Clinical relevance of somatic mutations in Chinese lung adenocarcinoma and their prognostic implications for survival.

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.

Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements.

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons. The elements' evolutionary history suggests that new regulatory information in the brain emerges primarily via smaller sequence mutations within conserved mammalian elements rather than entirely new human- or primate-specific sequences. However, primate-specific candidate elements, particularly those active during fetal brain development and in excitatory neurons and astrocytes, are implicated in the heritability of brain-related human traits. Additionally, we introduce PsychSCREEN, a web-based platform offering interactive visualization of PsychENCODE-generated genetic and epigenetic data from diverse brain cell types in individuals with psychiatric disorders and healthy controls.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Validating a Caregiving Rewarding Feelings scale among family caregivers of those diagnosed with schizophrenia in China.

INTRODUCTION: A culturally adaptive and easy-to-administer 12-item Caregiving Rewarding Feelings (CRF) scale has been developed in China yet never published in English and validated in another population. AIM: The current study aimed to validate the CRF among a community sample of Chinese caregivers of those diagnosed with schizophrenia. METHOD: A sample of 449 family caregivers was recruited for scale validation that included factorial validity, construct validity, measurement invariance, item analysis, internal consistency reliability, test-retest reliability, known-group validity, convergent validity and divergent validity. RESULTS: Confirmatory factor analysis supported the a priori three-factor structure. Construct validity was supported by high standard regression weight (SRW) and average variance extracted (AVE), measurement invariance across age and gender groups. The CRF showed good internal consistency and test-retest reliability. Known-group validity was confirmed by the higher CRF scores among caregivers with certain socio-demographics. The convergent validity of the CRF was supported by its positive correlations with social support, active coping and family functioning. The divergent validity of the CRF was supported by its negative associations with stigma, stress and depressive symptoms. CONCLUSIONS: This study confirmed the reliability and validity of the CRF specifically designed for caregivers in Chinese culture. IMPLICATIONS FOR PRACTICE: The CRF may be further applied and validated in other populations and other countries.

Analysis of hemorrhage upon ultrasound-guided percutaneous renal biopsy in China: a retrospective study.

PURPOSE: Ultrasound-guided percutaneous renal biopsy (PRB) has been considered as a golden standard for CKD diagnosis and is employed to identify potential therapeutic targets since 1950s. Post-biopsy hemorrhage is the most common complication, while severe bleeding complication might cause nephrectomy or death. Therefore, how to reduce the occurrence of complications while ensuring the success of PRB is always a clinical research topic. METHODS: This study retrospectively collected and established a renal biopsy database of each patient who underwent ultrasound-guided PRB at a tertiary teaching hospital from September 2017 to December 2020 through the Health Information System. All the data were statistically processed by SPSS software. RESULTS: A total of 1146 patients underwent PRB for various reasons. The overall rate of post-biopsy hemorrhage was 37.70% (432/1146). Of those bleedings, minor bleeding after PRB was found in 337 (29.41%), middle bleeding 84 (7.33%), major bleeding 11 (0.96%). Besides that, there were 96 patients (8.38%) reported their discomfort symptoms. There was no death. Females were at significantly increased risk of hemorrhagic complication than males (OR = 2.017, CI = 1.531-2.658). While the risk for hemorrhagic complication significantly decreased as BMI and platelet before renal biopsy increased (OR = 0.956, CI = 0.924-0.989; OR = 0.998, CI = 0.996-1.000). As the APTT time prolonged, the risk for hemorrhagic complication significantly increased (OR = 1.072, CI = 1.023-1.123). Those patients whose albumin were higher, also had higher risk for hemorrhagic complication than other patients (OR = 1.020, CI = 1.000-1.041). Specifically, postoperative urination within 4 h increased the risk for hemorrhagic complication (OR = 1.741, CI = 1.176-2.576). CONCLUSION: Our analysis finds that the incidence of post-biopsy bleeding complication is 37.70%, and its risk is associated with female, lower BMI, lower platelet before renal biopsy, prolonged APTT, higher albumin, and postoperative urination within 4 h. The findings highlighted the importance of perioperative management for renal biopsy, including adequate risk assessment, tailored careful observation after PRB. And medical staff should pay more attention to fluid management after ultrasound-guided PRB.

The apple transcription factor MdZF-HD11 regulates fruit softening by promoting Mdß-GAL18 expression.

