Objective To explore the correlation between kinesiophobia and disease uncertainty, personal mastery, cardiac discomfort symptoms in patients with acute myocardial infarction (AMI) during recovery period. Methods A total of 320 patients with AMI admitted to the hospital were enrolled between January 2020 and January 2024. According to the results of Tampa Scale for Kinesiophobia Heart (TSK-H), they were divided into AMI kinesiophobia group (n=166) and simple AMI group (n=154). The disease uncertainty was evaluated by Mishel Uncertainty in Illness Scale for Adults (MUIS-A), personal mastery was evaluated by Personal Mastery Scale (PMS), and cardiac discomfort symptoms were evaluated by cardiac discomfort symptom scale. The correlation between kinesiophobia and disease uncertainty, personal mastery, cardiac discomfort symptoms in AMI patients was analyzed by Pearson correlation analysis. Results The scores of MUIS-A and cardiac discomfort symptoms in AMI kinesiophobia group were higher than those in simple AMI group (P<0.05), and PMS scores were lower than those in simple AMI group (P<0.05). The score of kinesiophobia was significantly positively correlated with scores of disease uncertainty and cardiac discomfort symptoms (r=0.628, 0.689, P<0.05), while significantly negatively correlated with the score of personal mastery (r=-0.526, P<0.05). Conclusion Kinesiophobia is related to disease uncertainty, personal mastery and cardiac discomfort symptoms in AMI patients during recovery period. Clinical medical staffs should focus on patients with the above characteristics. The targeted intervention measures can improve kinesiophobia and promote recovery of patients.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective:To investigate the changes in hepatic phase II detoxification enzymes and their mechanism in metabolic associated steatohepatitis (MASH) induced by a methionine-choline-deficient (MCD) diet in mice.Methods:Ten C57BL/6J mice were randomly divided into two groups, with five mice in each group, and fed with a control diet (NCD group) and a methionine-choline-deficient diet (MCD group) for four consecutive weeks to establish the MASH model in mice. Mice body weight was recorded weekly. Mice peripheral blood and liver tissue samples were collected after four weeks. The liver histopathological changes were observed by hematoxylin-eosin staining and Sirius red staining in liver tissue. The levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were measured by an automatic biochemical analyzer. Triglyceride and total cholesterol were used to evaluate the lipid accumulation condition in the liver of mice with Oil red O staining. Real-time fluorescence quantitative PCR was used to detect the expression of liver inflammatory factors interleukin (IL)-1β and monocyte chemoattractant protein-1 (MCP-1) condition. Transcriptome sequencing and bioinformatics were used to analyze the changes in gene expression profiles in the liver of mice and screen differentially expressed genes. The expression conditions of phase Ⅱ detoxification enzymes glutathione S-transferase mu 4 (GSTM4), dihydronicotinamide riboside:quinone oxidoreductases (NQO-2), sulfotransferase 1β1 (SULT1β1), and uridine diphosphate glucuronosyltransferase 2 family, polypeptide A3(UGT2A3) were verified by real-time fluorescent quantitative PCR. Plasma malondialdehyde content, total antioxidant capacity (T-AOC), plasma and liver glutathione content were determined using commercial kits. The expression of nuclear factor E2-related factor 2 (Nrf2), GSTM4, and UGT1A6 was examined by Western blotting. The independent sample t-test was used for comparison between the groups. Results:The body weight of mice in the MCD group showed a gradual downward trend, while the body weight of mice in the NCD group did not change significantly following four weeks of different dietary feeding. The MCD group mice liver had yellow-white appearance with round edges. The liver/body mass index was significantly lower in the NCD group ( t=3.216, P<0.01). Hematoxylin-eosin staining showed that hepatocytes in the MCD group had an occurrence of fatty degeneration accompanied by inflammatory cell infiltration, with a higher NAFLD activity score (NAS) compared to the NCD group ( t=7.155, P<0.001). Sirius red staining showed that the the liver of the MCD group had mildly increased periportal fibers. Plasma biochemical tests indicated that plasma