Characteristics and treatment outcomes of co-infected tuberculosis patients with human immunodeficiency virus in Southeast China, 2012-2021.

BACKGROUND: Tuberculosis (TB) is a chronic respiratory infection. Co-infection with human immunodeficiency virus (HIV) has been a significant obstacle to TB control. Insufficient attention has been given to TB/HIV, and more information is needed to address this issue. We conducted an observational study to investigate the epidemiological characteristics, treatment outcomes and its associated factors of HIV-positive TB patients in Southeast China. METHODS: An observational study was conducted based on data collected directly from China National TB Surveillance System during 2012-2021. Epidemiological characteristics, drug resistance and outcomes were described as frequency (n) and percentage (%). Risk factors for unsuccessful outcomes were determined using univariate (chi-squared) and multivariate logistic regression analysis. RESULTS: A total of 347 TB/HIV cases were included, and the proportion of HIV-positive cases among all TB cases increased significantly from 0.06% to 2012 to 0.40% in 2021. The majority of cases were males (86.5%), non-local household registers (139, 40.1%), farmers or workers (179, 51.6%), and aged 40-59 (142, 40.9%). Of 347 cases, 290 (83.6%) had pulmonary TB (PTB), 10 (2.9%) had extra pulmonary TB (EPTB) and 47(13.5%) had both PTB and EPTB. A total A total of 258 (74.4%) were HIV positive prior to TB diagnosis. 8.0% (4/50) of cases were resistant to rifampicin (RIF) and 274 patients (83.8%) had successful outcomes. Being non-local (AOR = 2.193, 95% CI = 1.196-4.022, P = 0.011) and diagnosed HIV infection after TB (AOR = 2.365, 95% CI = 1.263-4.430, P = 0.007) were independent risk factors for unsuccessful outcomes of anti-TB treatment. CONCLUSION: During 2012-2021, the proportion of HIV-positive cases among all TB cases increased significantly in Southeast China. HIV-positive TB patients were significantly more likely to develop resistance to RIF and INH and unsuccessful anti-TB treatment. Non-local registration and becoming HIV positive after TB diagnosis were independent risk factors associated with unsuccessful outcomes.

Identification and characterization of long non-coding RNAs in intestinal immune regulation of largemouth bass, Micropterus salmoides, under acute heat stress.

Long noncoding RNAs (lncRNAs), which are RNA molecules that do not code for proteins and have a length exceeding 200 base pairs, have been found to play a crucial role in regulating intestinal immunity. The high mortality of various fish species induced by high temperatures is known to be associated with enteritis. Our investigation demonstrated that acute heat stress was responsible for inducing fish enteritis. However, the specific lncRNAs involved this process remains unknown. In this current study, we utilized intestinal sequencing data from the largemouth bass species Micropterus salmoides under acute heat stress, resulting in a total of 347,351,492 clean reads obtained from six cDNA libraries. A total of 3399 novel lncRNA transcripts originating from 2488 distinct lncRNA genes were successfully identified. Consistent with previous findings in other fish species, these lncRNAs demonstrated comparatively shorter transcript lengths when compared to protein-coding genes. Furthermore, a total of 216 novel lncRNA exhibited differential expression (DE) in the intestine of largemouth bass, meeting the criteria of absolute log2 fold change exceeding 2 and a p-value below 0.05. Additionally, these DE-lncRNAs were found to regulate 210 neighboring genes in a cis-regulatory manner. An examination of GO/KEGG enrichment revealed a notable enrichment of immune regulation (p < 0.05) among these cis-genes, with lncRNA MSTRG.8573.1 playing a significant role in regulating the jak-stat signaling pathway during this process. This study presents a comprehensive inventory of novel DE-lncRNA implicated in the development of enteritis in largemouth bass under acute heat stress. These findings offer valuable insights for future investigations on the regulation of lncRNAs to mitigate heat stress-induced fish enteritis.