Fruit ripening and the associated softening are major determinants of fruit quality and post-harvest shelf life. Although the mechanisms underlying fruit softening have been intensively studied, there are limited reports on the regulation of fruit softening in apples (Malus domestica). Here, we identified a zinc finger homeodomain transcription factor MdZF-HD11that trans-activates the promoter of Mdß-GAL18, which encodes a pectin-degradation enzyme associated with cell wall metabolism. Both MdZF-HD11 and Mdß-GAL18 genes were up-regulated by exogenous ethylene treatment and repressed by 1-methylcyclopropene treatment. Further experiments revealed that MdZF-HD11 binds directly to the Mdß-GAL18 promoter and up-regulates its transcription. Moreover, using transgenic apple fruit calli, we found that overexpression of Mdß-GAL18 or MdZF-HD11 significantly enhanced ß-galactosidase activity, and overexpression of MdZF-HD11 induced the expression of Mdß-GAL18. We also discovered that transient overexpression of Mdß-GAL18 or MdZF-HD11 in 'Golden Delicious' apple significantly increased the release of ethylene, reduced fruit firmness, promoted the transformation of skin color from green to yellow, and accelerated ripening and softening of the fruit. Finally, the overexpression of MdZF-HD11 in tomato also promoted fruit softening. Collectively, these results indicate that ethylene-induced MdZF-HD11 interacts with Mdß-GAL18 to promote the post-harvest softening of apple.

Thiamethoxam dynamics in pepper plants: Deciphering deposition and dissipation pattern across diverse planting modes and regions.

To reduce the application dosage of thiamethoxam (TMX), we investigated the deposition and dissipation patterns in a pepper-planted ecosystem under different planting modes across four regions in China, namely Hainan (HN), Zhejiang (ZJ), Anhui (AH) and Hebei (HB). This study focused on the deposition and dissipation of TMX at concentrations of 63.00, 47.25, 31.50, 23.63 and 15.75 g a.i.hm-2. As the application dose increased, the deposition amount of TMX initially increased in the plants and cultivated soil, showing obvious geographic differences in four cultivation areas. Surprisingly, the initial amount of TMX deposited the pepper-cultivated greenhouse of ZJ and AH was 1.1-2.1-fold and 1.0-3.6-fold higher than that in the open field system at the same application dose, respectively. In pepper leaves, stems, fruits and soil, the dissipation exhibited rapid growth and then slowed. However, the residual concentration showed an increasing trend, followed by a subsequent decrease in the pepper roots. In different planting regions, the dissipation rate of TMX followed the order HN > ZJ > AH > HB in pepper plants and cultivated soil. In comparison to the open field, the total TMX retention rate in greenhouse was higher, indicating overall greater persistence in the greenhouse conditions. These findings reveal the deposition and dissipation characteristics of TMX within the pepper-field ecosystem, offering a significant contribution to the risk assessment of pesticides.

Investigating the role of NPR1 in dilated cardiomyopathy and its potential as a therapeutic target for glucocorticoid therapy.

Background: Dilated cardiomyopathy (DCM), a specific form of cardiomyopathy, frequently presents clinically with either left ventricular or biventricular enlargement, often leading to progressive heart failure. In recent years, the application of bioinformatics technology to scrutinize the onset, progression, and prognosis of DCM has emerged as a fervent area of interest among scholars globally. Methods: In this study, core genes closely related to DCM were identified through bioinformatics analysis, including weighted gene co expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) and so on. The correlation was verified through experiments on DCM patients, DCM rat models, and core gene knockout mice. Subsequently, the effects of glucocorticoids on DCM and the regulation of core genes were observed. Result: In the present study, natriuretic peptide receptor 1 (NPR1) was identified as a core gene associated with DCM through WGCNA and ssGSEA. Significant impairment of cardiac and renal function was observed in both DCM patients and rats, concomitant with a notable reduction in NPR1 expression. NPR1 KO mice displayed symptomatic manifestations of DCM, underscoring the pivotal role of NPR1 in its pathogenesis. Notably, glucocorticoid treatment led to substantial improvements in cardiac and renal function, accompanied by an upregulation of NPR1 expression. Discussion: These findings highlight the critical involvement of NPR1 in the pathophysiology of DCM and its potential as a key target for glucocorticoid-based DCM therapy. The study provides a robust theoretical and experimental foundation for further investigations into DCM etiology and therapeutic strategies.

MicroRNA hsa-miR-320a-3p and Its Targeted mRNA FKBP5 Were Differentially Expressed in Patients with HIV/TB Co-Infection.

