Multicenter Evaluation of the Molecular Line Probe Assay for Multidrug Resistant Mycobacterium Tuberculosis Detection in China.

In order to evaluate the performance of a molecular Hain line probe assay (Hain LPA) for rapid detection of rifampicin and isoniazid resistance of Mycobacterium tuberculosis in China, 1612 smear positive patients were consecutively enrolled in this study. Smear positive sputum specimens were collected for Hain LPA and conventional drug susceptibility testing (DST). The sensitivity and specificity of Hain LPA were analyzed by using conventional DST as golden reference. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for rifampicin resistance detection were 88.33%, 97.66%, 81.54%, and 98.62%, respectively. The sensitivity, specificity, PPV and NPV for isoniazid resistance detection were 80.25%, 98.07%, 87.25%, and 96.78%, respectively. These findings suggested that Hain LPA can be an effective method worthy of broader use in China.

Efficacy and safety of Runzao Zhiyang capsule for chronic urticaria: a systematic review and meta-analysis of randomized controlled trials.

Background: Chronic urticaria (CU) is a commonly seen skin disorder featured by recurring wheals, with or without angioedema, lasting for at least 6 weeks. Runzao Zhiyang capsule (RZC) has been widely applied to treat patients with CU. This study is aimed at systematically evaluating the efficacy and safety of RZC in treating CU. Materials and Methods: Randomized controlled trials (RCTs) of RZC on treating CU from Chinese and English databases were searched. Data were collected by two independent researchers. The Cochrane Collaboration tool was adopted for evaluating the risk of bias. The meta-analysis was performed with Review Manager 5.3 software. Sensitivity analysis and publication bias assessment were conducted by Stata 14.0 software. Results: Totally 27 studies were included in the analysis, involving 2,703 patients. The pooled results showed that compared with second-generation H1-antihistamines (sgAHs) therapy alone, RZC combined with sgAHs is more effective in improving the total effective rate (RR = 1.32, 95% CI: 1.25 to 1.39, p < 0.00001), the quality of life measured by Dermatology Life Quality Index (DLQI) (MD = -2.63, 95% CI: -3.68 to -1.58, p < 0.00001) and the serum IFN-γ level (SMD = 3.10, 95% CI: 1.58 to 4.62, p < 0.0001), and reducing the recurrence rate (RR = 0.39, 95% CI: 0.27 to 0.55, p < 0.00001), the serum total IgE level (SMD = -2.44, 95% CI: -3.51 to -1.38, p < 0.00001), the serum IL-4 level (SMD = -2.96, 95% CI: -4.10 to -1.83, p < 0.00001), and the incidence of adverse events including dizziness, fatigue, dry mouth, and constipation (RR = 0.53, 95% CI: 0.33 to 0.85, p = 0.009; RR = 0.46, 95% CI: 0.26 to 0.84, p = 0.01; RR = 0.57, 95% CI: 0.34 to 0.95, p = 0.03; RR = 0.24, 95% CI: 0.07 to 0.85, p = 0.03). Conclusion: The current evidence indicates that RZC may be an efficient therapeutic regimen in patients with CU. Nevertheless, owing to the suboptimal quality of the included studies, more large-scale, well-designed RCTs are required to verify the obtained findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier: CRD42022313177.

A Case of Spontaneous Mediastinal and Subcutaneous Emphysema in a Patient with HIV-Infected Pneumonia.

BACKGROUND: Acquired immunodeficiency syndrome is a chronic infectious disease with high mortality and is caused by the Human Immunodeficiency Virus (HIV). Pneumonia caused by HIV is common, but it rarely causes spontaneous mediastinal and subcutaneous emphysema. CASE PRESENTATION: A 21-year-old man with severe pneumonia was hospitalized owing to dyspnea that had been persisting for 1 day; blood test results confirmed HIV infection. Initial chest Computed Tomography (CT) did not reveal mediastinal or subcutaneous emphysema. However, after 21 days of treatment, the patient experienced discomfort in the neck region and experienced the feeling of snowflakes on applying pressure. Chest CT showed mediastinal and subcutaneous emphysema, located in the bilateral cervical roots, anterior upper chest wall, left axillary chest wall, mediastinum, and other parts. Metagenomic Next Generation Sequencing (mNGS) of the sputum and blood samples suggested multiple pathogenic infections. Antiinfection treatment was initiated, and changes in the patient's condition were monitored. The patient's subcutaneous emphysema improved during the follow-up. CONCLUSION: In HIV-infected patients with sudden mediastinal and subcutaneous emphysema, mNGS can be used to determine the etiological agent during symptomatic treatment. Targeted antipathogen therapy is helpful in improving the condition of patients with subcutaneous emphysema.

