Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

A Hydrazine-Hydrazone Adamantine Compound Shows Antimycobacterial Activity and Is a Probable Inhibitor of MmpL3.

Tuberculosis remains an important cause of morbidity and mortality throughout the world. Notably, an important number of multi drug resistant cases is an increasing concern. This problem points to an urgent need for novel compounds with antimycobacterial properties and to improve existing therapies. Whole-cell-based screening for compounds with activity against Mycobacterium tuberculosis complex strains in the presence of linezolid was performed in this study. A set of 15 bioactive compounds with antimycobacterial activity in vitro were identified with a minimal inhibitory concentration of less than 2 µg/mL. Among them, compound 1 is a small molecule with a chemical structure consisting of an adamantane moiety and a hydrazide-hydrazone moiety. Whole genome sequencing of spontaneous mutants resistant to the compounds suggested compound 1 to be a new inhibitor of MmpL3. This compound binds to the same pocket as other already published MmpL3 inhibitors, without disturbing the proton motive force of M. bovis BCG and M. smegmatis. Compound 1 showed a strong activity against a panel ofclinical strains of M. tuberculosis in vitro. This compound showed no toxicity against mammalian cells and protected Galleria mellonella larvae against M. bovis BCG infection. These results suggest that compound 1 is a promising anti-TB agent with the potential to improve TB treatment in combination with standard TB therapies.

Sub-toxic levels of cobalt ions impair chondrocyte mechanostranduction via HDAC6-dependent primary cilia shortening.

Cobalt ions are the main wear particles associated with orthopaedic implants, causing adverse complications due to cytotoxicity and inflammatory mediators. Recent studies have shown that sub-toxic levels of cobalt ions regulate matrix synthesis and inflammation, but the influence of cobalt ions on mechanotransduction remains unclear. Previously, we reported that sub-toxic levels of cobalt ions modulated primary cilia, which are crucial for mechanotransduction. This study therefore aimed to investigate the effect of cobalt ions on chondrocyte mechanosensation in response to cyclic tensile strain and the association with primary cilia. Sub-toxic levels of cobalt ions impaired chondrocyte mechanosensation and affected the gene expression of aggrecan, collagen II and MMP-13. Moreover, cobalt ions induced HDAC6-dependent primary cilia disassembly, which was associated with either cytoplasmic or ciliary α-tubulin deacetylation. Pharmaceutical HDAC6 inhibition with tubacin restored primary cilia length and mechanotransduction, whereas chemical depletion of primary cilia by chloral hydrate prevented mechanosignalling. Thus, sub-toxic levels of cobalt ions impaired chondrocyte mechanotransduction via HDAC6 activation, which was associated with tubulin deacetylation and primary cilia shortening.

Low Dose of Emodin Inhibits Hypercholesterolemia in a Rat Model of High Cholesterol.

BACKGROUND Emodin has been widely used in traditional Chinese medicine, but few studies have tried to understand the mechanism of its anti-hypercholesterolemic effect. MATERIAL AND METHODS To delineate the underlying pathways, high-cholesterol diet (HCD)-fed Sprague-Dawley rats were orally administrated emodin or the lipid-lowering medicine simvastatin. Emodin was administered at 10, 30, or 100 mg/kg, while simvastatin was administered at 10 mg/kg. Parameters measured included lipid profiles (serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, aorta endothelium-dependent vasorelaxation in response to acetylcholine, and nitric oxide (NO) production. RT-qPCR and western blotting were performed to evaluate aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and hepatic LDL receptor (LDLR). Indices of liver and serum oxidation were also measured. RESULTS The atherogenic index was increased by the HCD but significantly reduced in all treatment groups. The HCD-fed experimental group treated with emodin at 10 mg/kg had significantly lower serum total-C and LDL-C and improved aorta vasorelaxation and enhanced NO production. Also, emodin significantly attenuated the lipid profiles and restored endothelial function, as reflected by upregulated expression of hepatic LDLR and p-eNOS, respectively. Furthermore, emodin at 10 mg/kg significantly enhanced superoxide dismutase activity, lowered the malondialdehyde level in both liver and serum, and enhanced catalase activity in serum. CONCLUSIONS The ability of emodin to inhibit hypercholesterolemia in HCD-fed rats was associated with lower serum total-C and LDL-C, restoration of aortic endothelial function, and improved antioxidant capacity. Low-dose emodin showed better protection of aortic endothelium and better antioxidant activity than did higher doses.

