Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial.

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).

Percutaneous Endoscopic Lumbar Discectomy for Calcified Lumbar Disc Herniation: A Retrospective Cohort Study, Systematic Review and Meta-Analysis.

BACKGROUND: Calcified lumbar disc herniation (CLDH) is a subtype characterized by calcification, leading to increased surgical complexity. Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive technique, but its effectiveness and complications in CLDH patients remain to be fully evaluated. OBJECTIVE: To assess the effectiveness and complications of PELD in treating CLDH patients. STUDY DESIGN: A retrospective cohort study combined with a systematic review and meta-analysis. SETTING: Department of Pain Medicine, an affiliated hospital of a university. METHODS: Data from patients who underwent PELD in our department between March 2020 and May 2021 were collected. Forty CLDH patients were included in the study group, and equally matched cases with uncalcified lumbar disc herniation (UCLDH) served as controls. A systematic search was conducted on October 5, 2022, using EMBASE, PubMed, Cochrane Library, the China Biology Medicine disk, the China National Knowledge Infrastructure, and the Wanfang databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used to calculate pooled results. RESULTS: Eighty patients were included in the retrospective cohort, and 41 studies were included in the meta-analysis. Both the retrospective cohort and meta-analysis consistently showed a significant decrease in visual analog scale (VAS) and Oswestry Disability Index (ODI) scores in the CLDH group after the operation. In the retrospective cohort, the excellent or good rate according to the MacNab classification was 85%, with no reported complications. The meta-analysis revealed a pooled excellent or good rate of 91.8% and a low complication rate of 2.9%. Combining the findings from our retrospective cohort and meta-analysis, we observed that the CLDH group had longer operation times and slightly higher postoperative ODI scores compared to the UCLDH group. LIMITATIONS: Small sample size and lack of long-term follow-up in the retrospective cohort, as well as limited inclusion of comparative studies in the meta-analysis. CONCLUSION: PELD is an effective and safe treatment option for CLDH patients. In comparison to UCLDH patients, CLDH patients may experience longer operation times and slightly slower functional recovery than those with UCLDH.

Effectiveness and safety of tuberculosis preventive treatment for contacts of patients with multidrug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk. OBJECTIVES: To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB. DATA SOURCES: EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions. STUDY ELIGIBILITY CRITERIA: We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease. PARTICIPANTS: Contacts of patients with MDR-TB. INTERVENTIONS: TPT. ASSESSMENT OF RISK OF BIAS: A modified version of the Newcastle-Ottawa Scale was used. METHODS OF DATA SYNTHESIS: Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed. RESULTS: Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively. DISCUSSION: TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa.

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Diabetes mellitus and latent tuberculosis infection: an updated meta-analysis and systematic review.

BACKGROUND: Previous studies have demonstrated an association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI). This study was conducted to update the current understanding of the association between DM and LTBI. By conducting a systematic review and meta-analysis using adjusted odds ratios (aOR) or risk ratios (aRR), we aimed to further explore the association between DM and LTBI and provide essential reference for future research. METHODS: We conducted comprehensive searches in Embase, Cochrane Library, and PubMed without imposing any start date or language restrictions, up to July 19, 2022. Our study selection encompassed observational research that compared from LTBI positive rates in both DM and non-DM groups and reported aRR or aOR results. The quality of the included studies was assessed utilizing the Newcastle-Ottawa Scale. Pooled effect estimates were calculated using random-effects models, along with their associated 95% confidence intervals (CI). RESULTS: We included 22 studies involving 68,256 subjects. Three cohort studies were eligible, with a pooled aRR of 1.26 (95% CI: 0.71-2.23). Nineteen cross-sectional studies were eligible, with a pooled aOR of 1.21 (95% CI: 1.14-1.29). The crude RR (cRR) pooled estimate for three cohort studies was 1.62 (95% CI: 1.03-2.57). Among the cross-sectional studies we included, sixteen studies provided crude ORs, and the crude OR (cOR) pooled estimate was 1.64 (95% CI: 1.36-1.97). In the diagnosis of diabetes, the pooled aOR of the HbA1c group was higher than that of self-reported group (pooled aOR: 1.56, 95% CI: 1.24-1.96 vs. 1.17, 95% CI: 1.06-1.28). CONCLUSION: Our systematic review and meta-analysis suggest a positive association between DM and LTBI. Individuals with DM may have a higher risk of LTBI compared to those without DM. These findings provide important insights for future research and public health interventions in managing LTBI in diabetic populations.

