Programmed cell death in Helicobacter pylori infection and related gastric cancer.

Programmed cell death (PCD) plays a crucial role in maintaining the normal structure and function of the digestive tract in the body. Infection with Helicobacter pylori (H. pylori) is an important factor leading to gastric damage, promoting the Correa cascade and accelerating the transition from gastritis to gastric cancer. Recent research has shown that several PCD signaling pathways are abnormally activated during H. pylori infection, and the dysfunction of PCD is thought to contribute to the development of gastric cancer and interfere with treatment. With the deepening of studies on H. pylori infection in terms of PCD, exploring the interaction mechanisms between H. pylori and the body in different PCD pathways may become an important research direction for the future treatment of H. pylori infection and H. pylori-related gastric cancer. In addition, biologically active compounds that can inhibit or induce PCD may serve as key elements for the treatment of this disease. In this review, we briefly describe the process of PCD, discuss the interaction between different PCD signaling pathways and the mechanisms of H. pylori infection or H. pylori-related gastric cancer, and summarize the active molecules that may play a therapeutic role in each PCD pathway during this process, with the expectation of providing a more comprehensive understanding of the role of PCD in H. pylori infection.

Wide-Range Excitation-Dependent Phosphorescence of Coordination Polymers Exhibiting Dynamic Anticounterfeiting, White-Light Emission, and Antibacterial Performance.

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

α-1 antitrypsin is promising for the identification of glaucoma severity and is associated with glaucomatous neural damage.

Aim: To investigate the association between plasma AAT level and glaucoma. Methods: 163 glaucoma patients and 111 healthy controls were recruited. The plasma AAT levels were measured by ELISA. Results: Plasma AAT level was significantly higher in glaucoma patients than those in healthy controls (p < 0.001). Patients with higher plasma AAT level exhibited severer disease stage (early vs. severe: p < 0.05; H-P-A; early vs. severe: p < 0.05; early vs. end-stage: p < 0.01; AGIS). ROC curves yielded that AAT can distinguish patients with early glaucoma from those with advanced glaucoma (early vs. severe: AUC: 0.616; H-P-A; early vs. severe: AUC: 0.763; early vs. end-stage: AUC: 0.660; AGIS). Conclusion: Plasma AAT is a useful biomarker for the identification of glaucoma severity.

[Box: see text].

VKH-like uveitis during donafenib therapy for hepatocellular carcinoma: a case report and review of the literature.

Background: The incidence of uveitis has risen with the use of targeted therapies, particularly prevalent in the administration of immune checkpoint inhibitors and MAP-kinase pathway inhibitors. We report the first case of VKH-like uveitis linked to Donafenib employed for the primary hepatocellular carcinoma, highlighting the necessity of ophthalmological follow-up in patients undergoing treatment with Donafenib. Case presentation: A 55-year-old man developed VKH-like symptoms, including sporadic white patches, tinnitus, headache, and mild bilateral vision reduction, after 18 months of treatment with Donafenib and Sintilimab for hepatocellular carcinoma. Based on ophthalmological examinations that fundus fluorescein angiography images demonstrating multiple focal areas of pinpoint hyperfluorescence, along with pooling indicative of neurosensory detachment and disc leakage in both eyes, choroid thickening in swept-source optical coherence tomography, and "sunset-glow" fundus appearance, a tentative diagnosis of VKH-like uveitis was made. Initially, his best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/80 in the left eye. Upon discontinuing Donafenib and starting a 3-month course of oral glucocorticoids, his BCVA improved to 20/30 in the right eye and 20/40 in the left eye. Conclusion: Targeted drugs have been commonly used for cancer treatment in recent years, but challenges of ocular side effects emerged gradually. To optimize patient outcomes, regular ophthalmological follow-ups are essential for those undergoing treatment with targeted therapies like Donafenib.

Professional Master of Health Science in Laboratory Medicine: Training Clinical Laboratory Scientists in an Integrated Program at a Research-Intensive University.

A 2-year professional master of health science program at the University of Toronto provides a unique integrated educational program to train allied health science personnel to practice as physician extenders and health care professionals in two high-demand clinical laboratory disciplines, Pathologists' Assistant (PA) and Clinical Embryologist (CE). This report describes an integrated graduate program developed and delivered in a research-intensive laboratory medicine department. The core courses in fundamental biomedical science and in general medical laboratory function and operations formed the foundation on which the requisite clinical skills required to practice as a PA or CE were subsequently delivered as comprehensive CE and PA specialty courses and practicums. Students acquired research skills through courses that teach research methods, critical analysis of research articles, and biostatistics for clinical research scientists. A capstone research project provided students the opportunity to design a research project relevant to the CE or PA fields, perform and analyze the findings, and present the project as an oral abstract and a written scientific article. Students learn to face the clinical challenges by focusing on critical analysis of evidence-based professional practice. The PA field received a 5-year accreditation. CE and PA students presented their clinical research at national and international meetings, with some receiving awards, and published scientific articles. All graduates found meaningful employment in their respective fields, and initial employer response has been favorable.

