Deciphering the role of cuproptosis-related lncRNAs in shaping the lung cancer immune microenvironment: A comprehensive prognostic model.

Cuproptosis plays an important role in cancer, but its role in lung cancer remains unknown. Transcriptional profiles, clinical details and mutation data were acquired from the Cancer Genome Atlas database through a variety of methods. The analysis of this publicly available data was comprehensively performed using R software along with its relevant packages, ensuring a thorough examination of the information. In this study, we conducted a detailed analysis of cuproptosis-related genes and lncRNA co-expression, identifying 129 relevant lncRNAs and establishing a prognostic model with four key lncRNAs (LINC00996, RPARP-AS1, SND1-IT1, TMPO-AS1). Utilizing data from TCGA and GEO databases, the model effectively categorized patients into high- and low-risk groups, showing significant survival differences. Correlation analysis highlighted specific relationships between individual lncRNAs and cuproptosis genes. Our survival analysis indicated a higher survival rate in the low-risk group across various cohorts. Additionally, the model's predictive accuracy was confirmed through independent prognostic analysis and ROC curve evaluations. Functional enrichment analysis revealed distinct biological pathways and immune functions between risk groups. Tumour mutation load analysis differentiated high- and low-risk groups by their mutation profiles. Drug sensitivity analysis and immune infiltration studies using the CIBERSORT algorithm further elucidated the potential treatment responses in different risk groups. This comprehensive evaluation underscores the significance of lncRNAs in cuproptosis and their potential as biomarkers for lung cancer prognosis and immune microenvironment.

Epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China during 2017-2022.

Background: Wuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic. Objective: This study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017-2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools. Methods: This study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis. Results: From 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools. Conclusion: We successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

Comparison of different peritoneal dialysis catheters on complication and catheter survival: A network meta-analysis of randomised controlled trials.

BACKGROUND: This network meta-analysis (NMA) aimed to compare the clinical advantage of four commonly used peritoneal dialysis catheters (PDCs) including the Swan neck segment with straight tip (Swan neck + S), Tenckhoff segment with straight tip (Tenckhoff + S), Swan neck segment with coiled tip (Swan neck + C) and Tenckhoff segment with coiled tip (Tenckhoff + C). METHODS: Randomised clinical trials were searched from PubMed, Embase, the Cochrane Register of clinical trials, China National Knowledge Infrastructure (CNKI) and ChinaInfo from their inception until July 31, 2022. Meta-analysis was performed using Stata 14.0 and RevMan 5.3.5 software to evaluate the four commonly used PDCs. RESULTS: Seventeen studies involved 1578 participants were included. NMA showed that compared with Swan neck + C, Swan neck + S significantly reduced catheter tip migration (OR 0.47 95% CI 0.22-0.99). Tenckhoff + S was more effective in reducing catheter dysfunction (OR 0.42, 95% CI 0.23-0.79), catheter tip migration with dysfunction (OR 0.19, 95% CI 0.05-0.78) and catheter removal (OR 0.56, 95% CI 0.34-0.93) which were consistent with the pairwise meta-analysis. According to the surface under the cumulative ranking curve, Swan neck + S emerged as the best PDC in the reduction of catheter tip migration (83.3%), followed by Tenckhoff + S (79.4%). Moreover, Tenckhoff + S (86.5%, 76.3%) and Swan neck + S (72.3, 86.9%) ranked as the first and second PDC for 1 and 2-year technique survival which was significantly higher than those of the other two PDCs. CONCLUSION: Our NMA showed Swan neck + S and Tenckhoff + S tended to be more efficacious than Swan neck + C and Tenckhoff + C in lowering the mechanical dysfunction and prolonging the technique survival, which may contribute to better clinical decisions. More randomised controlled trials with larger scales and higher quality are needed in order to obtain more credible evidence.

How Integrated Digital Tools Can Improve Tuberculosis Medication Adherence: A Longitudinal Study in China.

