Objective To investigate the discovery and disposal process and epidemiological characteristics of the first confirmed case of mpox (formerly named monkeypox) in Huai'an, Jiangsu Province, and to provide reference for the prevention and control of key infectious diseases in this region. Methods The on-site epidemiological investigation data of the first confirmed case of mpox on June 21, 2023, as well as the results of nucleic acid detection and gene sequencing of laboratory specimens were analyzed retrospectively. Possible sources of infection were explored. Results The first confirmed case of mpox was an AIDS patient, men who had sex with men (MSM), who had no history of travel abroad or outside the city within 21 days before the onset of the disease, but had interacted with some people outside the city, and the epidemiological trajectory was complex. The detection of mpox virus nucleic acid was positive (BioGerm reagent: Ct value 21.8, ZhuoCheng reagent: Ct value 21.2). According to genetic sequencing, the first confirmed case was classified as C.1.1 lineage of clade IIb. During the investigation on the source of infection of the first confirmed case, one new asymptomatic infected person was found. Based on the epidemiological investigation and laboratory results, the first confirmed case was believed to be caused by local infection, however, the source of infection was unclear. Although there was an epidemiological association with asymptomatic infected people, the direct evidence of mutual infection was insufficient, and it could not be ruled out that there was still a hidden transmission chain between regions. The source of infection of the asymptomatic infected person was presumed to be the first confirmed case or an unidentified person with whom he had high-risk sex and caused anal bleeding. Conclusion The first confirmed case is caused by local infection. Awareness of case diagnosis and reporting in medical institutions should be improved, and publicity and education should be provided to key exposed populations, especially those men who have sex with men, to prevent the occurrence of large-scale local epidemic.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Aim To investigate the possible mecha-nism of UNC5B-AS1 in regulating the malignant biolog-ical behavior of osteosarcoma cells.Methods RT-qPCR was used to detect the expression of UNC5B-AS1 in osteosarcoma cells MG63,osteosarcoma cells U2OS and osteoblast cells hFOB1.19.After overexpression and knockdown of UNC5B-AS1 in osteosarcoma cells,the proliferation,migration and apoptosis of osteosarco-ma cells were detected by CCK-8 assay,Transwell as-say and flow cytometry,respectively.At the same time,RT-qPCR and Western blot were used to detect the effects of UNC5B-AS1 overexpression and knock-down on the mRNA and protein expression of key fac-tors in the NF-κB signaling pathway.Results Com-pared with normal osteoblast hFOB1.19,UNC5B-AS1 expression was differentially increased in osteosarcoma cells MG63 and U2OS.Overexpression of UNC5B-AS1 significantly promoted the proliferation of osteosarcoma cells and significantly increased the migration ability of osteosarcoma cells,while the apoptosis rate markedly decreased,and NF-κB signaling pathway-related mR-NA and protein expressions apparently increased.Knockdown of UNC5B-AS1 evidently inhibited the pro-liferation of osteosarcoma cells and significantly re-duced the migration ability of osteosarcoma cells,while the apoptosis rate markedly increased,the NF-κB sig-naling pathway related mRNA and protein expression significantly reduced.Conclusions lncRNA UNC5B-AS1 is highly expressed in osteosarcoma cells,which may affect the malignant biological behavior of osteo-sarcoma cells by activating the NF-κB signaling path-way.

Objective:To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies,in order to provide reference for clinical infection control and treatment.Methods:The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed.They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation.The types of pathogens and their drug resistance were analyzed.Results:Two hundred and ninety-nine positive strains of pathogenic bacteria were detected.In the transplantation group,Gram-negative bacteria accounted for 68.5％(50/73),Gram-positive bacteria accounted for 6.8％(5/73),and fungi accounted for 24.7％(18/73).The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8％,and 11.5％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0％,and 56.2％to carbapenems.In the non-transplantation group,Gram-negative bacteria accounted for 64.1％(145/226),Gram-positive bacteria accounted for 31.0％(70/226),and fungi accounted for 4.9％(11/226).Gram-positive bacteria were mainly Enterococcus faecium(6.6％,15/226)and Coagulase-negative Staphylococci(6.2％,14/226).The fungi were all Candida tropicalis.The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8％,and 10.3％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3％,and 26.8％to carbapenems.Conclusion:The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied.Gram-negative bacteria is the main pathogenic bacteria.The resistance of pathogenic bacteria to antibiotics is severe.Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Glycogen storage disease (GSD) is a rare autosomal recessive inherited disease in clinic. The paper reported a case of GSD Ⅰ a diagnosed by genetic testing, who had been experiencing numerous joint pains for 4 years, and had increased serum creatinine and severe high lactic acid metabolic acidosis. The serum creatinine declined and acidosis recovered after active fluid therapy and acidosis correction. The paper summarized the characteristics of this GSD patient with renal insufficiency and the relevant literature contents, to improve the understanding of clinicians on the disease and treatment effect.