Among the PLWH (people living with HIV) population, the risk of developing active tuberculosis (TB) is increasing. Active TB also accelerates the deterioration of PLWH's immune function and is one of the leading causes of death in the PLWH population. So far, accurate diagnosis of active TB in the PLWH population remains challenging. Through data analysis of HIV/TB co-infection in the GEO database, the differentially expressed genes as well as their related microRNA (miRNA) were acquired and were further verified through clinical blood samples. Dual-luciferase assay was used to verify the mechanism of miRNA on mRNA. The enrichment of immune cells in database patient samples was analyzed by bioinformatics and finally verified by blood routine data. Our study found that FKBP5 (FK506 binding protein 5) was highly expressed in the HIV/TB co-infection group; hsa-miR-320a-3p was highly expressed in the HIV infection group but decreased in the HIV/TB co-infection group. Dual-luciferase assay results showed that hsa-miR-320a-3p mimics significantly reduced the relative luciferase activity of the WT-FKBP5 group; however, this phenomenon was not observed in the MUT-FKBP5 group. At the same time, as a key molecule of the immune-related pathway, FKBP5 is highly correlated with the amount of neutrophils, which provides a new suggestion for the treatment of the HIV/TB co-infection population. Our study found that hsa-miR-320a-3p can decrease FKBP5 expression, suggesting a potential regulatory role for FKBP5. The involvement of FKBP5 and its related molecule hsa-miR-320a-3p in HIV/TB co-infection proposes them as potential biomarkers for the diagnosis of active TB in the PLWH population.

Whole genome sequencing of drug resistance Mycobacterium tuberculosis from extra-pulmonary sites.

This study aimed to determinate characteristics of drug resistance Mycobacterium tuberculosis from patients with extra-pulmonary tuberculosis (EPTB). Patients were retrospectively studied from January 2020 to December 2021. All the isolates were cultured, tested drug susceptibility, and detected the gene mutation using whole genome sequencing. The correlations of whole genome sequencing, pattern of DR, patients' distribution, and transmission were analyzed. 111 DR-EPTB isolates included pre-XDR-TB (53.2%), MDR-TB (29.7%), and poly-DR-TB (12.6%). The resistant drugs were INH followed by RFP and SM. The genotypes of 111 strains were lineage 2 and lineage 4. KatG_p.Ser315Thr was main gene mutation for resistance to INH; rpsL_p.Lys43Arg for SM, rpoB_p.Ser450Leu for rifampicin, embB_p.Met306Val for ethambutol, gyrA_p.Asp94Gly for FQs, and pncA_p.Thr76Pro for PZA. The residence was a significant risk factor for cluster transmission by patients and phenotypic DR types of strains for lineage 2 transmission. In the local area of southwest China INH, rifampicin and SM were main drugs in patients with DR-EPTB. KatG_p.Ser315, rpoB_p.Ser450Leu, and rpsL_p.Lys43Arg were main gene mutations. Phenotypic DR types and residence were main risk of transmission.

Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A­heterozygous mice.

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.

Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB).

Recognizing schizophrenia using facial expressions based on convolutional neural network.

OBJECTIVE: Facial expressions have been served as clinical symptoms to convey mental conditions in psychiatry. This paper proposes to recognize patients with schizophrenia (SCZ) using their facial images based on deep learning algorithm, and to investigate objective differences in facial expressions between SCZ patients and healthy controls using deep learning algorithm and statistical analyses. METHODS: The study consists of two parts. The first part recruited 106 SCZ patients and 101 healthy controls, and videotaped their facial expressions through a fixed experimental paradigm. The video data were randomly divided into two sets, one for training a convolutional neural network (CNN) with the classification of "healthy control" or "SCZ patient" as output and the other for evaluating the classification result of the trained CNN. In the second part, all facial images of the recruited participants were put into another CNN separately, which was priorly trained with a facial expression database and will output the most likely facial expressions of the recruited participants. Statistical analyses were performed on the obtained facial expressions to find out the objective differences in facial expressions between the two recruited groups. RESULTS: The trained CNN achieved an overall accuracy of 95.18% for classifying "healthy control" or "SCZ patient." Statistical results on the obtained facial expressions demonstrated that the objective differences between the two recruited groups were statistically significant (p < .05). CONCLUSIONS: Facial expressions hold great promise as SCZ clues with the help of deep learning algorithm. The proposed approach would be potentially applied to mobile devices for autorecognizing SCZ in the context of clinical and daily life.

Effects of N fertilizer reduction combined with straw biochar application on the yield, Si, and N nutrition of double-cropping rice.

Nitrogen (N) and silicon (Si) are important nutritional elements for rice. However, excessive N fertili-zer application and the ignorance of Si fertilizer are common in practice. Straw biochar is rich in Si, which can be used as a potential Si fertilizer. In this study, we conducted a consecutive 3-year field experiment to explore the effects of N fertilizer reduction combined with straw biochar application on rice yield, Si and N nutrition. There were five treatments: conventional N application (180 kg·hm-2, N100), 20% N reduction (N80), 20% N reduction with 15 t·hm-2 biochar (N80+BC), 40% N reduction (N60), and 40% N reduction with 15 t·hm-2 biochar (N60+BC). The results showed that compared with N100, 20% N reduction did not affect the accumulation of Si and N in rice; 40% N reduction reduced foliar N absorption, but significantly increased foliar Si concentration by 14.0%-18.8%; while combined application of biochar significantly increased foliar Si accumulation, with an increase of Si concentration by 38.0%-63.3% and Si absorption by 32.3%-49.9%, but further reduced foliar N concentration. There was a significant negative correlation between Si and N concentration in mature rice leaves, but no correlation between Si and N absorption. Compared with N100, N reduction or combined application of biochar did not affect soil ammonium N and nitrate N, but increased soil pH. Nitrogen reduction combined application of biochar significantly increased soil organic matter by 28.8%-41.9% and available Si content by 21.1%-26.9%, with a significant positive correlation between them. Compared with N100, 40% N reduction reduced rice yield and grain setting rate, while 20% N reduction and combined application of biochar did not influence rice yield and yield components. In summary, appropriate N reduction and combined with straw biochar can not only reduce N fertilizer input, but also improve soil fertility and Si supply, which is a promising fertilization method in double-cropping rice fields.

Fungicide exposure accelerated horizontal transfer of antibiotic resistance genes via plasmid-mediated conjugation.

Co-pollution of soil with pesticide residues and antibiotic resistance genes (ARGs) is increasing due to the substantial usage of pesticides and organic fertilizers in greenhouse-based agricultural production. Non-antibiotic stresses, including those from agricultural fungicides, are potential co-selectors for the horizontal transfer of ARGs, but the underlying mechanism remains unclear. Intragenus and intergenus conjugative transfer systems of the antibiotic resistant plasmid RP4 were established to examine conjugative transfer frequency under stress from four widely used fungicides: triadimefon, chlorothalonil, azoxystrobin, and carbendazim. The mechanisms were elucidated at the cellular and molecular levels using transmission electron microscopy, flow cytometry, RT-qPCR, and RNA-seq techniques. The conjugative transfer frequency of plasmid RP4 between Escherichia coli strains increased with the rising exposure concentrations of chlorothalonil, azoxystrobin, and carbendazim, but was suppressed between E. coli and Pseudomonas putida by a high fungicide concentration (10 µg/mL). Triadimefon did not significantly affect conjugative transfer frequency. Exploration of the underlying mechanisms revealed that: (i) chlorothalonil exposure mainly promoted generation of intracellular reactive oxygen species, stimulated the SOS response, and increased cell membrane permeability, while (ii) azoxystrobin and carbendazim primarily enhanced expression of conjugation-related genes on the plasmid. These findings reveal the fungicide-triggered mechanisms associated with plasmid conjugation and highlight the potential role of non-bactericidal pesticides on the dissemination of ARGs.

Investigation of bedaquiline resistance and genetic mutations in multi-drug resistant Mycobacterium tuberculosis clinical isolates in Chongqing, China.

BACKGROUND: To investigate the prevalence and molecular characterization of bedaquiline resistance among MDR-TB isolates collected from Chongqing, China. METHODS: A total of 205 MDR-TB isolates were collected from Chongqing Tuberculosis Control Institute between March 2019 and June 2020. The MICs of BDQ were determined by microplate alamarblue assay. All strains were genotyped by melting curve spoligotyping, and were subjected to WGS. RESULTS: Among the 205 MDR isolates, the resistance rate of BDQ was 4.4% (9/205). The 55 (26.8%) were from male patients and 50 (24.4%) were new cases. Furthermore, 81 (39.5%) of these patients exhibited lung cavitation, 13 (6.3%) patients afflicted with diabetes mellitus, and 170 (82.9%) isolates belonged to Beijing family. However, the distribution of BDQ resistant isolates showed no significant difference among these characteristics. Of the 86 OFX resistant isolates, 8 isolates were XDR (9.3%, 8/86). Six BDQ resistant isolates (66.7%, 6/9) and two BDQ susceptible isolates (1.0%, 2/196) carried mutations in Rv0678. A total of 4 mutations types were identified in BDQ resistant isolates, including mutation in A152G (50%, 3/6), T56C (16.7%, 1/6), GA492 insertion (16.7%, 1/6), and A274 insertion (16.7%, 1/6). BDQ showed excellent activity against MDR-TB in Chongqing. CONCLUSIONS: BDQ showed excellent activity against MDR-TB in Chongqing. The resistance rate of BDQ was not related to demographic and clinical characteristics. Mutations in Rv0678 gene were the major mechanism to BDQ resistance, with A152G as the most common mutation type. WGS has a good popularize value and application prospect in the rapid detection of BDQ resistance.

