Objective: To analyze the distribution characteristics of fluoride and trichloromethane in drinking water in rural schools in Guizhou Province and assess their health risks, so as to provide a scientific basis for ensuring the safety of drinking water in rural schools. Methods: During the dry season (March to May) and wet season (July to September) of 2020 to 2022, 788 rural primary and secondary schools in agricultural counties (districts) in Guizhou Province were selected for investigation by using a direct sampling method. A total of 1 566 drinking water samples were collected from these schools, and the mass concentrations of fluoride and trichloromethane in the water samples were detected. The Mann-Whitney U test was used for intergroup comparison, and a health risk assessment model was employed to evaluate the health risks of students oral intake of fluoride and trichloromethane. Results: From 2020 to 2022, the mass concentrations of fluoride and trichloromethane in the drinking water of rural schools in Guizhou Province all met the standards, and the ranges were no detection to 0.99 mg/L and (no detection to 0.06)×10 -3 mg/L, respectively. The mass concentrations of fluoride in dry and wet seasons were 0.05(0.05,0.10), 0.05(0.05,0.10) mg/L, the mass concentrations of trichloromethane were [0.02(0.02,1.00)]×10 -3 , [0.02(0.02,1.00)]×10 -3 mg/L, the mass concentrations of fluoride in factory water and terminal water were 0.05(0.05,0.05), 0.05(0.05,0.10) mg/L, and the differences were not statistically significant ( Z=-0.04, -0.88, - 0.98 , P >0.05). There was a statistically significant difference in the mass concentration of trichloromethane between factory water and peripheral water [0.02(0.02,0.02)×10 -3 , 0.02(0.02,1.05)×10 -3 mg/L]( Z=-2.16, P < 0.05 ). The non-carcinogenic risk assessment values for students oral exposure to fluoride and trichloromethane were in the range of 0.01(0.01,0.03)-0.03(0.03,0.06) and [0.26( 0.26 ,14.54)]×10 -4 -[0.52(0.52,48.62)]×10 -4 , respectively, all of which were at acceptable levels; the carcinogenic risk assessment values for oral exposure to trichloromethane were in the range of [0.08(0.08, 4.51 )]×10 -7 -[0.16(0.16,15.07)]×10 -7 , indicating a low risk. Conclusions The health risks of students expore to fluoride and trichloromethane in drinking water in rural schools of Guizhou Province are low. It is necessary to strengthen the standardized management of disinfection in some rural drinking water projects and the monitoring of fluoride in water sources to reduce the exposure risk to children.

Objective: To explore the impact of household tobacco smoke exposure on adolescents attempted smoking behavior, so as to provide a reference for tobacco control policy formulation and evaluation. Methods: From September to November 2023, a stratified cluster random sampling method was employed to select 7 841 middle and high school students from 10 monitoring sites (districts/counties) in Beijing for a questionnaire survey. Rao-Scott Chi square test was used to assess differences in proportions across subgroups, and complex sampling design based multivariate Logistic regression analysis was conducted to explore the influence of parental smoking and secondhand smoke (SHS) exposure at home on adolescents attempted smoking behavior. Results: About 47.17% of adolescents reported to have at least one parent smoked, with 42.36% reported of having only the father smoked, 0.73% reported of having only the mother smoked, and 4.08% reported of having both parents smoked. About 34.66% of middle and high school students were reported SHS exposure at home in the past 7 days, with 10.98%, 4.79% and 18.89% reported SHS exposure for 1-2, 3-4 and 5-7 days. Compared to adolescents with non smoking parents, those with a smoking father or both smoking parents had higher rates of attempted smoking [ OR (95% CI )=1.45(1.06-1.98), 3.73(2.18-6.37), P < 0.05 ]. Compared to adolescents without SHS exposure at home in the past 7 days, those exposed for 3-4 or 5- 7 days had higher rates of attempted smoking [ OR (95% CI )=2.21(1.27- 3.84 ), 2.46(1.58-3.83), P <0.01]. Conclusions Household tobacco smoke exposure is associated with adolescent attempted smoking behavior. Parents should quit smoking and prohibit smoking at home to create a smoke free environment for adolescents.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

Objective To investigate the effect and mechanism of pomalidomide(POM)on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease(COPD).Methods Thirty-six SD rats were randomly divided into control group,model group and POM group,with 12 in each group,half male and half female.The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group.The rats in POM group were treated with POM(0.5 mg/kg,once a day for 1 week).The lung function,lung tissue pathology,the proportion of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-13 were observed and detected in each group.AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin(MUC)5AC and MUC5B in airway epithelium of rats.The expression levels of TNF-α receptor 1(TNFR1),IκB kinase(IKK),phosphorylated IKK(p-IKK)and P65 protein in lung tissue were detected by Western blotting.Results Compared with control group,model group showed significant decreased of tidal volume(TV),minute ventilation(MV),forced expiratory vital capacity(FVC),0.1s forced expiratory volume(FEV0.1)and 0.3 s forced expiratory volume(FEV0.3)(P<0.05),increased of the mean linear intercept(MLI)of the alveoli(P<0.01),decreased of the mean alveolar number(MAN)(P<0.01),increased of the proportion of neutrophils and lymphocytes in BALF sediment(P<0.05),and decreased of the proportion of macrophages in BALF sediment(P<0.01);increased of the levels of serum inflammatory factors TNF-α,IL-1β,IL-13 and IL-6(P<0.05),the proportion of goblet cells in airway epithelium(P<0.01),the secretion of MUC5AC and MUC5B in lung tissue(P<0.01),the content of TNFR1 and the ratio of p-IKK/IKK(P<0.01),the content of P65 in nucleus(P<0.01);and decreased of the content of P65 in cytoplasm(P<0.05).Compared with model group,after one week of POM treatment,POM group showed significant improved of the TV,MV,FVC,FEV0.1,FEV0.3,MLI and MAN of rats(P<0.05);decreased of the proportion of neutrophils and lymphocytes in BALF(P<0.05);increased of the proportion of macrophages(P<0.01);decreased of the levels of serum TNF-α,IL-1β,IL-6 and IL-13(P<0.05),the proportion of goblet cells in airway(P<0.01),the secretion of MUC5AC and MUC5B(P<0.01),and the expression of TNFR1,P-IKK and P65(nucleus)(P<0.05);and increased of the level of P65(cytoplasm)(P<0.01).Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats,which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.