Combination of Xpert MTB/RIF and MTBDRplus for Diagnosing Tuberculosis in a Chinese District.

BACKGROUND The incidence of tuberculosis (TB) remains high in many countries, including some middle- and high-income countries without financial constraints for diagnosis and treatment. The implementation of an improved algorithm for diagnosis using 2 rapid molecular tests should help reduce the TB burden. MATERIAL AND METHODS Between April 2018 and March 2019, sputum samples from 711 patients suspected of TB in Nanshan, Shenzhen, China, were included in this prospective study. All sputum samples were examined by smear microscopy, Mycobacterium Growth Indicator Tube (MGIT) 960 culture, and Xpert MTB/RIF. The sputum remnants of Xpert MTB/RIF were used for MTBDRplus to confirm the Xpert results both for the presence of TB bacilli and for resistance to rifampicin (RIF), and also to diagnose multidrug-resistant tuberculosis (MDR-TB). RESULTS In total, 200 (28.1%) of the 711 sputa were positive for TB by Xpert MTB/RIF, and the sputum remnants were used for MTBDRplus. The simultaneous use of Xpert MTB/RIF and MTBDRplus directly on sputum samples permitted accurate bacteriologic confirmation of TB in 64% (119/187) of cases and detection of 70% (7/10) of strains that were MDR. CONCLUSIONS The implementation of 2 rapid nucleic acid-based tests on sputum samples could facilitate the prompt and appropriate treatment of most TB cases.

CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in The Cancer Genome Atlas (TCGA) study.

BACKGROUND: Genetic alterations play an important role in the progression of colorectal cancer (CRC). Identifying new biomarkers to assess the prognosis of patients with CRC is critical. Cartilage intermediate layer protein 2 (CILP2) gene, screened from TCGA database by bioinformatics, may be closely related to the progression of CRC. CILP2 was barely reported with clinical features of tumors. MATERIALS AND METHODS: Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and the P value was calculated by the log-rank test. The Kaplan-Meier curves were tested by the log-rank test. RESULTS: CILP2 was statistically significantly higher expressed in the CRC tissues when compared with paired adjacent normal tissues in TCGA cohort (P < 0.001) and in the TMA cohort (P = 0.001). Also, CILP2 high expression was strongly correlated with T3/4 stage (P = 0.001), N1/2/3 stage (P = 0.005), M1 stage (P = 0.048), and higher clinical stage (UICC 2010 stage) (P < 0.001) in TCGA cohort, and also positively associated with T3/4 stage (P = 0.022) and higher clinical stage (UICC 2010 stage) (P = 0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be an independent prognostic factor (P = 0.003). CONCLUSION: We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in CRC.

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients: A Population-Based, Prospective Cohort Study.

BACKGROUND AND PURPOSE: Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. METHODS: A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. RESULTS: After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 µmol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 µmol/L) were 4.96 (3.03-8.12), 6.11 (3.44-10.85), and 1.84 (0.52-6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 µmol/L (27.92%) in patients with essential hypertension. CONCLUSIONS: Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.

Robustness of a new molecular dynamics-finite element coupling approach for soft matter systems analyzed by uncertainty quantification.

Key parameters of a recently developed coarse-grained molecular dynamics-finite element coupling approach have been analyzed in the framework of uncertainty quantification (UQ). We have employed a polystyrene sample for the case study. The new hybrid approach contains several parameters which cannot be determined on the basis of simple physical arguments. Among others, this includes the so-called anchor points as information transmitters between the particle-based molecular dynamics (MD) domain and the surrounding finite element continuum, the force constant between polymer beads and anchor points, the number of anchor points, and the relative sizes of the MD core domain and the surrounding dissipative particle dynamics domain. Polymer properties such as density, radius of gyration, end-to-end distance, and radial distribution functions are calculated as a function of the above model parameters. The influence of these input parameters on the resulting polymer properties is studied by UQ. Our analysis shows that the hybrid method is highly robust. The variation of polymer properties of interest as a function of the input parameters is weak.

Association between homocysteine and incidence of ischemic stroke in subjects with essential hypertension: a matched case-control study.

BACKGROUND: To assess the association between total plasma homocysteine (tHcy) and ischemic stroke (IS) in hypertensive subjects in a matched case-control study. METHODS: This is a 1:2 matched and population-based case-control study, all of the participants were recruited from the 60 communities in Shenzhen, China. Demographic and socioeconomic characteristics, medical records, lifestyle risk factors and other clinical characteristics were obtained from all of the subjects. The association between tHcy and incidence of IS was analyzed by using conditional logistic regression models. RESULTS: The median values of plasma tHcy were significantly higher in IS subjects than in non-IS subjects, especially in women. After adjusted for the confounding factors in Model 2, compared with the lowest quartile of tHcy, the odds ratios (ORs) and 95% CIs of the highest quartile of tHcy for IS were 0.83 (0.36-1.90) in men, 4.51 (1.29-15.7) in women and 1.31 (0.70-2.47) in the total subjects; the ORs and 95% CIs for IS per 5 µmol/L increase in homocysteine were 1.11 (0.99-1.22), 1.25 (1.03-1.58) and 1.15 (1.01-1.28) in men, women and total subjects, respectively. We observed significant associations in crude model, Model 1 and Model 2 in women for the comparison of tHcy ≥ 15 µmol/L versus < 15 µmol/L. Interaction analysis showed that the association of tHcy with IS was significant in women (p-interaction = 0.04). CONCLUSION: This matched case-control study indicates that tHcy may increase the susceptibility to IS in essential hypertension subjects, especially in women. Further large prospective cohort studies are needed to confirm our findings.

Spatio-temporal analysis of female breast cancer incidence in Shenzhen, 2007-2012.

INTRODUCTION: Breast cancer is a leading tumor with a high mortality in women. This study examined the spatio-temporal distribution of the incidence of female breast cancer in Shenzhen between 2007 and 2012. METHODS: The data on breast cancer incidence were obtained from the Shenzhen Cancer Registry System. To describe the temporal trend, the average annual percentage change (AAPC) was analyzed using a joinpoint regression model. Spatial autocorrelation and a retrospective spatio-temporal scan approach were used to detect the spatio-temporal cluster distribution of breast cancer cases. RESULTS: Breast cancer ranked first among different types of cancer in women in Shenzhen between 2007 and 2012 with a crude incidence of 20.0/100,000 population. The age-standardized rate according to the world standard population was 21.1/100,000 in 2012, with an AAPC of 11.3%. The spatial autocorrelation analysis showed a spatial correlation characterized by the presence of a hotspot in south-central Shenzhen, which included the eastern part of Luohu District (Donghu and Liantang Streets) and Yantian District (Shatoujiao, Haishan, and Yantian Streets). Five spatio-temporal cluster areas were detected between 2010 and 2012, one of which was a Class 1 cluster located in southwestern Shenzhen in 2010, which included Yuehai, Nantou, Shahe, Shekou, and Nanshan Streets in Nanshan District with an incidence of 54.1/100,000 and a relative risk of 2.41; the other four were Class 2 clusters located in Yantian, Luohu, Futian, and Longhua Districts with a relative risk ranging from 1.70 to 3.25. CONCLUSIONS: This study revealed the spatio-temporal cluster pattern for the incidence of female breast cancer in Shenzhen, which will be useful for a better allocation of health resources in Shenzhen.

[A prospective study on the association of plasma homocysteine level with stroke in hypertensive patients].