Inflammasomes in rheumatoid arthritis: a pilot study.

BACKGROUND: The inflammasome plays an important role in rheumatoid arthritis (RA), which has rarely been systematically reported. The aim of this study was to understand whether the levels of inflammasomes were related to the severity of RA disease, which might provide a stronger theoretical basis for RA treatment. METHODS: The mRNA expression levels of some inflammasomes and associated molecules, including IL-1beta and IL-18, in peripheral blood mononuclear cells (PBMCs) from 30 RA patients (n = 30) and 16 healthy control (HC) individuals were determined by quantitative real-time polymerase chain reaction (qRT‒PCR), and the levels of plasma IL-1beta and IL-18 were also measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the clinical characteristics and laboratory results of the patients were collected and analyzed in this study. RESULTS: The relative mRNA expression levels of NLRP3, NLRC4, AIM2, caspase-1, and IL-1beta were significantly higher and those of NLRP1, NLRP2 and NLRC5 were notably lower in the HC group than in the RA group. Moreover, the plasma IL-1beta and IL-18 levels were markedly increased in the RA group. Additionally, the mRNA level of AIM2 was negatively correlated with disease activity score 28 (DAS28) by stepwise linear regression analysis. erythrocyte sedimentation rate (ESR) was positively correlated with DAS28 by multiple linear regression analysis in the RA group. CONCLUSIONS: These findings imply the critical role of NLRP3, NLRC4, AIM2, caspase-1 and plasma IL-1beta and IL-18 in the pathogenesis of RA patients, which provides potential targets for the treatment of RA.

Risk of progression to active tuberculosis for indeterminate interferon-gamma release assay in immunocompromised individuals: a systematic review and meta-analysis.

BACKGROUND: Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). OBJECTIVES: To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023. STUDY ELIGIBILITY CRITERIA: Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening. PARTICIPANTS: Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON). REFERENCE STANDARD: None. ASSESSMENT OF RISK OF BIAS: A modified version of the Newcastle-Ottawa Scale. METHODS OF DATA SYNTHESIS: Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA. RESULTS: Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I2 = 0%) and 2.94 (95% CI, 1.78-4.85; I2 = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I2 = 13%) and 2.67 (95% CI, 1.24-5.79; I2 = 23%), respectively. DISCUSSION: Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.

Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis.

Objectives: We aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI). Methods: On 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results. Results: We included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%-4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59-1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16-0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11-5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children's pooled indeterminate rates (OR = 2.56, 95% CI 1.79-3.57) were significantly higher than those of adults, and the rates increased as the children's age decreased. Conclusion: On average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.

A novel oxidative-stress related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a primary malignant tumour of tubular epithelial origin and is most common in the urinary tract. Growing evidence suggests that oxidative stress (OS), generates high levels of reactive oxygen species (ROS) and free radicals, and plays a critical role in cancer in humans. However, the predictive value of OS-related long non-coding RNAs (lncRNAs) in ccRCC remains unclear. We constructed a predictive signature of survival based on OS-related lncRNAs that were obtained from The Cancer Genome Atlas (TCGA-KIRC), to predict the prognosis of patients with ccRCC. The signature comprised seven lncRNAs: SPART-AS1, AL162586.1, LINC00944, LINC01550, HOXB-AS4, LINC02027, and DOCK9-DT. OS-related signature of lncRNAs had diagnostic efficiency higher than that of clinicopathological variables, with an area of 0.794 under the receiver operating characteristic curve. Additionally, the nomogram based on risk scores and clinicopathological variables (age, gender, grade, stage, M-stage, and N-stage) showed strong predictive performance. Patients with high-risk were found to be more sensitive to the therapeutic drugs ABT.888, AICAR, MS.275, sunitinib, AZD.2281, and GDC.0449. Our constructed the predictive signature can independently predict the prognosis of patients with ccRCC; however, the underlying mechanism needs further investigation.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis.

BACKGROUND: QuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST). METHODS: PubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using "Mycobacterium tuberculosis Infections" and "QuantiFERON-TB-Plus" as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432). RESULTS: Of 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found. CONCLUSIONS: The diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.

