[Effects of macrophage glycolytic reprogramming on tuberculosis granuloma formation].

The formation of granulomatous lesions is a typical pathological feature of tuberculosis, and infection with Mycobacterium tuberculosis is the main cause. Although the mechanism underlying granuloma formation remains unclear, increasing evidence suggests that immune metabolism plays an important role. In this review, we summarized the latest advances in macrophage glycolytic reprogramming in tuberculosis granuloma formation to discover new methods for early diagnosis and provided new ideas for tuberculosis therapeutics based on the regulation of immune metabolism.

Screening and validation for core genes in osteoarthritic cartilage based on weighted gene co-expression network analysis.

OBJECTIVE: Osteoarthritis (OA) has the highest disability rate among chronic diseases. The burden on patients and public health care resources is increasingly evident due to increasing obesity rates and aging populations. So, there is still a lack of early diagnosis and treatment for OA. MATERIALS AND METHODS: A total of three OA cartilage tissue datasets (GSE1919, GSE32317, and GSE5235) were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially expressed genes and WGCNA of overlapping genes were performed using the R language package. Functional and immune infiltration analyses of overlapping genes were also carried out while hub genes were screened through LASSO regression analysis method and ROC curve. Finally, experimental validation was carried out through PCR and Western Blot analysis of rat cartilage. RESULTS: A total of 149 differentially expressed genes were screened, and they were mainly enriched in the cytokine-cytokine receptor interaction, rheumatoid arthritis, and interleukin (IL-17) signaling pathways. Four co-expression modules were obtained, of which the blue module was the most substantial morbidity associated with OA. Thirteen overlapping genes were identified based on significant module network topology analysis and differential genes, upon which their validation through LASSO regression analysis method and ROC curve was performed. From these, five signature genes were determined, before three potential core genes were finally identified after confirmation using the validation set. CONCLUSIONS: ATF3, FOSL2, and GADD45B may be hub genes to the osteochondropathy, and they are expected to be new biomarkers and drug targets in OA research.

[Relationship between valve ablation and bladder function in children with posterior urethral valves disorder].

This study is to investigate the effect of valve ablation on bladder function in patients with posterior urethral valves. The clinical data of patients with posterior urethral valves who received urodynamic examination before and after valve ablation were retrospectively analyzed.The bladder compliance improved during urine storage after operation, and the maximum detrusor pressure decreased during micturition. The postoperative urinary system ultrasound showed that the residual urine volume of the group with significantly improved upper urinary tract hydrocephalus was significantly less than that of the group with no improvement. The bladder compliance was significantly higher than that of the group with no improvement, and the maximum urine flow rate was significantly higher than that of the group with no improvement (all P<0.05). Valve ablation has limited effect on improving bladder function in patients with PUV. Valve incision can help improve the maximum bladder volume, residual urine volume and maximum urinary flow rate. It has a certain effect on bladder compliance and maximum detrusor pressure.

[Analysis of clinical characteristics of 21 cases of acute fibrinous and organizing pneumonia].

Objective: To summarize the clinical features of 21 cases of acute fibrinous and organizing pneumonia (AFOP) confirmed by pathology, thereby improving clinicians' understanding of this disease and avoiding misdiagnosis in clinical practice. Methods: Twenty-one patients diagnosed pathologically with AFOP from January 2016 to April 2019 were analyzed retrospectively. The clinical symptoms, laboratory examination results, imaging features, treatments and outcomes were analyzed comprehensively. Results: There were 10 males and 11 females, with an average age of (58±10) years. All the cases presented subacute disease onset. The main symptoms were cough, expectoration and fever. The results from laboratory examination showed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than the normal levels. The total number of leukocytes, the percentage of neutrophils, and procalcitonin were also higher than the normal levels. Among these patients, 4 cases showed positive sputum bacteriology. Nine patients were found to have probable etiological factors (infections in 4, tumors in 4 cases, and connective tissue disease in 1 case). Twelve patients had no confirmed etiological factors. As to radiological findings, the patterns were multiple patchy infiltrates(16/21), solitary mass (3/21) and multiple nodules in both lungs (2/21). Most lesions were subpleural in distribution (15/21), with air bronchogram sign (11/21), pleural effusion (9/21), and cavity (4/21). Three patients received anti-infective therapy only. The infiltration in lung disappeared within 2 months in one patient, but the lesion still existed in one case after three years of follow-up. However, one patient were lost during the follow-up. Eighteen patients were treated with oral glucocorticoids, and about 50% of the patients showed significant improvement in symptoms and imaging findings within one month. The average follow-up time was (22±10) months, and there was no death. Conclusions: The clinical and imaging findings of AFOP are nonspecific. The exact mechanism of its pathogenesis is not clear. Infection and tumor may be related to the pathogenesis of AFOP. AFOP with subacute onset has a good response to glucocorticoid treatment with a better prognosis.

