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Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434 . Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

Abstract Glucagon-like peptide 1 (GLP-1) can promote islet β cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. The aim of this study was to test the dynamic distribution of infused human MSCs and the therapeutic effect of combined MSCs and liraglutide, a long-acting GLP-1 analog, on preserving β cell function in severe nonobese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 wks post infusion, which was not affected by liraglutide treatment. Liraglutide significantly enhanced the function of MSCs to preserve islet β cells by reducing glucose levels 30 min post glucose challenge and increasing the content and secretion of insulin by islet β cells in severely diabetic mice. Infusion with MSCs significantly reduced insulitis scores but increased the frequency of splenic Tregs, accompanied by a reduction in plasma IFN-γ and TNF-α levels and an elevation of plasma IL-10 and transforming growth factor-β1 (TGF-β1) levels in NOD mice. Although liraglutide mitigated MSC-mediated changes in the frequency of Tregs and the level of plasma IL-10, it significantly increased the plasma TGF-β1 levels in severely diabetic mice. Therefore, our findings suggest that liraglutide could enhance the therapeutic efficacy of MSCs in the treatment of severe type 1 diabetes.

Puerarin is an isoflavone isolated from Radix puerariae. Emerging evidence shown that puerarin possesses therapeutic benefits that aid in the prevention of cardiovascular diseases. In this study, we evaluated the effects of puerarin on oxidative stress and cardiac fibrosis induced by abdominal aortic banding (AB) and angiotensin II (AngII). We also investigated the mechanisms underlying this phenomenon. The results of histopathological analysis, as well as measurements of collagen expression and cardiac fibroblast proliferation indicated that puerarin administration significantly inhibited cardiac fibrosis induced by AB and AngII. These effects of puerarin may reflect activation of Nrf2/ROS pathway. This hypothesis is supported by observed decreases of reactive oxygen species (ROS), decreases Keap 1, increases Nrf2 expression and nuclear translocation, and decreases of collagen expressions in cardiac fibroblasts treated with a combination of puerarin and AngII. Inhibition of Nrf2 with specific Nrf2 siRNA or Nrf2 inhibitor brusatol attenuated anti-fibrotic and anti-oxidant effects of puerarin. The metabolic effects of puerarin were mediated by Nrf2 through upregulation of UDP-glucuronosyltransferase (UGT) 1A1. The Nrf2 agonist tBHQ upregulated protein expression of UGT1A1 over time in cardiac fibroblasts. Treatment with Nrf2 siRNA or brusatol dramatically decreased UGT1A1 expression in puerarin-treated fibroblasts. The results of chromatin immunoprecipitation–qPCR further confirmed that puerarin significantly increased binding of Nrf2 to the promoter region of Ugt1a1. Western blot analysis showed that puerarin significantly inhibited AngII-induced phosphorylation of p38-MAPK. A specific inhibitor of p38-MAPK, SB203580, decreased collagen expression, and ROS generation induced by AngII in cardiac fibroblast. Together, these results suggest that puerarin prevents cardiac fibrosis via activation of Nrf2 and inactivation of p38-MAPK. Nrf2 is the key regulator of anti-fibrotic effects and upregulates metabolic enzymes UGT1A1. Autoregulatory circuits between puerarin and Nrf2-regulated UGT1A1 attenuates side effects associated with treatment, but it does not weaken puerarin’s pharmacological effects.

The present study was designed to find out the initial factor that triggered cognitive deficits induced by high-fat diets (HFD) and whether salvianolic acid B (Sal B) had beneficial role on cognition. Seven weeks' consumption of HFD resulted in higher food intake, dyslipidaemia, cognitive impairment and increasing hippocampal and frontal cortex oxidative stress (OS) without significant change in blood glucose and hippocampal inflammation. Microarray analysis data demonstrated that long-term potentiation (LTP) pathway was altered with down-regulation of genes against OS. Correlation analysis showed that hippocampal OS biomarkers had strong relations to Morris water maze performance. Sal B in drinking water (0.07 mg/ml) normalised the cognitive deficits through attenuating hippocampal redox status, altering LTP pathway and other biological pathways, up-regulating antioxidative genes expression. Thus, OS induced by HFD might be the initial factor that triggers cognitive impairment. Sal B was an efficient agent that exerted neuroprotective effects.

