Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To analyze the risk factors for complications of the retromandibular approach in patients with parotid gland posterior and lower pole tumors.Methods:A retrospective analysis was conducted on the clinical data of 140 patients with parotid posterior lower pole tumors admitted to the Xingtai Third Hospital from October 2019 to October 2021. They were divided into two groups based on whether complications occurred: the occurrence group and the non occurrence group. General data of the two groups of patients were collected, including age, gender, course of disease, previous surgical history, number of tumors, tumor length, resection range, facial nerve dissociation, tumor site resection frequency, and fascia preservation; Single factor and logistic multivariate analysis were conducted to determine the risk factors for complications of the posterior retromandibular approach in patients with parotid gland posterior and lower pole tumors.Results:A total of 140 patients with parotid gland posterior lower pole tumors underwent retromandibular approach treatment, with complications occurring in 38 cases (27.14%), including 7 cases of temporary facial paralysis, 10 cases of facial depression, 11 cases of Frey syndrome, 2 cases of fistula, and 8 cases of sensory abnormalities of the greater auricular nerve. Through logistic multivariate analysis, it was found that the number of tumors ≥ 2 ( OR=2.856), the resection range (total resection) ( OR=2.477), the number of surgeries ≥3 ( OR=5.637), facial nerve dissociation ( OR=3.526), and lack of fascia preservation ( OR=2.551) were all risk factors for postoperative complications in patients with parotid posterior pole tumors (all P<0.05). Conclusions:In clinical practice, relevant prevention and treatment measures should be formulated for these high-risk factors to reduce the incidence of postoperative complications.

Objective: Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a “morbid condition” which also needs medical attention. Methods: The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire. Results: For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC. Conclusion Our present findings supported the suggestion of subthreshold ADHD as “morbid condition,” which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

Objective:To explore the impact of weekend hospitalization on total hospitalization expenses for elderly patients with hip fracture under the geriatric orthopedic co-management.Methods:A retrospective analysis was conducted to analyze the clinical data of elderly patients with hip fracture who had been hospitalized for surgical treatment at Beijing Jishuitan Hospital from May 2015 to December 2020. They were divided into 2 groups based on their admission date. Group A was admitted from Monday to Thursday while Group B from Friday to Sunday. The general demographic data, diagnostic information, comorbidities, hospitalization expenses of the patients were collected. The differences in total hospitalization expenses, hospitalization time, rate of surgery within 48 hours and rate of hospital mortality between the 2 groups were analyzed by rank sum test, chi square test, correlation analysis, and multiple linear regression.Results:A total of 6,075 patients with hip fracture were included in this study, including 1,675 males and 4,400 females with a median age of 80 (74, 85) years. There were 3,935 ones in group A and 2,140 ones in group B. The total hospitalization expenses for group A was 58,160.52 (49,215.45, 72,748.94) yuan, insignificantly lower than those for Group B [58,412.90 (49,163.58, 72,712.61) yuan] ( P>0.05). The rate of surgery within 48 hours for group A was 75.8% (2,984/3,935), significantly higher than that for group B [49.3% (1,054/2,140)]. The hospitalization time for group A was 5 (4, 7) days, significantly less than that for group B [5 (4, 7) days] ( P<0.05). There was no significant difference in the rate of hospital mortality between the 2 groups ( P>0.05). Multiple linear regression analysis showed that total hospitalization expenses were significantly higher for patients admitted on weekends, hospitalization time was positively correlated with total hospitalization expenses, and total hospitalization expenses were significantly lower for the patients undergoing surgery within 48 hours ( P<0.05). Conclusion:Admission on weekends can increase total hospitalization expenses, prolong hospitalization time, and reduce rate of surgery within 48 hours for elderly patients with hip fracture.

Nervous systems must not only generate specific adaptive behaviors, such as reproduction, aggression, feeding, and sleep, but also select a single behavior for execution at any given time, depending on both internal states and external environmental conditions. Despite their tremendous biological importance, the neural mechanisms of action selection remain poorly understood. In the past decade, studies in the model animal Drosophila melanogaster have demonstrated valuable neural mechanisms underlying action selection of innate behaviors. In this review, we summarize circuit mechanisms with a particular focus on a small number of sexually dimorphic neurons in controlling action selection among sex, fight, feeding, and sleep behaviors in both sexes of flies. We also discuss potentially conserved circuit configurations and neuromodulation of action selection in both the fly and mouse models, aiming to provide insights into action selection and the sexually dimorphic prioritization of innate behaviors.
Animals ; Mice ; Male ; Female ; Drosophila melanogaster/physiology* ; Sexual Behavior, Animal/physiology* ; Instinct ; Neurons/physiology* ; Aggression/physiology*

Objective To understand the situation and the influencing factors of life quality in diabetic patients in Shanghai， and to develop effective intervention measures. Methods A total of 212 diabetic patients in Baoshan District， Shanghai were selected as the research objects. Diabetes specific quality of life scale （DSQL） was used to investigate the basic situation and quality of life of patients. Combined with biochemical detection indexes and questionnaire survey， data were analyzed by variance analysis and multiple linear stepwise regression analysis. Blood glucose level was assessed according to the 1999 WHO diagnostic criteria for type 2 diabetes. Results The overall quality of life score in the patients was 4.31±7.82， which was higher than the domestic norm. The best quality of life was in the dimension of physiological function with the score of 1.84±6.00， which was lower than the domestic norm. The next was the dimension of social relationship， and the worst was the dimension of treatment. The single factor analysis and multivariate analysis identified the following influence factors of quality of life in the patients： family history， educational level， exercise habit， blood glucose control and diet control. There was a negative correlation with educational level and blood glucose control， and a positive correlation with diet control. Conclusion The quality of life in the middle-aged diabetic patients was affected by the education level， blood glucose control and diet control. We suggest to strengthen the community management， health education， and improve the living habits.

Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.

Objective:To investigate the predictive value of tumor necrosis factor receptor-associated factor 6 (TRAF6) expression in the efficacy of radiotherapy for patients with esophageal squamous cell carcinoma (ESCC).Methods:A total of 278 patients with ESCC received radical radiotherapy in Yixing Cancer Hospital of Jiangsu Province from February 2012 to March 2015 were included. The expression of TRAF6 in esophageal cancer tissue was detected by immunohistochemistry. The correlations between the expression of TRAF6 and clinicopathological features, short-term efficacy of radiotherapy and survival of ESCC patients were investigated.Results:All the patients were divided into positive expression group ( n=194) and negative expression group ( n=84). TRAF6 expression was significantly associated with TNM stage and lymph node metastasis in ESCC patients ( χ2=13.670, P<0.001; χ2=45.497, P<0.001). The total effective rate of radiotherapy in the TRAF6 positive expression group was 62.9% (122/194), which was significantly lower than that of TRAF6 negative expression group (92.9%, 78/84), and the difference was statistically significant ( χ2=26.085, P<0.001). The median survival time of TRAF positive expression group was 51 months, while that of TRAF negative expression group was not reached, and the difference of survival curve between the two groups was statistically significant ( χ2=7.952, P=0.005). Further analysis showed that higher TNM stage, lymph node metastasis and positive expression of TRAF6 increased the risk of death in ESCC patients ( HR=1.96, 95% CI: 1.39-2.76; HR=1.72, 95% CI: 1.29-2.29; HR=2.31, 95% CI: 1.57-3.39). Conclusion:Patients with TRAF6 positive expression of ESCC have low radiotherapy sensitivity. TRAF6 may be a new target for diagnosis and treatment of ESCC patients, which provides a new idea for the diagnosis, treatment and prognosis of ESCC.

Angiogenesis is the core step of wound repair, and vascular endothelial progenitor cells (EPC) play an extremely important role during wound repair. Recent studies have shown that vascular EPC-derived exosomes (EPC-Exo) can protect vessels, promote the proliferation and migration of vascular endothelial cells, and have anti-inflammatory, anti-oxidant and anti-apoptotic effects on vascular endothelial cells. This article reviews the mechanism of vascular EPC-Exo in angiogenesis and its potential applications in wound repair in recent years.