Background: Poor medication adherence remains one of the major problems in the treatment of tuberculosis (TB) patients, while digital technologies have been proven effective to improve the treatment results. However, reports on the effectiveness of comprehensive practice integrating different intervention methods and technologies are limited. The aim of this study is to evaluate the effectiveness of an integrated digital adherence intervention for TB patients. Methods: We developed a digital adherence intervention platform integrating instant WeChat message, electronic medication monitors (EMMs), and manual reminders. The primary goal of the platform was to improve the accessibility of digital adherence technologies, and thus improve treatment adherence. TB patients were newly diagnosed at 10 TB-designated hospitals and came from 220 communities, from January to June 2022. The basic characteristics and treatment adherence of TB patients in WeChat, EMM, and conventional groups were compared, and the influencing factors of high medication adherence were analyzed by logistic regression. Results: A total of 2,498 TB patients were enrolled in the study, 14.5% were managed by digital technologies, 9.5% by WeChat, and 5.0% by EMM, respectively. After intervention, the median medication rate of TB patients was significantly higher in the WeChat group (95.3%) and EMM group (95.7%) compared with that of the conventional group (83.8%). On the contrary, the median number of missed medications among patients of the conventional group (nine times) was significantly higher than that in the WeChat (three times) group and EMM (three times) group. The proportion of high adherence (adherence medication rate ≥90%) among TB patients was 64.7%, 64.5%, and 43.2% in WeChat, EMM, and conventional group, respectively. Conclusions: The application of the integrated digital adherence intervention platform could significantly improve medication adherence among TB patients. The accessibility of digital adherence technologies could be improved by integrating complementary technologies in practice.

Regional Citrate Anticoagulation versus No Anticoagulation for CKRT in Patients with Liver Failure with Increased Bleeding Risk.

BACKGROUND: The opinions on the efficacy and safety of no anticoagulation versus regional citrate anticoagulation for continuous KRT (CKRT) were controversial in patients with severe liver failure with a higher bleeding risk. We performed a randomized controlled trial to assess no anticoagulation versus regional citrate anticoagulation for CKRT in these patients. METHODS: Adult patients with liver failure with a higher bleeding risk who required CKRT were considered candidates. The included participants were randomized to receive regional citrate anticoagulation or no-anticoagulation CKRT. The primary end point was filter failure. RESULTS: Of the included participants, 44 and 45 were randomized to receive regional citrate anticoagulation and no-anticoagulation CKRT, respectively. The no-anticoagulation group had a significantly higher filter failure rate (25 [56%] versus 12 [27%], P = 0.003), which was confirmed by cumulative incidence function analysis and sensitive analysis including only the first CKRT sessions. In the cumulative incidence function analysis, the cumulative filter failure rates at 24, 48, and 72 hours of the no-anticoagulation and regional citrate anticoagulation groups were 31%, 58%, and 76% and 11%, 23%, and 35%, respectively. Participants in the regional citrate anticoagulation group had significantly higher incidences of Ca 2+tot /Ca 2+ion >2.5 (7% versus 57%, P < 0.001), hypocalcemia (51% versus 82%, P = 0.002), and severe hypocalcemia (13% versus 77%, P < 0.001). However, most (73%) of the increased Ca 2+tot /Ca 2+ion ratios were normalized after the upregulation of the calcium substitution rate. In the regional citrate anticoagulation group, there was no significant additional increase in the systemic citrate concentration after 6 hours. CONCLUSIONS: For patients with liver failure with a higher bleeding risk who required CKRT, regional citrate anticoagulation resulted in significantly longer filter lifespan than no anticoagulation. However, regional citrate anticoagulation in patients with liver failure was associated with a significantly higher risk of hypocalcemia, severe hypocalcemia, and Ca 2+tot /Ca 2+ion >2.5. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: RCA for CRRT in Liver Failure and High Risk Bleeding Patients, NCT03791190 .

Identification of the novel markers of PPAR signalling affecting immune microenvironment and immunotherapy response of lung adenocarcinoma patients.