OBJECTIVE: To analyze the association between homocysteine (Hcy) and stroke in hypertensive patients. METHODS: This was a prospective cohort study conducted in 60 communities in Nanshan District, Shenzhen. Totally 5 488 patients with hypertension were included at baseline survey and followed for an average of 2.7 years. At the end of follow-up, 327 (5.96%) subjects were missing with unknown reasons. Hcy was detected by enzymatic cycling method. Head CT, MRI, cerebral angiography and transcranial Doppler ultrasound were performed in the patients. Stroke was defined based on the International Classification of Diseases (ICD10 coding I60-I64). RESULTS: After an average of 2.7-year follow-up, 197 developed new stroke. The incidence rate was 3.82%. Subjects whose Hcy levels were within the highest quartile (Q4) had higher risk to develop stroke compared with those whose Hey levels were within the lowest quartile (Q1). The HR (95% CI) were 7.4 (3.2-13.2) in total with 7.5(3.0-19.5) in men and 7.7 (2.7-22.1) in women after adjustment of age, sex, education, smoking, alcohol drinking, and BMI, physical activity, diabetes, depression, family history of stroke or coronary heart disease, years of hypertension, antihypertensive drugs, folic acid, systolic blood pressure, TC, glucose and TG. For every 5 µmol/L increase in Hcy, the HR (95% CI) of stroke increased 1.15-fold (1.09-1.21) in total subjects with 1.15 (1.08-1.21) in men and 1.19 (1.04-1.35) in women, respectively. No significant interactions on stroke could be found between Hcy and the above stratified factors. CONCLUSION: Elevated Hcy levels were associated with stroke in hypertensive patients.

Impacts of different slash disposals on soil and water erosion of high-intensity management Eucalyptus grandis × urophylla plantation.

Background: The slash disposal-burning forest-in high-intensity management Eucalyptus grandis × urophylla plantation has accelerated soil degradation. Statement of the problem: Slash disposals is a contributing factor, but its specific role in the correlation between rainfall-runoff and soil erosion remains elusive. Objectives: his study investigated the characteristics of rainfall-runoff and soil erosion resistance in different methods of slash disposals in plantation. Methods: Three methods of slash disposal, namely burning forest (BF), moving away (MA), and spreading evenly (SE), were established. A field simulation experiment of rainfall was conducted, and path analysis was used. Results: The findings revealed that the water holding, infiltrating properties and the time the rainfall-runoff generated of SE were increased by approximately 10∼20 %, 100 %, and 80 %, respectively, compared with BF and MA. Water loss, soil loss and nutrient loss were significantly reduced by 62.23 % and 61.56 %, 69.06 % and 49.55 %, and 58.8 % and 65.42 % in SE and BF compared to MA. Path analysis suggested that different from BF and MA, the correlation between soil water properties and rainfall-runoff factors in SE was weakened, simultaneously considering the result that SE had the lower proportions of silt for sediment component (75.31 %), it stabilized the soil structure. Conclusions and prospect: Consequently, SE mitigated the erosion force by reducing rainfall-runoff and enhancing the anti-erosion of soil through improved water properties, making it a viable slash disposal. This work provides a detailed description of the soil erosion characteristics of plantation, including water, soil, and nutrient losses caused by rainfall-runoff, as well as the soil anti-erosion due to different slash disposals. These findings offer valuable insights for the management of high-intensity Eucalyptus grandis × urophylla plantations.

ContraSurv: Enhancing Prognostic Assessment of Medical Images via Data-Efficient Weakly Supervised Contrastive Learning.

Prognostic assessment remains a critical challenge in medical research, often limited by the lack of well-labeled data. In this work, we introduce ContraSurv, a weakly-supervised learning framework based on contrastive learning, designed to enhance prognostic predictions in 3D medical images. ContraSurv utilizes both the self-supervised information inherent in unlabeled data and the weakly-supervised cues present in censored data, refining its capacity to extract prognostic representations. For this purpose, we establish a Vision Transformer architecture optimized for our medical image datasets and introduce novel methodologies for both self-supervised and supervised contrastive learning for prognostic assessment. Additionally, we propose a specialized supervised contrastive loss function and introduce SurvMix, a novel data augmentation technique for survival analysis. Evaluations were conducted across three cancer types and two imaging modalities on three real-world datasets. The results confirmed the enhanced performance of ContraSurv over competing methods, particularly in data with a high censoring rate.

Deep learning-based radiomics model can predict extranodal soft tissue metastasis in gastric cancer.