Current developments of gene therapy in human diseases.

Gene therapy has witnessed substantial advancements in recent years, becoming a constructive tactic for treating various human diseases. This review presents a comprehensive overview of these developments, with a focus on their diverse applications in different disease contexts. It explores the evolution of gene delivery systems, encompassing viral (like adeno-associated virus; AAV) and nonviral approaches, and evaluates their inherent strengths and limitations. Moreover, the review delves into the progress made in targeting specific tissues and cell types, spanning the eye, liver, muscles, and central nervous system, among others, using these gene technologies. This targeted approach is crucial in addressing a broad spectrum of genetic disorders, such as inherited lysosomal storage diseases, neurodegenerative disorders, and cardiovascular diseases. Recent clinical trials and successful outcomes in gene therapy, particularly those involving AAV and the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins, are highlighted, illuminating the transformative potentials of this approach in disease treatment. The review summarizes the current status of gene therapy, its prospects, and its capacity to significantly ameliorate patient outcomes and quality of life. By offering comprehensive analysis, this review provides invaluable insights for researchers, clinicians, and stakeholders, enriching the ongoing discourse on the trajectory of disease treatment.

Associations between antibacterial mouthwash use with sexual behaviours and sexually transmitted infections among Chinese men who have sex with men: a cross-sectional study.

Background Mouthwash is a commonly used product with the potential to prevent STIs. This study aimed to determine the association between mouthwash use frequency with sexual behaviours and STIs among Chinese men who have sex with men (MSM). Methods A cross-sectional study was conducted among MSM in Xi'an, China, from January to September 2022. Participants were categorised into non-mouthwash users, occasional (used it less than once every week) and frequent (used it more than once every week) mouthwash users. Multinomial logistic regression was performed to identify the association between mouthwash use frequency with sexual behaviours. Results Of 838 MSM included in the analysis, 621 (74.11%) reported never using mouthwash, whereas 47 (5.60%) used it occasionally and 170 (20.29%) used it frequently. Frequent mouthwash users had a lower prevalence of chlamydia compared with occasional users (8.33% vs 23.93%, P Conclusion MSM with more sexual partners or lower condom use frequency were more likely to be frequent mouthwash users. However, frequent mouthwash users had a lower chlamydia prevalence.

Low thermal quenching of metal halide-based metal-organic framework phosphor for light-emitting diodes.

Phosphor-converted white light-emitting diodes (PC-WLEDs) have attracted considerable attention in solid-state lighting and display. However, urgent issues of thermal quenching and high cost remain formidable challenges. Herein, a novel metal-organic framework (MOF) phosphor [CdCl2(AD)] was facilely prepared using a mixture of CdCl2 and acridine (AD) under solvothermal conditions. It shows intensive green emission with a long lifetime of 31.88 ns and quantum yield of 65% while maintaining 95% and 84% of its initial emission intensity after remaining immersed in water for 60 days and being heated to 150 °C, respectively. The low thermal quenching of this MOF material is comparable to or can even exceed that of commercial inorganic phosphors. The combination of experiments and theoretical calculations reveals that the alternating arrangement of delocalized AD π-conjugated systems and CdCl2 inorganic chains through strong coordination bonds and π⋯π stacking interactions imparts the MOF phosphor with high thermal stability and optoelectronic performance. The successful fabrication of green and white LED devices by coating [CdCl2(AD)] and/or N630 red phosphor on a 365/460 nm commercial diode chip suggests a promising and potential alternative to commercial phosphors.

Comparison of single-chain variable fragments and monoclonal antibody against dihydroartemisinin.

Immunoassay relies on antibodies, but traditional antibodies such as monoclonal antibody (mAb) require animal immunization and complex procedures. Single-chain variable fragment (scFv) becomes a potential alternative to mAb with advantages of the low cost, rapid and easy prepared. In the present study, we prepared scFvs against dihydroartemisinin (DHA) based on E. coli and HEK293T cell expression system, named MBP-scFv and scFv-Fc, respectively. Their properties were compared with the parent mAb. The calculated affinity constants of mAb, MBP-scFv and scFv-Fc were 2.1 × 108 L mol-1, 2.2 × 107 L mol-1 and 1.6 × 108 L mol-1, respectively. The half inhibitory concentration (IC50) of mAb, MBP-scFv and scFv-Fc were 1.16 ng mL-1, 2.15 ng mL-1 and 6.57 ng mL-1, respectively. Both the scFv showed less sensitive than the mAb based on the IC50. The cross-reactivities of MBP-scFv for artemisinin and artesunate exhibited similarities to the mAb, yet the cross-reactivities of scFv-Fc for these compounds exceeded those of the mAb significantly. The stability of the scFvs was ascertained to be maintained for over 5 days at room temperature, and for more than a month at both 4 °C and - 20 °C. After that, the indirect competitive enzyme-linked immunosorbent assays (icELISAs) based on the scFv from E. coli were used to detect the DHA content in eight drug samples, and the result was consistent with ultra-performance liquid chromatography simultaneously. Although scFv can be used for quantitative determination of drugs, but it still cannot completely replace mAb in immunoassay without evolution and modification.

Effects of ginseng berry saponins from panax ginseng on glucose metabolism of patients with prediabetes: A randomized, double-blinded, placebo-controlled, crossover trial.

BACKGROUND: Prediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects. PURPOSE: This study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy. STUDY DESIGN AND METHODS: In this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed. RESULTS: Compared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study. CONCLUSIONS: Among prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000).

Association between relative muscle strength and cardiovascular disease among middle-aged and older adults in China.

BACKGROUND: The association between sarcopenia and cardiovascular disease (CVD) is well known. However, the clinical diagnosis of sarcopenia is complex and not suitable for early clinical identification and prevention of CVD. Relative muscle strength (RMS) is a relatively quantitative and straightforward indicator, but its association with CVD remains unclear. Hence, the objective of this research was to investigate the correlation between RMS and CVD incidence. METHODS: This was a cross-sectional study, using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. CVD events were assessed through self-reported physician diagnoses. The RMS was determined by dividing the maximum grip strength by the appendicular skeletal muscle mass (ASM). This study used multivariate logistic regression and restricted cubic spline (RCS) curves to explore the correlation between RMS and CVD incidence. Additionally, we conducted subgroup analyses to provide additional evidence supporting the association between the two variables. RESULTS: A total of 8,733 people were included in our study, with 1,152 (13.19%) CVD patients and 7,581 (86.81%) non-CVD patients. When the data were grouped according to quartiles (Q) of RMS, the inverse association between CVD and RMS remained statistically significant even after controlling for all potential confounding factors. Compared with participants in Q1 of RMS, the ORs (95% CIs) of CVD among those in Q2-Q4 were 0.99 (0.83, 1.17), 0.81 (0.67, 0.98), and 0.70 (0.57, 0.85), respectively. Moreover, the RCS results showed a negative linear correlation between the RMS and CVD incidence (P for nonlinearity = 0.555). Subgroup analysis revealed no significant interaction in any of the groups except for the sex group (P for interaction = 0.046). CONCLUSION: Our study indicated a stable negative correlation between RMS and CVD incidence. RMS is helpful for the early identification and prevention of CVD.

Versatile Method of Engineering the Band Alignment and the Electron Wavefunction Hybridization of Hybrid Quantum Devices.

Hybrid devices that combine superconductors (S) and semiconductors (Sm) have attracted great attention due to the integration of the properties of both materials, which relies on the interface details and the resulting coupling strength and wavefunction hybridization. However, until now, none of the experiments have reported good control of the band alignment of the interface, as well as its tunability to the coupling and hybridization. Here, the interface is modified by inducing specific argon milling while maintaining its high quality, e.g., atomic connection, which results in a large induced superconducting gap and ballistic transport. By comparing with Schrödinger-Poisson calculations, it is proven that this method can vary the band bending/coupling strength and the electronic spatial distribution. In the strong coupling regime, the coexistence and tunability of crossed Andreev reflection and elastic co-tunneling-key ingredients for the Kitaev chain-are confirmed. This method is also generic for other materials and achieves a hard and huge superconducting gap in lead and indium antimonide nanowire (Pb-InSb) devices. Such a versatile method, compatible with the standard fabrication process and accompanied by the well-controlled modification of the interface, will definitely boost the creation of more sophisticated hybrid devices for exploring physics in solid-state systems.

Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.

Purpose: Age-related macular degeneration (AMD) is a chronic and progressive macular degenerative disease that culminates in a gradual deterioration of central vision. Despite its prevalence, the key biomarkers for AMD have not yet been fully elucidated. In this study, we aimed to efficiently identify biomarkers crucial for diagnosing AMD. Methods: Three datasets pertaining to retinal pigment epithelium (RPE)/choroid tissues associated with AMD were selected from the GEO database. The GSE50195 dataset was utilized to conduct weighted gene co-expression network analysis (WGCNA) for identifying module genes linked to AMD. KEGG and GO enrichment analyses were subsequently conducted on these module genes. GSE29801 and GSE135092 datasets were subjected to differential expression analysis to pinpoint the DEGs intersecting with the module genes. Subsequently, wet AMD (wAMD) and dry AMD (dAMD) mouse models were developed, from which RPE/choroid tissues were harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA, we selected the "antiquewhite4" module (r = 0.91 and p = 7e-07), which contains a total of 325 genes. Through the intersection of module genes with DEGs, nine hub genes were identified. Pathways involved in complement and coagulation cascades, ECM-receptor interactions, unsaturated fatty acid biosynthesis, and fatty acid elongation play important roles in AMD. Notably, CDH18 demonstrated notable variance across all three datasets. Post validation using RT-qPCR experiments revealed a significant downregulation of CDH18 in both dAMD and wAMD. EGLN3 was expressed at low levels in wAMD. In dAMD, EYA2, LTB, and PODXL were significantly downregulated, whereas APOC1 was notably upregulated. Western blot confirmed that CDH18 was lowly expressed in dAMD and wAMD mouse models. Conclusion: CDH18 was identified as the key gene involved in the pathogenesis of AMD. An imbalance of the complement and coagulation cascades is a potential mechanism of AMD. This study provides a novel idea for diagnosing and treating AMD in the future.

Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Examining the Effects of PrEP Use on Sexual Behaviors and Sexually Transmitted Infections Among Chinese Men who have Sex with Men: A Cross-Sectional Study.

Men who have sex with men (MSM) is a high-risk population for HIV and sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) is effective in HIV prevention. This study aims to examine the differences in sexual behaviors, STI prevalence and HIV/STI testing across subgroups of MSM with various PrEP use. Data were collected via a cross-sectional survey in an MSM community in Xi'an, Shaanxi, from 2022.01 to 2022.09. Participants were categorized as 'PrEP-naïve and unwilling to use', 'PrEP-naïve but willing to use', and 'current or former PrEP users'. Shannon index was used to assess sexual act diversity and multivariate logistic regression analyzed factors associated with PrEP use. Of the 1,131 MSM participants, 23.52% were PrEP-naïve and unwilling, 64.98% were PrEP-naïve but willing, and 11.49% were current or former PrEP users. The PrEP-naïve but willing group had the highest recent STI testing rates at 73.06% and showed greater sexual act diversity (Shannon index 1.61). This group also had the highest syphilis rates (7.49% vs. 6.47% and2.54%, p < 0.01). Younger age (18-30: OR = 0.39 (0.18-0.85); 31-40: OR = 0.43 (0.20-0.96)) and lower education (high school/vocational: OR = 0.15 (0.04-0.58); associate degree: OR = 0.21 (0.06-0.71)) were factors that negatively influenced PrEP use. Current or former PrEP users had the highest oropharyngeal gonorrhea (14.39% vs. 9.68% and 5.80%, p < 0.01) and overall gonorrhea rates (20.86% vs. 17.17% and 8.37%, p < 0.001). 'PrEP-naïve but willing' participants consistently demonstrated high-risk sexual behavior, increased STI testing, and more diverse sexual acts, whereas PrEP users had the highest STI prevalence.

Drug-Resistant Tuberculosis Case-Finding Strategies: Scoping Review.

BACKGROUND: Finding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown. OBJECTIVE: We therefore assessed the available literature on DR-TB case-finding strategies. METHODS: We looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp). RESULTS: We screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information. CONCLUSIONS: Existing descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies.

Fibrinogen-albumin ratio predicts treatment response in phospholipase A2 receptor-associated membranous nephropathy with nephrotic syndrome.

BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. METHODS: 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. RESULTS: In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. CONCLUSIONS: FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

Filling the gaps in icosahedral superatomic metal clusters.

Chemically modified superatoms have emerged as promising candidates in the new periodic table, in which Au13 and its doped M n Au13- n have been widely studied. However, their important counterpart, Ag13 artificial element, has not yet been synthesized. In this work, we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands, that fills the gaps in the icosahedral superatomic metal clusters. After further doping Ag13 template with different degrees of Au atoms, we gained insight into the evolution of their optical properties. Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure, and the electron transfer process changes from local excitation (LE) to charge transfer (CT) to LE. This study not only enriches the families of artificial superatoms, but also contributes to the understanding of the electronic states of superatomic clusters.

High sodium intake and fluid overhydration predict cardiac structural and functional impairments in chronic kidney disease.

Background: High sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear. Aims: The study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD. Methods: In all, 409 patients with CKD stages 1-4 (G1-G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman's correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression. Results: Of the enrolled patients with CKD, the median urinary protein was 0.94 (0.28-3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52-110.99) mL/min/1.73 m2. The distributions of CKD stages G1-G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171-4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses. Conclusion: The combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD.