Autophagy is the main degradation and recycling pathway for abnormal aggregates and damaged organelles in cells,and it maintains the normal metabolic balance and material renewal in cells.Autophagy has neuroprotective effects and can affect the functional state of the nervous system by regulating homeostasis,development,apoptosis,and other physiological processes of neurons and glial cells.In recent years,a large number of studies have shown that nervous system diseases are closely related to abnormal autophagy,and inhibition or overactivation of autophagy affects the occurrence and development of depression,neurodegenerative diseases,and schizophrenia.Understanding the mechanisms of autophagy in nervous system diseases is of great significance for their prevention and treatment.This paper mainly reviews the current progress of autophagy research and the above diseases of the nervous system,providing a reference for further research into these diseases.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

There are some issues in the process of patient treatment in the medical field, such as knowledge inequality, difficulties in doctor-patient trust and interdisciplinary cooperation, disciplinary barriers, excessive diagnosis and treatment, and structural imbalance of medical resources. In response to these issues, combined with the advantages of conceptual integration, professional integration, and resource integration of medical social work, this paper proposed a practical path for integrating medical social work services in the medical field. The main paths include micro path that systematization, comprehensiveness, and personalization of patient’s diagnosis and treatment process, the integration of intermediary path that integration of disciplinary and professional perspectives, concepts, and practices, and macro path that collaboration and coordination among society, community, and healthcare systems.

Objective     To analyze the echocardiographic characteristics of above grade 3+ mitral regurgitation (MR) patients by 3D transesophageal echocardiography (3D-TEE) in transcatheter edge-to-edge repair (TEER) and compare the intervention rate of TEER treatment in patients with different risk stratification. Methods     We retrospectively analyzed the clinical data of 91 patients with above grade 3+ MR in Anzhen Hospital between June 2021 and April 2022. There were 45 males and 46 females aged 66.5±15.9 years. According to pathogenesis, the patients were divided into different anatomical groups and risk stratification groups. There were 34 patients in a simple degenerative group (simple DMR group), 28 patietns in a complex disease group (Complex group), 14 patients in a simple ventricular  functional reflux group (simple VFMR group), 9 patients in a simple atrial functional reflux group (simple AFMR group), and 6 patients in a mixed functional reflux group (mixed FMR group). All patients were examined with a unified standard of transthoracic echocardiography (TTE) and 3D-TEE to compare the characteristic three-dimensional structural changes of the mitral valve in each group. According to the three partition strategy of preoperative anatomical evaluation of TEER, the risk stratification was conducted for the enrolled patients, which was divided into three regions from light to heavy: green area, yellow area, and red area. TEER treatment intervention rate of patients with different risk stratification was calculated. Results     Ant leaf angle and post leaf angle were negative in the simple DMR and Complex groups, and non-planar angle, prolapse height and prolapse volume were higher than those of the other groups (P=0.000). Ant leaf angle and post leaf angle were positive in the VFMR group and the mixed FMR group. Anterior and posterior (AP) diameter of valve ring (P=0.036), tenting height and tenting volume were higher than those of other groups (P=0.000).  AP diameter, tenting height and tenting volume were changed mildly in patients with simple AFMR. MR patients in red and yellow zone achieved a 28.1% TEER intervention rate. Conclusion     Standardized TTE and TEE examinations are crucial for the qualitative and quantitative diagnosis of MR in the echo core-lab. 3D-TEE mitral valve parameter can help determine the exact pathogenesis of MR and to improve the interventional rate of challenging MR patients.

Aortic stenosis (AS) is the most common primary valve lesion requiring surgery or transcatheter intervention in modern era. Its prevalence is rising rapidly as a consequence of the aging population. Transcatheter aortic valve replacement (TAVR) as a therapy option for older high-risk symptomatic severe AS patients has emerged and is currently extending its indications towards surgery intermediate- and low-risk subjects. Considering the common characteristics of frailty and high comorbidity among AS patients, cardiac rehabilitation (CR) has been proven to improve not only survival but also quality of life in previous reports. CR as a classⅠ recommendation in guidelines for the prevention and treatment of cardiovascular disease has been widely used in clinical practice. The purpose of this article is to sort out the current CR programs for TAVR patients in global medical management, and explore the CR optimization program fit for China medical model in post COVID-19 pandemic era.