Introduction Evidence of different smoking cessation interventions varies and has been assessed in many Cochrane reviews. We conducted an overview of these Cochrane reviews to summarize the effects of current interventions for smoking cessation. Methods Nine databases were searched from their inception to October 2024, with no restrictions on language. Two authors independently extracted data from the same studies simultaneously, double checking after extraction. A second round of examination was conducted on all the extracted contents by another author. We employed a measurement tool to assess systematic reviews (AMSTAR-2) to evaluate the methodological rigor of the included systematic reviews (SRs), synthesized the GRADE results as reported, and conducted a narrative synthesis. The research protocol was registered on PROSPERO (CRD42023388884). Results Seventy-one Cochrane reviews involving 3022 trials were included in this comprehensive analysis. The two predominant smoking cessation interventions were pharmacotherapy (24 SRs) and non-pharmacological therapy (31SRs). Overall, the methodological quality of all the reviews was good. Compared with placebo, the point effect size for each Cochrane review on relative risk (RR) regarding pharmacotherapies for prolonged abstinence rate ranged from 1.11 to 3.34, demonstrating high- or moderate-certainty evidence; whereas for non-pharmacological therapies, it varied from 0.79 to 25.38, but substantial heterogeneity was observed in most meta-analysis (I2>50%). Four studies investigating pharmacotherapies as interventions, adverse events were reported but no significant differences in outcomes were observed. Conclusions Pharmacotherapy demonstrated some efficacy in promoting prolonged abstinence rate, while the effectiveness of different non-pharmacological interventions for smoking cessation varied widely, highlighting the need for further research on the integration of pharmacotherapy and non-pharmacological therapies.

BackgroundThis study aimed to synthesize the recommendations for prediction models in cardiovascular clinical practice guidelines (CPGs) and assess the methodological quality of the relevant primary modeling studies.MethodsWe performed a systematic literature search of all available cardiovascular CPGs published between 2018 and 2023 that presented specific recommendations (whether in support or non-support) for at least one multivariable clinical prediction model. For the guideline-recommended models, the assessment of the methodological quality of their primary modeling studies was conducted using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).ResultsIn total, 46 qualified cardiovascular CPGs were included, with 69 prediction models and 80 specific recommendations. Of the 80 specific recommendations, 74 supported 57 models (53 were fully recommended and 4 were conditionally recommended) in cardiovascular practice with moderate to strong strength. Most of the guideline-recommended models were focused on predicting prognosis outcomes (53/57, 93%) in primary and tertiary prevention, focusing primarily on long-term risk stratification and prognosis management. A total of 10 conditions and 7 types of target population were involved in the 57 models, while heart failure (14/57, 25%) and a general population with or without cardiovascular risk factor(s) (12/57, 21%) received the most attention from the guidelines. The assessment of the methodological quality of 57 primary studies on the development of the guideline-recommended models revealed that only 40% of the modeling studies had a low risk of bias (ROB). The causes of high ROB were mainly in the analysis and participant domains.ConclusionsGlobal cardiovascular CPGs presented an unduly positive appraisal of the existing prediction models in terms of ROB, leading to stronger recommendations than were warranted. Future cardiovascular practice may benefit from well-established clinical prediction models with better methodological quality and extensive external validation.

ObjectiveThis study is to evaluate the effectiveness and frequency factors of endoscopic bougie dilatation in treating postoperative anastomotic stenosis of congenital esophageal atresia (CEA).MethodsThe clinical data of patients of anastomotic stenosis with endoscopic bougie were retrospectively analyzed. According to the number of dilation times (ND), patients were divided into two groups (Group 0: ND

Abstract Background The sensitivity of HIV screening assays often leads to a high rate of false-positive results, requiring retests and confirmatory tests. This study aimed to analyze the capability of signal-to-cutoff (S/CO) ratios of HIV screening assay to predict HIV infection. Methods A retrospective study on the HIV screening-positive population was performed at Zhongshan Hospital, Xiamen University, the correlation between HIV screening assay S/CO ratios and HIV infection was assessed, and plotted Receiver Operating Characteristic (ROC) curves were generated to establish the optimal cutoff value for predicting HIV infection. Results Out of 396,679 patients, 836 were confirmed to be HIV-infected, with an HIV prevalence of 0.21%. The median S/CO ratios in HIV infection were significantly higher than that in non-HIV infection (296.9 vs. 2.41, P

Introduction Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. Methods Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. Results Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14–2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 – -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. Conclusions Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Abstract Syphilis has resurged in many countries, which has called attention to vaccine development. Based on the immunization-based rabbit model of infection with the Nichols strain, this study explored the protective immune response of a controversial syphilis vaccine candidate, TprK, and found that immunization with full-length rTprK was effective in attenuating lesion development and accelerating lesion resolution, which could reduce the probability of the pathogen spreading to distant tissue sites to prevent the progression of the disease to some extent. Furthermore, the results revealed that immunization with rTprK not only rapidly induced a strong Th1-like cellular response but also elicited a humoral immune response to produce opsonic antibodies to enhance macrophage-mediated opsonophagocytosis. Although complete protection against infection was not achieved, the study provided a comprehensive and in-depth exploration of the immunogenicity of TprK and highlighted the importance of TprK as a promising syphilis vaccine component.

BackgroundSilicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis.MethodsIn this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis.ResultsA total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000–1.003, p

ABSTRACT: Objectives: To evaluate the possibility of using cerebrospinal fluid (CSF) ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light protein (NF-L) for the diagnosis of neurosyphilis (NS). Methods: A cross-sectional study of 576 subjects was conducted at Zhongshan Hospital from January 2021 to August 2022 to evaluate the diagnostic accuracy of CSF UCH-L1, GFAP, and NF-L for NS and analyze their correlations with CSF rapid plasma reagin (RPR), white blood cells (WBCs), and protein. Results: Patients with NS had higher CSF UCH-L1, GFAP, and NF-L levels than patients with syphilis/non-NS and nonsyphilis. Using a cut-off point of 652.25 pg/ml, 548.89 pg/ml, and 48.38 pg/ml, CSF UCH-L1, GFAP, and NF-L had a sensitivity of 85.11%, 76.60%, and 82.98%, with a specificity of 92.22%, 85.56%, and 91.11%, respectively, for NS diagnosis. Moreover, parallel and serial testing algorithms improved their sensitivity and specificity to 93.62% and 98.89%, respectively. Interestingly, levels between patients with NS who are CSF RPR-positive and -negative did not differ and showed a weak or moderate correlation with WBC and CSF protein in patients with syphilis. Conclusion: CSF UCH-L1, GFAP, and NF-L can be used as novel markers for the diagnosis of NS, independent of CSF RPR, WBC, and proteins.

ABSTRACT Heterogeneous tprK sequences have been hypothesized to be an important factor for persistent infection of Treponema pallidum subsp. pallidum (T. pallidum) in humans. Previous research has only explored tprK diversity using a rabbit model infected with almost clonal isolates, which is inconsistent with the fact that infected human isolates contain multiple heterogeneous tprK sequences. Here, we used the T. pallidum Amoy strain with heterogeneous tprK sequences to establish a rabbit infection model and explore longitudinal variations in the tprK gene under normal infection, immunosuppression treatment, and benzathine penicillin G (BPG) treatment using next-generation sequencing. The diversity of the tprK gene was high in all three groups but was highest in the control group and lowest in the BPG group. Interestingly, the overall diversity of tprK in all three groups decreased during infection, exhibiting a “more to less” trend, indicating that survival selection may be an important factor affecting tprK variation in the later infection stage. BPG treatment appeared to reduce the diversity of tprK but increased the frequency of predominant sequence changes, which might facilitate the escape of T. pallidum from the host immune clearance. Furthermore, the original predominant V region sequence did not disappear with disease progression but retained a relatively high proportion within the population, suggesting a new direction for tprK-related vaccine research. This study provides insights into longitudinal variations within the highly heterogeneous tprK gene sequences of T. pallidum and will contribute to further exploration of the pathogenesis of syphilis. IMPORTANCE The tprK variations are an important factor in persistent T. pallidum infection. A nearly clonal isolate has been used previously to investigate the mechanism of tprK gene variations; however, clinical T. pallidum isolates in infected humans exhibit multiple heterogeneous tprK sequences. Here, we use next-generation sequencing to explore longitudinal variations in the tprK gene under normal infection and immunosuppression and benzathine penicillin G treatment in a rabbit model infected with the Amoy strain with heterogeneous tprK sequences. The overall diversity of tprK in all three groups was high and decreased during infection, exhibiting a “more to less” trend. Benzathine penicillin G treatment reduced the diversity of tprK but increased the frequency of predominant sequence changes. Moreover, the original predominant V region sequence did not disappear as the disease progressed but remained at a relatively high proportion within the population. The research results give us a new understanding about tprK variation.

