Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression.Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide(LPS),and depressive behavior was detected by glucose preference test and open-field test.miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats.TargetScan database and mi RDB database were used to predict the target genes of miR-421.Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes.The impact of over-expression and inhibition of miR-421 on target genes was observed,then the influence of over-expression and inhibition of target genes on downstream factors was observed,and the related mechanism of miR-421 on depression was explored.Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats(P<0.001),Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats(P<0.001).Binding targets of Menin and miR-421 were predicted by TargetScan database,and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay.Menin expression was down-regulated while miR-421 was overexpressed(P<0.001),whereas it was up-regulated as miR-421 was inhibited(P<0.001).qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased(P<0.001),and IL-1β expression in the hippo-campus was significantly increased(P<0.01).When the expression of Menin was inhibited,the expressions of Caspase-3,NF-κB and IL-1β were increased(P<0.001),while the expressions of Caspase-3,NF-κB and IL-1β were decreased when Menin was overexpressed(P<0.001).Conclusions Inhibition of miR-421 expression can increase Menin expression,decrease Caspase-3 content,and reduce neuroinflammatory response,thereby improving depressive symptoms.

Objective To compare the different therapeutic efficacies between radiofrequency and cryoballoon ablation in atrial fibrillation(AF)patients with enlarged left atrium.Methods A total of 106 AF patients with enlarged left atrium(LAVI)>34ml/m2 who visited our center between December 2016 and May 2022 for catheter ablation were enrolled.They were divided into radiofrequency group(R-group)and cryoballoon group(C-group)according to the procedure.The recurrence of AF was compared between the two groups.Results The median follow-up time was 12 months and no death occurred.The rate of loss of follow-up was 3.8%.The overall recurrence rate of AF after ablation was 36.8%.There was no significant difference in clinical baseline between the two groups(P>0.05).The radiofrequency group had longer operation time(P<0.001),shorter X-ray time and less exposure(P<0.05);There was no significant difference in clinical baseline and postoperative complications between the two groups(P>0.05).The results of survival analysis showed that there was no significant difference in the survival rate of patients without atrial fibrillation/atrial flutter/atrial tachycardia between the two groups(P>0.05).Conclusion For AF patients with enlarged left atrium,the clinical effects of the two methods were similar.Cryoballoon takes a shorter time,while radiofrequency has a lower X-ray time and exposure dose for physicians and patients.Therefore,appropriate ablation methods should be selected according to the actual situation.

Objectives:To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer.Methods:Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m 2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results:All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period.Conclusions:LDER is safe and effective for the treatment of low rectal cancer.

Objective:To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation.Methods:This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results:A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ2=4.776, P=0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P>0.05). Conclusion:Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.

The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (72.3%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.

Objective To explore the MRI characteristics of neonatal subpial hemorrhage and its relationship with prognosis.Methods A total of 43 newborns with subpial hemorrhage were selected.The original images were observed and analyzed by two radiologists for their radiological characteristics.The prognosis was evaluated using standardized scales such as the Gesell Intelligence Scale,Wechsler Intelligence Scale,and Bayley Intelligence Scale according to age.Results Neonatal subpial hemorrhage could be divided into type Ⅰ,type Ⅱ,and type Ⅲ.Type Ⅰ and type Ⅱ subpial hemorrhage could be completely absorbed without any abnormalities in the brain parenchyma.Type Ⅲ subpial hemorrhage could be completely absorbed and accompanied by varying degrees of cerebral softening and gliosis changes,and some cases may form local subarachnoid cavities.The clinical prognosis of type Ⅰ and type Ⅱ was better than that of type Ⅲ,and the difference was statistically significant(P=0.013).Based on the different signal between subpial hemorrhage and adjacent cortex,subcortical white matter,and deep brain white matter,two MRI features,"yin-yang sign"and"sandwich sign",were proposed.Conclusion The"yin-yang sign"and"sandwich sign"can enhance the understanding and diagnosis of neonatal subpial hemorrhage by radiologists and clinicians.MRI classification can be used as an imaging indicator to predict the prognosis of such hemorrhage.

Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.