Objective:To summarize the clinical characteristics and laboratory diagnostic methods of infant botulism caused by Clostridium botulinum type B. Methods:Clinical data of 3 infants with type B botulism who were admitted to Children′s Hospital Affiliated to Capital Institute of Pediatrics from May to November 2018 were retrospectively analyzed. Botulinum toxin was detected in fecal samples or fecal enrichment solution of the patients, and Clostridium botulinum was cultured and isolated from fecal samples. Results:The age of onset of the patients (two boys and one girl) was 3, 3 and 8 months old, respectively. Two cases had the onset in May and one case had the onset in November. There were two cases with mixed feeding and one case with breast feeding. One case′s family members engaged in meat processing. All of them were previously healthy. All the children presented with acute flaccid paralysis, cranial nerve involvement and difficult defecation. Two cases had secondary urinary tract infection. Electromyograms of two cases showed that action potential amplitude of the motor nerve were lower than those of their peers. After treatments including intravenous human immunoglobulin, respiratory tract management, urethral catheterization, nasal feeding, etc., three cases recovered completely 2 to 4 months later. Type B botulinum toxin was detected in the fecal diluent of one patient, and the TPGYT enrichment solution and cooked meet medium of the feces of 3 patients, respectively. Clostridium botulinum B was identified from the feces of 3 infants after culture, isolation and purification. Conclusions:Combined with typical clinical manifestations including acute flaccid paralysis, cranial nerve involvement symptoms and difficult defecation examination, infant botulism can be clinically diagnosed. The detection of fecal botulinum toxin and the culture and isolation of Clostridium botulinum are helpful for the diagnosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.
Adoptive Transfer ; methods ; Carcinoma, Hepatocellular ; immunology ; therapy ; Humans ; Immunotherapy, Adoptive ; methods ; Liver Neoplasms ; immunology ; therapy ; Lymphocytes, Tumor-Infiltrating ; cytology ; Randomized Controlled Trials as Topic ; Receptors, Chimeric Antigen ; T-Lymphocytes ; cytology

Objective To establish the quality standards for salt eucommia dispensing granules. Methods The extractives were obtained by alcohol extraction method. HPLC was applied for the determination of pinoresinol diglucoside in dispensing granules. HPLC fingerprints were established by the contrast of Agilent 1260 HPLC, Waters HPLC and various chromatogram column. Results Pinoresinol diglucoside showed a good linear relationship ( Y = 2. 9594X + 3. 2825,R2 =0.9999) at 102.8-2056.0 mg?L-1 with average recovery of 99.85％ (RSD = 0.31％,n = 9). Conclusion The method is easy-operated and accurate,which has a good specificity for the quality control of common salt eucommia dispensing granules.

OBJECTIVE: To investigate the effects of sevelamer carbonate combined with routine treatment on serum inflammatory factors, heme oxygenase-1 (HO-1) and intact parathyroid hormone (iPTH) levels of chronic renal failure (CRF) patients with hyperphosphatemia.METHODS: Totally 60 chronic renal failure patients with hyperphosphatemia in department of renal internal medicine, Tangshan Workers' Hospital during Jan. 2014 to Jan. 2015 were divided into control group and observation group according to random number table, with 30 cases in each group. Control group received routine treatment as reducing blood glucose, lowering blood lipid, lowering blood pressure, reducing phosphorus, protecting kidney. Observation group was additionally given sevelamer carbonate (dose was 0. 8 g, 3 times a day, during meal) on the basis of control group, for 4 weeks. The levels of IL-6, CRP, HO-1, iPTH, Ca and P were compared between 2 groups. The occurrence of ADR was compared between 2 groups. RESULTS: Two cases were withdrewn from the study in each group, finally 28 cases were included in the study in each group. Before treatment, there was no statistical significance in each index between 2 groups (P>0. 05). Compared with before treatment, the serum levels of IL-6, CRP, iPTH and P in 2 groups were decreased significantly after treatment (P<0. 05), while serum level of Ca was increased significantly (P<0. 05); the improvement of above indexes in observation group were more dovious than control group (P<0. 05). There was no statistical significance in the incidence of ADR between 2 groups (P>0. 05). CONCLUSIONS: Sevelamer carbonate combined with routine treatment can effectively reduce the serum levels of IL-6, CRP, HO-1 and iPTH and regulate Ca and P metabolism of CRF patients with hyperphosphatemia with good safety.