OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Objective To construct one high-copy BAC vector with cloning capacity for large DNA fragment insertion and use it for the haplotype analysis of CYP2A6 gene.Methods Oligos including multiple cloning sites were annealed and ligated into the Hind Ⅲ/BamH Ⅰ site of pGEM-3Z and pBeloBACll,separately.Then,the intermediate vectors were digested by Hind Ⅲ and ligated together,so as to get the head-to-tail oriented high-copy BAC vector pBAC-BJH after the blue-white spotting test.STI PCR method was used for the amplification of whole CYP2A6 gene,and purified amplicon was double digested by BstB Ⅰ/Mlu Ⅰ and ligated into the same site of newly constructed vector pBAC-BJH.Several clones were then picked up and sequenced for the haplotype analysis of carriers with newly discovered CYP2A6 variant 355A＞T.Results One high-copy BAC vector pBAC-BJH with 7 newly added multiple cloning sites was successfully constructed.High copy number and multiple cloning sites were the advantages of this plasmid.With this vector,haplotype analysis result for 22C＞T,51A＞G,355A＞T in carrier with newly detected CYP2A6mutation was CGT.Conclusion One vector pBAC-BJH convenient for cloning large DNA fragment was successfully developed,and it can be used for the haplotype analysis of cytochrome p450 gene and cloning or sequencing of other genes with large genomic DNA inserts.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Bamboo jar therapy of Zhuang medicine is a combination of cupping therapy,acupuncture and hot compress of medicine,which is simple,convenient and cost-effective.There are differences in the production of bamboo cans(species,acquisition cycle,diameter,tank length,wall thickness),liquid medicine,and operation process among different regions.These three aspects hinder its wide application and promotion.Therefore,it is particularly important to formulate unified practice standards and norms.Based on the combination of literature research and clinical experience,this paper proposes a standardized draft to respond to the above three perspectives.The authors would like to provide a reference for doctors to understand and master this therapy,so that patients can enjoy this therapy.

Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.

【Objective】 To investigate the effects of formononetin (FMN) on cardiomyocyte apoptosis and HSP90/AKT in rats with dilated cardiomyopathy-mediated heart failure. 【Methods】 Echocardiography, ELISA, histological staining, and TUNEL staining were used to observe the protective effect of different doses of FMN on dilated cardiomyopathy-mediated heart failure in rats and the apoptosis of cardiomyocytes. The potential targets of formononetin on dilated cardiomyopathy-mediated heart failure were obtained from TCMSP, DisGeNet, GeneCards, and other databases, the key targets were obtained according to the protein-protein interaction (PPI) network, and the key targets were verified by molecular docking. Western blotting was used to further verify the regulatory role of key targets in the treatment of dilated cardiomyopathy-mediated heart failure with formononetin. 【Results】 Formononetin could reduce the levels of LVIDS, LVIDD, NT-pro BNP, cTn-T, CK, CK-MB, and LDH in rats with dilated cardiomyopathy-mediated heart failure, increase the levels of EF and FS, and reduce the apoptosis of cardiomyocytes. FMN had a strong binding effect on 10 key targets (AKT1, HSP90AA1, CASP3, MAPK1, MMP9, SRC, ALB, HRAS, IGF1, and EGFR) screened by network pharmacology, with HSP90AA1 and AKT1 having the strongest binding effect. Formononetin decreased the expression of HSP90, AKT and downstream CASP3 protein, but increased the expression of p-AKT in myocardial tissue. 【Conclusion】 Formononetin may inhibit the expression of HSP90, promote phosphorylation of AKT to p-AKT, and inhibit the expression of CASP3, thereby reducing the apoptosis of cardiomyocytes and improving myocardial tissue damage, so as to achieve the purpose of treating dilated cardiomyopathy-mediated heart failure.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Objective:To evaluate and summarize the best evidence related to the management of cancer-related fatigue in children with leukemia and provide an evidence-based basis for clinical practice.Methods:The search for the relevant guidelines and evidence synthesis from UpToDate, JBI, Cochrane Library, Registered Nurses′ Association of Ontario, Guidelines International Network, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, YiMaiTong Guideline Network, National Comprehensive Cancer Network, PubMed, CINAHL, EMbase, China National Knowledge Infrastructure, Wanfang, China Biology Medicine from January 1st, 2012 to May 1st, 2022. Two researchers evaluated the quality of the literature independently according to the unified standard and extracted the best evidence.Results:A total of 13 literatures were extracted, including three clinical practice guidelines, two evidence summaries and eight systematic reviews. Finally, 22 pieces of evidence were summarized, involving six aspects which were environmental management, cancer-related fatigue assessment, exercise management, adventure therapy, sleep management and psychosocial interventions.Conclusions:Best evidence for the management of cancer-related fatigue in children with leukemia, which should be used in conjunction with the environment, the child's age, physical ability, medical condition and psychological acceptability to develop an individualized symptom management plan to improve the quality of care and the child′s quality of life.