Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective:To analyze the psychological stress of infertile patients after COVID-19 epidemic and its related factors by Chinese version of the perceived stress scale (CPSS).Method:The basic information, reproductive history, impact of the epidemic, psychological status of patients undergoing assisted reproductive technology at the General Hospital of Northern Theater Command from March 29, 2021 to April 29, 2021 were collected by questionnaire. According to CPSS, group comparison and correlation analysis were used to explore factors related to patients' psychological stress.Results:A total of 251 valid questionnaires were received. The average CPSS score of the patients was 22.43±7.07. During the epidemic, about 33.86% (85/251) of the infertility patients postponed the fertilization plan; there were significant differences in the psychological stress among patients of different genders, occupations, and postponed fertilization plans at different stages of fertilization ( P=0.001, P=0.005, P=0.002). There was no significant difference in CPSS score between infertile patients who delayed treatment or not ( P>0.05). Correlation analysis showed that the perceived stress of patients was negatively correlated with their age, income, and delay duration ( r=-0.192, P=0.002; r=-0.323, P=0.001; r=-0.282, P=0.009). Among all patients who delayed treatment, patients with higher CPSS score would restart treatment sooner; most of the infertile patients knew little about the vaccine. Conclusion:The COVID-19 epidemic has caused a certain impact on the psychological pressure of infertile couples who accepted treatment in our hospital. The psychological care for infertile patients is particularly important. In the future, in order to dispel the doubts of infertile patients about the vaccine, we should pay attention to the correct scientific promotion of the COVID-19 vaccine during the treatment process.

Objective:To analyze the psychological stress of infertile patients after COVID-19 epidemic and its related factors by Chinese version of the perceived stress scale (CPSS).Method:The basic information, reproductive history, impact of the epidemic, psychological status of patients undergoing assisted reproductive technology at the General Hospital of Northern Theater Command from March 29, 2021 to April 29, 2021 were collected by questionnaire. According to CPSS, group comparison and correlation analysis were used to explore factors related to patients' psychological stress.Results:A total of 251 valid questionnaires were received. The average CPSS score of the patients was 22.43±7.07. During the epidemic, about 33.86% (85/251) of the infertility patients postponed the fertilization plan; there were significant differences in the psychological stress among patients of different genders, occupations, and postponed fertilization plans at different stages of fertilization ( P=0.001, P=0.005, P=0.002). There was no significant difference in CPSS score between infertile patients who delayed treatment or not ( P>0.05). Correlation analysis showed that the perceived stress of patients was negatively correlated with their age, income, and delay duration ( r=-0.192, P=0.002; r=-0.323, P=0.001; r=-0.282, P=0.009). Among all patients who delayed treatment, patients with higher CPSS score would restart treatment sooner; most of the infertile patients knew little about the vaccine. Conclusion:The COVID-19 epidemic has caused a certain impact on the psychological pressure of infertile couples who accepted treatment in our hospital. The psychological care for infertile patients is particularly important. In the future, in order to dispel the doubts of infertile patients about the vaccine, we should pay attention to the correct scientific promotion of the COVID-19 vaccine during the treatment process.

Objective:To analyze the characteristics of complex severe symptomatic carotid stenosis, and to summarize the surgical techniques of endovascular stent treatment.Methods:A total of 36 cases of complex carotid stenosis with stenosis greater than 90% from January 2013 to July 2019 were selected, among which 22 patients with subtotal occlusion with stenosis of 95%~99%, 6 patients with contralateral internal carotid artery occlusion, 4 elderly patients with severe twisted aortic arch and carotid artery, and 4 patients with angular distortions of internal carotid artery that were too close at the stenosis distal end. The characteristics of pathological change and the state of cerebral blood flow compensation under digital subtraction angiography (DSA) of these 4 above-mentioned complex types were analyzed. The techniques of endovascular surgery were summarized, focusing on the individualized surgical plan, perioperative management, patients′ tolerance, revascularization structure change, complication control, and the occurrence of restenosis and other related ischemic cerebrovascular events during the 1-year postoperative follow-up.Results:Among the cases treated with subtotal occlusion by carotid artery stenting (CAS) with proximal blood flow protection device, 1 case failed and 2 cases received a secondary stent implantation. The surgeries on the patients with contralateral occlusion were performed with preoperative sedation, appropriate elevation of blood pressure, and shortening the vessel occlusion time. The patients with insufficient support due to path distortion received coaxial multi guide wire with multiple switching long sheath assisting technology. Among the patients with angular distortions at stenosis distal end, the stent was successfully released at the proximal in 2 cases, the stent was released across the angle without affecting the blood flow in 1 case, and in 1 case the stent releasing across the angle was given up during the surgery due to the distal artery kinking. A total of 34 surgeries were success (94.4%), with the stenosis severity reducing from (93.1±3.2)% (before) to (21.5±4.8)% (after). In 3 cases, the patients had transient aphasia and contralateral limb hemiplegia and ischemic symptoms during the operation. There was no cerebral hemorrhage, cerebral infarction, or no in-stent restenosis during the one-year follow-up.Conclusion:CAS treatment in complex severe carotid stenosis requires individualized surgical procedures and perioperative management. Appropriate surgical plan can ensure the success and safety of the surgery.

Objective:To analyze the characteristics of complex severe symptomatic carotid stenosis, and to summarize the surgical techniques of endovascular stent treatment.Methods:A total of 36 cases of complex carotid stenosis with stenosis greater than 90% from January 2013 to July 2019 were selected, among which 22 patients with subtotal occlusion with stenosis of 95%~99%, 6 patients with contralateral internal carotid artery occlusion, 4 elderly patients with severe twisted aortic arch and carotid artery, and 4 patients with angular distortions of internal carotid artery that were too close at the stenosis distal end. The characteristics of pathological change and the state of cerebral blood flow compensation under digital subtraction angiography (DSA) of these 4 above-mentioned complex types were analyzed. The techniques of endovascular surgery were summarized, focusing on the individualized surgical plan, perioperative management, patients′ tolerance, revascularization structure change, complication control, and the occurrence of restenosis and other related ischemic cerebrovascular events during the 1-year postoperative follow-up.Results:Among the cases treated with subtotal occlusion by carotid artery stenting (CAS) with proximal blood flow protection device, 1 case failed and 2 cases received a secondary stent implantation. The surgeries on the patients with contralateral occlusion were performed with preoperative sedation, appropriate elevation of blood pressure, and shortening the vessel occlusion time. The patients with insufficient support due to path distortion received coaxial multi guide wire with multiple switching long sheath assisting technology. Among the patients with angular distortions at stenosis distal end, the stent was successfully released at the proximal in 2 cases, the stent was released across the angle without affecting the blood flow in 1 case, and in 1 case the stent releasing across the angle was given up during the surgery due to the distal artery kinking. A total of 34 surgeries were success (94.4%), with the stenosis severity reducing from (93.1±3.2)% (before) to (21.5±4.8)% (after). In 3 cases, the patients had transient aphasia and contralateral limb hemiplegia and ischemic symptoms during the operation. There was no cerebral hemorrhage, cerebral infarction, or no in-stent restenosis during the one-year follow-up.Conclusion:CAS treatment in complex severe carotid stenosis requires individualized surgical procedures and perioperative management. Appropriate surgical plan can ensure the success and safety of the surgery.

The establishment of a scientific salary system is a key measure to improve the incentive and re-straint mechanisms, adjust and optimize the relations of the production, release the reform “bonus”, and is also an important health care reform today. In order to establish a scientific salary system of medical personnel adapting to the health industry characteristics, the paper makes an investigation on the salary level in the years of 2010—2012 in Shanghai, and analyzes the main problems of the present performance pay policy. On this basis, starting from the point of the health industry characteristics, the paper builds the salary system of medical personnel containing the comprehensive budget management, theoretical workload for approval, authorized personnel, performance appraisal and distribution, structural proportion within the industry, fund distribution management through the establishment of the salary level’s average wage and social linkage mechanism, and builds a theoretical framework on salary system of medical personnel in Shanghai.