Using over-damped resistor-inductor-capacitor circuits to synthesize an adjustable high voltage rectangular pulse.

A novel method is proposed to synthesize an adjustable high voltage bipolar rectangular pulse by means of three over-damped resistor-inductor-capacitor nonsynchronous discharge circuits and the artificial current zero technology. The main advantage of the novel method is that the rise time and the flattop durations are adjustable independently. It is very suitable for the insulation test due to the output waveform being not sensitive to sample variety. A prototype was designed and tested. The results show that the prototype can output an adjustable unipolar rectangular pulse with 17 kV amplitude, 330 ns-5.45 µs flattop duration, and 110-350 ns rise time on an insulation sample.

Enrichment of regulatory T-cells in blood of patients with multidrug-resistant tuberculosis.

OBJECTIVE: To measure the percentage of regulatory T-cells (Treg) and the expression of signalling molecules in these cells from the peripheral blood of patients with multidrug-resistant tuberculosis (MDR-TB). DESIGN: Patients with drug-susceptible tuberculosis (S-TB), MDR-TB and healthy controls (HCs) were recruited into the study. Levels of CD4(+)CD25(+)Foxp3(+) Treg cells from peripheral blood, and programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible costimulatory (ICOS) molecule expression in the cells were measured using flow cytometry. Suppression mediated by Treg cells was assessed in carboxyfluorescein succinimidyl ester (CFSE) based suppression assays with autologous CD4(+)CD25(-) T-effector (Teff) cells. RESULTS: Presence of Mycobacterium tuberculosis resulted in a higher proportion of Treg cells in S-TB patients than in HCs, and even higher levels in MDR-TB patients. Moreover, Treg cells in MDR-TB patients constitutively expressed high-level PD-1, CTLA-4 and ICOS. In addition, when cultured with activated CD4(+)CD25(-) Teff cells, Treg cells potently suppressed proliferation of Teff cells. CONCLUSIONS: The high level of Treg cells found in the peripheral blood of tuberculosis patients may partly explain the poor immune response against M. tuberculosis, and could be a marker of MDR-TB.

Association of vitamin D-binding protein variants with chronic obstructive pulmonary disease: a meta-analysis.

Gene polymorphism of vitamin D-binding protein (VDBP) correlates with chronic obstructive pulmonary disease (COPD), but the results remain inconclusive. We aimed to explore the association between VDBP gene polymorphism and COPD. We searched MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure for publications addressing the association between VDBP gene polymorphism and COPD. After qualitative evaluation, randomized controlled trials were pooled using either a fixed- or a random-effect model depending upon the degree of heterogeneity. Eleven studies with 3144 subjects were included. The genotype group-specific component (GC)*1F-1F was significantly associated with COPD in Asians [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.07-2.81, P = 0.03], but not in Caucasians (OR = 1.44, 95%CI = 0.57-3.66, P = 0.45). A protective effect of GC*1F-1S was observed in Asians (OR = 0.70, 95%CI = 0.55-0.89, P = 0.003) but not in Caucasians (OR = 0.93, 95%CI = 0.69-1.24, P = 0.61). There was no association of GC*1S-1S, GC*2-1S and GC*1F-2 with COPD. As for alleles, GC*1F was a risk factor, whereas GC*1S was protective against COPD in Asians; GC*2 was not protective. The genotype GC*1F-1F or allele GC*1F was associated with increased susceptibility to COPD in Asians. No protective effect of genotype GC*2-2 against COPD was found. The protective effects of GC*1F-1S and GC*1S were observed in Asians but not in Caucasians. The VDBP gene polymorphism could be a potential marker for screening of COPD.

