OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Objective To analyze the current status and influencing factors of occupational stress, job burnout and sleep quality among workers in the secondary industry in Jinshan District, Shanghai City. Methods A total of 1 418 workers from six key industries in Jinshan District, Shanghai City were selected as the study subjects by the stratified cluster sampling method. The Occupational Stress Core Scale, Maslash Burnout Inventory General Survey and Pittsburgh Sleep Quality Index were used to investigate occupational stress, job burnout and sleep quality of the workers. Results The detection rates of occupational stress, job burnout and sleep disturbance among the study subjects were 33.6%, 65.4% and 23.3%, respectively. Multivariate logistic regression analysis showed that the workers with a monthly income <5 000 yuan had a higher risk of occupational stress than those with a monthly income ≥5 000 yuan (P<0.01). The workers with ≥5.0 years of service had a higher risk than those with <1.0 year (P<0.05). Lack of physical exercise, employment in medium- and large-sized enterprises, and shift work were risk factors of occupational stress in the workers (all P<0.01). The workers aged 18-<30 years had a higher risk of job burnout than those aged 45-<60 years (P<0.05). The workers monthly income <5 000 yuan was associated with a higher risk of job burnout than those with ≥9 000 yuan (P<0.05). The workers with 1.0-<10.0 years or ≥15.0 years of service had higher job burnout risks than those with <1.0 year (all P<0.05). Being unmarried, lack of physical exercise, and employment in medium- and large-sized enterprises were risk factor of job burnout in the workers (all P<0.05). The workers with an educational level of high school or above had a higher risk of sleep disturbance than those with junior school or below (P<0.05). The workers who work >56 hours per week had a higher risk than those working ≤40 hours per week (P<0.01). Conclusion There is a high detection rate of occupational stress, job burnout, and sleep disturbance in the secondary industry workers in Jinshan District, Shanghai City. Special attention should be given to workers with low income, lack of physical exercise, employment in medium- and large-sized enterprises, shift work, long service duration, and long weekly working hours to protect their physical and mental health.

Objective To investigate the mechanical effects of various height combinations of canine long-arm hooks and micro-im-plant anchorage on the retraction of maxillary anterior teeth in clear aligner treatment.It focuses on analyzing the stress distribution within the periodontal ligament and the movement tendencies of the anterior teeth,providing scientific evidence for optimizing orthodon-tic treatment strategies.Methods Three-dimensional finite element models were developed using CBCT scan data of patients and soft-ware including Mimics,Geomagic Studio,and Hypermesh.The models incorporated 16 different configurations of canine long-arm hooks(4,6,8,10 mm)and micro-implant anchorage(6,8,10,12 mm).Elastic traction forces of 3/16,3.5 oz were applied to these models.Simulations assessed how these variables influenced periodontal ligament stress distribution and the movement patterns of the maxillary anterior teeth.Results Stress during anterior teeth retraction was predominantly concentrated in the cervical and apex re-gions of the periodontal ligament,where it interfaced with the alveolar bone,indicating significant local concentration.Increasing the height of micro-implant anchorage and traction hooks markedly reduced positional changes in both the crown and apex.Specifically,when hooks exceeded 8 mm and anchorage heights surpassed 10 mm,canine movement became more uniform,preventing extrusion and minimizing the deepening of the overbite.Additionally,combinations of high traction hooks and high micro-implant anchorage promoted more uniform tooth movement,reducing unnecessary tipping and rotation.Conclusion In the retraction of maxillary anterior teeth with clear aligners,using high-position micro-implant anchorage and high-position traction hooks significantly enhances torque control of anterior teeth and effectively prevents deepening of the overbite.