[Engineering microbial consortia through synthetic biology approach].

There are a large number of natural microbial communities in nature. Different populations inside the consortia expand the performance boundary of a single microbial population through communication and division of labor, reducing the overall metabolic burden and increasing the environmental adaptability. Based on engineering principles, synthetic biology designs or modifies basic functional components, gene circuits, and chassis cells to purposefully reprogram the operational processes of the living cells, achieving rich and controllable biological functions. Introducing this engineering design principle to obtain structurally well-defined synthetic microbial communities can provide ideas for theoretical studies and shed light on versatile applications. This review discussed recent progresses on synthetic microbial consortia with regard to design principles, construction methods and applications, and prospected future perspectives.

Footprints of total coliforms, faecal coliforms and E. coli in a wastewater treatment plant and the probabilistic assessment and reduction of E. coli infection risks.

Wastewater contains various pathogenic microorganisms, and the disease of workers caused by exposure to wastewater at the wastewater treatment plants (WWTPs) is a growing concern. The footprints of total coliforms (TC), faecal coliforms (FC) and Escherichia coli (E. coli) in a conventional activated sludge WWTP during 12 consecutive months were clarified. It was found that TC, FC and E.coli in influent were significantly removed (log 4.71, log 4.43 and log 4.62, respectively) by WWTP with sand filtration playing a key role, and excess sludge was a major potential pathway for them flowing to the environment. Through quantitative microbial risk assessment (QMRA), hand-to-mouth ingestion of untreated wastewater and wastewater in secondary/efficient sedimentation tanks, as well as accidental ingestion of sludge in dewatering workshop presented the highest infection risks of pathogenic E.coli in the WWTP, considerably exceeded the U.S. EPA benchmark (≤1 × 10-4 pppy). PPE application and E.coli concentration reduction in wastewater or sludge were recommended to reduce the infection risks at these stages. Further, partial ozonation and dissolved ozone flotation thickening were investigated able to reduce the infection risks at the stages of secondary and tertiary treatment of wastewater or sludge treatment by 90- 98 %. The findings of this study would assist in selecting appropriate processes for the further sanitation of WWTPs.

Effects of antimony exposure on DNA damage and genome-wide variation in zebrafish (Danio rerio) liver.

Antimony (Sb) is a potentially toxic and carcinogenic cumulative contaminant that poses a serious threat to aquatic ecosystems. To better clarify the genotoxicity of Sb and its mechanism of action. In this study, we investigated DNA damage and genome-wide variation in the liver of a model organism, zebrafish (Danio rerio), under subacute Sb exposure and explored its potential toxicological mechanisms. The results showed that medium and high concentrations of Sb significantly reduced the total antioxidant capacity and increased the content of reactive oxygen species in zebrafish liver, and further studies revealed that it increased oxidative DNA damage and DNA-DNA cross-link (DDC), but had little effect on DNA-protein cross-link (DPC). The result of resequencing showed that the mutation sites of the genes with high concentrations of Sb were higher than those with medium concentrations, and the mutation was mainly a single nucleotide. The pathways significantly enriched for nonsynonymous single nucleotide polymorphisms (SNPs) and insertion/deletion mutations (InDels) variant genes in the coding regions of both the medium and high Sb-treated groups were ECM-receptor interactions, and the high Sb-treated group also included lysine degradation, hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This suggests that ECM-receptor interactions play an important role in the mechanism of antimony toxicity to the liver of zebrafish.

A Novel Form of Arginine-Chitosan as Nanoparticles Efficient for siRNA Delivery into Mouse Leukemia Cells.