BACKGROUND: The potential prognostic value of extranodal soft tissue metastasis (ESTM) has been confirmed by increasing studies about gastric cancer (GC). However, the gold standard of ESTM is determined by pathologic examination after surgery, and there are no preoperative methods for assessment of ESTM yet. PURPOSE: This multicenter study aimed to develop a deep learning-based radiomics model to preoperatively identify ESTM and evaluate its prognostic value. METHODS: A total of 959 GC patients were enrolled from two centers and split into a training cohort (N = 551) and a test cohort (N = 236) for ESTM evaluation. Additionally, an external survival cohort (N = 172) was included for prognostic analysis. Four models were established based on clinical characteristics and multiphase computed tomography (CT) images for preoperative identification of ESTM, including a deep learning model, a hand-crafted radiomic model, a clinical model, and a combined model. C-index, decision curve, and calibration curve were utilized to assess the model performances. Survival analysis was conducted to explore the ability of stratifying overall survival (OS). RESULTS: The combined model showed good discrimination of the ESTM [C-indices (95% confidence interval, CI): 0.770 (0.729-0.812) and 0.761 (0.718-0.805) in training and test cohorts respectively], which outperformed deep learning model, radiomics model, and clinical model. The stratified analysis showed this model was not affected by patient's tumor size, the presence of lymphovascular invasion, and Lauren classification (p < 0.05). Moreover, the model score showed strong consistency with the OS [C-indices (95%CI): 0.723 (0.658-0.789, p < 0.0001) in the internal survival cohort and 0.715 (0.650-0.779, p < 0.0001) in the external survival cohort]. More interestingly, univariate analysis showed the model score was significantly associated with occult distant metastasis (p < 0.05) that was missed by preoperative diagnosis. CONCLUSIONS: The model combining CT images and clinical characteristics had an impressive predictive ability of both ESTM and prognosis, which has the potential to serve as an effective complement to the preoperative TNM staging system.

Radiomics and Deep Learning in Nasopharyngeal Carcinoma: A Review.

Nasopharyngeal carcinoma is a common head and neck malignancy with distinct clinical management compared to other types of cancer. Precision risk stratification and tailored therapeutic interventions are crucial to improving the survival outcomes. Artificial intelligence, including radiomics and deep learning, has exhibited considerable efficacy in various clinical tasks for nasopharyngeal carcinoma. These techniques leverage medical images and other clinical data to optimize clinical workflow and ultimately benefit patients. In this review, we provide an overview of the technical aspects and basic workflow of radiomics and deep learning in medical image analysis. We then conduct a detailed review of their applications to seven typical tasks in the clinical diagnosis and treatment of nasopharyngeal carcinoma, covering various aspects of image synthesis, lesion segmentation, diagnosis, and prognosis. The innovation and application effects of cutting-edge research are summarized. Recognizing the heterogeneity of the research field and the existing gap between research and clinical translation, potential avenues for improvement are discussed. We propose that these issues can be gradually addressed by establishing standardized large datasets, exploring the biological characteristics of features, and technological upgrades.

Functional microorganisms in Baijiu Daqu: Research progress and fortification strategy for application.

Daqu is a saccharifying and fermenting starter in the production of Chinese Baijiu; its quality directly affects the quality of Baijiu. The production of Daqu is highly environment-dependent, and after long-term natural domestication, it is rich in a wide variety of microorganisms with a stable composition, which provide complex and diverse enzymes and flavor (precursor) substances and microbiota for Jiupei (Fermented grains) fermentation. However, inoculation with a relatively stable microbial community can lead to a certain upper limit or deficiencies of the physicochemical properties (e.g., saccharification capacity, esterification capacity) of the Daqu and affect the functional expression and aroma formation of the Daqu. Targeted improvement of this problem can be proposed by selecting functional microorganisms to fortify the production of Daqu. This review introduced the isolation, screening, identification and functional characteristics of culture-dependent functional microorganisms in Baijiu-brewing, the core functional microbiota community of Daqu, and the related research progress of functional microorganisms fortified Daqu, and summarized the fortifying strategies of functional microorganisms, aiming to further deepen the application of functional microorganisms fortification in Daqu fermentation and provide ideas for the flavor regulation and quality control of Baijiu.

The impacts of the national centralized drug procurement policy on the use of policy-related antibiotic agents: the case of Shaanxi province, China.

