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Jin-ning Wang,1,&ast; Wei Xie,2,&ast; Da-Wei Song,1,&ast; Jun Zou,1 Qi Yan,1 Tao Feng,1 Sheng-yang Jin,1 Chao Yang,1 Zong-ping Luo,1,3 Jun-jie Niu1 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zong-ping Luo, Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67781351, Email zongping_luo@yahoo.com Jun-jie Niu, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67780111, Email jjnewzzzx@sina.comBackground: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures.Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors.Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81± 8.60° postoperatively to 25.13± 8.91° at the final follow-up which showed a statistically significant difference (p< 0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p< 0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc–endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p< 0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis.Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc–endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.Keywords: percutaneous kyphoplasty, risk factors, re-kyphosis, disc–endplate complex injury, clinical efficacy

Yong Lin,1,2,* Bo-Mei Chen,3,* Xiao-Lu Yu,1,* Huo-Chun Yi,1 Jian-Jun Niu,1,2 Shu-Lian Li4 1Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 2Institution of Infectious Diseases, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 3Department of Human Resources, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 4Department of Gynecology, Xiamen Huli District Maternity and Child Care Hospital, Xiamen 361009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Jun NiuCenter of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of ChinaEmail niujianjun62@163.comShu-Lian LiXiamen Huli District Maternity and Child Care Hospital, Xiamen 361009, People’s Republic of ChinaEmail shu_lian_li@163.comIntroduction: CXCL14 was a significantly under-expressed mRNA in hepatocellular carcinoma tissues according to our microarray analysis, as well as head and neck squamous cell carcinoma and cervical squamous cell carcinoma. CXCL14 was considered a tumor suppressor in some studies; however, its role in HBV infection has not been identified.Methods: CXCL14 mRNA expression was quantified from 20 male HCC patients, and the fold change in cancer tissues was calculated by comparisons with normal adjacent tissues. Overall, 212 patients with chronic HBV infection and 180 HBV-free controls were recruited to investigate the association between CXCL14 polymorphisms and HBV progression as well as liver function parameters. Serum CXCL14 levels were determined by enzyme-linked immunosorbent assay (ELISA), and comparisons were made between different HBV status and different CXCL14 genotypes.Results: The mRNA expression of CXCL14 was 0.33-fold in HCC tissues when compared with adjacent tissues. The frequencies of rs2237062 and rs2547, but not rs2237061, were significantly different between patients with mild hepatitis and moderate-to-severe hepatitis. Moreover, rs2237062 and rs2547 polymorphisms correlated with impaired liver function parameters. ELISA results suggested that HBV-free controls had the highest level of CXCL14, while mild hepatitis patients had low levels, and patients with moderate-to-severe hepatitis had the lowest level. GA+AA genotypes of rs2547 were associated with reduced levels of serum CXCL14 because it introduced a stop codon at residue 109.Conclusion: CXCL14 was significantly suppressed in HBV-related HCC tissues, and its polymorphisms were linked with advanced stage chronic HBV infection and impaired liver function.Keywords: CXCL14, HBV infection, disease progression, polymorphism

Background: Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC., Method: This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed., Result: The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves., Conclusion: This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aim: To identify mtDNA and OGG1 as potential biomarker candidates for mechanical asphyxia., Method: The human tissues are divided into experimental group (hanging and strangulation) and control groups (hemorrhagic shock, brain injury group, and poisoning group). Detected the expression of OGG1 and integrity of mtDNA in cardiac tissue of each group. We used over-OGG1 vector and siRNA-OGG1 transfecting H9C2 cell line to observe the function of OGG1 in hypoxic cells., Results: 1. mtDNA integrity decreased in the mechanical asphyxia group, OGG1 expression increased in mechanical asphyxia groups. They can be biomarkers for mechanical asphyxia. 2. OGG1 increased first and decreased in hypoxia-induced H9C2 cells. OGG1 upregulated the TFAM, NRF1, and Bcl2 in hypoxia-induced H9C2. OGG1 downregulated cleaved-Caspase3 in hypoxia-induced H9C2 cells. 3. In the normoxia condition, NAC maintained mtDNA integrity and decreased the mitochondrial membrane potential and amount of ATP., Conclusion: mtDNA integrity and OGG1 expression can be biomarkers for mechanical asphyxia. OGG1 can maintain mtDNA integrity and maintain the stability of the mitochondrial membrane., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phosphorus-solubilizing microorganisms convert insoluble phosphorus in the soil into phosphorus that can be absorbed by plants. Soluble phosphate combines with heavy metals to form precipitation, reducing the content of available heavy metals, thereby reducing the absorption of heavy metals by crops, which plays an important role in the remediation of heavy metal-contaminated soil. The effects of the immobilization of Cd and Pb and the release of PO 4 3- by the phosphorus-solubilizing bacterium Klebsiella sp. M2 were studied through solution culture experiments. In addition, the effects of strain M2 on wheat uptake of Cd and Pb and its microbiological mechanism were also explored through pot experiments. The results showed that strain M2 reduced the concentrations of Cd and Pb and increased the concentration of PO 4 3- in the solution through cell wall adsorption and induced phosphate precipitation. Pot experiments showed that compared to those in the CK group and inactivated strain M2 group, inoculation with live strain M2 significantly increased （123%-293%） the contents of Ca 2 -P and Ca 8 -P in rhizosphere soil, decreased the content of DTPA-Cd （34.48%） and DTPA-Pb （36.72%） in wheat rhizosphere soil, and thus hindered the accumulation of Cd and Pb in wheat grains. Moreover, high-throughput sequencing results showed that strain M2 significantly increased the diversity of wheat rhizosphere bacterial communities； increased the relative abundance of Proteobacteria, Gemmatimonadetes, and Bacteroidota in wheat rhizosphere soil； and increased the proportion of heavy metal-immobilizing and phosphorus-promoting bacteria in wheat rhizosphere soil （mainly Sphingomonas , Nocardioides , Bacillus , Gemmatimonas , and Enterobacter ）. These bacterial genera played an important role in immobilizing heavy metals and preventing wheat from absorbing heavy metals. These results provide bacterial resources and theoretical basis for the bioremediation of heavy metal-contaminated farmland.

Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Objective: To identify efficacy and safety of pudendal nerve block in tubing through the third posterior sacral foramen for the treatment of pudendal neuralgia (PN). Methods: A retrospective study with 222 PN patients was conducted in the Department of Pain Management of Beijing Tsinghua Changgung Hospital from January 2020 to April 2023. These patients were divided into two groups based on their treatment methods: pudendal nerve block in tubing through the third posterior sacral foramen (observation group, n =101) and ultrasound-guided pudendal nerve block (control group, n =121). Primary outcome measure was the 90-day postoperative pain relief rate. Secondary outcome measures included visual analog scale (VAS) at 1, 7, 14, 30 and 90 d after surgery, the incidence of tramadol uses after surgery, postoperative self-rating anxiety scale (SAS) scores and the incidence of adverse events. Factors that influenced pain relief within 90 days after surgery were analyzed by using binary logistic regression analysis. Results: Observation group included 34 males and 67 females, aged (49.8±16.0) years old. Control group included 38 males and 83 females, aged (43.7±14.0) years old. The 90-day postoperative pain relief rate of the observation group patients was 38.6% (39/101), which was higher than the 24.0% (29/121) of the control group patients ( P =0.018). Both the observation group and the control group showed an interaction effect of time and group after treatment for VAS scores (both P <0.05). In intra-group comparison, the VAS scores at 1, 7, 14, 30 and 90 d after treatment in both groups were lower than those before treatment (all P <0.05). In inter-group comparison, the differences of the VAS scores were not statistically significant in the observation group compared with those in the control group at 1, 7, 14, 30 and 90 d after surgery (all P >0.05). The SAS score of the observation group at 90 d after surgery was 51.5±6.2, which was lower than the 53.4±5.8 of the control group ( P =0.022). There was no statistically significant difference in the incidence of postoperative tramadol uses and adverse events between the two groups (both P >0.05). Pudendal nerve block in tubing through the third posterior sacral foramen was a protective factor for pain postoperative relief in PN patients at 90 d after surgery ( OR =1.92, 95% CI : 1.05-3.48, P =0.033). Conclusion: Pudendal nerve block in tubing through the third posterior sacral foramen is a safe and effective minimally invasive treatment. It has a higher postoperative pain relief rate within 90 d after surgery, without increasing the uses of postoperative rescue analgesics and the incidence of adverse events.

Meteorological conditions play a key role in the occurrence and evolution of atmospheric complex pollution. Considering the different pollution formation mechanisms of PM 2.5 and O 3 , statistical calculation and in-depth learning methods were used to construct the PM 2.5 and O 3 meteorological condition indexes based on long-term pollution meteorological observation data. A research method was developed to study the meteorological characteristics and impact contribution of atmospheric complex pollution by using the meteorological condition index, and quantitative analysis of the distribution and variation of pollution excluding the influence of regional meteorological differences was also conducted. The results showed that in the summer of 2021, the pollution meteorological conditions in the key regions in central and eastern China were generally worse in the north and better in the south(index:"2+26" cities>the border area of Jiangsu, Anhui, Shandong, and Henan>the Yangtze River Delta) and the worst in June and the best in July. The "double high" pollution began to appear when the PM 2.5 meteorological condition index>30 and O 3 meteorological condition index>100; meanwhile, the unfavorable meteorological conditions for O 3 also promoted the increase in PM 2.5 concentration, resulting in the frequency of "double high" increases with the increase in O 3 meteorological condition index. Compared with that during the same period last year, ρ (PM 2.5 ) of each region decreased by 3.9 μg·m -3 , 3.3 μg·m -3 , and 1.4 μg·m -3 due to the contribution of the improvement in the pollution meteorological conditions, which is nearly 58.5% on average of the total decrease in PM 2.5 concentration. However, the change in O 3 pollution meteorological conditions was better in the north and worse in the south, and the overall deterioration in the Yangtze River Delta Region led to approximately 2.8 μg·m -3 growth for the O 3 concentration. The PM 2.5 and O 3 concentrations after excluding the impact of meteorological differences showed different distribution characteristics from the air quality monitoring, in which the high concentrations of PM 2.5 were distributed along the Bohai Sea, the inter-provincial border, and the south of the region, whereas the high concentrations of O 3 were concentrated along the Taihang Mountains, around Mount Tai, and in parts of the Yangtze River Delta. The daily concentration variations in a single city during a specific pollution control period could be used as a basis for evaluating the effectiveness of local supervision and control, which will provide a reference for the dynamic supervision and daily scheduling of local control management.

The level of HClO/ClO - in mitochondria is essential to keep the normal function of mitochondria. Therefore, it is meaningful to accurately and quickly monitor ClO - in mitochondria. In this work, a new triphenylamine-based fluorescence probe PDTPA was designed and synthesized, in which pyridinium salt and dicyano-vinyl group were introduced as mitochondria targeting site and reaction site for ClO - . The probe showed high sensitivity and fast fluorescence response (<10 s) in the detection of ClO - . Moreover, the probe PDTPA had good linearity in a wide concentration range of ClO - and its detection limit was calculated as 10.5 μM. Confocal fluorescence images demonstrated that the probe could target mitochondria and track the fluctuations of endogenous/exogenous ClO - levels in the mitochondria of living cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The migratory ability of microglia facilitates their rapid transport to a site of injury to kill and remove pathogens. However, the effect of Treponema pallidum membrane proteins on microglia migration remains unclear. The effect of Tp47 on the migration ability and autophagy and related mechanisms were investigated using the human microglial clone 3 cell line. Tp47 inhibited microglia migration, the expression of autophagy-associated protein P62 decreased, the expression of Beclin-1 and LC3-II/LC3-I increased, and the autophagic flux increased in this process. Furthermore, autophagy was significantly inhibited, and microglial cell migration was significantly increased after neutralisation with an anti-Tp47 antibody. In addition, Tp47 significantly inhibited the expression of p-PI3K, p-AKT, and p-mTOR proteins, and the sequential activation of steps in the PI3K/AKT/mTOR pathways effectively prevented Tp47-induced autophagy. Moreover, Tp47 significantly inhibited the expression of p-FOXO1 protein and promoted FOXO1 nuclear translocation. Inhibition of FOXO1 effectively suppressed Tp47-induced activation of autophagy and inhibition of migration. Treponema pallidum membrane protein Tp47-induced autophagy and inhibited cell migration in HMC3 Cells via the PI3K/AKT/FOXO1 pathway. These data will contribute to understanding the mechanism by which T. pallidum escapes immune killing and clearance after invasion into the central nervous system., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed., Methods: This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without human immunodeficiency virus (HIV) and to evaluate their diagnostic performance in neurosyphilis compared with CSF., Results: Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cutoff levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively., Conclusions: To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