The modification of chitosan (CS) has greatly expanded its application in the field of medicine. In this study, low-molecular-weight chitosan was modified with arginine (Arg) by a simple method. The identification by the Fourier transform infrared spectra (FTIR) showed that Arg was successfully covalently attached to the CS. Interestingly, Arg-CS was identified as nanoparticles by atomic force microscopy (AFM) and transmission electron microscopy (TEM), whose particle size was 75.76 ± 12.07 nm based on Dynamic Light Scattering (DLS) characterization. Then, whether the prepared Arg-CS nanoparticles could encapsulate and deliver siRNA safely was investigated. Arg-CS was found to be able to encapsulate siRNAs in vitro via electrostatic interaction with siRNA; the Arg-CS/siRNA complex was safe for L1210 leukemia cells. Therefore, modification of chitosan by Arg produces novel nanoparticles to deliver siRNA into leukemia cells. This is the first time to identify Arg-CS as nanoparticles and explore their ability to deliver Rhoa siRNA into T-cell acute lymphoblastic leukemia (T-ALL) cells to advance therapies targeting Rhoa in the future.

Engineering living materials by synthetic biology.

Natural biological materials are programmed by genetic information and able to self-organize, respond to environmental stimulus, and couple with inorganic matter. Inspired by the natural system and to mimic their complex and delicate fabrication process and functions, the field of engineered living materials emerges at the interface of synthetic biology and materials science. Here, we review the recent efforts and discuss the challenges and future opportunities.

The efficacy of traditional chinese medicine combined with hyperthermic intraperitoneal chemotherapy for malignant ascites: A systematic review and meta-analysis.

Objective: Malignant ascites (MA) is a common complication of terminal cancer, which seriously affects the life quality and prognosis of patients. Both hyperthermic intraperitoneal chemotherapy (HIPEC) and traditional Chinese medicine (TCM) preparations have achieved significant efficacy in the treatment of MA. The treatment strategy of TCM combined with HIPEC has been gradually promoted and applied in China. The purpose of this systematic review and meta-analysis was to assess the efficacy of TCM combined with HIPEC in the treatment of MA. Methods: Randomized controlled trials (RCTs) of TCM combined with HIPEC for MA were searched from seven electronic databases. Two researchers used the Cochrane Collaboration's tool to assess the risk of bias. Excel 2019 was used to establish a database for information extraction, RevMan 5.4 software was used to analyze the included test data, and STATA v16.0 was used to conduct Egger's test to further detect publication bias. Results: A total of 19 studies involving 1,504 patients were included in this meta-analysis. The results showed that compared with the single use of HIPEC, TCM combined with HIPEC could significantly improve the clinical efficacy (RR = 1.51, 95% CI [1.40, 1.63], p < 0.00001) and karnofsky performance status (KPS) score (MD = 8.16, 95% CI [6.46, 9.85], p < 0.00001), reduce the ascites volume (MD = -156.98, 95% CI [-213.71, -100.25], p < 0.00001). However, there was no statistical significance in reducing abdominal circumference between TCM combined with HIPEC and HIPEC alone (MD = -1.8, 95% CI [-4.57, -0.97], p = 0.2). Conclusion: This study found that TCM combined with HIPEC had a beneficial therapeutic effect on MA. However, more standard, double-blind, multicenter RCTs are needed to further confirm the efficacy of TCM combined with HIPEC in the treatment of MA. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42022319993.

Prediction of elevation of substantial fluctuation in coal seam floor based on surface spline function and its derivative.

With the increasing depth of coal mining, the geological stress and structure becomes more and more complex. The elevation of No.8 coal floor significantly undulates in the studied coal mine. Even though a lot of boreholes have been drilled, it remains difficult to predict the spatial distribution features and it becomes challenging to plan the tunnel for the working face. Consequently, there has been a great loss of production in the coal mine, therefore, it is of great significance to study the prediction method for coal floor elevation of the working face. The surface spline function can be regarded as an infinite flat plate deformation in pure bending. The fluctuation of the coal floor can be considered to be the result of multi-period tectonic stress applied on the coal seam, so, the prediction of elevation of the coal floor with surface spline method is feasible. An advantage of surface spline method is that any order differentiable smooth surface can be obtained without regular known lattice and boundary derivatives. In the paper, the complete expression of surface spline function is derived, which is used to predict the elevation of No.8 coal floor of the coal mine. The results show that the trend of elevation of the coal floor can be extrapolated by known data, and the maximum error is 20 m, the minimum error is 0 m, and the error of 80% of the data is less than 3 m. The general trend of the coal floor has been predicted well. However, local peaks and valleys could not be predicted correctly, therefore, the first and second order derivative are projected to predict the peaks and valleys in the head of the tunneling.

