Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

Objective To study the dynamic regulatory role of early growth response 4(EGR4)in mouse neurodevelopment.Methods Data on single-cell chromatin accessibility(single-cell assay for transposase-accessible chromatin by sequencing,scATAC-seq)and transcriptome(single-cell RNA sequencing,scRNA-seq)from seven key stages spanning from the embryonic period to adulthood was collected and analyzed.The transcription factor binding site network was inferred,a quantitative analysis from a temporal perspective was conducted,its functional modules were parsed,and the results were visualized.Results egr4 was significantly highly expressed from the late embryonic stage to adulthood,and specifically activated during the maturation of inhibitory neurons[parvalbumin(PV)and somatostatin(SST)subtypes].Moreover,its transcription was not directly regulated by changes in chromatin accessibility.Temporal network analysis indicated that EGR4 became a regulatory hub in the late embryonic stage and drove neuron differentiation and subtype specification.Functional enrichment analysis showed that EGR4 regulated the"cell differentiation"pathway through dynamic interacting factors,and there were subtype-specific interaction modules in PV/SST neurons respectively.Conclusion EGR4 can participate in the late-stage maturation of cortical neurons through a stage-specific regulatory network.This study provides a new perspective on mechanisms underlying the temporal logic of neural development.

Objectives:To evaluate the tricuspid valve(TV)geometric remodeling in patients with idiopathic pulmonary arterial hypertension(IPAH)by three-dimensional transthoracic echocardiography. Methods:Two-dimensional and three-dimensional transthoracic echocardiography were performed in 30 IPAH patients and 15 healthy controls,and the geometry parameters of TV were obtained by four-dimensional auto tricuspid valve quantitative(4D Auto-TVQ)in the right ventricular-focused apical view.Pulmonary arterial hypertension was determined by right heart catheterization within 48 hours of echocardiography. Results:The 4-chamber diameter,tricuspid annular(TA)perimeter,TA area,maximal tenting height,coaptation point height and tenting volume were larger in IPAH patients than those in healthy controls(all P＜0.05),2-chamber diameter was similar between two groups.In IPAH group,maximal tenting height and coaptation point height were moderately correlated with right ventricular end-diastolic volume(r=0.710,r=0.515,both P＜0.05),while TA perimeter,4-chamber diameter and TA area were moderately correlated with right atrial end-systolic volume(r=0.712,r=0.558,r=0.545,all P＜0.05). Conclusions:IPAH patients have larger maximal tenting height,coaptation point height and tenting volume,TA enlargement is mainly visible in 4-chamber diameter.TV tenting height is associated with right ventricular volume,but TA size is associated with right atrial volume in IPAH patients.

Herpes simplex virus encephalitis is the most common type of infectious encephalitis with a poor progno-sis,and some patients may develop recurrent or secondary autoimmune encephalitis.This article reports a case of anti-Ri antibody encephalitis secondary to herpes simplex virus encephalitis,in order to improve the understanding of this disease among clinicians and avoid misdiagnosis and missed diagnosis.Antibodies associated with paraneoplastic syndrome should be screened for patients with a previous history of tumor,and early diagnosis and immunotherapy play an important role in improving the prognosis of patients.

Objective:To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer.Methods:393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests.Results:367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant ( χ2 = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant ( χ2 = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant ( χ2 = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion:In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

Objective:To determine the clinical, pathological and imaging phenotypes of pediatric patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy to explore its diagnostic strategies.Methods:The clinical features of 10 pediatric patients with anti-HMGCR myopathy in the Department of Neurology, Peking University First Hospital from July 2014 to July 2021 were collected. Muscle biopsies were performed in all patients, with histological, enzymatic histochemical and immunohistochemical staining.Results:The male to female ratio was 6∶4, the age of onset was 3-16 (8.3±3.7) years, 2 cases had subacute onset, and 8 cases experienced chronic progressive onset. All patients presented with neck and proximal muscular weakness of all limbs. Skin rash was observed in 2 cases. Serum creatine kinase was 998-27 981 U/L. The electromyography results were available from 6 cases, who experienced myogenic changes. The muscle magnetic resonance imaging was performed in 5 cases and revealed muscle edema predominantly in posterior compartment of thigh, with mild fatty infiltrate in 2 cases. An initial diagnosis was limb-girdle muscular dystrophy in 7 cases, but with subsequently negative genetic testing. Muscle biopsies revealed scattered necrotic fibers and regenerating fibers, complement deposition in sarcolemma basement-membrane areas of non-necrotic fibers and a few of lymphocyte infiltrate in all specimens. Moreover, a high frequency of major histocompatibility complex Ⅰ expression in muscle fibers was observed in 9 cases, proliferation of connective tissue of endomysium in 8 cases, muscle fiber hypertrophy in 4 cases and vacuoles in 2 cases.Conclusions:Pediatric anti-HMGCR myopathy is frequently misdiagnosed as muscular dystrophy. Systematic consideration of anti-HMGCR myopathy and testing for myositis specific antibody in children with genetically unconfirmed muscular dystrophy may help the differential diagnosis.