Peroxisome proliferator-activated receptors (PPARs) are essential for cellular physiological processes. However, there is less research on the PPAR-related genes in lung adenocarcinoma (LUAD). Open-access data were get from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. All the analysis were conducted in the R software based on different R packages. In this study, we gauged the PPAR score employing a set of 72 PPAR-associated genes and probed the biological impact of this score on lung adenocarcinoma (LUAD). Subsequently, we established a unique signature composed of eight PPAR-related genes (ANGPTL4, ACSL3, ADIPOQ, FABP1, SLC27A1, ACOX2, PPARD and OLR1) to forecast the prognosis of LUAD. The signature's effectiveness in predicting survival was validated through the receiver operating characteristic curve in the TCGA-LUAD cohort. As per the pathway enrichment analysis, several crucial oncogenic pathways and metabolic processes were enriched in high-risk individuals. Further, we observed that these high-risk patients exhibited heightened genomic instability. Additionally, compared to the low-risk cohort, high-risk patients demonstrated diminished immune components and function. Intriguingly, high-risk patients exhibited a potential heightened sensitivity to immunotherapy and certain drugs, including Gefitinib, Afatinib, Erlotinib, IAP_5620, Sapitinib, LCL161, Lapatinib and AZD3759. The prognosis model based on eight PPAR-related genes has satisfactory prognosis prediction efficiency. Meanwhile, our results can provide direction for future studies in the relevant aspects.

Trends of a decade in risk factors of patient delay among pulmonary tuberculosis patients during fast aging and urbanization - analysis of surveillance data from 2008 to 2017 in Wuhan, China.

BACKGROUND: Tuberculosis (TB) is a leading infectious cause of morbidity and mortality worldwide. However, delay in health care seeking has remained unacceptably high. The aim of this study was to clarify the trend of patient delay and its associated risk factors during rapid aging and urbanization in Wuhan, China from 2008 to 2017. METHODS: A total of 63,720 TB patients registered at Wuhan TB Information Management System from January 2008 to December 2017 were included. Long patient delay (LPD) was defined as patient delay longer than 14 days. Independent associations of area and household identity with LPD, as well their interaction effect, were tested by logistic regression models. RESULTS: Among 63,720 pulmonary TB patients, 71.3% were males, the mean age was 45.5 ± 18.8 years. The median patient delay was 10 days (IQR, 3-28). A total of 26,360 (41.3%) patients delayed for more than 14 days. The proportion of LPD decreased from 44.8% in 2008 to 38.3% in 2017. Similar trends were observed in all the subgroups by gender, age and household, except for living area. The proportion of LPD decreased from 46.3 to 32.8% in patients living near downtown and increased from 43.2 to 45.2% in patients living far from downtown. Further interaction effect analysis showed that among patients living far from downtown, the risk of LPD for local patients increased with age, while decreased with age for migrant patients. CONCLUSION: Although the overall LPD among pulmonary TB patients declined in the past decade, the extent of reduction varied in different subgroups. The elderly local and young migrant patients living far from downtown are the most vulnerable groups to LPD in Wuhan, China.

Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis.

Background: Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis. Methods: To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis. Results: There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis. Conclusions: For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

Clinical characteristics and prognostic value of renal immune complex deposition in patients with light chain amyloidosis.

Although patients with light chain amyloidosis (AL) may present with co-deposition of amyloid and immune complexes (ICs) in renal biopsies, data on clinical characteristics and prognostic value of renal IC deposition are limited. A total of 73 patients with AL amyloidosis who were newly diagnosed by renal biopsy in Xijing Hospital (Xi'an, China) were divided into two groups (IC and non-IC groups). As a result, renal IC deposition was found in 26% of patients. Patients with IC deposition were associated with more urinary protein excretion and lower serum albumin. Notably, patients in the non-IC group achieved higher hematological overall response rate (81.5% vs. 47.4%, p = 0.007) and ≥VGPR rate (75.9% vs. 39.8%, p = 0.004) compared with those in IC group. Renal response rate was also higher in the non-IC group (63% vs. 31.6%, p = 0.031). With the median follow-up time of 19 months, a significantly worse overall survival was observed in patients with the IC group as compared with those without renal IC deposition in the Kaplan-Meier analysis (p = 0.036). Further multivariate analysis demonstrated that renal immune complex deposition was associated with worse overall survival in patients with AL amyloidosis (HR 5.927, 95% CI 2.148-16.356, p = 0.001).

