Search

Abstract Background The challenge of dealing with isolated reactive treponemal chemiluminescence immunoassay (CIA) results in clinical practice has prompted the development of a more efficient algorithm for distinguishing true infection from false reactivity in isolated CIA sera. Methods A prospective cohort study was conducted at Wuhan Tongji Hospital, involving 119,002 individuals screened for syphilis using CIA from January 1, 2015, to January 6, 2017. Samples with reactive CIA results underwent simultaneous testing with the T. pallidum passive particle agglutination assay (TPPA) and the rapid plasma reagin test (RPR). Additionally, a subgroup of 189 individuals with differing TPPA statuses was selected for further analysis using Western blotting (WB) and a modified TPPA assay (titer, 1:20). To identify the optimal serological approach for distinguishing true from false reactivity in sera with isolated reactive CIAs (CIA+TPPA−RPR−), two distinct algorithms were developed and evaluated. The first algorithm involved reflexively testing CIA+TPPA−RPR− sera with the modified TPPA, followed by WB if nonreactive. The second algorithm began with WB, followed by the modified TPPA if nonreactive or indeterminate. Results WB demonstrated lower sensitivity compared to TPPA, but it identified six syphilis cases among the 89 CIA+TPPA− samples. Both WB and modified TPPA exhibited a specificity of 100%. The two supplementary confirmatory algorithms detected 12 additional syphilis cases, with the first algorithm being more cost-effective and labor-saving. Conclusion A combination of a modified TPPA (titer, 1:20) and WB can serve as a reliable algorithm for distinguishing true syphilis infection from false reactive signals in isolated reactive CIA sera. Clinical trial number Not applicable.

IntroductionCisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatin- induced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear.MethodsTo investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques.ResultsHere, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin.DiscussionOur study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.

Abstract Background Despite the increasing survival rates, liver transplant patients experience numerous postoperative complications and encounter significant challenges in long-term self-management. This study aims to examine the effectiveness of empowerment education in enhancing self-management skills and self-efficacy among liver transplant recipients. Methods A randomized, single-blind, single-center trial was conducted in China between August 2019 and September 2020, involving liver transplant recipients. The intervention group received 12 weeks of empowerment education, while the control group received 12 weeks of routine education. .The study assessed the patients’ self-management and self-efficacy using the Liver Transplant Recipient Self-Management Questionnaire and the Self-efficacy for Managing Chronic Disease 6-Item Scale. Follow-up assessments were conducted at 1, 3, and 6 months after the intervention. Results Eighty-four patients were initially randomized to either the intervention group (n1 = 42) or the routine education group (n2 = 42). Twelve patients were excluded from the analysis due to loss of follow-up or discontinuation of the intervention, leaving 72 patients (n1 = 35, n2 = 37) for the final analysis. The scores for exercise and lifestyle management were significantly higher in the intervention group than in the control group at 1, 3, and 6 months after the intervention (t = 3.047, 5.875, 8.356, and t = 5.759, 4.681, 11.759, respectively; P

Abstract This study aimed to explore the changes of the vaginal microbiota and enzymes in the women with high-risk human papillomavirus (HR-HPV) infection and cervical lesions. A total of 448 participants were carried out HPV genotyping, cytology tests, and microecology tests, and 28 participants were treated as sub-samples, in which vaginal samples were characterized by sequencing the bacterial 16S V4 ribosomal RNA (rRNA) gene region. The study found the prevalence of HR-HPV was higher in patients with BV (P = 0.036). The HR-HPV infection rate was 72.73% in G. vaginalis women, which was significantly higher than that of women with lactobacillus as the dominant microbiota (44.72%) (P = 0.04). The positive rate of sialidase (SNA) was higher in women with HR-HPV infection (P = 0.004) and women diagnosed with cervical intraepithelial neoplasia (CIN) (P = 0.041). In HPV (+) women, the α-diversity was significantly higher than that in HPV (−) women. The 16S rRNA gene-based amplicon sequencing results showed that Lactobacillus was the dominant bacteria in the normal vaginal microbiota. However, the proportion of Gardnerella and Prevotella were markedly increased in HPV (+) patients. Gardnerella and Prevotella are the most high-risk combination for the development of HPV (+) women. The SNA secreted by Gardnerella and Prevotella may play a significant role in HPV infection progress to cervical lesions.

Abstract The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type (WT) and Tet2 −/− fetal livers, by multiplexed error robust fluorescence in situ hybridization. We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor signaling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are in direct contact with endothelial cells (ECs) in both WT and Tet2 −/− fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs, arterial ECs and sinusoidal ECs, and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.