Zusanli (ST36) Acupoint Injection With Dexamethasone for Chemotherapy-Induced Myelosuppression: A Systematic Review and Meta-Analysis.

OBJECTIVE: Myelosuppression is the most common adverse reaction of chemotherapy, which seriously affects the course of treatment. Zusanli (ST36) acupoint injection with dexamethasone has achieved good clinical efficacy in China. This study aimed to systematically evaluate the efficacy of ST36 acupoint injection with dexamethasone in the treatment of chemotherapy-induced myelosuppression (CIM). METHODS: Randomized controlled trials of CIM treated with ST36 acupoint injection with dexamethasone were retrieved from eight electronic databases. We used the Cochrane Collaboration tool to assess the risk of bias. Excel 2010 was used to establish a database for information extraction, and RevMan 5.3.0 software was used to analyze the included test data. GRADE profiler 3.6 software was used to grade the quality of evidence for the outcome indicators of the study. RESULTS: A total of 17 studies involving 1177 patients were included in this meta-analysis. The results showed that, compared with conventional western medicine (CWM), ST36 acupoint injection with dexamethasone could significantly improve the clinical total effective rate [RR=1.95, 95% CI (1.53, 2.49), P <0.00001] and increase white blood cell (WBC) (MD=1.38, 95% CI (0.74, 2.01), P<0.0001) and hemoglobin (Hb) levels [MD=3.89, 95% CI (1.57, 6.20), P=0.001]. In addition, ST36 acupoint injection with dexamethasone can shorten recovery time of myelosuppression [MD=-3.94, 95% CI (-4.97 to -2.91), P<0.00001] and improve Karnofsky performance status [MD=10.7, 95% CI (1.36, 20.05), P=0.02<0.05]. However, there was no significant difference among ST36 acupoint injection with dexamethasone and CWM in platelet (PLT) elevation [MD=4.61, 95% CI (-10.14, 19.35), P=0.54]. CONCLUSION: This study found that ST36 acupoint injection with dexamethasone had a positive effect on CIM. However, more studies with well-designed, large sample size, strict randomization, and clear descriptions about detection and reporting processes are needed in the future to further confirm the efficacy of ST36 acupoint injection with dexamethasone in the treatment of CIM. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/, identifier CRD42021223979.

Impact of anti-cancer therapy on disease severity and mortality in cancer patients with COVID-19: a systematic review and meta-analysis.

Background: Cancer patients are more vulnerable to Coronavirus disease-2019 (COVID-19) and have a higher risk of adverse outcomes than the general population. Therefore, it is necessary to evaluate whether anti-cancer therapies such as surgery, chemotherapy, immunotherapy, and targeted therapy will increase the severity and mortality of cancer patients with COVID-19.Methods: Relevant articles were retrieved from PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). The search time was from December 1, 2019 to January 23, 2021. Meta-analysis was conducted using Revman 5.3 statistical software.Results: A total of 26 studies were included in this meta-analysis, involving 5571 cancer patients infected with SARS-CoV-2. Meta-analysis showed that surgery, chemotherapy, immunotherapy and targeted therapy were not associated with disease severity or mortality (107/688, OR =1.30, 95% CI[0.79, 2.13], P =0.30; 1956/2674, OR =1.27, 95% CI [0.95, 1.69], P =0.10; 342/1455, OR =1.20, 95% CI [0.90, 1.61], P =0.21; 503/1378, OR =0.92, 95% CI [0.72, 1.19], P =0.54, respectively).Conclusion: In cancer patients with COVID-19, anti-cancer therapy had no adverse effect on disease severity or mortality. Further research is necessary to determine the complex interrelationship between anti-cancer therapy, particularly chemotherapy, and COVID-19.