Objective To evaluate the efficacy of Huachansu tablets combined with transarterial chemoembolization(TACE)for treatment of primary hepatocellular carcinoma(HCC)and prognostic influence factors.Methods One hundred and eight patients with HCC were recruited according to the inclusion and exclusion criteria.Patients were randomly divided into treatment group and control group.The treatment group was treated with Huachansu tablets combined with TACE,and the control group was treated with TACE alone,with overall survival time(OS)and progression-free survival time(PFS)as the evaluation indexes.The COX regression analysis was used to evaluate the survival and prognostic effects and their influence factors in both groups.Results A total of 108 HCC patients were enrolled.The OS was 13.5 months in treatment group and 9.2 months in control group;the PFS was 6.8 months in treatment group and 5.3 months in control group,and the differences were significant statistically(all P<0.05).Multivariate COX regression analysis showed that Child-Pugh grade and cirrhosis were the independent risk factors for PFS in HCC patients.Child-Pugh grade were the independent risk factors for OS in HCC patients.ALBI is a protective factor for OS in HCC patients.Conclusions The treatment of HCC by Huachansu tablets combined with TACE can delay the progression of HCC and prolong PFS and OS of the patients with HCC.Child-Pugh grade,cirrhosis status,and ALBI were important factors affecting the prognosis of the patients with HCC.

N6-methyladenosine(m6A)denotes the addition of a methyl group to the sixth nitrogen atom of ade-nosine,a common occurrence in eukaryotic RNA.The m6A modifications govern RNA splicing,translocation,stability,and translation into proteins.The RNA methyltransferases,like methyltransferase-like protein 3(METTL3),METTL14,and Wilms'tumor 1-associated protein(WTAP),are responsible for these modifications,while the removal process in-volves demethylases,specifically fat mass and obesity-associated protein(FTO)and ALKB homolog 5(ALKBH5).Recog-nition of these modifications is facilitated by m6A-binding proteins,such as YTH family proteins and insulin-like growth factor 2 mRNA-binding proteins(IGF2BPs).The m6A modification regulators are involved in the onset and progression of non-small-cell lung cancer through multiple mechanisms.This review concentrates on the biological functions and molecu-lar mechanisms of m6A modification-related regulatory factors in the malignant progression of non-small-cell lung cancer.

Objective:To explore the medication law of gilles de la Tourette syndrome (TS) in ancient TCM books through data mining.Methods:TS related disease information was searched by searching Chinese Medicine Collection Database 4.0 and Chinese Medical Classics 5.0 about liver wind, convulsion, infantile convulsion, slow infantile convulsion, Chi Zong, Jin Ti Rou Yu, chronic spleen wind. Excel 2022 software was used to input the main symptoms, etiology and pathogenesis, treatment methods and prescriptions of each disease, and the frequency, property and taste, meridian tropism and efficacy of medication were analyzed. Gephi 0.9.2 software was used to analyze the complex network of Chinese materia medica data to find out the core drugs. SPSS Statistic 25.0 software was used for clustering analysis of high-frequency Chinese materia medica (top 50 in frequency ). SPSS Modeler 14.2 software was used to analyze the association rules of high-frequency Chinese materia medica based on Apriori algorithm. Results:Totally 692 ancient prescriptions were included, involving 436 kinds of Chinese materia medica. The top five in terms of frequency were: Scorpio, Cinnabaris, Moschus, Typhonii Rhizoma, Gastrodiae Rhizoma appeared the most frequently. The main property was cold, the main taste was pungent, and mainly into the liver, spleen, and heart meridians; the core drugs were Bombyx Batryticatus, Pinelliae Rhizoma, and Glycyrrhizae Radix et Rhizoma. Clustering analysis could be divided into 8 categories. Correlation analysis showed that Scorpio→Bombyx mori Linnaeus and Cinnabaris had the highest support, while Cinnabaris→Bovis Calculus→Moschus→Scorpio had the highest confidence.Conclusions:Ancient doctors believed that the disease location of TS-related diseases are mainly liver, heart, spleen and kidney, and the pathogenic factors were mainly wind, fire, phlegm, blood stasis and deficiency. The insect snakes used in prescription drugs are used to search for wind and eliminate pathogenic factors, the epigraphy is used to calm the nerves and calm the wind, and the herbs are used to soothe the wind, clear heat, calm the liver and dispel phlegm.