Melanoma is a highly malignant immunogenic tumor. Although immunotherapy represented by immune checkpoint inhibitors can markedly improve the survival rate of patients with metastatic melanoma, nearly half of patients are still tolerant or resistant to immunotherapy, with high incidence of immune-related adverse reactions. This review focuses on the key difficulties in tolerance, resistance and immune-related adverse reactions to current melanoma immunotherapy, and summarizes corresponding strategies and research advances. By intervening in the immunosuppressive microenvironment in melanoma, screening precise biomarkers, and optimizing immunotherapy-based combination strategies, the problem of tolerance and resistance to immunotherapy can be solved. Moreover, the combination of traditional immunotherapy and nanotechnology can also greatly reduce the occurrence of immune-related adverse reactions. In the future, more extensive and in-depth research on the tumor immune microenvironment will help to explore the best immunotherapy regimens for melanoma.

Objective To investigate the effect of neonatal overfeeding on the expression of lipid metabolic associated enzymes and molecular mechanisms in the livers of rats. Methods Male Sprague-Dawley rats were randomly assigned to litter sizes of three group ( small litters,SL group) or ten ( normal litters,NL group) on postnatal day 3. Body weight,milk intake,liver and fat pad (epididymal and retroperitonea) weight,and hepatic histological anal-ysis were recorded in week 2 and week 3,respectively. The levels of lipids were detected by the automatic biochemical analyzer. The mRNA expressions of acetyl-CoA carboxylase ( ACC) ,lipoprotein lipase ( LPL) ,liver-type fatty acid-binding protein (L-FABP), carnitine palmitoyltransferase 1(CPT1),microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator activated receptorα(PPARα) in liver were determined by real time PCR;the protein expressions of SREBP-1c and PPARα were determined by Western lot. Results As early as week 2,the body weight of rats in SL group began to elevate (t=-5. 997,P<0. 001) and food intake (t=-3. 462,P=0. 002) compared with the rats in NL group,and persistent to weaning (body weight:t=-17. 019,P<0. 001;food intake:t=-2. 276,P=0. 031). By the time of 3 weeks old,SL rats increased visceral fat pad [ret-roperitonea (t=-7. 643,P<0. 001),epididymal (t=5. 997,P=0. 001)],liver weight (t=-7. 812,P<0. 001),hepatosomatic index (t=-3.829,P=0. 003) and serum triglyceride (TG) level (t=-2. 703,P=0. 022) compared with those of NL rats,as well as the level of hepatic ACC mRNA (t=-3. 751,P=0. 007),LPL (t=-2. 721,P=0. 017) and L-FABP mRNA (t=-2. 521,P=0. 026) . While CPT1 mRNA (t=-1. 531,P=0. 155) and MTP mRNA (t=-1. 741,P=0. 098) levels remained unchanged in both groups. Hepatic SREBP-1c mRNA expression increased in SL rats after 2 to 3 weeks (t=-2. 836,P=0. 016),paralleled with ACC and LPL mRNA expression;while the mRNA and protein expression of PPARα re-mained unchanged (t=-0. 854,P=0. 411). Conclusions Postnatal overfeeding can promote higher liver pad and dyslip-idemia at the time of weaning. The process may be regulated by up-regulated expression of ACC, LPL and L-FABP. SREBP-1c may be participated in the regulation of ACC,a rate-limiting enzyme involved in lipogenesis.

Objective:To investigate mechanism of imatinib mesylate induced apoptosis of primary CD3+T cells.Methods:The CD3+T cells were stimulated by 0-100 nmol/L imatinib for 24 h,cell apoptosis was detected by flow cytometry;Caspase-3,Caspase-8, A20 and NF-κB expression levels were detected by Real-time quantitative PCR and Western blot.Results: IM significantly increased apoptosis of T cell;Caspase-3 and A20 gene expression levels were upregulated and NF-κB expression level was downregulated both in gene and protein levels.Conclusion:IM increased apoptosis of T cell by upregulating A20 expression.

Hunan University of Chinese Medicine has improved the implementation of animal ethics education from the aspects of carrying out elective courses, emphasizing the implementation of pre-class learning, integrating ethics education into experimental teaching, cultivating students' good medical literacy in a subtle way, and further deepening their learning by offering elective courses of animal ethics. The results show that the opening of elective courses and the enforcement of experimental animal ethics education in experimental classes have greatly strengthened the students' experimental animal ethics, which is conducive to the formation of students' medical literacy.