ALT, AST, and triglyceride levels were significantly higher in the MCD group than those in the NCD group ( t=8.920, P<0.001; t=6.696, P<0.001; t=3.904, P<0.01). Oil red O staining showed that a large number of lipid droplets accumulated in the liver tissue of the MCD group and were more severe than those in the NCD group ( t=7.405, P<0.001). The triglyceride content was significantly higher in the liver of the mice in the MCD group than that in the NCD group ( t=3.559, P<0.01), and the expression of inflammatory factors IL-1β and MCP-1 was significantly increased ( t=2.562 and 2.391, respectively, P<0.05). Transcriptome sequencing analysis showed that the expression profile of genes related to lipid metabolism was changed in the liver tissue of the mice in the MCD group. The expression of multiple phase Ⅱ detoxification enzymes was significantly downregulated. Real-time fluorescence quantitative PCR verification demonstrated that the expression of four phase Ⅱ detoxification enzymes GSTM4, NQO2, SUIL1β1, and UGT2A3 were significantly lower in the liver of the mice in the MCD group than those in the NCD group ( t=2.498, 3.570, 3.768, and 4.166, respectively, P<0.05). The detection kit showed that compared with the NCD group, the malondialdehyde content in the liver of mice in the MCD group increased ( t=3.601, P<0.01), while the plasma total glutathione ( t=11.93, P<0.001) and reduced glutathione levels were significantly reduced ( t=3.635, P<0.01). The total antioxidant capacity of the liver decreased ( t=2.872, P<0.05), and the total glutathione and reduced glutathione levels in the liver were significantly increased ( t=3.175 and 3.064, P<0.05). Western blotting showed that the expression of Nrf2, GSTM4, and UGT1A6 proteins was significantly lower in the MCD group than that in the NCD group ( t=3.385, 2.990, 2.168, P<0.05). Conclusions:The expressions of multiple phase Ⅱ detoxification enzymes and antioxidant capacity are reduced in the liver of MASH mice induced by the MCD diet, and its mechanism is related to the down-regulation of the expression of the upstream regulatory factor Nrf2 protein.

Ornithine transcarbamylase(OTC)is a member of the transcarbamylase protein family,commonly found in the mitochondrial matrix of living organisms.It generally functions in a trimeric form and can catalyze the production of L-ornithine to L-citrulline.OTC is mainly expressed in the liver and intestines of mammals,playing an important role in the urea cycle and amino acid homeostasis.This article introduces the research progress of OTC genes,proteins,physiological functions,the impact of OTC deficiency on body health,and the diagnosis and treatment of OTC deficiency.

Objective:To establish a fluorescent quantitative RT-PCR assay based on N_sgRNA of SARS-CoV-2 and preliminarily apply it on real samples.Methods:Recombinant plasmid, specific primers and probes of N_sgRNA were designed and synthesized based on Wuhan-Hu-1/2019_MN908947 and synthesis mechanism of subgenomic RNA (sgRNA). Using recombinant plasmid as amplification templates, the optimal reaction conditions and reaction system were screened according to the Ct value, fluorescence intensity, and shape of amplification curve and was evaluated for sensitivity, reproducibility, and specificity. Meanwhile, the possibility of practical application of the method was explored by testing 172 clinical samples and 256 municipal wastewater samples. Results:A qRT-PCR assay for N_sgRNA in SARS-CoV-2 was initially established. The detection limit of the assay was 20 copies/mL, and the variation coefficients of in-batch (0.002%~0.767%) and batch to batch repetition (0.016%~0.752%) were less than 1%. Only N_sgRNA recombinant plasmid was detected in the specificity assay. So the method is more highly sensitive, specific and reproducible. The RatiosgRNA/ gRNA of clinical samples HK.3, EG.5.1, JN.1 and their sub-lineages and their corresponding urban sewage samples in epidemic period were significantly different ( P<0.05). There is a strong correlation between the median of RatiosgRNA/ gRNA in clinical samples and sewage samples in the same period (correlation coefficient r=1.000, P=0.010). Conclusions:In this study, a qRT-PCR method for detecting N_sgRNA of SARS-CoV-2 was established and the method has the characteristics of higher sensitivity, stronger specificity and better repeatability, and it can be used to detect SARS-CoV-2 infectivity.