The Partial Role of KLF4 and KLF5 in Gastrointestinal Tumors.

BACKGROUND: KLF4 and KLF5 are members of the KLF transcription factor family, which play an important role in many gastrointestinal tumors. To gain a deeper insight into its function and role, bioinformatics was used to analyze the function and role of KLF4 and KLF5 in gastrointestinal tumors. METHODS: Data were collected from several online databases. Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN database analysis, Kaplan-Meier Plotter analysis, LOGpc system, the Pathology Atlas, and the STRING website were used to analyze the data. We download relevant data from TCGA and then perform GO enrichment and KEGG enrichment analysis. The effects of KLF5 on gastric cancer cell proliferation were measured by CCK-8 assay. The effect of KLF5 on the expression of CyclinD1 and MMP9 was detected by Western blot. RESULTS: KLF4 and KLF5 were differentially expressed in normal and tumor tissues of the gastrointestinal tract, and their differential expression is related to several genes or pathways. KEGG analysis showed that KLF5 was coexpressed with endocytosis-related genes. KLF5 promotes the proliferation of gastric cancer cells and the expression of metastasis-related molecules. CONCLUSION: KLF4 and KLF5 are of great significance for developing gastrointestinal tumors and can be used as therapeutic targets.

PD-1/PD-L1 inhibitors-based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies.

With the widespread use of PD-1/PD-L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD-1/PD-L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved considerable efficacy in clinical trials. However, due to the primary, adaptive, and acquired resistance to these mAbs, the efficacy of this immunotherapy is not satisfactory. Theories also vary as to why the difference in efficacy occurs. The alterations of PD-L1 expression and the interference of cellular immunity may affect the efficacy. These mechanisms demand to be revealed to achieve a sustained and complete objective response in patients with aRCC. Tyrosine kinase inhibitors have been proven to have synergistic mechanisms with PD-1/PD-L1 mAb in the treatment of aRCC, and CTLA-4 mAb has been shown to have a non-redundant effect with PD-1/PD-L1 mAb to enhance efficacy. Although combinations with targeted agents or other checkpoint mAbs have yielded enhanced clinical outcomes in multiple clinical trials nowadays, the potential of PD-1/PD-L1 mAbs still has a large development space. More potential mechanisms that affect the efficacy demand to be developed and transformed into the clinical treatment of aRCC to search for possible combination regimens. We elucidate these mechanisms in RCC and present existing combination therapies applied in clinical trials. This may help physicians' select treatment options for patients with refractory kidney cancer.

Loss of the Tumor Suppressor HACE1 Contributes to Cancer Progression.

HACE1 belongs to the family of HECT domain-containing E3 ligases, which plays an important role in the occurrence, invasion and metastatic process in many human malignancies. HACE1 is a tumor suppressor gene that is reduced in most cancer tissues compared to adjacent normal tissue. The loss or knocking out of HACE1 leads to enhanced tumor growth, invasion, and metastasis; in contrast, the overexpression of HACE1 can inhibit the development of tumors. Hypermethylation reduces the expression of HACE1, thereby promoting tumor development. HACE1 can inhibit the development of inflammation or tumors via the ubiquitination pathway. Therefore, HACE1 may be a potential therapeutic target, providing new strategies for disease prevention and treatment.

Disturbed Th17/Treg Balance in Patients with Non-small Cell Lung Cancer.

The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction. The concentrations of interleukin (IL)-1ß, IL-6, IL-10, IL-17, IL-23, and transforming growth factor-beta (TGF-ß1) were also measured by enzyme-linked immunosorbent assay analysis (ELISA). The frequency of circulating Th17 cells and Treg cells was increased in samples derived from patients with NSCLC, accompanied by the upregulation of Foxp3 and RORγt. However, a negative correlation between Treg cells and Th17 cells was found in patients with NSCLC. Additionally, the Th17/Treg ratio and the related cytokines were also significantly higher in patients with NSCLC than in healthy controls. Furthermore, the frequency of Th17 cells was positively correlated with IL-1ß, IL-6, and IL-23 in patients with NSCLC, and the frequency of Treg cells was positively correlated with TGF-ß1 and IL-10. More importantly, the Th17/Treg ratio was positively correlated with the CEA concentrations in patients with NSCLC. Our data indicated that Th17 and Treg subset are involved in the immunopathology of NSCLC. Distinct cytokine environment might play a key role in the differentiation of the Th17 and Treg cells in NSCLC. Reconstituting an adequate balance between Th17 and Treg may be beneficial in the treatment of NSCLC.