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.

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 investigate the effects of granulocyte colony-stimulating factor(G-CSF)combined with tadalafil(TD)on endometrial receptivity and pregnancy outcomes in patients with thin endometrium(TE).Methods Patients with TE in the department of reproductive medicine of the First Hospital of Qinhuangdao from May 2020 to March 2023 were selected as the study subjects.They were divided into a experimental group(G-GSF combined with TD)and a control group(G-GSF)according to the different treatment regimens.The endometrial receptivity[endometrial thickness(EMT),endometrial volume(EMV),endometrial blood flow peak systolic flow rate/end diastolic flow rate(EBF-S/D),endometrial fractionation,endometrial blood flow fractionation,uterine artery pulsatility index(AUPI),uterine artery resistance index(AURI)and uterine arterial peak systolic flow rate/end diastolic flow rate(AU-S/D)]of the TE patients before and after treatment(the endometrial transition day)were compared;the endometrial receptivity on endometrial transformation day,post-treatment pregnancy outcomes[embryo implantation rate(EIR),clinical pregnancy rate(CPR),and early miscarriage rate(ABR)],and the incidence of adverse reactions during treatment were compared between the two groups.Results A total of 60 patients were included in the study,with 30 in each group.Before treatment,the difference in endometrial receptivity between the two groups was not statistically significant(P＞0.05).Compared with the pre-treatment period,the EMT,EMV,the proportion of type A endometrium and the proportion of type Ⅱ+Ⅲ endometrial blood flow significantly increased in the two groups after treatment on the endometrial transformation day increased significantly(P＜0.05),while the EBF-S/D,AUPI,AURI and AU-S/D significantly decreased(P＜0.05).EMT and EMV were greater in the experimental group than in the control group(P＜0.05),whereas EBF-S/D,AUPI,AURI and AU-S/D were less than those in the control group(P＜0.05).Compared with the control group,the differences in the proportion of endometrium,the proportion of endometrial blood flow,EIR,CPR and ABR in the experimental group were not statistically significant(P＞0.05).No adverse reactions occurred during treatment in both groups.Conclusion G-CSF combined with TD can improve endometrial receptivity in TE patients with high safety,but there is no effect on pregnancy outcome.

Objective:To investigate the correlation between serum albumin, urea nitrogen and Fazekas scores and cognitive function scores in patients with mild and medium ischemic stroke.Methods:Clinical data of 160 patients with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS)≤7 scores admitted to the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from June 2021 to April 2023 were selected for a cross-sectional study. According to the Montreal Cognitive Assessment (MoCA) score, they were divided into normal cognitive group (28 cases) (MoCA≥26 scores), mild to moderate cognitive impairment group (74 cases) (MoCA 15-<26 scores), and severe cognitive impairment group (58 cases) (MoCA<15 scores). Demographic characteristics, serological indicators and imaging data of patients were collected, and the correlation between serum albumin, urea nitrogen and Fazekas scores and the total score of MoCA and the scores of each cognitive domain was analyzed. One-way ANOVA was used for comparison between the normal distribution and homogeneous variance data sets, LSD analysis was used for pairwise comparison, Kruskal-Wallis H test was used between the skew distribution or heterogeneous variance data sets. Bonferroni correction analysis was used for pairwise comparison. Chi-square test or Fisher exact probability method was used after the comparison between the count data sets. Spearman Spearman correlation analysis was performed on serum albumin, urea nitrogen and Fazekas scores with MoCA scores and cognitive domain scores. Multivariate ordered Logistic regression was used to analyze the independent risk factors of cognitive function in acute stage of mild and medium ischemic stroke patients. Results:The incidence of cognitive impairment in patients with acute mild and medium ischemic stroke was 82.50% (132/160). Comparison of age ((56.71±7.35), (60.32±10.20), (66.40±11.88) years old), sex (male/female: (23/5, 58/16, 33/25)), the proportion of education level above high school (25.0%(7/28), 16.2%(12/74), 6.9%(4/58)), hemoglobin ((149.26±14.91), (144.85±16.85), (137.63±17.22) g/L), albumin (39.5 (37.0, 41.2), 38.6(35.6, 40.8), 37.4 (34.5, 39.8) g/L), urea nitrogen (5.30 (4.00, 6.60), 4.81 (4.00, 6.32), 5.86 (4.55, 6.97) mmol/L), Hamilton Anxiety Scale (HAMA) score (5.0 (2.0, 10.0), 7.5 (5.0, 11.0), 10.0 (6.0, 14.3) scores),Hamilton Depression Scale (HAMA) score (5.5 (3.0, 12.5), 7.0 (4.0, 11.0), 9.5 (5.0, 14.0) scores), and Fazekas score (2.00 (1.25, 3.00), 2.00 (1.00, 4.00), 3.00 (2.00, 5.00) scores) among cognitive normal group, mild to moderate cognitive impairment group, and severe cognitive impairment group of patients, the difference were statistically significant (the statistical values were F=9.68, χ 2=9.29, χ 2=30.77, F=5.31, H=7.06, H=6.71, H=12.37, H=8.91, and H=10.96, respectively;the P values were <0.001, 0.010, <0.001, 0.006, 0.029, 0.035, 0.002, 0.012, and 0.004, respectively ). The total score of MoCA was negatively correlated with Fazekas score and serum urea nitrogen, but positively correlated with serum albumin ( r s values were -0.250, -0.168, and 0.212, respectively; P values were 0.001, 0.036, and 0.009, respectively). Serum albumin was positively correlated with scores in visual space and execution, naming, attention and orientation, serum urea nitrogen was negatively correlated with scores in language and orientation, and Fazekas score was negatively correlated with scores in visual space and execution, orientation, attention and language ( r s values were 0.291, 0.196, 0.191, 0.209, -0.205, -0.180, -0.248, -0.193, -0.188, and -0.183, respectively; P values were <0.001, 0.017, 0.020, 0.011, 0.012, 0.027, 0.002, 0.016, 0.020, and 0.023, respectively). Multiple Logistic regression analysis showed that low albumin ( OR=0.884, 95% CI: 0.813-0.963, P=0.005) and high urea nitrogen ( OR=1.195, 95% CI: 1.003-1.425, P=0.047) and high Fazekas scores ( OR=1.401, 95% CI: 1.132-1.733, P=0.002) were independent risk factors for cognitive function, while high education level was a protective factor ( OR=0.062, 95% CI: 0.019-0.202, P<0.001). Conclusion:The incidence of acute cognitive impairment is high in patients with mild and medium ischemic stroke. Higher education level is a protective factor for cognitive function. Low albumin, high urea nitrogen and high Fazekas score are independent risk factors for cognitive function.

Chronic internal carotid artery occlusion, a common clinical lesion caused by atherosclerosis, was also one of the common vascular diseases in the middle and old age. It could slow down the blood flow rate of blood vessels, which leaded to changes in the blood supply of brain tissue, and secondary causes abnormal metabolism of brain nerves and brain tissue. At the same time, long-term cerebral hypoperfusion would induce cognitive impairment, which would seriously affect the quality of life of patients. At present, there were two main treatment methods: drug conservative treatment and intravascular intervention, but there was still a great controversy about the survival of the fittest in these two treatment methods. This paper reported the clinical, imaging, therapeutic strategy and prognosis of a case of severe intracranial and extracranial multiple vessel stenosis and occlusion, in order to provide reference for the early diagnosis and treatment of such patients.

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.

Objective To develop a risk prediction model for postoperative malnutrition in children with congenital heart disease(CHD)and to verify it both internally and externally.Methods By a convenience sampling method,300 CHD children treated at a tertiary hospital in Shandong Province from January 2018 to December 2021 were selected as a modeling group,and 129 children from January 2022 to June 2023 were selected as a validation group.Data on patient demographics,disease-specific variables,therapeutic interventions,and nursing care parameters were collected.Single factor and logistic regression were employed to construct a risk prediction model for postoperative malnutrition in CHD children,and the nomogram was drawn and its prediction effect was evaluated.Results The incidence of postoperative malnutrition among CHD children was 33.10％.Logistic regression analysis revealed that risk factors for malnutrition in children included birth weight＜2.5 kg,preoperative malnutrition,negative fluid balance 1 week after surgery,and long duration of cardiopulmonary bypass(P＜0.05).The area under the receiver operating characteristic curve of the modeling group was 0.933;the sensitivity was 83.30％;the specificity was 90.90％.The Hosmer-Lemeshow test showed that x2=7.765(P=0.457).The AUC of the validation group was 0.918;the sensitivity was 87.20％;the specificity was 90.00％.The Hosmer-Lemeshow test showed that x2=4.947(P=0.763).Calibration curves for both groups indicated good calibration of the model,and the clinical decision curves demonstrated its practical clinical utility.Conclusion The risk prediction model developed in this study exhibits good predictive ability,which can provide a reference for medical staff to early identify high-risk infants for postoperative malnutrition following CHD surgery and to formulate targeted intervention measures.