Objective: To develop an instrument for measuring nursing outcomes classification in Chinese cerebral hemorrhage patient and test its reliability and validity. Methods: Based on Nursing Outcomes Classification, the primary item pool was formulated through literature review, semi-structured interviews and group meeting, the items were selected by expert consultation. Totally 186 elderly adults were selected to test the reliability and validity. Results: The final scale consisted of 5 dimensions and 34 items. The content validity index of the total scale was 0.912, the content validity index of each item was 0.833-1.000. Exploratory factor analysis extracted five common factors and the cumulative variance contribution rate was 63.189%; and the correlation coefficient between the total scale and each dimension were 0.760-0.874. The correlation coefficient of Stroke-Specific Quality of Life between total scale and each dimension were 0.789, 0.568-0.659. The Cronbach α was 0.960 for the total scale, the Cronbach α of dimensions were 0.858-0.932. The intraclass correlation coefficient of the scale and each dimension were 0.965, 0.885-0.935. Conclusions Cerebral Hemorrhage Patient Nursing Outcomes Classification Assessment Scale has good reliability and validity, which can be used to evaluate cerebral hemorrhage.

Objective To understand the awareness rate of macrosomia related knowledge and influencing factors among pregnant women in Zhejiang province and provide evidence for the improvement of pre-gestational and prenatal care. Methods A face to face questionnaire survey was conducted among 1 512 pregnant women selected through multistage cluster random sampling from 20 counties(district)in Zhejiang. Macrosomia-related knowbedge awareness and related factors were analyzed. Results A total of 1 494 valid questionnaires were analyzed,the awareness rate was 40.7%for macrosomia diagnostic criteria(95%CI:38.2%-43.2%),55.0%for the cause of macrosomia(95%CI:52.4%-57.6%) and 62.4% for prevention related knowledge(95%CI:59.9%-64.9%) and the awareness rate of both the cause and the prevention related knowledge was 49.0%(95%CI:46.4%-51.6%). Multivariate logistic regression analysis showed that the third trimester of pregnancy(OR=1.906,95%CI:1.128-3.221),urban residence(OR=1.335,95%CI:1.014-1.756),educational level of junior college(OR=2.474,95%CI:1.635-3.744)and educational level of regular college or above (OR=2.072,95%CI:1.338-3.209),receiving health education about health pregnancy(OR=1.936, 95%CI:1.509-2.484)and self-learning about the knowledge of health pregnancy(OR=2.065,95%CI:1.338-3.189)were the influencing factors to the awareness rate of macrosomia diagnostic criteria and prevention related knowledge of macrosomia among pregnant women. The awareness rate of the cause and prevention related knowledge of macrosomia was higher in older age group(OR=2.103,95%CI:1.330-3.323). Conclusion Among the pregnant women in Zhejiang,the awareness rate of macrosomia diagnostic criteria was less than 50%. Therefore,it was necessary to strengthen the health education during pre-gestational and gestational periods among reproductive women,especially the education about pregnancy health in rural area.

Objective:To investigate the role of 1, 25-dihydroxyvitamin D3 [1.25(OH) 2D 3] in liver lipid metabolism so as to provide the clues for elucidating the mechanism of non-alcoholic fatty liver. Methods:26 SD rats were randomly divided into control group (methionine-choline-sufficient diet, MCS), model group (methionine-choline-deficiency diet, MCD) and intervention group [MCD+1.25(OH) 2D 3]. The intervention, control, and model group was given 3 ng/100 g 1.25(OH) 2D 3 peanut oil solution per day by gavage according to body mass. After 4 weeks the experiment was ended up, and the blood was collected from the inferior vena cava to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The liver tissue was collected to observe the liver morphological and pathological changes (oil red O and HE staining). The changes in the level of liver total triglyceride (TG) content and liver lipid metabolism-related genes [fatty acid transfer protein (FAT/CD36), acetyl-coenzyme A carboxylase (ACC1)] mRNA and protein were detected. One-way analysis of variance was used to compare the means between groups. Results:Oil red O staining and HE staining showed that lipid droplet-vacuoles were significantly increased in the liver tissue of the model group than that of the intervention group. The liver TG content (2.23 ± 0.98) μmol/g of the intervention group was significantly lower than that of the model group (3.53 ± 1.06) μmol/g ( F = 5.930, P = 0.035). The ALT content of the intervention group (35.99±9.54) U/L was significantly lower than that of the model group (57.65 ± 19.42) U/L ( F = 13.790, P = 0.034). The AST content of the intervention group (16.9 ± 3.73) U/L was significantly lower than that of the model group (27.81 ± 13.31) U/L ( F = 3.084, P = 0.046). The relative expression levels of mRNA and protein (mRNA: 1.21 ± 0.61, protein: 1.54 ± 0.75) of FAT/CD36 in the intervention group were significantly lower than those of the model group (mRNA: 2.31 ± 0.81, protein: 2.83 ± 1.42) (mRNA: F = 8.370, P = 0.001, protein: F = 7.212, P = 0.043). The relative expression level of mRNA and protein of ACC1 (mRNA: 0.89 ± 0.54, protein: 0.28 ± 0.11) were also significantly lower than those in model group (mRNA: 1.39 ± 0.19, protein: 0.47 ± 0.24) (mRNA: F = 3.948, P = 0.036, protein: F = 10.933, P = 0.048). Conclusion:1.25(OH) 2D 3 can reduce liver fat deposition in rats fed with MCD by inhibiting the expression of fat / CD36 and ACC1.