The reliable folding of proteins is essential for their biological activities, while misfolding may lead to severe diseases, such as Alzheimer’s disease. However, our current knowledge of protein folding arises mainly from studies on small, single-domain proteins rather than multidomain proteins, although the latter make up most of proteins in the cell. Due to complex topological structures and potential interdomain interactions, the refolding of many multidomain proteins often passes through long-lived partially folded intermediates and exhibits complex kinetics. Here, we survey recent progress in understanding the folding and misfolding of multidomain proteins in vitro, with particular reference to theoretical aspects, and briefly summarize the researches on how ribosome regulates folding kinetics of nascent chains during translation in vivo, such as the environmental effects of the ribosome, translation rate effects, and self-interactions effects of polypeptide chain. In addition to these important advances, many questions are still waiting for answer, including: Can a purely structure-based model capture the complex folding kinetics of some multidomain proteins caused by the significant energetic frustration? Is the energy landscape of cotranslational folding still perfectly funnel-like? Are the observed principles that ribosome promotes the proper folding of proteins universal? To what extent does cotranslational folding affect nonnative interactions? Collectively, to address these issues, further innovation and improvement on both experimental techniques and the computational models are in great demand.

The three-dimensional architecture of the genome affects genomic functions. Here, the authors developed Multiplexed Imaging of Nucleome Architectures to measure multiscale chromatin folding, RNA profiles, and associations of numerous genomic regions with nuclear lamina and nucleoli in the same, single cells in heterogeneous tissue.

Cisplatin is widely used as a chemotherapeutic drug to treat various solid tumors. However, it often induces severe side effects, including nephrotoxicity, which limits its application in clinical settings. Furthermore, the underlying mechanisms of action are unclear. Here, we applied whole-transcriptome RNA sequencing to a cisplatin-induced acute kidney injury (CP-AKI) mouse model to evaluate competing endogenous RNA (ceRNA) networks. We found 4460 mRNAs, 1851 long non-coding RNAs, 101 circular RNAs, and 102 microRNAs significantly differentially expressed between CP-AKI and control mice. We performed gene set enrichment analysis to reveal the biological functions of the mRNAs and constructed non-coding RNA-associated ceRNA networks in CP-AKI mice. Two ceRNA regulatory pathways, Lhx1os-203/mmu-miR-21a-3p/Slc7a13 and circular RNA_3907/mmu-miR-185-3p/Ptprn, were validated using quantitative real-time PCR. The protein–protein interaction network indicated that Il6, Cxcl1, Cxcl2, and Plk1 serve as hub genes and are highly connected with the inflammatory response or DNA damage. Transcription factors, such as Stat3, Cebpb, and Foxm1, regulate gene expression levels in CP-AKI. Our study provides insight into non-coding RNA-associated ceRNA networks and mRNAs in CP-AKI and identifies potential treatment targets.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy available so far. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nano- and micron-sized heterogeneous vesicles that can be secreted by almost all cell types. Importantly, EVs contain many biologically active materials, such as RNAs, DNAs, proteins, and lipids, from their parental cells, which can be transported to their recipient cells to mediate intercellular communication and signaling. Accumulating studies demonstrated that EVs, mainly exosomes and microvesicles, participated in the pathophysiological process of DN. Recently emerging studies also found that the contents of EVs in the urine (miRNAs, mRNAs, and proteins) could be used as potential biomarkers for DN. Therefore, in this mini-review, the generation, isolation methods, and biological function of EVs were introduced, and then the current information about the mechanism and the diagnostic value in the development of DN was summarized. Moreover, the review also discussed the future challenges of exploring the role of EVs in kidney disease.

Abstract Background Helcococcus ovis, belonging to the genus of Helcococcu in Peptostreptococcaceae, is one kind of facultative anaerobic and gram-positive cocci, which was first isolated from a mixed infection in sheep in 1999. To our knowledge, it’s known as an invasive pathogen in animals, and never been reported as a human pathogen in published literature. The aims of this work are to describe the first report of H. ovis which was recovered from the artificial eye of human case and perform a literature review. Case presentation A 26 year-old man reporting pyogenic infection with an artificial eye attended ophthalmic ward in Tongji hospital. After physical examination, clinical and laboratory investigations, the diagnosis of eye infection caused by Helcococcus ovis and Staphylococcus aureus was established. Receiving a medico-surgical approach, the patient was successfully treated. The treatment consisted in intravenous cefotaxime and ornidazole, levofloxacin eye drops during two weeks and removing of right artificial eye with debridement. Conclusions We describe here the first known case of H. ovis which was recovered from human artificial eye. This report different from previous data found in the literature emphasizes the invasive potential of this bacterial species as a pathogen in human. Prospectively, the application of next generation sequencing tools would contribute to a more accurate classification of clinical strains.

Abstract Background Diarrhea is the leading infectious cause of childhood morbidity and mortality. Among bacterial agents, diarrheagenic Escherichia coli (DEC) is the major causal agent of childhood diarrhea in developing countries, particularly in children under the age of 5 years. Here, we performed a hospital-based prospective study to explore the pathotype distribution, epidemiological characteristics and antibiotic resistance patterns of DEC from

Abstract Background Escherichia coli clinical sequence type 131 (ST131) has emerged as an extensively antimicrobial resistant E. coli clonal group in recent years throughout the world. The aim of this study was to investigate the prevalence and molecular characteristics of ST131 among unselected E. coli clinical isolates in a Chinese university hospital. Methods Seven hundred consecutive E. coli isolates were collected at a Chinese university hospital between 2014 and 2015. Isolates belonging to ST131 were identified by PCR and multilocus sequence typing (MLST), and then characterized for antibiotic resistance, CTX-M-type extended-spectrum β-lactamase genes, fluoroquinolone resistance genes, O types, phylogenetic groups, virulence factors and PFGE patterns. Results Overall, 83 (11.6%) isolates were identified as ST131 group. The H30 lineage accounted for 53 (63.9%) of the ST131 isolates, including 13 H30-Rx and 40 H30 non-Rx. The remaining 30 isolates belonged to H41 lineage. Two O types were identified in this study: O25b (66.3%) and O16 (33.7%). Compared with O25b-B2-ST131 isolates, O16-B2-ST131 isolates harbored less virulence factors of adhesins. ST131 H30 Rx isolates had significantly higher virulence score than those of other isolates. O16-B2-ST131 isolates were shown to have a lower resistance to quinolones than O25b-B2-ST131 isolates. 5 nonsynonymous mutations (GyrA S83 L, D87N, ParC S80I, E84V and ParE I529L) were strongly associated with ST131 H30 and O25b isolates. Results of PFGE demonstrated that these isolates were classified into 68 pulsotypes and these subtypes were grouped into 23 different PFGE clusters using 70% similarity cut-off value. Conclusions This is the first study to reveal the prevalence and molecular characteristic of ST131 clonal group among consecutive clinical E. coli isolates in China. Our findings demonstrated that ST131 lineage accounts for a small proportion of clinical E. coli isolates in China, which included two major groups: O25b-B2-ST131 and O16-B2-ST131. Our results implies that O16-B2-ST131 subclone may be an important type of E. coli ST 131 in China, which suggests that future studies should not ignore such clone in this country.

Objectives: The results of the T-SPOT.TB (T-SPOT) assay are reduced in immunocompromised patients with active tuberculosis (ATB), and it is difficult using T-SPOT results to distinguish ATB from latent tuberculosis infection (LTBI) in this condition. The aim of this study was to determine the performance of the TBAg/PHA ratio in T-SPOT assay in the diagnosis of ATB in immunocompromised patients. Methods: One hundred and forty three immunocompromised ATB patients and 124 LTBI individuals were diagnosed according to conventional tests and T-SPOT assay. Results: The results of T-SPOT assay are of no value in the diagnosis of ATB in immunocompromised patients. However, the number of phytohaemagglutinin (PHA) spot-forming cells (sfc) in T-SPOT assay was substantially decreased in immunocompromised ATB patients compared with that in LTBI individuals. Receiver operating characteristic (ROC) analysis revealed that a further calculation of the TBAg/PHA ratio (the larger of the ESAT-6/PHA and CFP-10/PHA) showed a better performance in distinguishing these two diseases. Using the threshold value of 0.316, the sensitivity and specificity for distinguishing immunocompromised ATB patients from LTBI individuals were respectively 79.21 and 94.05%. Conclusions: Our findings suggest that the TBAg/PHA ratio might have some significance for the diagnosis of TB disease in immunocompromised patients.