PCR can be a supplement to Treponema serological testing. However, its sensitivity is not satisfactory for blood sample testing. The aim of this study was to investigate whether pretreatment with red blood cell (RBC) lysis could enhance the yield of Treponema pallidum subsp. pallidum DNA extraction from blood. We developed and verified the efficacy of a quantitative PCR (qPCR) assay that utilizes TaqMan technology to specifically detect T. pallidum DNA by targeting the polA gene. Simulation media with 10 6 to 10 0 treponemes/mL were prepared in normal saline (NS), whole blood, plasma, and serum, and RBC lysis pretreatment was performed on a portion of whole blood. Then, blood samples drawn from 50 syphilitic rabbits were divided in parallel into five groups, labeled whole blood, whole blood/lysed RBCs, plasma, serum, and blood cells/lysed RBCs. DNA extraction and qPCR detection were performed. The detection rate and copy number were compared among different groups. The polA assay showed good linearity and an excellent amplification efficiency of 102%. In the simulated blood samples, the detection limit of the polA assay reached 1 × 10 2 treponemes/mL in whole blood/lysed RBCs, plasma, and serum. However, the detection limit was only 1 × 10 4 treponemes/mL in NS and whole blood. Among the blood samples from syphilitic rabbits, whole blood/lysed RBCs showed the best detection rate (82.0%), while the detection rate for whole blood was only 6%. The copy number of whole blood/lysed RBCs was higher than that of whole blood. RBC lysis pretreatment can significantly improve the yield of T. pallidum DNA from whole blood, and the yield is better than that from whole blood, plasma, serum, and blood cells/lysed RBCs. IMPORTANCE Syphilis is a sexually transmitted disease caused by T. pallidum that can spread into the blood. T. pallidum DNA can be detected in blood by PCR but with low sensitivity. Few studies have applied RBC lysis pretreatment to blood T. pallidum DNA extraction. This study shows that the detection limit, detection rate, and copy number of whole blood/lysed RBCs were better than those of whole blood, plasma, and serum. After RBC lysis pretreatment, the yield of low concentrations of T. pallidum DNA was improved, and the low sensitivity of blood-based T. pallidum PCR was improved. Therefore, whole blood/lysed RBCs are the ideal sample for acquiring blood T. pallidum DNA., Competing Interests: The authors declare no conflict of interest.

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The invasive capability of Treponema. pallidum is central to its infection process. Matrix metalloproteinases (MMPs), which are specifically inhibited by the tissue inhibitors of metalloproteinases (TIMPs), play a pivotal role in promoting pathogenic invasion by destroying tissue barriers within the body. This study aimed to explore the effect of T. pallidum protein Tp0136 on the balance of MMPs/TIMPs in human dermal vascular smooth muscle cells (HDVSMCs) and the related underlying mechanisms. A number of in vitro studies were conducted to access the impact of recombinant Tp0136 protein on the balance of MMPs/TIMPs in HDVSMCs. The involvement of the PI3K, MAPK, and NF-κB signaling pathways in this process was also investigated. Tp0136 induced the mRNA and protein expressions of MMP1 in HDVSMCs in a concentration-dependent way. In addition, MMP1/TIMP1 and MMP1/TIMP2 ratios were also increased. Furthermore, the study demonstrated that treatment of HDVSMCs with Tp0136 activated the PI3K, MAPK, and NF-κB signaling pathways. Inhibition of PI3K, JNK, P38, and NF-κB, suppressed MMP1 expression and reduced the induction of MMP1/TIMP1 and MMP1/TIMP2 ratios by Tp0136. These findings demonstrate that Tp0136 enhanced the expression of MMP1 involving the PI3K, MAPK, and NF-κB signaling pathways in HDVSMCs, and thus generated the unbalance of MMPs/TIMP, which could contribute to the early spread of T. pallidum and pathogenesis of syphilis., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Purpose: The accuracy of level of anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a great concern. We aimed to compare the efficacy of anti-SARS-CoV-2 antibody detection kits from two manufacturers in evaluating the efficacy of SARS-CoV-2 vaccines., Methods: The immune responses and consistency of four anti-SARS-CoV-2 antibodies were evaluated using two manufacturers' antibody kits (A and B) in 61 subjects within 160 days after vaccination with the CoronaVac vaccine., Results: The total seropositivity rates of neutralizing antibodies and IgM antibodies detected by kit A were higher than those detected by kit B (P = 0.003 and P < 0.001, respectively). Conversely, the total seropositivity rates of total antibodies and IgG antibodies were higher in kit B than kit A (P < 0.001 and P < 0.001, respectively). The consistency rates showed less than 90% agreement between the kits for the detection of the four antibodies, and the κ score showed moderate or substantial consistency. The half-lives of neutralizing antibodies, total antibodies, and IgG antibodies within 160 days after vaccination, detected by kit A were 63.88 days, 80.50 days, and 63.70 days, respectively and by kit B were 97.06 days, 65.41 days, and 77.99 days, respectively., Conclusion: The efficacy of antibody detection differed between the two commercial anti-SARS-CoV-2 antibody kits, although there was moderate consistency, which may affect the clinical application and formulation of the vaccine strategy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Context.—: Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors., Objective.—: To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs., Design.—: The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination., Results.—: The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P < .001). The area under the receiver operating characteristic curve for total antibody levels for the prediction of seropositivity for neutralizing antibodies was 0.881 (P < .001), and that for anti-RBD IgG antibody levels was 0.937 (P < .001)., Conclusions.—: Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination.

Aim: The present study examined the membrane location of cardiolipin antigen in treponemes. Materials & methods: The authors used different methods to disrupt the outer membrane of treponemes, detected the location of the cardiolipin antigen and analyzed the immune response in rabbits immunized with various antigens. Results: All organisms were labeled with nontreponemal antibodies on immunoelectron and fluorescence microscopy, except the citrate buffer-treated group, which is a method leading to relatively complete removal. Except for citrate buffer-treated spirochetes, all treponemes produced low-titer, nontreponemal antibodies in immunized rabbits. Conclusion: These findings indicated that the cardiolipin antigen was localized in the outer membrane of spirochetes. This study provided further evidence of the origin of nontreponemal antibodies during Treponema pallidum infection.

