Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

OBJECTIVE: To explore the toxicological mechanism of drug-induced liver injury(DILI) in rats induced by cantharidin(CTD). METHODS: SD rats were exposed to different doses of CTD(0.061 4, 0.092 1, 0.184 1 mg·kg−1) by oral gavage for 28 d. Liver index and serum liver function indictors were detected. HE staining was used to evaluate the pathological changes of liver. Then the proteins in endoplasmic reticulum stress(ERS), autophagy, and apoptosis-pathway were detected by Western blotting. RESULTS: The liver index was increased in CTD groups. The ALT, AST, LDH, ALP and T-Bil were increased by CTD with a dose-dependent manner. Disrupted hepatic architecture and dilatation of central vein were observed after CTD intervention. The protein expression levels of GRP78, CHOP, ATF4, Beclin-1, LC3, Caspase-3, Caspase-8, and Bax/Bcl-2 were increased after CTD intervention. Molecular docking results revealed that GRP78, ATF4, and Beclin-1 could directly interconnect with CTD. CONCLUSION CTD can activate ERS, autophagy and synergistically inducing downstream apoptosis in rat, providing a novel insight into the mechanism of CTD-induced DILI.

Objective:To investigate the correlation between plasma fibrinogen/serum albumin ratio (FAR) and the degree of cerebral artery stenosis in patients with acute cerebral infarction (ACI).Methods:Clinical data of 189 patients with acute cerebral infarction diagnosed and treated in the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from January 2021 to March 2023 were selected for retrospective analysis. Digital subtraction angiography (DSA) was improved, and they were divided into four groups according to the degree of intracranial vascular stenosis according to NASCET grading method: no stenosis group (47 cases), mild stenosis group (45 cases), moderate stenosis group (39 cases) and severe stenosis and occlusion group (58 cases). The differences of basic data, plasma fibrinogen/serum albumin ratio (FAR) and other inflammatory indicators among all groups were compared, and the correlation between FAR level and the severity of cerebral artery stenosis was analyzed. Multivariate Logistic regression was used to explore the factors influencing to cerebral artery stenosis and ROC curve was used to evaluate the diagnostic value of FAR in the degree of cerebral artery stenosis in cerebral infarction patients.Results:There were significant differences in blood neutrophil (NEU), mean platelet volume (MPV), fibrinogen (FIB), fibrinogen (FIB), albumin (ALB) and FAR among the 4 groups (statistical values were H=11.50, H=8.44, F=5.16, H=30.93, H=40.38; all P<0.05). Correlation analysis showed a positive correlation between FAR and the degree of cerebral artery stenosis ( r=0.455, P<0.05). Multivariate Logistic regression showed that FAR was an independent risk factor for the degree of cerebral artery stenosis ( OR=1.445, 95% CI=1.261-1.655, P<0.001). Conclusion:FAR is an independent risk factor for cerebral artery stenosis in patients with acute cerebral infarction (ACI), and may be a new biomarker for predicting cerebral artery stenosis.

Objective To explore the application value of ultrasound-guided use of bupivacaine for subarachnoid block in hip replacement surgery for elderly femoral neck fractures.Methods A total of 108 elderly patients who underwent hip replacement surgery at Ganzhou Traditional Chinese Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into conventional anesthesia group and ultrasound guided anesthesia group by means of random number table,54 cases in each group.Patients in the conventional anesthesia group received routine general anesthesia;Patients in the ultrasound guided anesthesia group received unilateral lumbar anesthesia with bupivacaine under ultrasound-guided guidance.Compare the effectiveness of two anesthesia methods during surgery.Results Compared with the conventional anesthesia group,the anesthesia effect of the ultrasound guided anesthesia group was better(P<0.05);The surgery time,amount of bleeding during surgery,postoperative recovery time,and length of hospital stay in the ultrasound guided anesthesia group were all lower than those in the conventional anesthesia group(P<0.05).The ultrasound guided anesthesia group performed better in terms of hemodynamic stability,with a smaller range of changes,and significantly lower pain scores at different postoperative time points compared to the conventional anesthesia group(P<0.05).Conclusion In elderly patients undergoing hip replacement surgery,using ultrasound-guided bupivacaine for subarachnoid block can achieve ideal anesthesia and analgesic effects compared to traditional general anesthesia,shorten drug onset time,alleviate pain in elderly patients,maintain hemodynamic stability,and have significant clinical application effects.

OBJECTIVE To identify the chemical constituents of the modified Yupingfengsan formula. METHODS UPLC-Q- Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS & CONCLUSIONS Totally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O- glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.

This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P＜0.05),while the level of IL-10 was significantly decreased(P＜0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P＜0.05)and IL-10 was sig-nificantly increased(P＜0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P＜0.05)and increased the levels of growth hormone(GH)(P＜0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P＜0.05)and up-regula-ted that of STAT3(P＜0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.

Objective To design and test the reliability and validity of patient admission nursing assessment sheet of integrated Chinese and westem medicine ward.Methods On the basis of literature research,with traditional Chinese medicine"look,hear,ask and pulse-taking"as the basic framework,physical discrimination as the evaluation outcome,combined with the general nursing evaluation points of patients admitted to hospital,we designed the patient admission nursing assessment sheet of integrated Chinese and westem medicine ward,and then we adopted the Delphi method to conduct an inquiry on the draft of the admission sheet.In April 2022,3 clinical nurses were selected to evaluate 160 admitted patients from Integrated Traditional Chinese and Western Medicine Department of a tertiary A comprehensive hospital in Hubei Province,and Fleiss'Kappa coefficient and content validity coefficient were used to test the reliability and validity.Results The recovery rates of the 2 rounds of expert correspondence questionnaires were 95.45％and 100％.The authority coefficients were 0.931 and 0.957;the Kendall harmony coefficients were 0.101 and 0.106(P＜0.01);the importance scores of articles were 4.13～4.82;the coefficient of variation was 0.07～0.19 in 2nd round of expert correspondence.The final nursing assessment list for inpatients in the integrated Chinese and Western medicine ward included 3 parts:general demographic data assessment,four-Chinese medicine diagnosis assessment/physical discrimination,and nursing risk assessment,and there are 32 evaluation contents in the assessment sheet.The Fleiss'Kappa coefficient of this assessment sheet was 0.602(P＜0.001);the item content validity index was 0.857～1.000,and the overall content validity index was 0.920.Conclusion The admission nursing assessment sheet for inpatients in integrated Chinese and Westem medicine wards has good reliability and validity,and it is suitable for the integrated Chinese and Westem medicine wards.