ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg^-1）， Jieyu prescription （12.03 g·kg^-1）， WJP （16.71 g·kg^-1）， and fluoxetine （2.6 mg·kg^-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.

ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.

Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.

Objective:To investigate the association of serum fibroblast growth factor 23(FGF23) level with insulin resistance(IR) and sex hormone levels in patients with polycystic ovary syndrome(PCOS).Methods:A retrospective study was performed in eighty-seven patients with PCOS, fifty-seven patients with simple IR, and sixty-one healthy women who were admitted to Affiliated Hospital of Zunyi Medical University during October 2021 and November 2022. According to the homeostasis model assessment-IR index, all subjects were divided into normal control group( n=61), IR group( n=57), PCOS without IR group(PCOS group, n=15), and PCOS+ IR group( n=72). The levels of serum FGF23, adiponectin, and sex hormones in all groups were compared, and their correlations with glucose and lipid metabolism indicators were analyzed. Results:The FGF23 level was significantly elevated in the IR group, while markedly reduced in the PCOS group and PCOS+ IR group, with the PCOS group showing a significantly lower concentration. The adiponectin levels were significantly decreased in the IR group, PCOS group, and PCOS+ IR group(all P<0.05). The correlation analysis showed that FGF23 level was positively correlated with adiponectin and sex hormone binding globulin, and negatively correlated with luteinizing hormone, luteinizing hormone/follicle stimulating hormone, and free testosterone index(all P<0.05). Logistic regression results indicated that both FGF23 and adiponectin could be used as good indicators for the diagnosis of PCOS and PCOS with IR(all P<0.05). Conclusion:FGF23 is closely related to IR and androgen as well, and under certain conditions, it can reflect the severity of IR and hyperandrogenemia in PCOS patients. The cutoff value of FGF23 obtained in this study can provide a good reference for the diagnosis of PCOS diseases.

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.

Objective:To summarize the best evidence for the prevention and management of radiation esophagitis in patients with chest tumors, so as to provide basis for the prevention and management of radiation esophagitis in patients.Methods:The research question was proposed based on the population, intervention, professional, outcome, setting and type of evidence (PIPOST) model, and guidelines, expert consensus, clinical decision-making, evidence summary, systematic review, and randomized controlled trials on the prevention and management of radiation esophagitis in chest tumor patients were systematically searched on UpToDate, BMJ Best Practice, Cochrane Library, PubMed, American Society of Clinical Oncology, China National Knowledge Infrastructure, WanFang Data, and other databases and websites based on the "6S" model. The search period was from database establishment to August 1, 2023. Two researchers independently evaluated the quality of the literature and extracted and integrated evidence from the literature that met the quality standards.Results:A total of ten articles were included, including three guidelines, one expert consensus, one systematic review, two systematic evaluations, and three randomized controlled trials. Twenty-three pieces of evidence were summarized from six dimensions of building multidisciplinary teams, screening and evaluation, nutritional support, drug and non-drug prevention, integrated traditional Chinese and western medicine treatment, and health education.Conclusions:The included evidence can provide a theoretical basis for the prevention and management of radiation esophagitis in patients undergoing chest tumor radiotherapy. Clinical medical and nursing personnel can provide personalized interventions to patients based on clinical practice.

Objective:To systematically evaluate the qualitative research of virtual reality rehabilitation experience of cardiovascular disease patients, and provide reference for clinical application and improvement of virtual reality rehabilitation.Methods:Qualitative research on virtual reality rehabilitation experience of cardiovascular disease patients was electronically retrieved in the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, Medline, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Database. The search period was from database establishment to October 2023. The literature was evaluated according to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The aggregation integration method was used to integrate research results.Results:Six articles were included and 25 research results were extracted. Similar results were summarized and integrated into 10 new categories, and synthesized into three integrated results, including perceived benefits of virtual reality rehabilitation for cardiovascular disease patients, perceived barriers to virtual reality rehabilitation for cardiovascular disease patients, and the needs and expectations of cardiovascular disease patients for virtual reality rehabilitation.Conclusions:Virtual reality rehabilitation is a supplement and continuation of traditional cardiac rehabilitation, and its effectiveness has been recognized by most cardiovascular disease patients. Future research should enrich the content and participation forms of virtual reality rehabilitation based on patients' personalized needs, strengthen team building, provide social support, and enhance the accessibility and experience of using virtual reality rehabilitation systems for cardiovascular disease patients.

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans ; Mice ; Animals ; Cell Line, Tumor ; Nitric Oxide Donors/pharmacology* ; Sesquiterpenes/pharmacology* ; Leukemia/drug therapy* ; Biological Assay ; Cell Proliferation