ABSTRACT TprK antigenic variation is acknowledged as an important strategy developed by Treponema pallidum to achieve immune evasion. Previous studies applied short-read sequencing to explore tprK gene sequence diversity in clinical samples; however, due to the limitations of short-read sequencing, it was difficult to determine the linkage between the seven V regions, and crucial information about full-length tprK variants was lost. Although two recent studies explored complete tprK gene profiles in natural human syphilis infection, there are still too few profiled full-length tprK variants among clinical T. pallidum isolates to fully understand the characteristics of TprK coding diversity. Here, Pacific Biosciences (PacBio) long-read sequencing was applied to examine the diversity of full-length tprK variants in 21 clinical T. pallidum isolates from 11 patients with primary syphilis and 10 patients with secondary syphilis. A total of 398 high-confidence full-length sequences, which presented remarkable sequence heterogeneity, were found. However, these full-length tprK variants exhibited limited variation in length and GC content, showing 24 length types and average GC content of 51.5 ± 0.42% and 51.6 ± 0.26% for primary and secondary syphilis samples, respectively. Additionally, the combined patterns of mutated V regions generating new tprK variants were obviously different in primary and secondary syphilis samples. The diversity of tprK gene sequences in primary syphilis samples may represent the underlying variability of the bacterium; conversely, the variability of the tprK gene in secondary syphilis samples may more accurately reflect how T. pallidum escapes host immune clearance. These data highlight the tprK gene as an important coding gene that shows conflicting genetic characteristics but underlies the persistence of spirochete infection. IMPORTANCE The resurgence of syphilis in both low- and high-income countries has attracted attention, and persistent infection by the pathogen has long been a research focus. The tprK gene, encoding the hypervariable outer membrane protein, is thought to be responsible for pathogen immune evasion and persistent infection. Here, PacBio long-read sequencing was applied to examine the diversity of full-length tprK variants in 21 clinical T. pallidum isolates from 11 patients with primary syphilis and 10 patients with secondary syphilis. The results showed that the sequences of the tprK gene were remarkably heterogeneous; however, the sequences presented limited variation in length and GC content. The investigation of the combined patterns of the V regions allowed us to gain insight into the features of the tprK gene generating new variants at different clinical stages. The findings of this study will be helpful for further exploration of the pathogenesis of syphilis.

To evaluate the application of cycle threshold (Ct) values of coronavirus disease 2019 (COVID-19) patients in predicting epidemic dynamics and monitoring surface contamination. The Ct value of reverse transcriptase-polymerase chain reaction for SARS‑CoV-2 from COVID-19 patients inbound overseas in Xiamen, China was collected from October 2020 to December 2021, and the correlation of patients' Ct values with epidemic dynamics and surface contamination was evaluated. The results showed that there was an extreme inverse correlation of positivity rate in the current calendar month (ORF1ab, r = −0.692, P = 0.004; N,r = −0.629, P = 0.012) and the following calendar month (ORF1ab,r = −0.801, P = 0.001; N,r = −0.620, P = 0.018) with the median Ct values. Ct value showed better performance for monitoring surface contamination, with the area under the curve value 0.808(95 %CI: 0.748–0.869) for ORF1ab and 0.807(95 %CI:0.746–0.868) for the N gene. The patients’ ORF1ab Ct value

Abstract Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a “malignant” phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P

BackgroundNontreponemal and treponemal tests for analyzing cerebrospinal fluid to confirm the existence of neurosyphilis have been widely used, so we aim to evaluate and compare their performance on the cerebrospinal fluid in the diagnosis of neurosyphilis.MethodsWe conducted a systematic literature search on five databases and utilized a bivariate random-effects model to perform the quantitative synthesis.ResultsNontreponemal tests demonstrated a pooled sensitivity of 0.77 (95% CI: 0.68–0.83), a pooled specificity of 0.99 (95% CI: 0.97–1.00), and a summary AUC of 0.97 (95% CI: 0.95–0.98). The pooled sensitivity, pooled specificity, and summary AUC of treponemal tests were 0.95 (95% CI: 0.90–0.98), 0.85 (95% CI: 0.67–0.94), and 0.97 (95% CI: 0.95–0.98), respectively. The pooled specificity of all nontreponemal tests varied minimally (ranging from 0.97 to 0.99), with TRUST (0.83) having a higher pooled sensitivity than VDRL (0.77) and RPR (0.73). Among all treponemal tests, EIA has outstanding diagnostic performance with a pooled sensitivity of 0.99 and a pooled specificity of 0.98.ConclusionNontreponemal tests exhibited a higher pooled specificity, and treponemal tests exhibited a higher pooled sensitivity in diagnosing neurosyphilis on cerebrospinal fluid. TRUST may be a satisfactory substitute for VDRL. EIA is a prospective diagnostic tool that deserves further study in the future. Our study may be useful to clinical laboratories in selecting appropriate serological tests on the cerebrospinal fluid for the diagnosis of neurosyphilis.

Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.

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.