The Efficacy of Heat-Clearing (Qingre) and Detoxifying (Jiedu) Traditional Chinese Medicine Gargle for Chemotherapy-Induced Oral Mucositis: A Systematic Review and Meta-Analysis.

Objective: Chemotherapy-induced oral mucositis (CIOM) is an extremely serious complication of cancer. In China, the heat-clearing (Qingre) and detoxifying (Jiedu) traditional Chinese medicine QRJD-TCM gargle has been widely used to treat CIOM. To date, no systematic evaluation has been conducted on the clinical efficacy of QRJD-TCM gargle in treating CIOM. The objective of this systematic review and meta-analysis was to evaluate the efficacy of QRJD-TCM gargle in the treatment of CIOM. Methods: Relevant randomized controlled trials (RCTs) comparing QRJD-TCM gargle with conventional Western medicine mouthwash (CWMM) for CIOM were confirmed by systematically searching PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, and Sinomed until October 20, 2020. Two researchers independently assessed the risk of bias according to the Cochrane risk-of-bias criteria. Excel 2010 was used in setting up a database of extracted information, and RevMan 5.3.0 was used in analyzing included trial data. The composition of the QRJD-TCM gargle was evaluated. Results: A total of 25 articles were included in this meta-analysis. Results showed that compared with CWMM, QRJD-TCM gargle can reduce the incidence of CIOM (OR = 0.23, 95% CI [0.18, 0.29], p < 0.00001) and severity of CIOM (grade I-II: OR = 0.36, 95%CI [0.28, 0.46], p < 0.00001; grade III-IV: OR = 0.15, 95%CI [0.09, 0.28], p < 0.00001). In addition, QRJD-TCM gargle improved the effective rate of CIOM (OR = 15.91, 95% CI [7.93, 31.89], p < 0.00001). Conclusion: QRJD-TCM gargle is effective in preventing and treating CIOM. However, more standard, double-blind, and multicenter randomized controlled studies are needed to further confirm the efficacy of QRJD-TCM gargle in the prevention and treatment of CIOM.

Endoplasmic reticulum-associated degradation mediated by MoHrd1 and MoDer1 is pivotal for appressorium development and pathogenicity of Magnaporthe oryzae.

Most secretory proteins are folded and modified in the endoplasmic reticulum (ER); however, protein folding is error-prone, resulting in toxic protein aggregation and cause ER stress. Irreversibly misfolded proteins are subjected to ER-associated degradation (ERAD), modified by ubiquitination, and degraded by the 26S proteasome. The yeast ERAD ubiquitin ligase Hrd1p and multispanning membrane protein Der1p are involved in ubiquitination and transportation of the folding-defective proteins. Here, we performed functional characterization of MoHrd1 and MoDer1 and revealed that both of them are localized to the ER and are pivotal for ERAD substrate degradation and the ER stress response. MoHrd1 and MoDer1 are involved in hyphal growth, asexual reproduction, infection-related morphogenesis, protein secretion and pathogenicity of M. oryzae. Importantly, MoHrd1 and MoDer1 mediated conidial autophagic cell death and subsequent septin ring assembly at the appressorium pore, leading to abnormal appressorium development and loss of pathogenicity. In addition, deletion of MoHrd1 and MoDer1 activated the basal unfolded protein response (UPR) and autophagy, suggesting that crosstalk between ERAD and two other closely related mechanisms in ER quality control system (UPR and autophagy) governs the ER stress response. Our study indicates the importance of ERAD function in fungal development and pathogenesis of M. oryzae.