Background: Pudendal neuralgia (PN) is one of the most common forms of genital pain. Only 42.2% of PN patients respond to the first-line treatment. Novel neuromodulation techniques in the treatment of refractory PN patients are urgently required., Objectives: The aim of this study was to evaluate the treatment effects and adverse events of sacral nerve stimulation (SNS) for patients with refractory PN., Study Design: A prospective nonrandomized study., Setting: This prospective analysis included 33 patients who received the phase II surgical implantation., Methods: A total of 55 eligible PN patients were recruited for SNS treatment after informed consent, and 33 of 55 patients with a minimum 50% improvement were candidates for surgical implantation. Visual Analog Scale (VAS) scores, Self-rating Anxiety and Depression Scale, Quality of life score (SF-36), and sleep monitoring indicators before and after surgery were used to assess the effects of SNS on patients with refractory PN., Results: Thirty-three patients were included in the final analysis, involving 24 women and 9 men with a mean age of 49.5 years (26-70 years). There was a favorable decrease in pain severity (VAS scores) from 7.1 ± 1.1 at baseline to 6.1 ± 1.0 on postoperative day 1, and 2.8 ± 0.7 at 1 week, 1.7 ± 0.5 at 1 month, 1.1 ± 0.7 at 6 months, and 1.0 ± 0.6 at 12 months after surgery, respectively (P < 0.05). The mean score of each section of SF-36 after SNS was significantly higher than that at baseline (P < 0.05). Total sleep time and sleep time in each period were significantly prolonged after SNS implantation compared with that before surgery (6 months vs Pre, total: 5.32 ± 1.49 hours vs 3.66 ± 1.19 hours, deep: 2.52 ± 0.63 hours vs 1.36 ± 0.43 hours, light: 1.78 ± 0.42 hours vs 0.99 ± 0.30 hours, rapid eye movement: 1.41 ± 0.29 hours vs 0.89 ± 0.27 hours, P < 0.05). No serious device complications were reported during the follow-up period., Limitations: Large-scale randomized clinical trials are warranted to evaluate the risk factors for prediction of refractory PN., Conclusions: These data imply that SNS can have beneficial effects on patients with refractory PN.

Background: Determining what quarantine period and detection strategy are more effective and sustainable remains a challenge for further prevention and social stability., Methods: From October 2020 to December 2021, 290,547 inbound overseas travelers were subject to government quarantine in Xiamen, China. The detection rate of COVID-19 during different quarantine periods using dual or single nucleic acid testing reagents., Results: The COVID-19 positive rate was 1.79% (519/290,547). The detection rates during the 7-day, 14-day and 14+7-day quarantine periods using the dual reagents were 78.4%, 91.7%, and 100%, respectively. The detection rate of the 7-day, 14-day and 14+7-day quarantine periods were 73.99%, 86.51%, and 94.22%, respectively, using the Liferiver reagent and 72.25%, 84.59%, and 91.91%, respectively, using the Daan reagent. Based on the 14+7 day strategy, dual nucleic acid testing reagent strategy detected all imported cases, but 30 cases (5.78%) were not detected via Liferiver reagent and 42 (8.09%) cases not detected via Daan reagent., Conclusion: A 14+7-day quarantine period and dual nucleic acid testing reagent strategy are effective screening methods for COVID-19 among inbound overseas travelers. The superior detection rate of these strategies reduce the risk of secondary transmission of the SARS-CoV-2 virus., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group ( P >0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95% CI :13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial ( t =-1.04, P >0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.

The study aimed to explore the neutrophil's spatial distributions used to estimate the histological age of contused skeletal muscle, and assessed the accuracy of various indicators, such as the proportion of neutrophils, "neutrophil mean distance," and distribution of neutrophils in areas of "contiguous contour lines." Fifty-five Sprague-Dawley rats were divided randomly into a control group and contusion groups at 1, 1.5, 2, 3, 4, and 6 h, as well as 1, 3, 5, and 15 days, post-injury (n = 5 per group). Nuclei and neutrophils were detected by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. At 0-24 h after injury, the distribution of neutrophils at distances of 100, 200, 300, 400, 500, and 600 µm from adjacent blood vessels was determined, and the best samples were screened to estimate wound age. To estimate wound age as accurately as possible, Fisher discriminant analysis (FDA) of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils was performed, and 100.0% and 95.0% of the original and cross-validated cases were correctly classified, respectively. The spatial distribution of neutrophils at different distances from adjacent blood vessels showed a strong correlation with the histological age of contusion skeletal muscle, and the combination of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils could be used to accurately estimate wound age., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Age at natural menopause (ANM) is an important index for women's health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood., Methods: Aiming to better characterize the genetic architecture of ANM, we conducted genome-wide association study (GWAS) meta-analyses in European-specific as well as trans-ancestry samples by using GWAS summary statistics from the following 3 large studies: the Reproductive Genetics Consortium (ReproGen; N = 69 626), the UK Biobank cohort (UKBB; N = 111 593) and the BioBank Japan Project (BBJ; N = 43 861), followed by a series of bioinformatical assessments and functional annotations., Results: By integrating the summary statistics from the 3 GWAS of up to 225 200 participants, this largest meta-analysis identified 49 novel loci and 3 secondary signals that were associated with ANM at the genome-wide significance level (P < 5 × 10-8). No population specificity or heterogeneity was observed at most of the associated loci. Functional annotations prioritized 90 candidate genes at the newly identified loci. Among the 26 traits that were genetically correlated with ANM, hormone replacement therapy (HRT) exerted a causal relationship, implying a causal pattern by which HRT was determined by ANM., Conclusion: Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: In cases of sudden death, the prevention of sudden cardiac death and the analysis of the cause of death after sudden cardiac death have always been a difficult problem. Therefore, clinical research and forensic pathological identification of sudden cardiac death are of great significance. In recent years, metabolomics has gradually developed into a popular field of life science research. The detection of "metabolic fingerprints" of biological fluids can provide an important basis for early diagnosis of diseases and the discovery of potential biomarkers. This article reviews the current research status of sudden cardiac death and the research on metabolomics of cardiovascular diseases that is closely related to sudden cardiac death and analyzes the application prospects of metabolomics in the identification of the cause of sudden cardiac death., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: Long noncoding RNAs (lncRNAs) are closely associated with the development of hepatocellular carcinoma (HCC). The present study conducted a genome-wide microarray analysis and qPCR validation to obtain comprehensive insights into this issue., Methods: Thirty male HCC patients with chronic HBV infection were included in the present study. Primary HCC tissue and normal tissue were collected. Double-stranded complementary DNA synthesized from 10 pairs of samples was labeled and hybridized to a microarray chip. Further analyses, such as hierarchical clustering, gene ontology (GO) and pathway analyses, were performed. In addition, qPCR validation was performed on tissue samples and additional serum samples., Results: The microarray analysis identified 946 upregulated and 571 downregulated lncRNAs and 1720 upregulated and 1106 downregulated mRNAs. Among these RNAs, ENST00000583827.1 (fold change: 21) and uc010isf.1 (fold change: 18) were the most over- and underexpressed lncRNAs in the HCC tissues, respectively. For the mRNAs, KIF20A (fold change: 26) and HEPACAM (fold change: 50) were the most over- and underexpressed in the HCC tissues, respectively. The GO analysis demonstrated that the most differentially expressed mRNAs were related to the response of metal ions. The pathway analysis also suggested that the most enriched pathway was mineral absorption., Conclusions: The subsequent qPCR validation exhibited high consistency with the microarray analysis, except for three lncRNAs. The qPCR analysis also demonstrated that TCONS&#95;00008984 had a 767-fold overexpression level in HCC tissues when compared with normal tissues, and this finding was confirmed in the serum samples; therefore, TCONS&#95;00008984 has the potential to serve as a diagnostic marker or prognostic indicator. The GO and pathway analyses indicated that exposure to inorganic elements may be involved in HCC risk.

