BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

Background Ozone (O₃) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O₃ concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O₃ risk assessment and related policy making. Objective To quantitatively evaluate the effects of O₃ exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. Methods Data of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O₃ concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P₂₅) and the 75th percentile (P₇₅) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m⁻³ increase in daily maximum 8 h concentration of O₃ (O₃-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O₃. Results The associations between O₃ and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P<0.05), with the greatest effect size observed at lag03. The ER values of death from cardiovascular and cerebrovascular diseases in general population, male residents, and people aged 65 years and older, from coronary heart disease in male residents, and from stroke in general population increased by 1.02% (95%CI: 0.36%, 1.69%), 1.40% (95%CI: 0.47%, 2.34%), 0.87% (95%CI: 0.19%, 1.55%), 1.96% (95%CI: 0.49%, 3.44%), and 1.02% (95%CI: 0.07%, 1.98%) for a 10 µg·m⁻³ increase in O₃-8 h concentration at lag03, respectively. During the warm season (from April 1 to September 30), the ER values of death from cardiovascular and cerebrovascular diseases and coronary heart disease per 10 µg·m⁻³ increase in O₃ were 1.18% (95%CI: 0.33%, 3.33%) and 2.69% (95%CI: 0.39%, 5.03%), while the O₃ effect was only statistically significant on cardiovascular and cerebrovascular diseases during the cold season (from October 1 to March 31 next year). At the middle and high temperature levels, the ER values of death from cardiovascular and cerebrovascular diseases increased by 1.63% (95%CI: 0.32%, 2.96%) and 1.14% (95%CI: 0.17%, 2.12%) respectively. The two-pollutant models showed similar results after including other pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, fine particulate matter, or inhalable particulate matter). Conclusion Ambient O₃ pollution may increase the mortality risks of cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke in Minhang District of Shanghai.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Secondary organic aerosol(SOA)produced by photooxidation of styrene and other aromatic compounds is a major part of fine particles in urban atmosphere.In this study,the measurement of component and content of SOA formed from photooxidation of styrene in smog chamber using synchronous radiation vacuum-ultraviolet photoionization aerosol mass spectrometer(VUV-PIAMS)was conducted.Photoionization mass spectra of styrene SOA was detected by synchrotron radiation photon with 10.5 eV,and the proportion of main components was quantified based on the peak area of each ion peak.The photoionization efficiency curve of ion peak was obtained under synchrotron radiation photons in the range from 7.5 to 11.5 eV,and then the ionization potential was acquired for qualitative analysis of the component structure.The results showed that the photoionization mass spectra of styrene SOA mainly contained ion peaks at m/z 106,108,120 and 122,and the ionization potentials of each peak were(9.41±0.03)eV,(8.93±0.03)eV,(9.24±0.03)eV and(9.25±0.03)eV,respectively.Combined with quantum chemistry calculation and off-line measurement verification of infrared absorption spectra and electrospray ionization mass spectra,it was determined that benzaldehyde,benzyl alcohol,4-vinylphenol and benzoic acid were main components of styrene SOA,accounting for 32.5%,17.5%,25%and 15%of the measured components,respectively,and the generated quantity ratio was 13∶7∶10∶6.VUV-PIAMS could overcome the disadvantages of off-line method,and could on-line detect component and content of SOA,proving a useful tool to measure the chemical components and reveal the formation process of SOA particles.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation(SPKT)recipients and deceased donor kidney transplant(DDKT)recipients in patients with type 2 diabetes mellitus(T2DM)complicated with end-stage renal disease(ESRD),and to analyze the risk factors affecting patient survival post-SPKT.Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27,2003,to January 1,2021,were retrieved from the United Network for Organ Sharing(UNOS)database.A total of 50 230 cases were selected based on inclusion criteria,with 48 669 cases in DDKT group and 1561 cases in SPKT group.Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups,and propensity score matching(PSM)was utilized to balance confounding factors between the groups.Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.Results Compared with DDKT group,recipients in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),shorter dialysis and transplant waiting times(P<0.001),a higher percentage of private medical insurance(P<0.001),a lower proportion of previous transplants(P<0.001),a younger age at diabetes diagnosis(P<0.001),and a lower incidence of peripheral vascular disease(P=0.033).Compared with DDKT group,the donors in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),and a lower prevalence of hypertension and diabetes history(P<0.001).In terms of transplant-related factors,the SPKT group had a shorter donor kidney cold ischemia time(P<0.001),a higher degree of HLA mismatch(P<0.001),and a lower Kidney Donor Profile Index(KDPI)(P<0.001)when compared with DDKT group.The SPKT group had lower serum creatinine levels at discharge(P<0.001),lower rates of postoperative delayed graft function(DGF)and acute rejection(AR)(P<0.001),but longer hospital stays(P<0.001)when compared with DDKT group.Kaplan-Meier survival analysis curves,both original and after propensity score matching(PSM),consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group(P<0.001).Cox regression model analysis indicated that recipient age,recipient race,donor age,and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.Conclusions For ESRD patients with T2DM,SPKT offers improved long-term graft and patient survival rates compared with DDKT.Recipient age,recipient ethnicity,donor age,and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To analyze the epidemiological and clinical characteristics of patients with monkeypox.Methods Data of 17 patients with monkeypox hospitalized in a hospital in Nanning City from July to October 2023 were collected retrospectively.The epidemiological history,clinical manifestations,laboratory examinations,treat-ment and prognosis were analyzed and summarized.Results All 17 patients were male,with a median age of 28 years old.Fifteen(88.2％)patients were men who had sex with men(MSM)within 21 days prior to onset.Major clinical manifestations were rash and fever.Rashes distributed mainly in the anus,perineum and genitals(82.4％),followed by the trunk and limbs(52.9％),head and face(35.3％),while soles and palms were rare.Some patients had swollen inguinal lymph nodes.All patients were discharged from hospital after improvement,with an average hospital stay of 7 days.Conclusion The monkeypox epidemic in Nanning area of Guangxi occurs mainly in MSM population,with fever and rashes as the major symptoms.All patients have mild disease and good prognosis.

This study was aimed at analyzing the molecular epidemiological characteristics of all 14 cases of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018,to provide a scientific basis for prevention,control,and treatment.The genomic sequence was obtained through high-throughput gene sequencing after nucleic acid extraction.Homolo-gy analysis,evolution analysis,mutation locus analysis,and homology modeling were performed in bioinformatics analysis software.The nucleotide homology and amino acid homology of the HA gene in 14 human infected H7N9 viruses were(97.39％-100％)and(98.38％-100％),respectively.The nucleotide homology of the NA gene and the amino acid homology ranged from 97.73％to 100％.All viruses were low pathogenic avian influenza viruses belonging to the Yangtze River Delta lin-eage and were divided into two subclades,which were most similar to the A/Hunan/02650/2016 vaccine strain.All HA pro-teins G186V and T160A were mutated;13 strains of Q226L were mutated;and none of the four key neuraminidase inhibitor resistance sites of NA protein were mutated.All sites of M2 protein S31N and V27A were mutated,all sites of PB1 protein T368V were mutated,and all sites of PA protein K356R were mutated.Xinjiang H7N9 virus exhibited double receptor bind-ing,and was resistant to amantadine drugs and sensitive to neuraminidase inhibitors,which may be used in early disease sta-ges.Strengthened monitoring and timely detection of avian in-fluenza virus genome changes will be critical for prevention and control,and formulation of countermeasures.