Deposition and dissipation of difenoconazole in pepper and soil and its reduced application to control pepper anthracnose.

The initial deposition amount, dissipation dynamics, retention rate, and field control efficacy of difenoconazole in pepper-soil system were studied with different application dosages, planting regions and patterns. The initial deposition amount of difenoconazole under the same application dosage showed the following order: fruits < cultivated soils < lower stems < upper stems < lower leaves < upper leaves, open field < greenhouse, and Changjiang < Cixi < Hefei < Langfang, respectively, which increased with increasing application dosage. The dissipation rates in leaves, stems, fruits and cultivated soils exhibited an initially fast and then slow trend, while the retention rates displayed a tendency of first increasing and then stabilizing with increasing application dosages. After 7 d of difenoconazole application, the retention rates at five concentrations were 10.3%- 39.1%, and the field efficacy mostly reached the minimum effective dose. These results suggested that difenoconazole could be reduced by 25% based on the minimum recommended dose meeting the requirements of field control efficacy for controlling pepper anthracnose.

[Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors].

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

The impact of blood pressure on the risk of postbiopsy bleeding during the whole procedure of percutaneous kidney biopsy.

PURPOSE: To investigate whether BP is related to postbiopsy bleeding in patients undergoing native percutaneous kidney biopsy (PKB) and to evaluate the dynamic changes in blood pressure (BP) pre- and post-kidney biopsy. METHODS: A retrospective cross-sectional study was conducted. The whole-procedural systolic (SBP) and diastolic (DBP) BP for patients undergoing ultrasound-guided native PKB from October 2017 to December 2020 were recorded in the study. Propensity score matching was used to minimize selection bias. SBP and DBP were analyzed as the main risk factors for bleeding complications. Receiver operating characteristic (ROC) curves were employed to explore the optimal BP thresholds to differentiate between bleeding and nonbleeding. The rates of major bleeding complications were analyzed according to BP thresholds through logistic analysis. RESULTS: Of 1146 biopsies, 432 (37.7%) patients suffered from postbiopsy bleeding, 88 (7.7%) patients had major bleeding complications, and 344 (30.0%) patients had minor bleeding complications. In the original data, for patients with SBP ≥ 160 mmHg before PKB, the rate of major bleeding complications was 17.6% (7.5% for SBP < 160 mmHg), and the rate of major bleeding complications was 19.0% in patients with DBP ≥ 100 mmHg (7.5% for DBP < 100 mmHg). For patients with DBP ≥ 85 mmHg to 100 mmHg after PKB, the rate of major bleeding complications ranged from 9.5 to 17.5%. The rate of major bleeding complications was lower (6.6-7.3%) in patients with DBP < 100 mmHg to 85 mmHg. CONCLUSION: Patients who have high-level BP during the native PKB perioperative period are at higher risk for postbiopsy bleeding. High-level BP here does not refer to traditional hypertension according to the guidelines for the diagnosis and treatment of hypertension, but rather BP above a certain threshold related to bleeding risk.

Mycobacterium tuberculosis PE_PGRS1 promotes mycobacteria intracellular survival via reducing the concentration of intracellular free Ca2+ and suppressing endoplasmic reticulum stress.

Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis (TB). And the PE_PGRS family members of M. tuberculosis are closely associated with virulence and antigen presentation but with function largely elusive. PE_PGRS1(Rv0109) contained 7 Ca2+ binding domains of GGXGXD/NXUX (X is any amino acid), which can reduce intracellular Ca2+ surge. In addition, PE_PGRS1 can mitigate the activation of PERK branch in endoplasmic reticulum (ER) stress by down-regulating the expression of CHOP, Bip, p-PERK, p-eIF2α, and ATF4. Interestingly, we found that two splicing variations of Bax/Bcl-2, Baxß, and Bcl-2α, were differentially expressed after infection with Ms_PE_PGRS1, and may be involved in the regulation of apoptosis. Hence, this study identified that PE_PGRS1 is a novel calcium-associated protein that can decrease intracellular Ca2+ levels and the PERK axis. And the weakening of the PERK-eIF2α-ATF4 axis reduces THP-1 macrophages apoptosis, promotes the survival of mycobacteria in macrophages.