In total, 49 clinical samples were analyzed using two typing schemes, Enhanced Centers for Disease Control and Prevention (ECDC) and multilocus sequence typing (MLST), to describe the molecular characteristics of circulating Treponema pallidum isolates in Xiamen between 2016 and 2017. In addition, genetic mutations potentially related to antibiotic resistance of T. pallidum were also analyzed. Forty five samples were fully typed by ECDC, and 14 different subtypes were detected. The most common subtype was 16d/f (24.4%), followed by 14d/f (20.0%). All forty nine samples were successfully typed by MLST, while only four allelic profiles were identified, including three SS14-like profiles and one Nichols-like profile. Among them, the major allelic profile was 1.1.8 (85.7%). Interestingly, the allelic profile 1.3.1 widespread in Europe and North America was not detected in this region. Additionally, A2058G mutation in 23S rRNA was found in all detectable samples (38/38), and no mutation in 16S rRNA was observed (36/36). Four non-synonymous single-nucleotide polymorphisms in penicillin-binding protein genes were found in the 35 samples eligible for Sanger sequencing. Among them, the variant in tp0500 (P564I) can only be found in the SS14-like isolates. Homoplastic changes in tp0760 (I415F/I415M) and tp0705 (A506V/A506T) were found. Moreover, the variant tp0705 A506V and the variant tp0705 A506T separately appeared in the SS14-like isolates and Nichols-like isolates, respectively. This study showed that the genotypes of T. pallidum isolates in Xiamen between 2016 and 2017 were different from those in other geographic areas. The resistance-related variants of T. pallidum isolates identified in this study could provide awareness for clinicians in the treatment of syphilis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Liu, He, Zhu, Liu, Lin, Niu and Yang.)

Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.

Objective: Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC)., Methods: After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model., Results: In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80-0.90) and 0.88 (95% CI, 0.82-0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9-10.2), 0.16 (95% CI, 0.11-0.23), and 44 (95% CI, 25-79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias., Conclusion: Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application., (© American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since the end of 2019, China and other regions around the world have been facing a pandemic of novel coronavirus pneumonia (COVID-19). The virus is highly transmissible, and the human population is generally susceptible. Most patients with osteoporosis are postmenopausal women or elderly people with hypoimmunity, so the osteoporosis clinic has become a new hotspot for corona virus infection. During the COVID-19 pandemic, it is necessary to establish standardized out-patient protocols to provide safe and effective treatment for osteoporosis patients and medical staff. In an osteoporosis clinic, we advocate the following suggestions to prevent and control osteoporosis during the pandemic period: (1) specialized diagnosis and treatment techniques for osteoporosis patients in the outpatient care, including enhancing the prevention for outpatient medical staff, strengthening awareness of COVID-19 prevention, strictly screening outpatients with COVID-19 infection, and insistent administration of anti-osteoporosis drugs during outbreaks; (2) home prevention for osteoporosis patients including keeping windows open, exposing them to sunlight, supplementing them with enough protein, exercising regularly, and administrating calcium supplements; and (3) simplifying the follow-up and evaluation of osteoporosis using online platforms.

Background: This study aimed to evaluate real-time polymerase chain reaction coupled with multiplex probe melting curve analysis (PCR-MCA) for pathogen detection in patients with suspected bloodstream infections (BSIs). Methods: A PCR-MCA assay was developed for simultaneous identification of 28 kinds of the most common pathogens and two resistance genes within a few hours. The diagnostic performance of the PCR-MCA assay was determined and compared to the results of blood culture. Results: A total of 2,844 consecutive new episodes of suspected BSIs in 2,763 patients were included in this study. There were 269 episodes of pathogens identified by blood culture. For all the pathogens tested, the PCR-MCA assay exhibited a sensitivity of 88.8% (239/269), specificity of 100% (2,575/2,575), and agreement of 98.9% (2,814/2,844). For the pathogens on the PCR-MCA list, the PCR-MCA results had a sensitivity of 99.2% (239/241), specificity of 100% (2,575/2,575), and agreement of 99.9% (2,814/2,816) compared with the results of blood culture. For seven samples with multiple pathogens identified simultaneously during one blood culture investigation, the PCR-MCA assay verified the results of the blood culture, with an agreement rate of 100% for each. Conclusion: The PCR-MCA assay could discover 88.8% of the pathogens in clinical practice, showing excellent diagnostic performance vs. that of blood culture for pathogen detection in patients with suspected BSIs, and would contribute to rapid diagnosis and correct antibiotic administration., (Copyright © 2019 Xiao, Shen, Zhao, Yao, Yang and Niu.)