Objective To investigate the mechanical effects of various height combinations of canine long-arm hooks and micro-im-plant anchorage on the retraction of maxillary anterior teeth in clear aligner treatment.It focuses on analyzing the stress distribution within the periodontal ligament and the movement tendencies of the anterior teeth,providing scientific evidence for optimizing orthodon-tic treatment strategies.Methods Three-dimensional finite element models were developed using CBCT scan data of patients and soft-ware including Mimics,Geomagic Studio,and Hypermesh.The models incorporated 16 different configurations of canine long-arm hooks(4,6,8,10 mm)and micro-implant anchorage(6,8,10,12 mm).Elastic traction forces of 3/16,3.5 oz were applied to these models.Simulations assessed how these variables influenced periodontal ligament stress distribution and the movement patterns of the maxillary anterior teeth.Results Stress during anterior teeth retraction was predominantly concentrated in the cervical and apex re-gions of the periodontal ligament,where it interfaced with the alveolar bone,indicating significant local concentration.Increasing the height of micro-implant anchorage and traction hooks markedly reduced positional changes in both the crown and apex.Specifically,when hooks exceeded 8 mm and anchorage heights surpassed 10 mm,canine movement became more uniform,preventing extrusion and minimizing the deepening of the overbite.Additionally,combinations of high traction hooks and high micro-implant anchorage promoted more uniform tooth movement,reducing unnecessary tipping and rotation.Conclusion In the retraction of maxillary anterior teeth with clear aligners,using high-position micro-implant anchorage and high-position traction hooks significantly enhances torque control of anterior teeth and effectively prevents deepening of the overbite.

Objective:To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID).Methods:Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People′s Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants.Results:A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c. 676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c. 184_185delAC variant of the BTK gene, and the c. 472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c. 184_185delAC and CYBB: c. 472A>T variants were classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c. 184_185 position of the BTK gene, the c. 472 position of the CYBB gene, and the c. 676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. Conclusion:WES is an important tool to infer and analyze the carryier status for couples who had given births to children died of PID and improve the positive detection rate.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Oral squamous cell carcinoma(OSCC)is the predominant type of oral cancer,while some patients may develop oral multiple primary cancers(MPCs)with unclear etiology.This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs.Clinicopathological data from patients with oral single primary carcinoma(SPC,n=202)and oral MPCs(n=34)were collected and compared.Copy number alteration(CNA)analysis was conducted to identify chromosomal-instability differences among oral MPCs,recurrent OSCC cases,and OSCC patients with lymph node metastasis.Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients.Additionally,CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients.Our findings revealed that,in contrast to oral SPC,females predominated the oral MPCs(70.59%),while smoking and alcohol use were not frequent in MPCs.Moreover,long-term survival outcomes were poorer in oral MPCs.From a CNA perspective,no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis.In addition to commonly mutated genes such as CASP8,TP53 and MUC16,in oral MPCs we also detected relatively rare mutations,such as HS3ST6 and RFPL4A.Furthermore,this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals,and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Objective To investigate the prevalence and molecular characteristics of Anaplasma infections in sheep and goats in Anhui Province in 2020, so as to provide insights into ovine anaplasmosis prevention and control. Methods A total of 355 fresh blood samples were collected from 7 sheep and goat farms in Linquan County of Fuyang City, Lixin County of Bozhou City, Yu'an District of Lu'an City, Wangjiang County of Anqing City, Nanling County of Wuhu City, and Tianchang City and Fengyang County of Chuzhou City in Anhui Province from June to December 2020. A. bovis and A. phagocytophilum 16S ribosomal RNA (16S rRNA) gene, A. ovis major surface protein 4 (MSP4) gene and A. capra citric acid synthase (gltA) gene were amplified using PCR assay in all blood samples, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was calculated in sheep and goats. In addition, the positive amplification products were sequenced and subjected to genetic evolutionary analysis. Results The overall prevalence of Anaplasma infections was 17.5% (62/355) in sheep and goats in Anhui Province, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was 2.8% (10/355), 2.5% (9/355), 2.5% (9/355), and 7.0% (25/355), while the prevalence of A. bovis and A. phagocytophilum, A. phagocytophilum and A. ovis, A. phagocytophilum and A. capra and A. bovis, A. phagocytophilum and A. ovis co-infections was 0.8% (3/355), 1.1% (4/355), 0.3% (1/355) and 0.3% (1/355), respectively. No Anaplasma was detected in the sheep and goat farms in Fengyang County, while at least three Anaplasma species were detected in other sheep and goat farms, with co-infections of multiple Anaplasma species identified. The prevalence of Anaplasma infections was 14.7% (24/163) in goats and 19.8% (38/192) in sheep, and the prevalence of Anaplasma infections was 31.0% (31/100) in goats and sheep under 6 months of age, and 12.2% (31/255) in goats and sheep at ages of 6 months and older, respectively. A. bovis, A. phagocytophilum, A. ovis and A. capra were identified in sheep and goats of different breeds and ages. Conclusions Multiple Anaplasma species infections were commonly prevalent in goats and sheep in Anhui Province in 2020, notably A. phagocytophilum, A. ovis and A. capra, which have zoonotic risks. Improved surveillance and prevention and control of Anaplasma infections are required in sheep and goats in Anhui Province.

Objective To analyze coating properties of porous artificial joints,including coating morphology and coating mechanical properties,and summarize the range of coating properties of current mainstream products,to provide references for the design and development of new products,as well as provide the basis for the long-term implant removal analysis.Methods Samples for the surface morphology,shear strength,and tensile strength of the coatings used in the experiment were prepared in accordance with ASTM F1854,ASTM F1044,and ASTM F1 147 standards,respectively.The coatings were processed using plasma spraying.The surface morphology(coating thickness,porosity,and pore intercept)of the coatings for all 17 products(Nos.1-17)was tested;for products Nos.1-7 and Nos.15-16,the shear strength test between the coating and substrate was conducted first in accordance with the test method of ASTM F1044.Then,according to the test method of ASTM F1 147,the tensile strength test between the coating and substrate was conducted.For product No.17,the shear and tensile strengths of the composite coating and simple titanium coating were tested,respectively,according to the test method of ASTM F1044 and ASTM F1 147.Results A total of 15 products(88.2％)had coating thicknesses between 300 μm and 500 μm.There were 16 metal-coated products(Nos.1-16),of which 11(68.75％of the total)had coating porosities between 30％and 50％,and 14(87.5％of the total)had coating pore intercepts between 50 μm and 150 μm.The mechanical properties of the coatings were independent of the substrate material used.The shear and tensile strengths of the composite coatings with hydroxyaptite(HA)were significantly lower than those of the pure metal coatings.Conclusions For the design and manufacture of artificial joints with porous coatings,the performance of the coating can be referred to the following indexes:the coating thickness is 300-500 μm,the coating porosity is 30％-50％,the coating pore intercept is 50-150 μm.The substrate materials can be selected based on the use of the product.The effects of a lower bonding force on product performance should be considered when designing prostheses with composite coatings containing HA.This range of performance metrics provides control for long-term clinical extraction analyses.

Objective:To study the alveolar bone remodeling of maxillary anterior teeth after extraction treatment and 2-year recovery period in adolescent patients with maxillary anterior arch protrusion.Methods:15 adolescent patients with maxillary anterior arch protru-sion were included,2 maxillary first premolars were extracted and implant anchorage combined with sliding method were used to close the extraction gap.CBCT images were taken before treatment(T0),after treatment(T1)and 2 years of recorvery period(T2),respectively.After multi-plane reconstruction with Dophin Imaging,the alveolar bone area(ABA)changes of maxillary central incisor,lateral incisor and canine at cementoenamel junction(CEJ-3 mm),root neck,central part,and root tip were measured and recorded as TAC,TA1,TA2 and TA3 respectively.The labial palatal alveolar crest to CEJ bone height(BH)of each tooth was recorded as BCL,BCP respectively.The data were analyzed by IBM SPSS statistics 25.0.Results:In T0-T2 phase,TA1 of each tooth was reduced.In T0-T1 phase,the horizontal adsorption of teeth was significantly correlated with ΔBCP,followed by ΔTA3.In T0-T2 phase,ΔBCP,ΔTA2,ΔTA3 and the horizontal adsorption of teeth showed low negative correlation.In T0-T1 phase,the vertical reduction of teeth was significantly positively correlated with ΔTAC,followed by low correlation with ΔTA3 and ΔTA1.Conclusion:In the treatment of anterior arch protrusion after extraction correction in adolescent patients the more the vertical reduction and horizontal adsorption of teeth in the treatment phase,the more the alveolar bone thickness and height around the tooth root in the maintenance phase,which were significantly positively correlated.Reasonable control of the vertical move-ment of teeth in the alveolar bone can improve the periodontal condition around the teeth to a certain extent.