Survival outcome among patients with out-of-hospital cardiac arrest who received cardiopulmonary resuscitation in China: a systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the survival outcomes among patients with out-of-hospital cardiac arrest (CA) who received cardiopulmonary resuscitation (CPR) in China. METHODS: Relevant studies, published between January 1, 2010 and September 5, 2022, were retrieved from databases, including EMBASE, PubMed, Cochrane Library, the China Biology Medicine disk, China National Knowledge Infrastructure, and Wanfang databases. We included clinical studies in which all patients were diagnosed with CA and underwent out-of-hospital CPR, and the outcome variables were at least one of the following: return of spontaneous circulation (ROSC), survival to admission, survival to hospital discharge, 1-month survival, achieved good neurological outcomes, and 1-year survival. Two investigators independently extracted the study data and assessed its quality using a modified Newcastle-Ottawa Scale tool. The data were pooled using random-effects models. RESULTS: Of the 3620 identified studies, 49 (63,378 patients) were included in the meta-analysis. The pooled ROSC rate was 9.0% (95% confidence interval [CI] 7.5-10.5%, I2 = 97%), the pooled survival to admission rate was 5.0% (95% CI 2.7-8.0%, I2 = 98%), and the pooled survival to discharge rate was 1.8% (95% CI 1.2-2.5%, I2 = 95%). Additionally, the ROSC rate of patients with bystander CPR was significantly higher than that of those without bystander CPR, and the pooled odds ratio (OR) was 7.92 (95% CI 4.32-14.53, I2 = 85%). The ROSC rate of participants who started CPR within 5 min was significantly higher than that of those who started CPR after 5 min, and the pooled OR was 5.92 (95% CI 1.92-18.26, I2 = 85%). The ROSC rate of participants with defibrillation was significantly higher than that of those without defibrillation, and the pooled OR was 8.52 (95% CI 3.72-19.52, I2 = 77%). CONCLUSION: The survival outcomes of out-of-hospital CPR in China are far below the world average. Therefore, the policy of providing automated external defibrillators (AEDs) in public places and strengthening CPR training for healthcare providers and public personnel should be encouraged and disseminated nationwide. Trial registration This study was registered in PROSPERO (CRD42022326165) on 29 April 2022.

Risk factor analysis and clinical decision tree model construction for diabetic retinopathy in Western China.

BACKGROUND: Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. AIM: To build a clinical prediction model that will enable early prevention and treatment of DR. METHODS: In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. RESULTS: Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. CONCLUSION: Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. IMPORTANCE Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.

Positive rates of interferon-γ release assay and tuberculin skin test in detection of latent tuberculosis infection: A systematic review and meta-analysis of 200,000 head-to-head comparative tests.

OBJECTIVE: To compare the positive rates of IGRA and TST in detection of LTBI. METHODS: We searched PubMed, Embase, and the Cochrane Library on March 12, 2022. A random-effects model was used to calculate pooled results. RESULTS: We included 458 head-to-head studies. Compared with immunocompetent controls, TST positive rate in immunosuppressed population decreased more than IGRA positive rate (OR 0.36 [95% CI: 0.31 to 0.41] versus 0.53 [0.46 to 0.61]). In immunocompetent BCG-vaccinated individuals, IGRA positive rate in low-TB burden areas was significantly lower than TST positive rate, but the difference was decreased in high-TB burden areas (OR 0.75 [0.60 to 0.94]). Additionally, IGRA positive rate was equal to that of TST in the elderly (OR 0.98 [0.66 to 1.46]). CONCLUSION: TST is more susceptible to immunosuppression than IGRA. The effect of BCG on TST might be weakened in high-TB burden areas, and TST response waned in the elderly. REVIEW REGISTRATION: PROSPERO CRD42020180163.

Association Between the Individual and Combined Effects of the GSTM1 and GSTT1 Polymorphisms and Risk of Leukemia: A Meta-Analysis.