Juvenile hormone analogue (JHA) insecticides are endocrine disrupters that interfere with hormonal action in insects by mimicking their juvenile hormones (JH). As the structure and functions of methyl farnesoate in crustaceans are similar to those of JH in insects, exogenous JHA insecticides could have adverse effects on the development and reproduction of crustaceans. This study examined the toxic effects of two JHA insecticides, fenoxycarb and methoprene, on a freshwater shrimp model of cherry shrimp, Neocaridina davidi. Both insecticides had detrimental effects on cherry shrimp, but fenoxycarb was more toxic than methoprene. Chronic exposure to these insecticides reduced the shrimp's body length and molting frequency. Based on transcriptome annotations for N. davidi, we identified important gene homologues that were active in both insect JH biosynthetic and degradative pathways as well as JH and ecdysteroid signaling pathways. Chronic treatments with JHAs had significant effects on these genes in N. davidi. Our transcriptomic analysis showed that genes involved in the pathways related to cuticle development, serine protease activity, and carbohydrate, peptide and lipid metabolic processes were differentially expressed in shrimp exposed to JHAs. These results demonstrate the toxicity of fenoxycarb and methoprene to freshwater crustaceans and indicate the need to monitor the use of JHA insecticides., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients., (Copyright © 2019. Published by Elsevier Inc.)

Background: Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens., Objective: To gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients., Methods: We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls., Results: A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t-test, including trimethylamine N-oxide, l-arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N-oxide was 3.922 times in patients with syphilis than healthy controls., Conclusion: Trimethylamine N-oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum., (© 2019 European Academy of Dermatology and Venereology.)

Background: Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown., Methods: Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) ( n  = 272) and The Cancer Genome Atlas (TCGA) ( n  = 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction., Results: In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588)] and TCGA [eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others., Conclusions: Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

The mechanism underlying the stealth property of neurosyphilis is still unclear. Global metabolomics analysis can provide substantial information on energy metabolism, physiology and possible diagnostic biomarkers and intervention strategies for pathogens. To gain better understanding of the metabolic mechanism of neurosyphilis, we conducted an untargeted metabolomics analysis of cerebrospinal fluid (CSF) from 18 neurosyphilis patients and an identical number of syphilis/non-neurosyphilis patients and syphilis-free patients using the Agilent, 1290 Infinity LC system. The raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst 4.0. Metabolites with a variable importance in projection (VIP) greater than one were validated by Student's T -test. A total of 1,808 molecular features were extracted from each sample using XCMS software, and the peak intensity of each feature was obtained. Partial-least squares discrimination analysis provided satisfactory separation by comparing neurosyphilis, syphilis/non-neurosyphilis and syphilis-free patients. A similar trend was obtained in the hierarchical clustering analysis. Furthermore, several metabolites were identified as significantly different by Student's T -test, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, hypoxanthine, and S -methyl-5'-thioadenosine. Notably, 87.369-fold and 7.492-fold changes of N-acetyl-L-tyrosine were observed in neurosyphilis patients compared with syphilis/non-neurosyphilis patients and syphilis-free patients. These differential metabolites are involved in overlapping pathways, including fructose and mannose metabolism, lysosomes, ABC transporters, and galactose metabolism. Several significantly expressed metabolites were identified in CSF from neurosyphilis patients, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, and hypoxanthine. These differential metabolites could potentially improve neurosyphilis diagnostics in the future. The role of these differential metabolites in the development of neurosyphilis deserves further exploration.

Background: The highly variable tprK gene of Treponema pallidum has been acknowledged to be one of the mechanisms that causes persistent infection. Previous studies have mainly focused on the heterogeneity in tprK in propagated strains using a clone-based Sanger approach. Few studies have investigated tprK directly from clinical samples using deep sequencing., Methods/principal Findings: We conducted a comprehensive analysis of 14 primary syphilis clinical isolates of T. pallidum via next-generation sequencing to gain better insight into the profile of tprK in primary syphilis patients. Our results showed that there was a mixture of distinct sequences within each V region of tprK. Except for the predominant sequence for each V region as previously reported using the clone-based Sanger approach, there were many minor variants of all strains that were mainly observed at a frequency of 1-5%. Interestingly, the identified distinct sequences within the regions were variable in length and differed by only 3 bp or multiples of 3 bp. In addition, amino acid sequence consistency within each V region was found among the 14 strains. Among the regions, the sequence IASDGGAIKH in V1 and the sequence DVGHKKENAANVNGTVGA in V4 showed a high stability of inter-strain redundancy., Conclusions: The seven V regions of the tprK gene in primary syphilis infection demonstrated high diversity; they generally contained a high proportion sequence and numerous low-frequency minor variants, most of which are far below the detection limit of Sanger sequencing. The rampant variation in each V region was regulated by a strict gene conversion mechanism that maintained the length difference to 3 bp or multiples of 3 bp. The highly stable sequence of inter-strain redundancy may indicate that the sequences play a critical role in T. pallidum virulence. These highly stable peptides are also likely to be potential targets for vaccine development., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Recently, neurosyphilis was found to be associated with diabetes mellitus (DM). Whether the association was specific to neurosyphilis among central nervous system (CNS) infections, and whether neurosyphilis is associated with other prevalent metabolic disorders deserves further study., Methods: An in-depth cross-sectional study was conducted with 74 neurosyphilis patients and 74 sex- and age-matched patients with other CNS infections. DM-, hypertension-, and dyslipidemia-related factors were compared between patients with neurosyphilis and those with other CNS infections., Results: The prevalence rates of hypertension and hyperlipidemia in neurosyphilis patients were 45.9 and 21.4%, respectively, which were higher than those in patients with other CNS infections (45.9 vs. 28.4%, p = 0.027; 21.4 vs. 8.3%, p = 0.028). In addition, neurosyphilis patients had significantly higher systolic blood pressure (BP; median 139 mm Hg; interquartile range [IQR] 121-151 mm Hg), -diastolic BP (median 83 mm Hg; IQR 76-89 mm Hg), total cholesterol (median 4.86 mmol/L; IQR 3.80-5.51 mmol/L), low-density lipoprotein (median 3.39 mmol/L; IQR 2.52-3.95 mmol/L), and apolipoprotein A1 (apoA1; median 1.31 g/L; IQR 1.06-1.52 g/L) levels and lower apoB/A1 ratios (median 0.67; IQR 0.49-0.99) than patients with other CNS infections (p< 0.05). There were no differences in the DM-related factors between patients with neurosyphilis and those with other CNS infections (p> 0.05)., Conclusion: Potential association between neurosyphilis and metabolic disorders was found among CNS infections. The results could have important implications for clinical practice, alerting more clinicians to this issue., (© 2019 S. Karger AG, Basel.)

Sevoflurane is an experimental potent yet volatile anesthesia agent characterized by a low blood/gas partition coefficient. However, exposure to sevoflurane in neonatal mice has been speculated to result in learning deficits and abnormal social behavior. The aim of the present study was to investigate the relationship between sevoflurane and miR-96, in an attempt to identify the means by which it mediates IGF1R to influence the cognitive dysfunction (CD) in neonatal rats. Relationship between differentially expressed miRNAs and sevoflurane concentration was identified. The potential underlying regulatory mechanisms involved with sevoflurane were investigated through the administration of varying concentrations of the agent (1%, 2% and 4%), combined with miR-96 mimic or an inhibitor. A target prediction program was utilized, while the luciferase activity was determined in order to verify whether miR-96 targets IGF1R. The mRNA and protein levels of IGF1R, Bcl-2, Bax, and caspase-3 were measured followed by the determination of hippocampal neuron apoptosis. Learning and memory performance was assessed using the Morris water maze (MWM) test and step-down test. The obtained results highlighted a positive correlation between miR-96 and the concentration of sevoflurane, while miR-96 was confirmed to negatively target IGF1R. Our analyses indicated that 4% sevoflurane had a significantly stronger effect on reducing the levels of IGF1R and Bcl-2, while elevating the levels of miR-96, Bax and caspase-3 more so than that of 1% or 2% sevoflurane, which resulted in increased hippocampal neuron apoptosis but diminished the learning and memory performance of the rats. The addition of miR-96 mimic was demonstrated to exacerbate the influence of sevoflurane on hippocampal neurons as well as the cognitive function of the rats. The key findings of our study highlighted the role of miR-96 in the potential mechanism of sevoflurane anesthesia-induced CD in neonatal rats through the downregulation of IGF1R., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A large-scale arsenic slag-contaminated site was selected to determine soil pollution characteristics and the degree of ecological risk of a large-scale contaminated site. In this study, 184 site soil samples, 101 agricultural soil samples, and 14 arsenic slag samples were collected and the pollution characteristics and ecological risk of As were evaluated using multivariate statistics, geostatistics, and the geoaccumulation and potential ecological risk index methods. The results show that the average As contents in site soil, agricultural soil, and arsenic slag are 1333.0, 358.1, and 17316.1 mg·kg -1 , respectively. The degree of contamination of As exceeds the national standard Ⅲof the environmental soil quality. The results of the vertical and three-dimensional distributions of contamination show that As is accumulated to different extents in different strata. The accumulation in the site surface soil is the most serious. The As concentrations in site soil samples are higher than that in agricultural soil samples. The potential ecological risk index method shows that all mean potential ecological risk indexes exceed 100 in different strata. Moreover, the percentage of samples in site and agricultural soils at medium pollution level ratios is 58.21% and 61.39%, respectively, illustrating that the As pollution of soil samples from this contaminated site and surrounding farm areas is serious.

In this work, we employed real-time PCR analysis targeting tp0574 to investigate the effects of different processing procedures on the yield of T. pallidum DNA from blood to improve assay sensitivity. The T. pallidum DNA yields following red blood cell lysis pretreatment were 40.4 times greater from whole blood and 32.4 times greater from residual hematocytes than yields without pretreatment. For the simulated whole-blood experiments, the T. pallidum DNA yields from the lower layer were 2.8, 4.6, 7.3, 12.6, 15.24, 16.7, 65.1 and 73.1 times those from the upper layer following centrifugation at 500×, 1000×, 2000×, 4000×, 5000×, 7000×, 10,000× and 20,000 × g, respectively. However, the T. pallidum DNA yields from blood clots were only 1.0% at different centrifugal forces. The experiment with infected rabbit blood showed results similar to those mentioned above. In addition, sample processing time (within 48 h) and storage temperature (4 °C and 25 °C) did not affect T. pallidum DNA extraction efficiency. The T. pallidum DNA yield can be significantly improved by red blood cell lysis pretreatment and appropriate centrifugation. Furthermore, the T. pallidum DNA extraction yield is greater from whole blood or residual hematocytes from anti-coagulated blood than from plasma, serum or blood clots., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1β production and its influence on macrophage polarization triggered by T. pallidum., Results: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1β and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1β secretion in T. pallidum-treated macrophages, and the observed production of IL-1β occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1β by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1β release from T. pallidum-treated macrophages., Conclusions: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1β secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1β production in macrophages in response to T. pallidum infection involves K + efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Anticardiolipin antibody (ACA) includes beta2-glycoprotein I-dependent (β2-GPI-dependent) and β2-GPI-independent forms. The appearance of β2-GPI-dependent ACA and its association with blood coagulation have never been investigated in subjects with classical biological false-positive syphilis reactions (CBFP). In total, 146 CBFP subjects, 465 syphilis patients and 64 presumed antiphospholipid antibody syndrome (pAPS) patients were enrolled, and β2-GPI-dependent ACA IgA/IgG/IgM and anti-β2-GPI IgA/IgG/IgM antibodies were detected via chemiluminescence assay. Conventional blood coagulation indices were measured to analyze their associations with these autoantibodies. In current study, the positive rate of β2-GPI-dependent ACA in CBFP subjects was 22.60%, which was significantly higher than that in syphilis patients (3.87%) (P < 0.001) and similar to that in pAPS patients (32.81%) (P = 0.119). The predominant autoantibody isotypes were IgG in CBFP subjects and pAPS patients and IgM in syphilis patients. Positive autoantibody rates were independent of rapid plasma reagin titers. CBFP and pAPS subjects had longer prothrombin times (P < 0.001) and activated partial thromboplastin times (APTTs, P < 0.001) but lower fibrinogen concentrations (P = 0.022) and platelet counts (P < 0.001) than syphilis patients. APTTs were prolonged in CBFP, syphilis and pAPS subjects with positive autoantibodies compared with those in subjects with negative autoantibodies (P < 0.05). In conclusion, ACAs in CBFP and syphilis subjects are heterogeneous; β2-GPI-dependent ACA constitutes a significant proportion of ACAs in CBFP subjects, while β2-GPI-independent ACA predominates in syphilis patients. CBFP subjects are more prone to blood coagulation disorders than syphilis patients, and these autoantibodies may impact the intrinsic coagulation cascade in CBFP subjects, similar to pAPS patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The origin of nontreponemal antibodies during syphilis infection is hotly debated. Here, we analyzed the immune response in rabbits immunized with various antigens. Inactivated treponemes elicited the production of low-titer nontreponemal antibodies in some rabbits. Cardiolipin combined with bovine serum albumin also induced anticardiolipin antibody production. These findings indicate that Treponema pallidum contained a cardiolipin antigen with weak immunogenicity. However, active T. pallidum induced higher nontreponemal antibody production with strong immunogenicity at an earlier time point, and the antibody titer was consecutive, suggesting the high nontreponemal antibody titer resulted from the combined effects of both the T. pallidum cardiolipin antigen and the damaged host-cell cardiolipin antigen during syphilis infection, the latter of which plays a major role in the induction of nontreponemal antibody production. Our study provides direct animal evidence of the origin of nontreponemal antibodies during T. pallidum infection.