Meta-analytical association between angiotensin-converting enzyme gene polymorphisms and sarcoidosis risk.

Previous reports identified an association between sarcoidosis and an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme. Our meta-analysis of articles published between March 1996 and June 2013 identified studies in the PubMed, EMBASE, and the China National Knowledge Infrastructure databases. We examined whether angiotensin-converting enzyme polymorphisms influence sarcoidosis susceptibility. The strength of the association between I/D polymorphisms and sarcoidosis risk was measured based on the odds ratio and 95% confidence interval. Analysis was based on recessive and dominant models. Ethnic subgroup analysis from 18 articles (1882 cases and 3066 controls) showed that DD homozygote carriers were at a slightly increased risk of sarcoidosis compared with II homozygotes and DI heterozygotes (P = 0.03). Comparison of DD plus DI vs II revealed no significant association with sarcoidosis in group and ethnic subgroup analysis. We found that the I/D polymorphism in the angiotensin-converting enzyme gene was not associated with a major risk of sarcoidosis.

Ketamine used as an acesodyne in human breast cancer therapy causes an undesirable side effect, upregulating anti-apoptosis protein Bcl-2 expression.

Ketamine is a dissociative anesthetic agent that has been widely used in surgery and for relieving pain in chronic cancer patients. We applied ketamine to breast cancer cell line MDA-MB-231 to detect the effect of treatment and molecular mechanisms involved. We found that ketamine can upregulate the level of anti-apoptosis protein Bcl-2, which promotes breast cancer cell invasion and proliferation. Knockdown of Bcl-2 could inhibit the increase of Bcl-2 and reduce the invasion and proliferation caused by ketamine in human breast cancer cells. Our findings provide new insight into the effects of ketamine in cancer treatment; we suggest that ketamine, which has been widely used in cancer operations and for relieving pain in chronic cancer patients, may be not the best choice because it can worsen the cancer through promotion of anti-apoptosis.

Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a lethal global threat. Insights into the immune regulation of MDR-TB are urgently needed for the development of new treatments; however, the T cell response to an MDR-TB infection in human remains unclear. In the present study, the proportion of Th1 and Th2 cell subsets and the level of related T cell subset cytokines in peripheral blood were investigated. We detected that an MDR-TB infection resulted in suppressed Th1 and Th2 cell activation, which was more remarkable in patients with MDR-TB than that in drug-sensitive tuberculosis (DS-TB) sufferers when compared to healthy controls (HCs). In addition, MDR-TB infection down-regulated the expression of IFN-γ, IL-2, and IL-10, and up-regulated IL-4, IL-6, and TNF-α expression. Our data suggest that the disturbance between protective and pathogenic effects induced by the immunosuppression of Th1- and Th2-type responses is a substantial characteristic of MDR-TB infections.

Biosynthesis of fusarochromanone and its monoacetyl derivative by Fusarium equiseti.

One fluorescent compound previously named TDP-2 was isolated and purified from a rice culture of Fusarium equiseti (Alaska 2-2). Mass spectral and nuclear magnetic resonance data indicated that it is a C-3'-N-acetyl derivative of fusarochromanone, a newly discovered mycotoxin. Time course studies of synthesis of these two compounds on autoclaved rice and Czapek-Dox medium enriched with soybean peptone indicated that fusarochromanone was converted to TDP-2 in the cultures. A high concentration of peptone in the liquid medium may stimulate both fusarochromanone synthesis and its conversion to TDP-2.