Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint， the mechanism of which is closely related to signaling pathways， such as osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）. Traditional Chinese medicine has the characteristics of multiple components and targets， and is widely used for the treatment of autoimmune diseases due to its low toxicity， strong specificity， and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways， regulating immune inflammatory responses， and inhibiting biological processes such as bone destruction， ectopic osteogenic differentiation， cell apoptosis， and autophagy.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To evaluate the healthcare accessibility and quality of diagnosis and treatment services of Internet hospitals in China.Methods:One hundred and eighty Internet hospitals in 60 cities were seleted based on the sampling of development levels in the eastern, central and western regions of China. From April to May 2023, standardized patients methodology was applied to evaluate the accessibility(including the number of Internet hospitals, functional settings, online doctor status, the doctor′s attending rate and consultation fees) and diagnosis and treatment service quality(including the diagnosis and treatment services quality, response speed and patient′s evaluation) of Internet hospitals.Results:The average opening rate of Internet hospitals in China was 52.9% (560/1 058), the average online rate of doctors was 64.2% (1 099/1 713), the average doctor′s attending rate was 33.6% (112/333), the average consultation fee was 4.85 yuan, the average score of consultation was 1.92 out of 9, the average score of diagnosis and treatment was 1.12 out of 4, the average score of the response speed was 1.70 out of 3, and patient satisfaction was 2.73 out of 3.Conclusions:The Internet hospital accessibility in China is unevenly developed, and the overall quality of diagnosis and treatment is low. It is recommended to accurately position and optimize the function of Internet hospital, establish the incentive mechanism for online consultation doctors, construct and improve the regulatory system of Internet hospital diagnosis and treatment, so as to improve the accessibility and quality of diagnosis and treatment of Internet hospitals.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Objective:To investigate the effect of positive and negative pressure extubation on mechanical ventilation patients in the intensive care unit (ICU).Methods:A prospective randomized controlled study was performed, 105 ICU patients who successfully passed the spontaneous breathing test (SBT) after mechanical ventilation of Nanjing Jiangbei Hospital Affiliated to Nantong University from January 2019 to March 2021 were enrolled. According to random number table method, they were randomly divided into positive pressure extubation group (53 cases) and negative pressure extubation group (52 cases). During extubation, all patients were placed in semi-decubitus position (raising the head of bed at an angle range from 30°- 45°), the secretions from mouth, nose, throat and trachea were removed. In the negative pressure extubation group, the sputum suction tube was inserted into the tracheal tube and passed over the distal opening to carry out continuous negative pressure suction in the tracheal tube after disconnecting the ventilator. Meanwhile, after the tracheal tube balloon was evacuated, the sputum suction tube was pulled out together with the tracheal tube. In the positive pressure extubation group, the patients were guided to inspiratory forcibly under the original SBT mode. When the patients reached the inspiratory peak, the ballon was evacuated and the tracheal tube was removed. After extubation, all patients were given nasal catheter oxygen inhalation (oxygen flow 5 L/min). Arterial blood gas analysis indexes [pH value, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2)] were recorded 5 minutes and 1 hour after extubation in both groups. Vital signs (including tachypnea, tachycardia, elevated blood pressure and decreased oxygen saturation) and complications (including severe cough, airway hyperresponsiveness and pneumonia) were observed 30 minutes after extubation in both groups. Results:Five minutes after extubation, blood gas analysis showed that the PaO 2 of positive pressure extubation group was significantly higher than that of negative pressure extubation group [mmHg (1 mmHg≈0.133 kPa): 123.4±30.2 vs. 111.0±21.1, P < 0.05], the pH value and PaCO 2 in positive pressure extubation group were slightly lower than that of negative pressure extubation group [pH value: 7.411±0.042 vs. 7.419±0.040, PaCO 2 (mmHg): 39.7±4.7 vs. 40.5±5.6], but the differences were not statistically significant (both P > 0.05). One hour after extubation, the pH value, PaO 2 and PaCO 2 in positive pressure extubation group were slightly lower than those in negative pressure extubation group, but the differences were not statistically significant. Within 30 minutes after extubation, the incedences of tachypnea, tachycardia, elevated blood pressure and oxygen desaturationin in positive pressure extubation group were significantly lower than those in negative pressure extubation group [tachypnea: 9.4% (5/53) vs. 28.8% (15/52), tachycardia: 15.1% (8/53) vs. 32.7% (17/52), elevated blood pressure: 11.3% (6/53) vs. 30.8% (16/52), oxygen desaturation: 7.5% (4/53) vs. 34.6% (18/52), all P < 0.05], the incidence of severe cough in positive pressure extubation group was significantly lower than that in negative pressure extubation group [9.4% (5/53) vs. 30.8% (16/52), P < 0.05], but there was no significant difference in the incidence of complications of airway hyperresponsiveness between the two groups [1.9% (1/53) vs. 5.8% (3/52), P > 0.05]. No pneumonia occurred in both groups within 48 hours after extubation. Conclusion:The positive pressure extubation method can ensure full oxygenation of patients undergoing mechanical ventilation in ICU, avoid hypoxia, and reduce the occurrence of hypoxia and severe cough, which is more conducive to the stability of vital signs.

ObjectiveTo determine the seroprevalence of anti-Streptococcus pneumoniae immunoglobulin G （IgG） antibody and its risk factors in the elderly attending physical examination. MethodsTwo communities were randomly selected， in which the elderly aged over 60 years attending physical examination in the community health care centers were included in the study. A questionnaire survey was conducted， companied by examination for serum anti-Streptococcus pneumoniae IgG antibody. In addition， data of physical examination was collected. Chi-square test and multivariate logistic regression were utilized to determine the risk factors associated with seroprevalence of anti-Streptococcus pneumoniae antibody. ResultsA total of 635 participants were included. The average age was （73.2±7.4） years old. Forty-nine （7.72%） participants tested positive for anti-Streptococcus pneumoniae IgG antibody. The seroprevalence differed by gender （6.49% in male and 8.86% in female）， smoking （5.48% in smokers and 8.01% in non-smokers）， history of pneumonia （7.89% in those suffered from pneumonia in the past year and 7.71% in those didn^’t have pneumonia）， history of common cold （10.38% in those had common cold in the past year and 5.87% in those didn’t have cold）， obesity （15.62% in those with obesity and 6.83% in those without obesity）. Further multivariate logistic regression showed the seroprevalence of anti-Streptococcus pneumoniae IgG significantly increased in the elderly with history of common cold （OR： 2.24； 95%CI： 1.21‒4.14）and obesity （OR： 2.81； 95%CI： 1.26‒6.26）. ConclusionSeroprevalence of anti-Streptococcus pneumoniae IgG antibody is low in the elderly attending physical examination. It warrants improving the vaccination of pneumococcal polysaccharide vaccine for the elderly with obesity and susceptibility to common cold.

OBJECTIVE: To summarize and analyze the diagnostic ideas of new occupational lung tumors in Guangdong Province.METHODS: According to the Law of the People′s Republic of China on the Prevention and Control of Occupational Disease and the GBZ 94-2002 Diagnostic Criteria of Occupational Cancer, the key diagnostic points of 6 new occupational lung tumors diagnosed in Guangdong Province from 2010 to 2011 were analyzed. RESULTS: There were 9 cases of 6 new kinds of new occupational tumors were diagnosed in Guangdong Province in 2010-2011. The cases included 3 occupational lung cancer of coke oven workers, 2 occupational lung cancer caused by asbestos, 1 occupational mesothelioma caused by asbestos, 1 occupational lung cancer caused by arsenate, 1 occupational lung cancer caused by chromate salt, and 1 occupational lung cancer caused by asphalt. During the process, the diagnosis was based on the principles of the comprehensive analysis and the attribution diagnosis, combined with occupational history, occupational disease hazard exposure history, clinical data and auxiliary examination results. If the patients were diagnosed with a primary tumor, the patients′ exposure history to occupational carcinogens should be tracked, traced and confirmed, and the diagnosis should be confirmed by referring to the list of occupational carcinogens and literature reports of the International Labor Organization, and not limited to only the personnel in a particular industry. CONCLUSION: During the diagnostic process of occupational tumors, attention should be paid to confirm the exposure history of occupational carcinogen. The key is to determine the exposure of corresponding occupational carcinogen, the route and the time of exposure and the incubation period.

Objective: To evaluate the effect of epigallocatechin gallate (EGCG) on T helper cell 1 (Th1) and Th2 in psoriasis patients. Methods: A total of 33 patients with plaque-type psoriasis vulgaris were enrolled, and peripheral blood mononuclear cells (PBMC) were isolated and cultured. The appropriate concentration of EGCG was determined by methyl thiazol tetrazolium (MTT) assay. PBMC at exponential growth phase were divided into 2 groups to be treated with EGCG (EGCG group) or not (control group) for 24 hours. Flow cytometry was performed to determine proportions of Th1 and Th2 cells, enzyme-linked immunosorbent assay (ELISA) to detect levels of Th1 (interleukin[IL]-2, interferon[IFN]-γ) and Th2 cytokines (IL-4, IL-10) in the cell culture supernatant, and real-time quantitative RCR (qRT-PCR) to determine the mRNA expression of T-bet (a Th1 transcription factor) and GATA3 (a Th2 transcription factor) . Statistical analysis was carried out by using t test. Results: According to the MTT assay results, EGCG at a non-toxic concentration of 60 μmol/L was chosen for subsequent experiments. Compared with the control group, the EGCG group showed significantly decreased number of Th1 cells (t = 3.43, P = 0.026) , increased number of Th2 cells (t = 6.68, P = 0.026) , and decreased Th1/Th2 ratio (P < 0.05) . The levels of IL-2 and IFN-γ in the culture supernatant of PBMC were both significantly lower in the EGCG group (824.45 ± 101.21 ng/L, 1 623.62 ± 185.56 ng/L respectively) than in the control group (1 568.32 ± 196.45 ng/L, 3 287.63 ± 235.54 ng/L respectively) , while the levels of IL-4 and IL-10 were significantly higher in the EGCG group (389.48 ± 46.63 ng/L, 285.95 ± 53.28 ng/L respectively) than in the control group (225.38 ± 26.92 ng/L, 165.46 ± 32.25 ng/L respectively) . Compared with the control group, the EGCG group showed significantly decreased T-bet mRNA expression (t = 11.99, P < 0.001) , but increased GATA3 mRNA expression (t = 18.62, P < 0.001) . Conclusion EGCG can reduce the number of Th1 cells, inhibit the production of Th1 cytokines and transcription factors, and increase the number of Th2 cells and the production of Th2 cytokines and transcription factors, followed by the modulation of Th1/Th2 immune imbalance.

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development.Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations.To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia,we examined patterns of dysmorphology caused by Hh signalling inhibition.Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 or 150 mg·kg-1 body weight at preselected time points between embryonic days (E)8.5 and 12.5.The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg·kg-1.Exposure between E9.5 and E10.5 induced frontal bone dysplasia,micrognathia and limb defects,with administration at E10.5 producing the most pronounced effects.This model showed decreased ossification of the frontal bone with downregulation of Hh signalling.The osteoid thickness of the frontal bone was significantly reduced.The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.