Comparative diagnostic utility of metagenomic next-generation sequencing, GeneXpert, modified Ziehl-Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: A multi-center, retrospective study in China.

BACKGROUND: Early diagnosis of tuberculosis meningitis (TBM) remains a great challenge during clinical practice. The diagnostic efficacies of cerebrospinal fluid (CSF)-based mycobacterial growth indicator tube (MGIT) culture, modified Ziehl-Neelsen (ZN) staining, Xpert MTB/RIF, and metagenomic next-generation sequencing (mNGS) for TBM remained elusive. METHODS: A total of 216 adult patients with suspicious TBM were retrospectively enrolled in this multi-cohort study. The diagnostic performances for MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS using CSF samples were evaluated. RESULTS: Uniform clinical case definition classified 88 (40.7%) out of 216 patients as the definite TBM, 5 (2.3%) patients as probable TBM cases, and 24 (11.1%) patients as possible TBM cases. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite TBM were 25.0%, 76.1%, 73.9%, and 84.1%, respectively. Negative predictive values (NPVs) were 66.0%, 85.9%, 84.8%, and 90.1%, respectively. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite, probable, and possible TBM were 18.8%, 57.3%, 55.5%, and 63.2%, respectively. Negative predictive values (NPVs) were 51.0%, 66.4%, 65.6%, and 69.7%, respectively. mNGS combined with modified ZN stain and Xpert could cover TBM cases against a composite microbiological reference standard, yielding 100% specificity and 100% NPV. CONCLUSION: Metagenomic next-generation sequencing detected TBM with higher sensitivity than Xpert, ZN staining and MGIT culture, but mNGS cannot be used as a rule-out test. mNGS combined with Xpert or modified ZN staining could enhance the sensitivity of diagnostic tests for TBM.

Efficacy of guselkumab compared with adalimumab for psoriasis: a meta-analysis of randomized controlled studies.

Introduction: The efficacy of guselkumab versus adalimumab for psoriasis remains controversial. Aim: We conducted a systematic review and meta-analysis to explore the influence of guselkumab versus adalimumab on treatment efficacy for psoriasis. Material and methods: We have searched PubMed, Embase, Web of Science, EBSCO, and Cochrane library databases for randomized controlled trials (RCTs) published until March 2021 and assessing the efficacy and safety of guselkumab versus adalimumab for psoriasis. This meta-analysis was performed using the random-effects model. Results: Three RCTs were included in the meta-analysis. Overall, compared with adalimumab for psoriasis, guselkumab was associated with improved PASI 100 (OR = 2.18; 95% CI: 1.47 to 3.23; p = 0.0001), PASI 90 (OR = 2.63; 95% CI: 2.11 to 3.27; p < 0.00001), PASI 75 (OR = 3.10; 95% CI: 2.35 to 4.08; p < 0.00001) and PGA 0/1 (OR = 2.04; 95% CI: 1.26 to 3.31; p = 0.004), as well as decreased DLQI (SMD = -0.24; 95% CI: -0.34 to -0.13; p < 0.00001). In addition, guselkumab resulted in higher DLQI score 0/1 (OR = 1.88; 95% CI: 1.51 to 2.33; p < 0.00001) than adalimumab. Conclusions: Guselkumab showed better efficacy than adalimumab for psoriasis.

Concurrent tuberculous chorioretinitis with choroidal neovascularization and tuberculous meningitis: a case report.

BACKGROUND: Tuberculosis (TB) remains a severe health burden worldwide. The manifestation of concurrent tuberculous cerebral and ocular involvements associated with TB is uncommon. CASE PRESENTATION: We report a 17-year-old girl with concurrent tuberculous cerebral and ocular involvements and visual impairment due to choroidal neovascularization. This study emphasizes the definite diagnosis with the combination of ophthalmological examination, multimodal imaging and routine tuberculosis testing, and the proper management with intravitreal anti-VEGF injection accompanied by systemic anti-tuberculosis therapy. CONCLUSION: Combined applications of routine TB tests, fundus multimodal imaging and diagnostic therapy greatly help the clinician to establish a precise diagnosis and in monitoring the therapeutic response.

Durvalumab supplementation for non-small-cell lung cancer: a meta-analysis study.

BACKGROUND: Durvalumab supplementation may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of durvalumab supplementation on efficacy for NSCLC. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of durvalumab supplementation on efficacy in patients with NSCLC. Overall survival and progression-free survival were included for this meta-analysis. RESULTS: Four RCTs were finally included in the meta-analysis. Overall, compared with control group for NSCLC, durvalumab supplementation showed significantly improved survival rate (odd ratio [OR] = 1.64; 95% confidence interval [CI] = 1.31 to 2.06; P < 0.0001), overall survival ( hazard ratio [HR] = 0.73; 95% CI = 0.61 to 0.87; P = 0.0003), progression-free survival rate (OR = 2.31; 95% CI = 1.78 to 3.01; P < 0.00001) and progression-free survival (HR = 0.71; 95% CI = 0.54 to 0.95; P = 0.02), and had the capability to reduce the incidence of grade ≥ 3 adverse events (OR = 0.26; 95% CI = 0.16 to 0.42; P < 0.00001). CONCLUSIONS: Durvalumab supplementation is effective to improve the efficacy for NSCLC.