Metabolomics analysis of the potential toxicological mechanisms of diquat dibromide herbicide in adult zebrafish (Danio rerio) liver.

Although diquat is a widely used water-soluble herbicide in the world, its sublethal adverse effects to fish have not been well characterised. In this study, histopathological examination and biochemical assays were applied to assess hepatotoxicity and combined with gas chromatography-mass spectrometry (GC-MS)-based metabolomics analysis to reveal overall metabolic mechanisms in the liver of zebrafish (Danio rerio) after diquat exposure at concentrations of 0.34 and 1.69 mg·L-1 for 21 days. Results indicated that 1.69 mg·L-1 diquat exposure caused cellular vacuolisation and degeneration with nuclear abnormality and led to the disturbance of antioxidative system and dysfunction in the liver. No evident pathological injury was detected, and changes in liver biochemistry were not obvious in the fish exposed to 0.34 mg·L-1 diquat. Multivariate statistical analysis revealed differences between profiles obtained by GC-MS spectrometry from control and two treatment groups. A total of 17 and 22 metabolites belonging to different classes were identified following exposure to 0.34 and 1.69 mg·L-1 diquat, respectively. The metabolic changes in the liver of zebrafish are mainly manifested as inhibition of energy metabolism, disorders of amino acid metabolism and reduction of antioxidant capacity caused by 1.69 mg·L-1 diquat exposure. The energy metabolism of zebrafish exposed to 0.34 mg·L-1 diquat was more inclined to rely on anaerobic glycolysis than that of normal zebrafish, and interference effects on lipid metabolism were observed. The metabolomics approach provided an innovative perspective to explore possible hepatic damages on fish induced by diquat as a basis for further research.

Transmission of multidrug-resistant tuberculosis within family households by DTM-PCR and MIRU-VNTR genotyping.

BACKGROUND: Drug-resistant tuberculosis (TB) continues to be a public health threat. There are few studies on transmission and genotyping of MDR-TB family households in China. This study aimed to investigate transmission of multidrug-resistant tuberculosis (MDR-TB) within family households by deletion-targeted multiplex polymerase chain reaction (DTM-PCR), mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTR) genotyping. METHODS: Among 993 MDR-TB patients registered from Wuhan Institute for Tuberculosis Control, drug resistance and the time interval between the index patients and secondary patients were analyzed in 49 MDR-TB patients from 23 families, in which 22 MDR-TB strains from 11 families who had matched strains were genotyped by DTM-PCR and standard 24-loci MIRU-VNTR genotyping method. RESULTS: The time interval between the index patients and the secondary patients ranged from half a month to 110 months. Thirteen secondary patients developed active MDR-TB within two years and accounted for 50% (13/26) of all secondary patients. Among eleven pairs of MDR-TB families, six pairs had identical genotypes, the cluster rate was 54.5% (12/22); three pairs had a single MIRU-VNTR locus variation. If a single MIRU-VNTR locus variation was tolerated in the cluster definition, the cluster rate raised to 81.8% (18/22). CONCLUSIONS: The family households of MDR-TB patients are at risk for infection of MDR-TB. To reduce transmission, MDR-TB patients should be diagnosed earlier and promptly treated in an effective manner, meanwhile, the close family contacts should be screened for TB infection.

Transmission of multidrug-resistant Mycobacterium tuberculosis in Wuhan, China: A retrospective molecular epidemiological study.