The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1β and TNF-α) expression in a dose- and time-dependent manner. However IL-10 cytokine expression decreased at the mRNA and protein levels. Additionally, the expression of the M1 surface marker iNOS was up-regulated with incubation time, and the expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR-NFκB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p-IκBα, were significantly higher in the T. pallidum-treated macrophages than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory cytokine expression was suppressed in T. pallidum-induced M1 macrophages pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-κB inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings revealed that T. pallidum promotes the macrophage transition to pro-inflammatory M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR and NF-κB pathway activation in T. pallidum stimulates M1 macrophages. This study provides novel insights into the innate immune response to T. pallidum infection., (Copyright © 2018. Published by Elsevier B.V.)

A novel glucoside bletilloside A (1) was isolated from the tubers of Bletilla striata, together with seven known compounds (2-8). Their structures were determined on the basis of extensive spectroscopic analyses. All compounds were evaluated for the inhibition on NO production effects in RAW 264.7 macrophage cells, while militarine (4) and dactylorhin A (5) exhibited moderate inhibitory effects.

Background: Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection., Methods: During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level., Results: We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480., Conclusions: TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease.

Objectives: The aim of this study was to evaluate the risk factors for pneumonia due to extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) and to analyse the molecular epidemiology of ESBL-KP in Xiamen, China., Methods: A case-control study was conducted at Zhongshan Hospital from January 2014 to August 2015. Medical records of patients with nosocomial pneumonia caused by K. pneumoniae were collected. A total of 40 cases with ESBL-KP infection and 90 controls with non-ESBL-KP infection were included. The sequence types (STs) of the 40 ESBL-KP strains were determined by multilocus sequence typing (MLST)., Results: Univariate analysis primarily revealed an association between the following seven risk factors and ESBL-KP infection (P<0.10): length of hospitalisation; use of cephalosporins; use of quinolones; presence of a nasogastric tube; presence of an intravenous catheter; mechanical ventilation; and cerebrospinal fluid drainage. Furthermore, multivariate analysis revealed that use of cephalosporins and presence of a nasogastric tube were independent risk factors for ESBL-KP infection (P<0.05), with adjusted odds ratios of 3.473 [95% confidence interval (CI) 1.105-10.911; P=0.033] and 2.488 (95% CI 1.083-5.715; P=0.032), respectively. MLST identified 28 STs. The main STs were ST23 (10.0%) and ST37 (10.0%); three novel STs were identified., Conclusions: Use of cephalosporins and presence of a nasogastric tube are independent risk factors for ESBL-KP infection. In addition, the discovery of three novel STs serves as a reminder to continuously monitor outbreaks of ESBL-KP infection., (Copyright © 2017. Published by Elsevier Ltd.)

This study aimed to determine whether a serological response could predict the normalization of cerebrospinal fluid (CSF) abnormalities at 6 months after treatment in human immunodeficiency virus (HIV)-negative neurosyphilis patients. A total of 123 neurosyphilis patients were recruited at baseline, 58 of these patients undergoing treatment, repeated CSF examinations and serological tests for syphilis at 6 months after treatment were included in the follow-up study. Before treatment, the CSF rapid plasma reagin (RPR) titer, CSF Treponema pallidum particle agglutination (TPPA) titer, CSF leukocyte count, and CSF protein concentration were correlated with both serum RPR and TPPA titers. At 6 months after treatment, 28 and nine patients achieved serological responses of RPR and TPPA tests, respectively. The sensitivities of the serological response of RPR and TPPA tests for identifying the normalization of CSF abnormalities were 60.0∼83.3% and 17.1~22.2%, respectively; and 75.0∼91.3% of patients showing serological response of RPR test also achieved CSF normalization, suggesting that the serological response could predict CSF normalization to some degree. Particularly, in patients with ≥8-fold decreases in the serum RPR titer, the CSF RPR, CSF leukocyte count, and CSF protein concentration had normalized, and follow-up lumbar puncture could be reduced considering the resolution of neurological symptoms.

Treponema pallidum ssp. pallidum (T. pallidum), the causative agent of the sexually transmitted disease syphilis, is an uncultivatable human pathogen. The geographical differences in T. pallidum genomes leading to differences in pathogenicity are not yet understood. Presently, twelve T. pallidum genomes are available to the public, all of which are American in origin and often co-infect patients with human immunodeficiency virus (HIV). In this study, we examined the T. pallidum subsp. pallidum strain Amoy, a syphilis pathogen found in Xiamen, China. We sequenced its genome using Illumina next-generation sequencing technology and obtained a nearly (98.83%) complete genome of approximately 1.12 Mbps. The new genome shows good synteny with its five T. pallidum sibling strains (Nichols, SS14, Mexico A, DAL-1, and Chicago), among which SS14 is the strain closest to the Amoy strain. Compared with strain SS14, the Amoy strain possesses four uncharacterized strain-specific genes and is likely missing six genes, including a gene encoding the TPR domain protein, which may partially account for the comparatively low virulence and toxicity of the Amoy strain in animal infection. Notably, we did not detect the 23S rRNA A2058G/A2059G mutation in the Amoy strain, which likely explains the sensitivity of Amoy strain to macrolides. The results of this study will lead to a better understanding of the pathogenesis of syphilis and the geographical distribution of T. pallidum genotypes.