A pilot study of minimal invasion combined PDL/Nd:YAG laser in treating facial epidermoid cyst.

OBJECTIVES: To compare the efficacy and complication of minimal invasion and combined pulsed dye laser/Nd:YAG laser and traditional surgical excision in the treatment of facial epidermoid cyst. METHODS: A total of 100 patients with facial epidermoid cyst aged from 16 to 65 years and cyst diameter ranged from 0.3 to 3.0 cm were treated and followed up. Patients were divided into the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment group and traditional surgical excision group. All patients were followed up for 12 months including scar size, recurrence rate, incidence of complications, and patient global satisfaction. RESULTS: The mean operative time in the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment was 15.23 ± 7.02 minutes, which is significantly shorter than that of surgical excision (27.26 ± 10.12 minutes, P < .05). After 12 months, the average scar size in minimal invasion and combined pulsed dye laser/Nd:YAG laser group was 0.54 ± 0.35 cm, while that of traditional surgical excision group was 1.77 ± 0.81 cm (P < .05). No statistical difference was found between two groups in the wounds split, hematoma, early and late recurrence rates (P > .05), while the patients' global satisfaction in the pulsed dye laser/Nd:YAG laser group is much higher than that of the traditional surgical excision group. CONCLUSION: The treatment of minimal invasion and combined pulsed dye laser/Nd:YAG laser is effective and safe for medium-size facial epidermoid cysts. For facial epidermoid cyst ranging for 0.3 cm to 3.0 cm, considering the cosmetic factors, minimal invasion and combined pulsed dye laser/Nd:YAG laser should be particularly recommended.

Long non-coding RNA GLIDR accelerates the tumorigenesis of lung adenocarcinoma by miR-1270/TCF12 axis.

Lung adenocarcinoma (LUAD) is a deadly cancer with a high incidence worldwide. Long noncoding RNAs (lncRNAs) have been confirmed to have the regulatory effects on the occurrence and development of LUAD. But the specific functions of lncRNA GLIDR in LUAD are still not explicit and need to be investigated. On the basis of the outcomes of RT-qPCR experiments, the relative expression of GLIDR was evidently up-regulated in LUAD cells, while that of miR-1270 was down-regulated. The down-regulation of GLIDR inhibits cell proliferation in accordance with the results of CCK-8, EdU and colony formation assays, and accelerates cell apoptosis according to the results of flow cytometry and JC-1 analyses. Luciferase reporter, RNA pull down and RIP assays indicated that GLIDR could sponge miR-1270 in LUAD. Additionally, TCF12 was proved as the target gene of miR-1270. Furthermore, rescue experiments indicated that overexpression of TCF12 could offset the inhibitory functions of silencing GLIDR on cell behaviors. In brief, this study has demonstrated that GLIDR/miR-1270/TCF12 axis plays the crucial role in LUAD, which offers a new insight into researches on molecular mechanism concerning LUAD and provides with a new perspective for LUAD treatment.

Mammalian target of the rapamycin pathway is involved in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease associated with an increased risk of type 2 diabetes and cardiovascular disease. Many factors may contribute to NAFLD development and progression, but the exact mechanisms are still not fully understood. In this study, Sprague-Dawley rats were fed either a standard diet (control group), a high-fat diet for 8 weeks (the HFD-8 group) or a high-fat diet for 16 weeks (the HFD-16 group). The HFD animals showed high levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and insulin resistance index (Homa-IR). Mild and severe steatosis was found in both the HFD-8 and HFD-16 groups, respectively. Compared with the controls, mRNA levels of mTOR, S6K1, IL-1α, IL-6 and TNFα were significantly increased in the HFD-8 and HFD-16 groups. IRS-1 mRNA was significantly increased in the HFD-8 group, but not in the HFD-16 group. The protein levels of mTOR, pmTOR(Ser2448), S6K1, pIRS-1(Ser307), IL-1α and IL-6 were significantly increased in the HFD-8 and HFD-16 groups. The protein levels of pmTOR(Ser2448) and IL-1α were significantly higher in the HFD-16 group compared to those in the HFD-8 group. However, the protein expression level of mTOR did not differ significantly between the HFD-8 and HFD-16 groups. The pIRS-1(Tyr102) level was significantly lower in both the HFD-8 and HFD-16 groups when compared to that in the control group, and the pIRS-1(Tyr102) level was significantly lower in the HFD-16 group compared to that of the HFD-8 group. pmTOR(Ser2448) was positively correlated with the TNFα mRNA level, and pIRS-1(Ser307) was positively correlated with pmTOR(Ser2448), TNFα, S6K1 and mTOR. pIRS-1(Tyr102) was negatively correlated with pmTOR(Ser2448), TNFα, S6K1 and mTOR. These data indicate that mTOR contributes to insulin resistance and chronic liver inflammation, and may play an important role in the development and progression of NAFLD.