ABSTRACT: How multidrug-resistant tuberculosis (MDR-TB) spreads and expands in Wuhan population is not clear. The study aimed to determine the transmission patterns of MDR-TB in Wuhan city, China, including 149 patients with MDR-TB.Tuberculosis isolates were genotyped by deletion-targeted multiplex polymerase chain reaction, mycobacterial interspersed repetitive unit-variable number tandem repeat typing, and sequencing of drug resistance-associated genes. The risk factors of genomic-clustering were analyzed with logistic regression. The genomic-clustering patients were deeply investigated.The analysis identified 111 unique and 11 clustered genotypes (38 isolates). The clustering rate was 25.50% and the minimum estimate proportion of recent transmission was 18.12%. Two clusters (5 isolates) shared the same mutation, the remain 9 clusters (33 isolates) had different mutation. Logistic regression showed that older than 60 years (adjusted OR 2.360, 95% CI:1.052-5.292) was an independent factor associated with the genomic-clustering of MDR-TB. Among the 38 genomic-clustering cases, 14 cases had epidemiological transmission links. The most common type of transmission link was social contact.The local transmission of MDR-TB in Wuhan was really an issue. The elderly population might be the high-risk groups for transmission of MDR-TB, and the community or public transportation might be the main transmission places.

Short-term effects of distance training on peritoneal dialysis-related complications during the transmission control of COVID-19 epidemic in China.

OBJECTIVE: To observe the effects of distance training on patients with continuous ambulatory peritoneal dialysis (CAPD) during the transmission control of the COVID-19 epidemic in China. MATERIALS AND METHODS: CAPD patients from Xijing Hospital received a traditional training before the transmission control of COVID-19 epidemic, while they received a distance training dominated by WeChat and telephone during the transmission control of COVID-19 epidemic in China. Incidence and cure rate of PD-related peritonitis and catheter-related non-infectious complications were compared. All patients were followed up for 30 days from the date of complication. RESULTS: PD-related peritonitis, catheter displacement, and catheter occlusion had no significant difference, and the cure rate of PD-related peritonitis, catheter displacement, and catheter occlusion also had no significant difference in two comparisons despite the cure rate of PD-related peritonitis being slightly higher before (90.9%) than during (80%) the transmission control of COVID-19 epidemic. CONCLUSION: Distance training mode had a similar effect compared to the traditional training mode in the prevention and treatment of PD-related peritonitis and catheter-related non-infectious complications. PRACTICE IMPLICATIONS: Distance training model is an effective training mode that can be implemented in a short time during the epidemic period of serious infectious diseases.

Epidemiological characteristics of pulmonary tuberculosis among students in Wuhan from 2011 to 2020 / 中国学校卫生

Objective@#To analyze the epidemiological characteristics of pulmonary tuberculosis among students in Wuhan from 2011 to 2020, and to provide a basis for the scientific development of interventions and strategies.@*Methods@#Epidemiological distribution, time of onset and treatment, as well as treatment outcomes of student tuberculosis in Wuhan from 2011 to 2020 registered in the national tuberculosis information management system were described.@*Results@#During 2011-2020, 4 337 student tuberculosis patients in Wuhan were registered. The average annual incidence rate was 22.44/10 million, and the annual decreasing rate of 7.86% The incidence of male and female patients was 1.76:1, and the incidence rate of male was higher than that of female( χ 2=184.18, P <0.01). Most of patients aged 19-22 years old, accounting for 47.89%; Tuberculosis reports were highest during March to May, and September to November, and lowest during January to February, and July to August. Student patients were mainly concentrated in Hongshan District, Jiangxia District and Wuchang District, where schools were more distributed in Hongshan District, Dongxihu District, Wuchang District and Xinzhou District. The median duration from tuberculosis onset to treatment was 9(3, 21) days, which varied significantly by region, age, nationality, and patient residence ( Z =-9.25, 47.14, 9.88,43.96, P <0.01). The treatment and outcome of student tuberculosis patients were varied significantly by year and nationality( P <0.05).@*Conclusion@#The incidence of student tuberculosis in Wuhan City showed a slow downward trend. Most of student tuberculosis are college and high school students. Time and place of case detection are relatively fixed. The time of treatment and the outcome of treatment vary significantly. Tuberculosis prevention and control strategies should be formulated according to the local conditions according to the tuberculosis distribution characteristics, as well as enhancing surveillance, health promotion, active discovery and supervision management of tuberculosis in school settings.

Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK-52E cells via an inflammatory pathway.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTI) are commonly treated with broad-spectrum antibiotics, but treatment has limitation due to causes of nephrotoxicity in uroepithelial cells. Recently, the researcher focuses their research on alternative therapy for the treatment of UTI. This study evaluated the anti-infectious effect of crocetin against adherence of pathogenic [2-14 C]-acetate labeled Escherichia coli (MTCC-729) to rat proximal renal tubular cells (NRK-52E cells) and explores the possible mechanism of action. MATERIALS AND METHODS: In vitro cytotoxicity and radio acetate labeled tests were performed on NRK-52E cells. The rats were divided into five different groups as follows: normal control (NC), disease control (DC), and various doses of crocetin (1.25, 2.5, and 5 mg/kg) treated group rats. White blood cells in blood, urine, and bacterial colony counts were estimated at regular intervals. Pro-inflammatory cytokines, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), and interleukin-8 (IL-8), were also estimated. In the current study, we estimated the mRNA expression of toll-like receptor-4 (TLR-4) and toll-like receptor-2 (TLR-2) in the renal and bladder tissues. RESULTS: Crocetin significantly (p < .05) inhibited the adherence of E. Coli in NRK-52E cells. Crocetin suppresses the lipid peroxidation (LPO) 42% in cells treated with H2 O2 cells without crocetin. The white blood cells (WBC) count in blood and urine were augmented and crocetin treatment significantly (p < .05) reduced the WBC in urine and blood. The pro-inflammatory cytokines, such as IL-6, MCP-1, IL-10, and IL-8, significantly (p < .05) increased in the DC group and crocetin significantly (p < .05) reduced the pro-inflammatory cytokines. Dose-dependent treatment of crocetin significantly reduced the mRNA expression of TLR2 and TLR4 in the renal and bladder tissues. CONCLUSION: Crocetin considerably reduced the bacterial adherence to NRK-52E cells, attenuated the H2 O2 induced toxicity in NRK-52E cells and also improved the renal tubular function, and reduced the inflammatory response via altering the inflammatory and antioxidant markers. PRACTICAL APPLICATION: As we all know that urinary tract infection is the most common disease worldwide. In this study, we scrutinized the protective effect of crocetin against urinary tract infection. Crocetin treatment considerably reduced the zone of inhibition and improved radioactivity. Crocetin significantly reduced the levels of cytokines and inflammatory mediators. Crocetin can be used as a protective drug in the treatment of urinary tract infections.

A comparative study of cyclophosphamide, thalidomide and dexamethasone (CTD) versus bortezomib and dexamethasone (BDex) in light-chain amyloidosis.

BACKGROUND: Cyclophosphamide, thalidomide, and dexamethasone (CTD) or bortezomib and dexamethasone (BDex) show substantial efficacy in patients with amyloid light-chain (AL) amyloidosis, especially in Chinese patients. Currently, both regimens are recommended as primary treatment options for AL amyloidosis, but no comparative study has been reported. METHODS: We retrospectively evaluated the outcomes of 81 AL patients who received CTD (n = 42) or BDex (n = 39) and used Mayo stage 2012 to match 26 pairs of patients. RESULTS: In the whole cohort, the overall hematologic responses were 86% vs 91% in the CTD and BDex groups, including a complete response of 56% vs 71% based on an intention-to-treat (ITT) analysis. One- and 2-year overall survival (OS) was 90.2% and 81.7% with CTD, and 87.6% and 82.7% with BDex. After matching, BDex regimen induced a significantly deeper and more rapid hematologic response over CTD, but no statistically significant difference in OS (ITT analysis, P = 0.24; 6-month landmark analysis, P = 0.48). Cardiac response rates were similar, while there was a trend for higher renal responses in patients treated with BDex (68% vs 44%, P = 0.09). Additionally, BDex was associated with significantly improved survival in patients with advanced disease (Mayo stage III or worse; P = 0.009). Patients treated with BDex reported more episodes of severe hematologic toxicity and diarrhea. CONCLUSIONS: CTD and BDex are effective treatments for Chinese patients with AL amyloidosis, but BDex regimen appears superior to CTD in achieving a more rapid and deeper clonal response, and in improving OS in patients with advanced disease.