[Analysis on traditional Chinese medicine prescriptions treating cancerous fever based on grey screening method combined with multivariate analysis method and discovery of new prescriptions].

Cancerous fever is one of the common symptoms of advanced malignant tumors,which seriously affects the quality of life and survival of patients. At present,the clinical research on the treatment of cancerous fever by traditional Chinese medicine is limited,and there is a lack of research on the medication rules from multiple dimensions of disease-symptom-syndrome. The treatment of cancerous fever has not made substantial progress. In this study,we collected the literature on treatment of cancerous fever in Chinese medicine,and concluded that common syndrome types include Yin deficiency type,Qi deficiency type,Yang deficiency type,blood stasis type,damp-heat accumulation type,toxic heat flourishing type and liver meridian stagnated heat type. Two hundreds and fifty-seven prescriptions for Chinese medicine and 249 flavors for single medicine were extracted. The analysis of the drug composition of the drug found that the cancerous fever treatment was mainly based on heat-clearing drugs and deficiency-nourishing drugs. Apriori association analysis of the drug found that the second and third related drugs were mainly Rehmanniae Radix,Moutan Cortex,Artemisiae Annuae Herba,Trionycis Carapax and Anemarrhenae Rhizoma. The top five gray correlation degrees were Psoraleae Fructus,Bupleuri Radix,Hordei Fructus Germinatus,Scutellariae Radix and Massa Medicata Fermentata. And seven new prescriptions were evolved. The results showed that the treatment of cancerous fever can be started from the disease-symptom-syndrome,nourishing Yin and clearing heat is an important method for " disease differentiation and treatment". The combination of Bupleuri Radix and Scutellariae Radix is the embodiment of " symptom differentiation and treatment". The new prescriptions conform to the idea of " syndrome differentiation and treatment" of traditional Chinese medicine can provide reference for clinical medication. The grey screening method combined with multivariate analysis method was used to analyze the prescription rules of Chinese medicine in the treatment of cancer fever,which followed the black box structure of traditional Chinese medicine,made the potential rule of prescriptions explicit,broadened its thinking of Chinese medicine treatment,and made up for the deficiency of traditional analysis methods.

Efficacy of XELOX adjuvant chemotherapy for gastric mixed adenoneuroendocrine carcinoma: A case report.

RATIONALE: Mixed adenoneuroendocrine carcinoma (MANEC) is a rare neoplasm, and consensus on the treatment is unavailable. PATIENT CONCERN: A 60-year-old Chinese man presented with obstructive symptoms while eating and paroxysmal stomach pain for more than a month. DIAGNOSIS: MANEC was diagnosed based on clinical manifestations, imaging findings, and pathological examinations. INTERVENTIONS: The patient underwent radical gastrectomy and received XELOX adjuvant chemotherapy (oxaliplatin 200 mg day 1 + capecitabine 1.5 g twice a day) after surgery. OUTCOMES: After 4 cycles of XELOX adjuvant chemotherapy were administered, abdominal computerized tomography and liver magnetic resonance showed liver metastasis. LESSONS: The therapy of gastric MANEC is based on surgical operation, and adjuvant chemotherapy program has an important influence on its prognosis. Therefore, further studying the effectiveness of XELOX adjuvant chemotherapy for gastric MANEC is necessary.

The complete mitochondrial genome of Carassius auratus var. high back crucian carp (Cypriniformes: Cyprinidae).

In this study, the complete mitochondrial genome sequence of Carassius auratus var. high back crucian carp (C. auratus var.) was determined (GenBank accession number is KT756205). The mitochondrial genome sequence of C. auratus var. was a circular molecule with 16 581 bp in length, and contained 37 typical animal mitochondrial genes, including 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a control region (D-loop). Four nucleotide compositions and their relative proportions of the entire mitogenome was 26.19% C, 16.06% G, 31.57% A and 26.18% T, with contents of A + T and G + C being 57.75% and 42.25%, respectively.