Background: Fourteen meta-analyses reported the individual effects of the GSTM1 and GSTT1 polymorphisms on leukemia risk. However, over 40 studies were not included in previously published meta-analyses. Moreover, one key aspect was that previous meta-analyses did not conduct the false-positive test on the aforementioned issues. Furthermore, previous meta-analyses did not observe the combined effects of GSTM1 present/null and GSTT1 present/null polymorphism with leukemia risk. Therefore, we conducted the current study to further analyze these associations. Objectives: This study aimed to investigate the association between the individual and combined effects of the GSTM1 present/null and GSTT1 present/null polymorphisms and the risk of leukemia. Methods: A meta-analysis was performed applying Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Moreover, false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP) were applied to investigate the false-positive results. Results: The individual GSTM1 and GSTT1 null genotypes and combined effects of the two genes were associated with a significantly increased leukemia risk in overall and several subgroup analyses, such as Asians, Caucasians, and so on. Then, further analysis was conducted using FPRP and BFDP. Significant associations were considered as "positive" results on the GSTM1 null genotype with leukemia risk in overall populations (FPRP < 0.001 and BFDP = 0.006), Asians (FPRP < 0.001 and BFDP < 0.001), and East Asian population (FPRP < 0.001 and BFDP = 0.002). For the GSTT1 null genotype, significant associations were regarded "positive" results in overall populations, acute myeloid leukemia (AML), Asians, and East Asian population. For the combined effects of the GSTM1 and GSTT1 polymorphisms, significant associations were also considered "positive" results in the overall analysis of Asians, Indians, and East Asian population. Conclusion: This study strongly indicates that the individual GSTM1 and GSTT1 null genotypes and combined effects of the two genes are associated with increased leukemia risk in Asians, especially in the East Asian population; the GSTT1 null genotype is associated with increased AML risk; the combined effects of the two genes are associated with increased leukemia risk in Indians.

Comprehensive analyses of transcriptomes induced by Lyme spirochete infection to CNS model system.

BACKGROUND: Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment. METHODS: In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR). RESULTS: A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR. CONCLUSION: Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis.

Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis.

INTRODUCTION: Borrelia burgdorferi sensu lato (Bb) infection, the most frequent tick-transmitted disease, is distributed worldwide. This study aimed to describe the global seroprevalence and sociodemographic characteristics of Bb in human populations. METHODS: We searched PubMed, Embase, Web of Science and other sources for relevant studies of all study designs through 30 December 2021 with the following keywords: 'Borrelia burgdorferi sensu lato' AND 'infection rate'; and observational studies were included if the results of human Bb antibody seroprevalence surveys were reported, the laboratory serological detection method reported and be published in a peer-reviewed journal. We screened titles/abstracts and full texts of papers and appraised the risk of bias using the Cochrane Collaboration-endorsed Newcastle-Ottawa Quality Assessment Scale. Data were synthesised narratively, stratified by different types of outcomes. We also conducted random effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO (CRD42021261362). RESULTS: Of 4196 studies, 137 were eligible for full-text screening, and 89 (158 287 individuals) were included in meta-analyses. The reported estimated global Bb seroprevalence was 14.5% (95% CI 12.8% to 16.3%), and the top three regions of Bb seroprevalence were Central Europe (20.7%, 95% CI 13.8% to 28.6%), Eastern Asia (15.9%, 95% CI 6.6% to 28.3%) and Western Europe (13.5%, 95% CI 9.5% to 18.0%). Meta-regression analysis showed that after eliminating confounding risk factors, the methods lacked western blotting (WB) confirmation and increased the risk of false-positive Bb antibody detection compared with the methods using WB confirmation (OR 1.9, 95% CI 1.6 to 2.2). Other factors associated with Bb seropositivity include age ≥50 years (12.6%, 95% CI 8.0% to 18.1%), men (7.8%, 95% CI 4.6% to 11.9%), residence of rural area (8.4%, 95% CI 5.0% to 12.6%) and suffering tick bites (18.8%, 95% CI 10.1% to 29.4%). CONCLUSION: The reported estimated global Bb seropositivity is relatively high, with the top three regions as Central Europe, Western Europe and Eastern Asia. Using the WB to confirm Bb serological results could significantly improve the accuracy. More studies are needed to improve the accuracy of global Lyme borreliosis burden estimates. PROSPERO REGISTRATION NUMBER: CRD42021261362.

Application of Droplet Digital PCR to Detection of Mycobacterium tuberculosis and Mycobacterium leprae Infections: A Narrative Review.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) infection, which has seriously endangered human health for many years. With the emergence of multidrug-resistant and extensively drug-resistant MTB, the prevention and treatment of TB has become a pressing need. Early diagnosis, drug resistance monitoring, and control of disease transmission are critical aspects in the prevention and treatment of TB. However, the currently available diagnostic technologies and drug sensitivity tests are time consuming, and thus, it is difficult to achieve the goal of early diagnosis and detection drug sensitivity, which results in limited control of disease transmission. The development of molecular testing technology has gradually achieved the vision of rapid and accurate diagnosis of TB. Droplet digital PCR (ddPCR) is an excellent nucleic acid quantification method with high sensitivity and no need for a calibration curve. Herein, we review the application of ddPCR in TB diagnosis and drug resistance detection and transmission monitoring.