Regional citrate anticoagulation versus no-anticoagulation for continuous venovenous hemofiltration in patients with liver failure and increased bleeding risk: A retrospective case-control study.

OBJECTIVE: There are controversial opinions on anticoagulation for continuous venovenous hemofiltration (CVVH) in patients with liver failure (LF) and increased bleeding risk. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation for CVVH in these patients. METHODS: The included patients were divided into RCA and no-anticoagulation group according to the CVVH anticoagulation strategy they accepted for CVVH. Filter lifespan, bleeding, citrate accumulation, catheter occlusion, and totCa/ionCa ratio were evaluated as outcomes. RESULTS: In the original cohort, the filter lifespan of the RCA group (41 patients, 79 filters) was significantly longer than the no-anticoagulation group (62 patients, 162 filters) (> 72 hours vs 39.5 hours (IQR 31.2-47.8), P = 0.002). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (HR = 0.459, 95%CI 0.26-0.82, P = 0.008). Four episodes of totCa/ionCa > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose and blood flow. No obvious citrate accumulation was observed in these patients. In the matched cohort, the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group (P = 0.013) as well. No significant difference in the episodes of totCa/ionCa > 2.5 was observed between the two matched groups (P = 0.074). Both in the original cohort and the matched cohort, the bleeding, acidosis, alkalosis, and catheter occlusion incidences were not significantly different between the two groups. CONCLUSIONS: In LF patients with increased bleeding risk who underwent CVVH, RCA could prolong the filter lifespan and be safely used with careful blood gas monitoring and citrate dose adjusting. Further prospective, randomized, control studies are warranted to obtain robust evidences.

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide.

BACKGROUND: The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial. METHODS: This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0 g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD. RESULTS: All patients were followed for a medial of 33.2 months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73 m2 per year. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups. CONCLUSION: Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.

Kaempferol ameliorates Cisplatin induced nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathways.

Anticancer drug like Cisplatin are associated with serious problem like nephrotoxicity. The effect of Kaempferol is a plant-derived flavonoid compound. The present work evaluated the effect of Kaempferol in mouse model of Cisplatin mediated nephrotoxicity also the involved mechanism. Oxidative stress, kidney function, histology, inflammation, apoptosis, level of proteins, Nrf2 translocation and its effect on cascades such as NF-κB and ERK were studied. It was observed that the pre-treatment of KPF reduced the Cisplatin mediated oxidative stress, inflammation, apoptosis and ameliorated renal injury and its functioning. Kaempferol suppressed the Cisplatin induced infiltration of mononuclear cells, levels of TNF-α, iNOS, IL-12, activation of NF-κB, phosphorylation of IκBα and nuclear translocation of p65 in renal tissues. Also KPF attenuated Cisplatin mediated phosphorylation of p38, ERK1/2 and JNK in renal tissues. KPF also corrected the levels of renal antioxidants and elevated the nuclear levels of HO-1 and Nrf2 in renal tissues. KPF attenuated the Cisplatin mediated apoptosis via down-regulating the levels of TP53, Bax/Bcl2 imbalance, activating caspase-3/9 and PARP. The outcomes conclude that KPF ameliorates Cisplatin-mediated nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathway.