ObjectiveTo investigate the change in the activity of hepatitis B virus （HBV）-specific CD8⁺ T cells after pegylated interferon-α-2b （PEG-IFN-α-2b） therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b （180 μg/week， subcutaneous injection） antiviral therapy. The study endpoint was HBsAg clearance （course of treatment<48 weeks） or 48 weeks （course of treatment≥48 weeks）. Peripheral blood mononuclear cells were isolated at baseline and study endpoint， and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ. A total of 17 HLA-A^*02-restricted patients were selected， and CD8⁺ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8⁺ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells， and the levels of HBV DNA， cytotoxic molecules， and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands， and the cytotoxicity of HBV-specific CD8⁺ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% （16/53）. There were no significant differences in peripheral blood T cell counts （CD3⁺， CD4⁺， and CD8⁺ T cells） between baseline and study endpoint （P>0.05）. At study endpoint， there was a significant increase in the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ （U=177.50， t=11.90， U=186.50， all P<0.001）， and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8⁺ T cells than those without HBsAg clearance （U=120.50， t=2.73， U=121.50， all P<0.01）. In the direct- and indirect-contact co-culture systems at study endpoint， HBV-specific CD8⁺ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells （all P<0.001） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （all P<0.05）； in the direct-contact co-culture system， HBV-specific CD8⁺ T cells induced significant increases in the mortality rate of HepG2.2.15 cells （13.62%±3.27% vs 11.39%±2.40%， t=2.27， P=0.030） and the secretion of perforin and granzyme B （t=72.50， U=52.50， both P<0.05）. In the direct- and indirect-contact co-culture systems， compared with HBV-specific CD8⁺ T cells from the patients without HBsAg clearance， the HBV-specific CD8⁺ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA （P<0.05） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （P<0.05）. ConclusionPEG-IFN-‍α‍-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection， and the activity of HBV-specific CD8⁺ T cells is significantly enhanced， which is closely associated with HBsAg clearance.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Myostatin (Mstn) is known as growth/differentiation factor-8 (GDF-8). Knockout or knockdown of Mstn gene promotes muscle development and reduces fat content. Here we prepared Mstn knockdown mice by RNA interference, then the morphology of the skeletal muscle, the content of triglyceride (TG), the content and composition of fatty acids in the skeletal muscle were detected. The expression of Mstn reduced in muscle of Mstn knockdown mice compared to the controls. The cross sectional areas of the skeletal muscle myofibers were significantly larger while the content of TG was less than that of the controls, and the ratios of n-3/n-6 and unsat/sat in the knockdown mice increased significantly. Subsequently, we detected the expression of genes associated with fatty acid metabolism. The expression of the genes associated with lipolysis and fatty acid transportation were up-regulated, while the genes associated with fatty acid synthesis were down-regulated. Of these genes, the up-regulation of a gene associated with β oxidation, Cpt1b, was up-regulated remarkably. We further detected the enzyme activity of CPT1 in skeletal muscle and obtained the same results with gene expression. Moreover, chromatin immunoprecipitation assay was performed and we found that SMAD3, a transcription factor downstream of Mstn, directly binds to the promoter of Cpt1b gene. These results showed that knockdown of Mstn up-regulated the expression of Cpt1b through the binding of SMAD3 to the promoter of Cpt1b, then promoted the β oxidation metabolism of intramuscular fatty acids.
Animals ; Carnitine O-Palmitoyltransferase/metabolism* ; Fatty Acids ; Lipid Metabolism ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism* ; Myostatin/metabolism* ; Oxidation-Reduction ; Up-Regulation

Objective:To investigate the role of signal lymphocyte activating molecule family member 5 (SLAMF5) in liver transplantation rejection in SD rats.Methods:Forty-five male SD rats without special pathogens, weight 260-300 g, aged 10-12 weeks were included. Among them, forty male SD rats (20 donors and 20 recipients respectively) were established with reference to the " two cuff" method. 15 liver transplantation model rats were randomly divided into 1 week (LT-1W) group, 2 weeks (LT-2W) group and 3 weeks (LT-3W) group, with 5 rats in each group, and 5 normal rats were taken as the normal control group. The expressions of SLAMF5, CD4 and CD8 were detected by polymerase chain reaction (PCR), Western blot and immunohistochemistry. The correlations between SLAMF5 expression in the lymphocyte infiltration area and the rejection activity index was analyzed.Results:The levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin were significantly higher in LT-1W group, LT-2W group and LT-3W group than those in the normal control group (all P<0.05). PCR results showed that the relative expression of SLAMF5 mRNA were (5.44±1.11), (4.69±1.12), (2.18±0.68) respectively, which were increased in LT-1W group, LT-2W group and LT-3W group than those in normal control group (1.01±0.23), and the differences were statistically significant (all P<0.05). Immunohistochemical staining showed that SLAMF5 and CD4, CD8 positive T cells were mainly distributed in the portal area, hepatic lobule area and around the proliferative bile duct, and there was a certain overlap. Correlation analysis showed that there was a positive correlation between the expression of SLAMF5 in the lymphocyte infiltration area and the rejection activity index ( r=0.519, P=0.048). Conclusion:The expression of SLAMF5 is increased after liver transplantation in SD rats, and there is a correlation between SLAMF5 expression and liver transplantation rejection in rats.

Objective:To analyze the department distribution and workload of China′s physician team, and promote the establishment of a well-structured physician team.Methods:Based on the relevant data of Health Statistics Yearbook, the distribution of departments and workload of diagnosis and treatment of physicians during the 13th Five-Year Plan period were analyzed. Results:During the " 13th Five-Year Plan" period, the number of physicians increased by an average of 6.11% per year, of which the average annual growth rate in medical cosmetology and rehabilitation medicine exceeded 10%, and the number of infectious disease physicians declined. The daily visits per physician decreased by an average of 4.67% per year, and the daily inpatients per physician decreased by 4.14%. Among them, the daily visits per physician in infectious diseases, preventive health care, oncology had increased overall, and the daily inpatients per physician in medical cosmetology, dental had decreased the most.Conclusions:It is suggested to optimize the professional structure and department distribution in accordance with the principle of " matching medical service needs with a certain workload" , and promote the establishment of a physician team with reasonable distribution to better meet medical service needs.

Objective:To investigate and analyze the loss of personnel in health institutions, and put forward the suggestions.Methods:The staff turnover in various health institutions was analyzed based on a continuous monitoring data from 2012 to 2019.Results:In 2012-2019, the turnover rate of health institutions had generally remained at about 1.5%-2.0%. In 2015-2019, the natural attrition rate was 0.44%-0.70% and the job-changing rate was 0.06%-0.12%. Among all kinds of institutions, the loss of staff in township health centers and Centers for Disease Control and Prevention were the most serious.Conclusions:Some new characteristics have emerged in the flow of health personnel, which have gradually adapted to the demand for health services, and the role of market mechanisms in the allocation of health human resources has gradually emerged.For the institutions with serious attrition, it is suggested to strengthen policy integration, guide the rational flow of health personnel.

The authors systematically reviewed the progress of health human resources development, personnel management system and conceptual changes from 2011 to 2020 in China, and analyzed the status quo in this regard. The past 10 years have witnessed rapid progress of health human resources, namely better personnel management system and constant innovation in human development concepts. As required by the strategy of empowering the country with talents in the new era, as well as the overall promotion for the Healthy China initiative and the high-quality development of the health industry, higher requirements have been put forward for the quantity and quality, structural distribution and management innovation of health human resources. Therefore it is necessary to further expand the coverage of talents work and innovate talents policy, thus keeping the upgrade of the capability and competence of health talents.

Health manpower is key to the functioning of the health system. There exists a general need to strengthen health human resources in countries at large as they achieve universal health coverage. Through the systematic collection and sorting out of the declarations, initiatives, guidelines in the world and topics at the World Health Assemblies on health manpower-related issues since 2000, this paper summarized and analyzed the key issues and trends on health manpower planning, education and training, international migration, and compensation management, in order to provide reference for China′s health manpower management and practice.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.