The clinical manifestations and examination results of a case of Creutzfeldt-Jakob disease (CJD) admitted to the Department of Neurology of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences in August 2020 were analyzed, and a comprehensive neuropsychological assessment and assessment of apraxia were conducted. The neuropsychological characteristics of apraxia in CJD patient and the progress in the research and evaluation of apraxia were reviewed. The patient was a 65-year-old male with insidious onset and progressive symptoms, whose clinical manifestations were apraxia, rapidly progressing dementia, and extrapyramidal symptoms. The magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in bilateral cerebral hemispheres, and 14-3-3 protein in cerebrospinal fluid was positive, which were consistent with the probable CJD diagnostic criteria. The patient exhibited prominent signs and symptoms of ideomotor apraxia. It has been reported in the literature that apraxia can also be the main neuropsychological manifestation of CJD. It is necessary to pay attention to the standard evaluation and timely identification of apraxia in clinical diagnosis.

OBJECTIVETo understand the awareness rate of macrosomia related knowledge and influencing factors among pregnant women in Zhejiang province and provide evidence for the improvement of pre-gestational and prenatal care.

METHODSA face to face questionnaire survey was conducted among 1 512 pregnant women selected through multistage cluster random sampling from 20 counties (district) in Zhejiang. Macrosomia-related awareness and related factors were analyzed.

RESULTSA total of 1 494 valid questionnaires were analyzed, the awareness rate was 40.7% for macrosomia diagnostic criteria (95% CI: 38.2%-43.2%), 55.0% for the cause of macrosomia (95% CI: 52.4%-57.6%) and 62.4% for prevention related knowledge (95% CI: 59.9%-64.9%) and the awareness rate of both the cause and the prevention related knowledge was 49.0% (95% CI: 46.4%-51.6%). Multivariate logistic regression analysis showed that the third trimester of pregnancy (OR = 1.906, 95% CI: 1.128-3.221), urban residence (OR = 1.335, 95% CI: 1.014-1.756), educational level of junior college (OR = 2.474, 95% CI: 1.635-3.744) and educational level of regular college or above (OR = 2.072, 95% CI: 1.338-3.209), receiving health education about health pregnancy (OR = 1.936, 95% CI: 1.509-2.484) and self-learning about the knowledge of health pregnancy (OR = 2.065, 95%CI: 1.338-3.189) were the influencing factors to the awareness rate of macrosomia diagnostic criteria and prevention related knowledge of macrosomia among pregnant women. The awareness rate of the cause and prevention related knowledge of macrosomia was higher in older age group (OR = 2.103, 95% CI: 1.330-3.323).

CONCLUSIONAmong the pregnant women in Zhejiang, the awareness rate of macrosomia diagnostic criteria was less than 50%. Therefore, it was necessary to strengthen the health education during pre-gestational and gestational periods among reproductive women, especially the education about pregnancy health in rural area.

China ; epidemiology ; Female ; Fetal Macrosomia ; epidemiology ; Health Knowledge, Attitudes, Practice ; Humans ; Pregnancy ; Pregnant Women ; psychology ; Surveys and Questionnaires

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.