes of coronary heart disease with depression and other body and spirit diseases,which are related to river water,and propose the corresponding treatment methods.[Methods]By using the method of image thinking,this paper links the transformation of cloud and rain with the Qi and blood of human body,which is the common cause of body and spirit diseases.At the same time,this paper links the cause of coronary heart disease with depression with river water,and treats the disease with the method of treating water.[Results]The transformation between clouds and rain in nature is similar to the transformation of Qi and blood in the human body.Qi and blood come from the same source and affect each other,and Qi and blood remain smooth,so as not to cause physical and mental diseases.The root cause of coronary heart disease with depression is that Qi and blood are not smooth,and a series of lesions they produce are similar to the blockage of the river,so it is necessary to regulate Qi and blood according to the different stages of the disease,with the method of strengthening the spleen,promoting blood circulation,detoxification and opening depression.[Conclusion]Inspiring ideas through the analogy of image thinking can correctly understand and treat coronary heart disease with depression,which is also the purpose of image thinking.

Background A variety of substances in drinking water are hazardous to human health and there are health risks associated with ingestion of these substances via drinking water. Objective To assess the carcinogenic and non-carcinogenic health risks of drinking water in Shijiazhuang from 2014 to 2021. Methods The collection, preservation, and testing of 10529 drinking water samples (including finished water and tap water) in Shijiazhuang were conducted from 2014 to 2021 and followed the Standard examination methods for drinking water (GB/T 5750—2006). The health risks of 15 chemicals in drinking water by oral exposure were assessed using the US Environmental Protection Agency's four-step method combined with Monte Carlo simulation. Results Among the 15 chemicals in drinking water assessed for their health risks at general exposure levels and high exposure levels via oral route in Shijiazhuang from 2014 to 2021, the leading three chemicals and related values of carcinogenic risks for adults were cadmium (1.11×10⁻⁴, 2.98×10⁻⁴), arsenic (5.88×10⁻⁵, 1.56×10⁻⁴), and chromium (5.48×10⁻⁵, 2.41×10⁻⁴), and the leading three chemicals and related values of non-carcinogenic risks were fluoride (3.57×10⁻¹, 6.57×10⁻¹), arsenic (1.31×10⁻¹, 3.47×10⁻¹), and nitrate (1.14×10⁻¹, 5.98×10⁻¹). The health risk values of trichloromethane and aluminum were elevated but still in acceptable ranges. Drinking water-associated health risk values were higher in males than in females, such as the cancer risk for general exposure levels of arsenic in men was 5.76×10⁻⁵, compared to 5.72×10⁻⁵ in women. The health risk values of cadmium, chromium, fluoride, nitrate, and other chemicals in ground water were higher than those of surface water, and the health risk values of trichloromethane and carbon tetrachloride were lower than those in surface water, such as the non-carcinogenic risk value for general exposure levels of fluoride in groundwater was 3.61×10⁻¹, compared to 2.27×10⁻¹ in surface water. Factors such as water transmission and distribution links, water period, and season affected the health risks of drinking water. The general exposure levels of trichloromethane in tap water had a higher carcinogenic risk of 1.75×10⁻⁷ compared with 8.17×10⁻⁸ in finished water. The general levels of arsenic exposure was higher in the dry season at 1.36×10⁻¹, compared with 1.26×10⁻¹ in the wet season. Conclusion Except that the carcinogenic risk of cadmium at general exposure levels in Shijiazhuang exceeds the maximum acceptable range recommended by US Environmental Protection Agency, the health risk values of the remaining 14 chemicals are below the maximum acceptable risk. The carcinogenic risk values of arsenic and chromium and the non-carcinogenic risk values of fluoride, arsenic, and nitrate are relatively high, but do not exceed the maximum acceptable ranges. The emphasis should be on the management of drinking water in highly exposed areas and populations.

Objective:To construct a hypoglycemia random forest prediction model for older adults with type 2 diabetes, and assess the model′s prognostication performance through internal and external verification.Methods:From August 2022 to January 2023, 300 older adults with type 2 diabetes in Beijing Hospital were selected. The demographic characteristics, medical history, laboratory tests, and other data of the patients were collected, and the data set was randomly divided into the training set and verification set in a ratio of 7∶3. The hypoglycemia prediction model for older adults with type 2 diabetes was constructed and optimized based on the random forest algorithm. The calibration curve was used to evaluate the model′s calibration, and the ROC was used to evaluate the model′s discrimination. The clinical applicability of the model was assessed by the decision curve analysis. The risk factors for hypoglycemia in the older adults were explored by prioritizing the contributions of variables in prediction. The Bootstrap method was used for internal validation, and the validation set was used for external validation.Results:Among the 300 older adults with type 2 diabetes, 128 cases (42.67%) experienced hypoglycemia within one week. The predictive contributions of risk factors in the model were ranked as follows: the number of episodes of hypoglycemia in one month, HDL-C, heart disease, diabetes knowledge and education, combination therapy, age, duration of diabetes, staple food restriction, glycosylated hemoglobin, and gender. The internal and external calibration curves of the hypoglycemia random forest model for the older adults with type 2 diabetes fluctuated around the diagonal, indicating that the calibration degree of the predictive model is good. The AUROC of internal verification was 0.823 (95% CI 0.752-0.894), the sensitivity and specificity were 0.867 and 0.698, respectively. The external verification was 0.859 (95% CI 0.817 - 0.902), and sensitivity and specificity were 0.789 and 0.804, respectively, showing that the overall discrimination of the prediction model was good. The DCA curves were far from the all-positive line and all-negative line, which indicated that the prediction model had good clinical applicability. Conclusions:The predictive effect of this model is good, and it is suitable for predicting the risk of hypoglycemia in older adults with type 2 diabetes, and it provides a reference for early hypoglycemia screening and predictive intervention for this kind of patients.

Objective:To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Methods:Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing , multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.Results:A heterozygous deletion variant, c. 4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. Thevariant was classified as pathogenic(PVS1 + PM2+ PM6)according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father’s TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA. Conclusion:The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients .