Objective: To examine the causal relationship between gut microbiota and noninfectious gastroenteritis using bidirectional Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of noninfectious gastroenteritis. Methods: Genome-wide association study (GWAS) data of gut microbiota were obtained from the MiBioGen database, comprising 18 340 participants. GWAS data of noninfectious gastroenteritis were obtained from the IEU OpenGWAS database, including 416 adult cases and 7 235 adult controls. The bidirectional MR analysis between gut microbiota and noninfectious gastroenteritis was conducted using inverse-variance weighted method. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analyses demonstrated statistically significant associations between a higher risk of noninfectious gastroenteritis and Clostridium gangrenexotoxin genus (OR=2.201, 95%CI: 1.295-3.740) and Ruminococcaceae UCG-013 genus (OR=2.683, 95%CI: 1.258-5.720). Conversely, statistically significant associations were observed between a lower risk of noninfectious gastroenteritis and Eubacterium hallii group (OR=0.534, 95%CI: 0.307-0.927), Lachnospiraceae NK4A136 group (OR=0.490, 95%CI: 0.252-0.953), and Oxalobacter formigenes group (OR=0.561, 95%CI: 0.348-0.903). Reverse MR analysis showed no evidence for the causal association between the aforementioned five types of gut microbiota and noninfectious gastroenteritis (all P>0.05). Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy (all P>0.05). Conclusion Clostridium gangrenexotoxin genus and Ruminococcaceae UCG-013 genus were risk factors for the noninfectious gastroenteritis, while Eubacterium hallii group, Lachnospiraceae NK4A136 group and Oxalobacter formigenes group were protective factors for the noninfectious gastroenteritis.

Objective To explore the effects of S100 calcium-binding protein A9 (S100A9) gene knockout on the phenotype of systemic lupus erythematosus (SLE) in mice and to clarify the role of S100A9 in the pathogenesis of SLE. Methods Ten female C57BL/6 wild-type and S100A9 knockout (S100A9-KO ) mice were selected, with five wild-type and five S100A9-KO B6 mice receiving imiquimod (IMQ) cream to establish SLE mouse model. The other five wild-type and five S100A9-KO B6 mice were treated as control groups by wiping the skin of the right ear with a cotton swab. After 8 weeks, the mice were sacrificed. The serum was collected from each mouse to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, immunoglobulin G (IgG), B cell activating factor (BAFF), and interleukin 6 (IL-6) using ELISA. The levels of serum creatinine were determined using a sarcosine oxidase method. Urine was collected to measure urinary protein concentration. Kidneys were collected and stained with hematoxylin and eosin (H&E) for evaluating histological changes. Results After IMQ treatment, the length and weight of spleen, levels of serum creatinine, anti-dsDNA antibodies, IgG, BAFF, IL-6, and urinary protein in the IMQ B6 group and IMQ S100A9-KO B6 group were significantly higher than those of the control groups. Lupus-like changes including increased glomerular volume and tubular epithelial swelling were observed in kidneys from the IMQ and IMQ S100A9-KO groups. However, compared with the IMQ B6 group, the IMQ S100A9-KO B6 group exhibited milder levels of serum and urine indicators as well as the lupus-like symptoms. Conclusion IMQ could induce lupus-like symptoms in both wild-type B6 mice and S100A9-KO B6 mice, but the lesions in S100A9 knockout mice are milder. Theses results suggested that S100A9 is involved in and promotes the pathogenesis of SLE.
Animals ; Lupus Erythematosus, Systemic/chemically induced* ; Female ; Calgranulin B/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Phenotype ; Mice ; Interleukin-6/blood* ; Disease Models, Animal ; Antibodies, Antinuclear/blood* ; B-Cell Activating Factor/blood* ; Immunoglobulin G/blood* ; Kidney/pathology*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To investigate the pathogen of an acute gastroenteritis outbreak in a school in Taizhou, and to understand the epidemiological characteristics and patterns of the outbreak and the etiology of the pathogen.Methods:Twelve anal swab samples from patients who met the suspected case definition during the outbreak in March 2024 were collected. FilmArray GI was used to screen 22 common pathogens in the 12 samples, and the real-time fluorescent RT-PCR was performed for verification. Nested RT-PCR was used to amplify and sequence the nucleotide sequence of the viral capsid region VP1, and the variability of the sequence sites was analyzed. Based on the sequence relationship, a molecular phylogenetic tree was constructed and the viral genotypes were determined. Molecular transmission network analysis was conducted by integrating field epidemiological information.Results:The VP1 gene sequences were obtained from 8 of the 12 specimens. Systematic evolution showed that the molecular typing of the 8 strains of Sapoviuses (SaV) was all GI.6 genotype, and there was a C/T mutation at position 1236 in the VP1 gene. The inferred molecular transmission network was largely consistent with the information from the field epidemiological investigation, such as the initial infected person being the earliest case of the outbreak, and there was a closer transmission link between the two teachers.Conclusions:This article reported a school outbreak caused by a SaV GI.6 type. We speculated a more reliable molecular transmission network, estimated the rate of gene mutation and provided a reasonable elaboration for the C/T mutation at position 1236 of the VP1 gene.

Objective:To investigate the risk factors of amputation in patients with diabetic foot ulcer (DFU) in order to improve the prognosis and reduce the amputation rate.Methods:The clinical data of 359 DFU patients admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2017 to August 2021 were retrospectively analyzed, and they were divided into amputation group (161 cases) and non-amputation group (198 cases) according to whether amputation surgery was performed. Demographic characteristics, Wagner grading and other data of the two groups were collected. Forward step logistic regression analysis was used to identify independent risk factors for amputation, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each risk factor for amputation in DFU patients.Results:There were significant differences between the amputation and non-amputation groups in terms of previous amputation history, peripheral vascular diseases (PVD), diabetic foot secondary osteomyelitis, diabetic nephropathy (DN), history of angioplasty, Wanger grade, K +, age, white blood cell count, C-reactive protein, high density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate, cardiac troponin T, and cardiac troponin I, lactic acid (all P<0.05). Previous amputation history ( OR=2.329, 95% CI: 1.092-4.970, P=0.029), DN ( OR=4.091, 95% CI: 2.222-7.532, P<0.001), PVD ( OR=2.556, 95% CI: 1.487-4.395, P=0.001), diabetic foot secondary osteomyelitis ( OR=6.332, 95% CI: 3.595-11.153, P<0.001), Wagner grade were independent risk factors for amputation in DFU patients, HDL-C ( OR=0.392, 95% CI: 0.182-0.842, P=0.016) were protective factors for amputation in DFU patients. Moreover, the combined accuracy of the above factors in predicting amputation in DFU patients was high, and the area under ROC curve was 0.839 (95% CI: 0.798-0.880), sensitivity was 83%, and specificity was 73% ( OR=0.05). Conclusions:Previous amputation history, DN, PVD, diabetic foot secondary osteomyelitis and Wagner grade are independent risk factors for amputation in DFU patients, while HDL-C is a protective factor for amputation in DFU patients. Further investigation will help to establish a stratified system for predicting the risk of diabetic foot, so as to achieve better individualized treatment.

Objective:To investigate the risk factors of amputation in patients with diabetic foot ulcer (DFU) in order to improve the prognosis and reduce the amputation rate.Methods:The clinical data of 359 DFU patients admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2017 to August 2021 were retrospectively analyzed, and they were divided into amputation group (161 cases) and non-amputation group (198 cases) according to whether amputation surgery was performed. Demographic characteristics, Wagner grading and other data of the two groups were collected. Forward step logistic regression analysis was used to identify independent risk factors for amputation, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each risk factor for amputation in DFU patients.Results:There were significant differences between the amputation and non-amputation groups in terms of previous amputation history, peripheral vascular diseases (PVD), diabetic foot secondary osteomyelitis, diabetic nephropathy (DN), history of angioplasty, Wanger grade, K +, age, white blood cell count, C-reactive protein, high density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate, cardiac troponin T, and cardiac troponin I, lactic acid (all P<0.05). Previous amputation history ( OR=2.329, 95% CI: 1.092-4.970, P=0.029), DN ( OR=4.091, 95% CI: 2.222-7.532, P<0.001), PVD ( OR=2.556, 95% CI: 1.487-4.395, P=0.001), diabetic foot secondary osteomyelitis ( OR=6.332, 95% CI: 3.595-11.153, P<0.001), Wagner grade were independent risk factors for amputation in DFU patients, HDL-C ( OR=0.392, 95% CI: 0.182-0.842, P=0.016) were protective factors for amputation in DFU patients. Moreover, the combined accuracy of the above factors in predicting amputation in DFU patients was high, and the area under ROC curve was 0.839 (95% CI: 0.798-0.880), sensitivity was 83%, and specificity was 73% ( OR=0.05). Conclusions:Previous amputation history, DN, PVD, diabetic foot secondary osteomyelitis and Wagner grade are independent risk factors for amputation in DFU patients, while HDL-C is a protective factor for amputation in DFU patients. Further investigation will help to establish a stratified system for predicting the risk of diabetic foot, so as to achieve better individualized treatment.

Objective:To investigate the pathogen of an acute gastroenteritis outbreak in a school in Taizhou, and to understand the epidemiological characteristics and patterns of the outbreak and the etiology of the pathogen.Methods:Twelve anal swab samples from patients who met the suspected case definition during the outbreak in March 2024 were collected. FilmArray GI was used to screen 22 common pathogens in the 12 samples, and the real-time fluorescent RT-PCR was performed for verification. Nested RT-PCR was used to amplify and sequence the nucleotide sequence of the viral capsid region VP1, and the variability of the sequence sites was analyzed. Based on the sequence relationship, a molecular phylogenetic tree was constructed and the viral genotypes were determined. Molecular transmission network analysis was conducted by integrating field epidemiological information.Results:The VP1 gene sequences were obtained from 8 of the 12 specimens. Systematic evolution showed that the molecular typing of the 8 strains of Sapoviuses (SaV) was all GI.6 genotype, and there was a C/T mutation at position 1236 in the VP1 gene. The inferred molecular transmission network was largely consistent with the information from the field epidemiological investigation, such as the initial infected person being the earliest case of the outbreak, and there was a closer transmission link between the two teachers.Conclusions:This article reported a school outbreak caused by a SaV GI.6 type. We speculated a more reliable molecular transmission network, estimated the rate of gene mutation and provided a reasonable elaboration for the C/T mutation at position 1236 of the VP1 gene.

Objective:To investigate the effect of interleukin-12(IL-12)on liver lesions and oxidative stress pathway in Sjo-gren's syndrome mice,and to clarify the possible mechanism of liver lesions in Sjogren's syndrome.Methods:Saliva flow rate,liver function,liver pathology and IL-12 level were measured in NOD,IL-12 knockout(IL-12KO)NOD and C57BL/6(B6)mice.Different concentrations of IL-12 and JAK2,TYK2 inhibitors were applied to mouse hepatoma cells.The oxidative stress index of mouse serum and cell culture supernatants of each group were determined.Results:Compared with the other two groups of mice,the NOD mice had significantly higher GOT and GPT(P<0.05),and decreased serum GSH-PX,SOD and CAT(P<0.05).CAT,GSH,GSH-PX and SOD were decreased,while MDA was increased in mice treated with different concentrations of IL-12.JAK2/TYK2 inhibitors reversed regulatory effects of IL-12 on SOD,GSH and MDA in hepatoma cells(P<0.05).Conclusion:IL-12 may aggravated liver damage of Sj?gren's syndrome through promoting oxidative stress of hepatocytes.

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

Objective:To investigate the pharmacological basis and mechanism of Anti-cancer Essence Formula in the treatment of gastric cancer based on network pharmacology,and to provide bioinformatics basis for the clinical treatment of gastric cancer with traditional Chinese medicine.Methods:The active ingredients of Anti-cancer Essence Formula were searched in TCMSP database,and the targets of the active ingredients were further obtained using UniProt database.The targets of gastric cancer were obtained using GeneCards,OMIM and TTD databases.Cytoscape 3.9.1 software was used to build the"Disease-Component-Target"network.String database and Cytoscape 3.9.1 software were used to construct the PPI network.The transcript levels of the core genes were analyzed by UALCAN database,and the relationship between core gene expression and patient survival was analyzed by Kaplan-Meier plotter.GO function and KEGG pathway enrichment analyses were performed by DAVID database.Results:There were 236 active ingredients of Anti-Cancer Essence Formula,and 16 key targets were screened by PPI network.MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8 and EGFR were abnormally expressed in gastric cancer tissues(P＜0.05),and all of them showed correlation with the prognosis of gastric cancer patients(P＜0.05).GO analysis was mainly enriched in cell division,cell proliferation and apoptosis,and KEGG analysis was mainly enriched in cancer pathway,MAPK signaling pathway,Relaxin signaling pathway,TNF signaling pathway,T-cell receptor signaling pathway,Prolactin signaling pathway,and PI3K-Akt signaling pathway.Conclusion:Anti-cancer Essence Formula is characterized by the synergistic effect of multi-components,multi-targets,and multi-pathways.It mainly acts on the targets of MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8,and EGFR through the active ingredients such as quercetin,kaempferol,β-sitosterol,and racemic carvacrol.It also regulates the signaling pathways of MAPK,Relaxin,TNF,T-cell receptor,Prolactin,and PI3K-Akt.