Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans ; Gastrointestinal Microbiome/physiology* ; Depression/microbiology* ; Gastrointestinal Diseases/physiopathology* ; Brain ; Animals ; Brain-Gut Axis ; Gastrointestinal Tract/microbiology*

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.

OBJECTIVE To investigate the relationship between metformin and sarcopenia-related traits. METHODS Based on the data from publicly genome-wide association study-related databases， using single nucleotide polymorphisms strongly associated with metformin as instrumental variables， the two-sample Mendelian randomization （MR） analysis methods [inverse variance weighting （IVW） method， MR-Egger regression method and weighted median estimator method] were employed to investigate the relationship between metformin and three sarcopenia-related traits （low grip strength， muscle mass and walking speed）. Cochran’s Q test was used to assess heterogeneity， MR-Egger intercept test was used to detect horizontal pleiotropy， and leave-one-out analysis was performed for sensitivity analysis. RESULTS The results of IVW method showed that metformin use was significantly associated with an increased risk of low grip strength （β＝1.550， 95%CI was 0.389-2.711， P＝0.009） and reduced limb muscle mass （right leg lean body mass： β＝－0.665， 95%CI was －1.018-－0.312， P＜0.001； left leg lean body mass： β＝－0.710， 95%CI was －1.049-－0.371，P＜0.001； right arm lean body mass： β＝－0.471， 95%CI was －0.890-－0.053， P＝0.027； left arm lean body mass： β＝－0.463， 95%CI was －0.865-－0.061， P＝0.024），but was not associated with walking speed. The results or causal effects of the other two methods are consistent with it. The Cochran’s Q test indicated some degree of heterogeneity in the result of this study. No horizontal pleiotropy was detected by the MR-Egger intercept test. The sensitivity analysis suggested that the results of this study were stable. CONCLUSIONS Metformin may increase the risk of sarcopenia.

Objective:To assess the efficacy of high-flow nasal cannula oxygen therapy for the respiratory support after tracheal extubation under general anesthesia in neonates.Methods:This was a prospective randomized controlled study. Ninety-four neonates undergoing general surgery under general anesthesia with endotracheal intubation and endotracheal tube removal following surgery from December 2022 to November 2023 in the Third Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups ( n=47 each) by the random number table method: conventional oxygen therapy group (group C) and high-flow nasal cannula oxygen therapy group (group H). After the endotracheal tube was removed, group H underwent high-flow nasal cannula oxygen therapy: oxygen flow was 2 L·kg -1·min -1, the concentration and humidity of oxygen were both 100%, and the temperature was 37 ℃. Group C underwent conventional mask ventilation with the oxygen flow rate 5 L/min, oxygen concentration 100%, ventilation frequency about 25-35 times/min. The outcome measures were recorded from the time after extubation to the time before discharge from the operating theatre. The main outcome measures were the minimum SpO 2 and hypoxemia (SpO 2<90%), choking, laryngospasm and asphyxia. The secondary outcome measures were respiratory rate (immediate extubation, immediate discharge), minimum HR, and time to discharge from the operating theatre. Results:Compared with group C, the lowest SpO 2 was significantly increased, the incidence of hypoxemia and respiratory rate immediately after discharge from the operating room was decreased ( P<0.05), and no significant changes were found in the incidence of choking, laryngospasm and asphyxia, the lowest heart rate, respiratory rate immediately after tracheal extubation and time to discharge from the operating theatre in group H( P>0.05). Conclusions:High-flow nasal cannula oxygen therapy can improve oxygenation and significantly reduce the risk of hypoxemia when used for the respiratory support after tracheal extubation under general anesthesia in neonates.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs.

Objective:To evaluate the impact of the reform of the county medical community on the expenditure of medical insurance funds, and to provide references for maintaining the stability of the medical insurance fund and deepening the reform of the medical community.Methods:Medical insurance data of urban and rural residents in M County, Yunnan province from 2016 to 2019 were collected, and a discontinuous time series model was used to analyze the impact of county medical community reform on medical insurance fund expenditures.Results:Since the reform, the number of patients discharged from county-level hospitals has shown a downward trend, averaging a decrease of 25.996 people per month; yet increases have emerged with the average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure, averaging a monthly increase of 90.931 yuan, 50.014 yuan and 1.528 yuan respectively. The average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure of the township hospitals all showed an upward trend, averaging a monthly increase of 31.191 yuan, 38.678 yuan and 0.085 yuan respectively. The flow of external medical insurance funds of the medical community has shown a continuous upward trend, averaging a monthly increase of hospitalization fund expenditures of 33.005 yuan, and a monthly increase of outpatient overall fund expenditures of 4.896 yuan overall.Conclusions:The M County medical community should further strengthen the top-level design, explore the reform of medical insurance payment methods, improve the regional information platform, standardize the referral system, and strengthen supervision to deepen the construction of the medical community to ensure the sustainable operation of medical insurance funds.

Objective:To analyze the related factors affecting the use of autogenous arteriovenous fistula (AVF), and provide a theoretical basis for prolonging the service life of AVF in hemodialysis patients.Methods:This was a retrospective study. The patients undergoing AVF and using it to maintain hemodialysis (MHD) in the First Affiliated Hospital of Nanchang University from October 2004 to June 2017 were selected as study subjects to discuss the relevant factors affecting the service life of AVF. The data of general information, dialysis and laboratory examinations were collected through questionnaire surveys, hospital case system and hemodialysis record sheets. The patients were divided into the patency group and the dysfunction group according to the status of AVF, and the related factors were compared. Multivariate Cox proportional hazard model was used to analyze the influencing factors, and Kaplan-Meier survival curve was used to determine the service life of AVF, respectively.Results:A total of 187 subjects were included in the study. The patency group had 140 cases and the dysfunction group had 47 cases. There were statistically significant differences in the proportion of diabetes, the level of serum albumin, uric acid and parathyroid hormone (PTH) between the two groups (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that diabetes ( HR=9.348, 95% CI 3.507-24.918, P<0.001) and hypoalbuminemia ( HR=12.650, 95% CI 2.925-54.714, P=0.001) were risk factors for the short service life of AVF. The results of Kaplan-Meier analysis showed that the service life of AVF in patients with diabetes was significantly shorter than that in MHD patients without diabetes (Log-rank χ2=13.191, P<0.001); the service life of AVF in patients with hypoalbuminemia was significantly shorter than that without hypoalbuminemia (Log-rank χ2=13.591, P<0.001). Conclusions:Diabetes mellitus and hypoalbuminemia are risk factors for the short service life of AVF. Therefore, intervention programs should be formulated to extend the service life of AVF.