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Objective:To study the role and specific mechanisms of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme for glycometabolism, mediated reduction stress in arsenic-induced malignant transformation of cells.Methods:Immortalized human skin keratinocyte-forming cells (HaCaT cells) were treated with sodium arsenite (NaAsO 2) at a concentration of 0.0 (control group) and 1.0 μmol/L (arsenic group), and malignant transformation indicators were tested using cell growth kinetics assay, cell scratch assay, and soft agar colony formation assay. At different stages of arsenic treatment (0, 1, 7, 14, 21, 28, 35 passages of cells), the effects of NaAsO 2 on glycometabolism in HaCaT cells were determined using corresponding reagent kits and Western blot, including glucose-6-phosphate (G6P), lactate, acetyl CoA, G6PD levels, as well as protein expression levels of hexokinase 2 (HK-2), 6-phosphofructose-2-kinase/fructose-2, 6-diphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase 1 (PDK1), 6-phosphoglucose dehydrogenase (PGD), and G6PD. Mitochondria were extracted, and the effects of NaAsO 2 on HaCaT cells and mitochondrial redox [reduced nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP +) ratio, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio] were determined using corresponding reagent kits. The effect of G6PD on reduction stress and NaAsO 2-induced malignant transformation of HaCaT cells was determined using small interfering RNA (siRNA) intervention method. Results:Compared 1.0 μmol/L NaAsO 2-cultured HaCaT cells up to 35 generations (T-HaCaT cells) with matching passage 0.0 μmol/L NaAsO 2-cultured HaCaT cells [(33.797 ± 0.280) h, 0.177 ± 0.015, 13.667 ± 2.625], the multiplication time [(24.042 ± 0.479) h] was shorter ( t = 30.45, P < 0.001), the cell migration rate (0.396 ± 0.039) was higher ( t = 9.08, P < 0.001), and the number of colonies formed in soft agar (73.667 ± 4.450) was higher ( t = 20.11, P < 0.001). Compared with matching passage control group cells and 0 generation of the same group, G6P level in the arsenic group was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05), lactate and G6PD levels were higher at passages 14, 21, 28 and 35 ( P < 0.05), acetyl CoA level was lower at passages 21, 28 and 35 ( P < 0.05), and protein expression levels of HK-2, PFKFB3, PDK1, PGD, and G6PD were higher at passages 7, 14, 21, 28 and 35 ( P < 0.05). The NADPH/NADP + ratio of cells was higher at passages 1, 14, 21, 28 and 35 ( P < 0.05), GSH/GSSG ratio was higher at passages 21, 28 and 35 ( P < 0.05). The ratio of mitochondrial NADPH/NADP + was higher at passages 1, 7, 21, 28 and 35 ( P < 0.05), the GSH/GSSG ratio was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05). G6PD expression was silenced by siRNA in T-HaCaT cells, compared with the T-HaCaT con siRNA-treated group, the T-HaCaT G6PD siRNA-treated group had lower NADPH/NADP + and GSH/GSSG ratios in both cells and mitochondria ( P < 0.05), longer cell multiplication time, lower cell migration rate, and fewer soft agar colonies ( P < 0.05). Conclusion:During the malignant transformation of HaCaT cells induced by NaAsO 2, G6PD and other enzymes related to glycometabolism are activated, leading to reprogramming of glycometabolism, resulting in an imbalance of cell redox homeostasis and enhanced reduction stress in cells and mitochondria, thereby promoting NaAsO 2 induced malignant transformation of HaCaT cells.

Objective:To systematically evaluate the correlation between chronic non-occupational arsenic exposure and hypertension.Methods:A literature search was conducted through Web of Science, Pubmed, Embase, Cochrane Library, WanFang Data, China National Knowledge Infrastructure (CNKI), VIP Chinese Journal Service Platform (VIP) Database and China Biomedical Literature Database to comprehensively collect epidemiological literature related to chronic non-occupational arsenic exposure and hypertension published domestically and internationally for inclusion in the study, with a time limit from database establishment to January 1, 2023. Meta-analysis of dichotomous variables was conducted using Stata MP15 software, with odds ratio ( OR) value [95%confidence interval( CI)] as the effect evaluation indicator. A random-effects model or a fixed-effects model was selected for comprehensive quantitative analysis according to the heterogeneity results; the sources of heterogeneity were identified through subgroup analysis; a funnel plot was used for qualitative analysis of publication bias and the results were further assessed by Egger test. Stata 15.0 software was then used to analyze the dose-response relationship between chronic non-occupational arsenic exposure and hypertension using restricted cubic spline function and generalized least squares estimation (GLST) method. Results:Twenty-nine articles ( n = 127 258) were finally included, including 24 English articles and 5 Chinese articles. Through Meta-analysis, the combined OR value (95% CI) for hypertension was 1.07 (1.04 - 1.09), with a statistically significant difference ( P < 0.05). The combined OR values (95% CI) for urinary arsenic, drinking water arsenic, and hair arsenic in subgroup analysis were 1.10 (1.04 - 1.17), 1.13 (1.07 - 1.20), and 2.55 (1.55 - 4.20), respectively. The combined OR values (95% CI) for cross-sectional studies, case-control studies and cohort studies were 1.11 (1.06 - 1.16), 1.13 (1.04 - 1.23) and 1.04 (1.00 - 1.07), respectively. For every unit (μg/L) increase in arsenic exposure in drinking water, the risk of hypertension increased by 0.13% [ OR value (95% CI): 1.001 269 (1.000 104 - 1.002 434), P < 0.05]. Conclusions:There is a correlation between chronic non-occupational arsenic exposure and adult hypertension, with urinary arsenic, drinking water arsenic and hair arsenic as possible exposure markers. There is a non-linear dose-response relationship between chronic non-occupational arsenic exposure and adult hypertension.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.