Objective To explore the effects of evidence-based nursing combined with multi-dimensional health education on negative emotions and postoperative rehabilitation of patients undergoing elective surgery for cholecystolithiasis.Methods A total of 100 patients with cholecystolithiasis who underwent elective surgery in Yixing Traditional Chinese Hospital Medicine from September 2023 to August 2024 were selected.The patients were assigned to control group and observation group by PEMS3.1 for Windows completely random(two groups and multiple groups)program,with 50 cases in each group.The control group received routine nursing,and the observation group received evidence-based nursing combined with multidimensional health education on the basis of routine nursing.The intervention duration of the two groups was 7 days.Visual analogue scale(VAS)scores,negative emotions(self-rating anxiety scale[SAS]and self-rating depression scale[SDS]),postoperative complications,and postoperative rehabilitation were compared between the two groups.Results The VAS scores at 24 h and 72 h after surgery were lower than those at 6 h after surgery in both groups,especially in the observation group(P<0.05).The scores of SAS and SDS in both groups after intervention were significantly decreased compared with those before intervention,and the scores of negative emotions in the observation group after intervention were significantly lower than those in the control group(P<0.05).The total incidence of gastrointestinal discomfort,biliary fistula and wound infection/bleeding in the observation group was significantly lower than that in the control group(4.00%vs.18.00%,P<0.05).The time of getting out of bed,the time of anal exhaust,the time of resuming normal diet and the time of hospitalization in the observation group were significantly lower than those in the control group(P<0.05).Conclusion The combination of evidence-based nursing and multi-dimensional health education during perioperative period of cholecystolithiasis surgery can reduce postoperative pain,improve the positive attitude of treatment,reduce complications,and promote the recovery of the disease.

Objective To investigate the correlation between serum amyloid A(SAA)level and disease se-verity in children infected with severe acute respiratory syndrome coronavirus 2(COVID-19).Methods A to-tal of 116 children infected with COVID-19 admitted to the Department of Pediatrics of the hospital from De-cember 2022 to April 2023 were included and divided into asymptomatic/mild group and moderate/severe group according to the severity of the disease.In addition,65 healthy children who received health examination during the same period were selected as the control group.Serum SAA levels in children in acute stage and convalescent stage were detected by enzyme-linked immunosorbent assay.Results Compared with the control group,the serum SAA level in the children infected with COVID-19 was significantly increased in the acute stage(P＜0.05).The area under the receiver operating characteristic(ROC)curve(AUC)of SAA levels in the acute stage for diagnosing children with COVID-19 infection was 0.926(95％CI:0.886-0.966).In SARS-CoV-2 infected children,the SAA levels in the acute stage in the asymptomatic/mild group and the moderate/severe group were 2.71(1.29-10.86)mg/L and 37.78(18.58-92.62)mg/L,the differences were statistically significant between the two groups(Z=5.782,P＜0.001).In addition,serum SAA was pos-itively correlated with severity of SARS-CoV-2 by Spearman analysis(r=0.657,P＜0.001).Serum SAA lev-els were also significantly positively correlated with C-reactive protein(CRP),immunoglobulin(Ig)M,IgG,IgA and neutralizing antibody(NAb)in acute stage(P＜0.05).The AUC of serum SAA level in acute stage for diagnosing the moderate/severe children with SARS-CoV-2 was 0.889(95％CI:0.842-0.955),which was higher than that of CRP(P＜0.05).Compared with serum antibodies(IgM,IgG,IgA and NAb),the rate of serum SAA positive(≥5.55 mg/L)in children in acute stage was significantly higher(P＜0.05).The positive rate of serum SAA in convalescent children was significantly lower than that of serum antibody(P＜0.05).Conclusion Elevated serum SAA in acute phase is associated with increased risk of SARS-CoV-2 infec-tion and disease severity in children.Serum SAA is promising as a good biomarker for monitoring SARS-CoV-2 infection and severity in children.