OBJECTIVES: The purpose of NCDP policy was to reduce the price of drugs. However, it is unclear that a reduction in the price of a single antibiotic will lead to an increase in other alternatives, which is crucial for antibiotic management. The aim of this study was to evaluate the impact of policy on the consumption of policy-related antibiotic. METHODS: Quasi-experimental interrupted time series methods were used to assess the effects of the policy. RESULTS: After the implementation of the policy, the consumption of the winning products increased rapidly, with a significant difference in growth (ß2 = 88.03). For nonwinning products, the level of purchase volume decreased (ß2=-22.83) in the intervention group, and after adding the comparison group, this number fell further in statistical significance (ß2=-114.53). Among all the nonwinning products, the level of purchase volume (ß2=-73.59) and expenditures (ß2=-346.71) of the generic drugs that passed the conformance evaluation decreased significantly after the policy in the difference model. The purchase volume of J01DC, J01DD and total antibiotics significantly increased in control group compared with the intervention. CONCLUSION: The implementation of the volume-based procurement policy promoted the use of winning products and decreased the usage of its alternative watch antibiotics.

Combined analysis of metagenome and transcriptome revealed the adaptive mechanism of different golden Camellia species in karst regions.

Camellia sect. Chrysantha is an important rare and protected plant species. Some golden Camellia species grow in karst soil while others grow in acidic soil. In order to study the adaptation mechanism of golden Camellia to the karst environment, four species of golden Camellia growing in the karst soil (Camellia pubipetala, Camellia perpetua, Camellia grandis, and Camellia limonia) and four species growing in the acidic soil (Camellia nitidissima, Camellia euphlebia, Camellia tunghinensis, and Camellia parvipetala) were selected for this study. Combining the metagenome and transcriptome, the structure and function of the rhizosphere microbial communities and the gene expression in roots of golden Camellia were analyzed. The results showed that the rhizosphere microbial communities in different golden Camellia were significantly different in abundance of Acidobacteria, Actinobacteria, Candidatus_Rokubacteria, Nitrospirae, Planctomycetes, and Candidatus_Tectomicrobia. The proportion of Candidatus_Rokubacteria was significantly higher in the rhizosphere soil of four species of golden Camellia grown in karst areas, compared to C. nitidissima, C. euphlebia, and C. tunghinensis. The linear discriminant analysis Effect Size showed that C. parvipetala was similar to karst species in the enrichment of ABC transporters and quorum sensing. During the transcriptome analysis, numerous upregulated genes in four karst species, including CYP81E, CHS, F3H, C12RT1, NAS, and CAD, were found to be enriched in the secondary metabolite synthesis pathway in the KEGG library, when compared to C. tunghinensis. This study provides information for plant adaptation mechanisms on the rhizosphere soil microbial composition and gene expression in secondary metabolic pathways to karst habitats and its distribution in karst areas.

Association of PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population.

BACKGROUND: Autophagy can inhibit the survival of intracellular microorganisms including Mycobacterium tuberculosis (Mtb), and the PI3K/AKT/mTOR pathway plays a crucial role. This study investigated the association between PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms and pulmonary tuberculosis (PTB) susceptibility. METHODS: KEGG pathway and gene ontology (GO) databases were searched for genes belonging to the PI3K/AKT/mTOR and autophagy pathways. Thirty SNPs in nine genes were identified and tested for their associations with tuberculosis in 130 patients with PTB and 271 controls. We constructed genetic risk scores (GRSs) and divided the participants into 3 subgroups based on their GRSs:0-5, 6-10, and 11-16. RESULTS: This analysis revealed that the AKT1 (rs12432802), RPTOR (rs11654508, rs12602885, rs2090204, rs2589144, and rs2672897), and TSC2 (rs2074969) polymorphisms were significantly associated with PTB risk. A decreasing trend was observed (P trend 0.020), in which a lower GRS was associated with a higher risk of PTB ([6-10] vs. [0-5]: OR (95%CI) 0.590 (0.374-0.931); [11-16] vs. [0-5]: OR (95%CI) 0.381 (0.160-0.906)). CONCLUSIONS: Polymorphisms in AKT1, RPTOR, and TSC2 may influence susceptibility to PTB.