Background. Escherichia coli sequence type 131 (ST131) is an important multidrug-resistant extraintestinal pathogen, which can cause many kinds of infections. Integrons may play a crucial role in the dissemination of antibiotic resistance genes. The purpose of this study was to characterize the prevelance of integrons among E. coli ST131 strains in China. Methods. Eighty-three E. coli ST131 isolates were used in this study. The antibiotic susceptibility test was performed by the disk diffusion method. The presence and characterization of class 1, 2, and 3 integrons, as well as promotor of gene cassettes and other antimicrobial resistance genes, were detected by PCR and DNA sequencing. Transfer of integrons was carried out using a broth culture mating method. Clonal relatedness of E. coli ST131 isolates was analyzed by PFGE. Results. Overall, 26.5% (22/83) of the E. coli ST131 isolates carried class 1 integrons. Class 2 and 3 integrons were not found in this study. Two types of gene cassette arrays were demonstrated in this study and were as follows: dfrA17-aadA5 and aac(6′)-Ib-cr-cmlA5. Only one type of Pc promoter variant was detected among 22 integron-positive isolates (PcW). In vivo transfer of integron was successful for 9 of integron-positive E. coli ST131 isolates harboring resistance gene cassettes. Results of PFGE demonstrated that the integron-positive E. coli ST131 isolates were grouped into 12 different PFGE clusters. Conclusions. Our study showed a low prevalence of integrons was detected in E. coli ST131. Continued surveillance of this mobile genetic element should be performed to study the evolution of antibiotic resistance among E. coli ST131.

Diabetic nephropathy (DN) is one of the most serious chronic kidney diseases and the major cause of end-stage renal failure worldwide. The underlying mechanisms of DN are complex and required to be further investigated. Both innate immunity and renin-angiotensin system (RAS) play critical roles in the pathogenesis of DN. Except for traditional functions, abnormally regulated RAS has been proved to be involved in the inflammatory process of DN. Toll-like receptor 4 (TLR4) is the most deeply studied pattern recognition receptor in the innate immune system, and its activation has been reported to mediate the development of DN. In this review, we aim at discussing how dysregulated RAS affects TLR4 activation in the kidney that contributes to the exploration of the pathogenesis of DN. Understanding the interplay of RAS and TLR4 in inducing the progression of DN may provide new insights to develop effective treatments.

Embryonic miscarriage severely affects the life quality and physical and mental state of pregnant women. However, the detailed mechanism underlying embryonic miscarriage is not fully understood. This study is aimed at analyzing embryonic miscarriage. We collected samples from 25 normal pregnant women and 25 embryonic miscarriage patients of similar age to analyze microbiota isolated from the vagina. Crude examination of the vagina isolates showed that compared with the control group, 80% of the embryonic miscarriage group contained a significantly lower number of Lactobacillus, the major healthy microbe in the vagina. Furthermore, the levels of Th1 and Th2 secreted cytokine interleukin 2 (IL-2) and interleukin10 (IL-10), respectively, were examined. Results showed that the IL2 level was higher, and IL10 level was lower in the embryonic miscarriage group than in the control group, whereas the IL2/IL10 level was higher in the embryonic miscarriage group than in the control group. This finding suggested that the immune response was suppressed in the embryonic miscarriage group. To further dissect the microbiota of the vagina in the two groups, 16S rDNA sequencing was performed. Bioinformatics analysis showed that 1096 and 998 overlapped operational taxonomic units were identified from the embryonic miscarriage and control groups, respectively. At the genus level, the relative abundance of Fam_Finegoldia, Lac_Coprococcus_3, and Lac_Roseburia significantly differed in the embryonic miscarriage group. Overall, our analyses provided potential biomarkers for embryonic miscarriage and elucidated the causative relationship between microbiota and immune responses and may enable the possible diagnosis and therapeutics of early pregnancy loss.

The function of lymphocytes is the key to reflect the immune status of hosts. Evaluation of lymphocyte function is a useful tool to monitor the effect of immunosuppressive treatment and predict the prognosis of immune-mediated diseases (e.g., cancer, autoimmune diseases, and infectious diseases). As the lymphocytes have various activities, such as activation, cytotoxicity, and cytokine secretion, it is a challenge to evaluate the function of lymphocytes in clinical practice and the reference intervals (RIs) of lymphocyte function are rarely reported. The present study showed that the secretion of IFN-γ was well correlated with the activation, chemotaxis, and cytotoxicity of CD4+, CD8+ T cells, and NK cells, which suggests that IFN-γ production can be used as a symbol of lymphocyte function. We therefore created a simple method to detect the function of CD4+, CD8+ T cells, and NK cells simultaneously according to IFN-γ secretion by using whole blood instead of peripheral blood mononuclear cells. We further established the RIs of lymphocyte function (CD4+ T cells: 15.31–34.98%; CD8+ T cells: 26.11–66.59%; NK cells: 39.43–70.79%) in healthy adults. This method showed good reproducibility for the evaluation of lymphocyte function. The established RIs were suitable for use in other centers based on the validation data. We also validated the RIs in individuals with different immune status, and the results showed that kidney transplant recipients and infants (0–1 year) had a decreased lymphocyte function, whereas T cells in systemic lupus erythematosus patients exhibited an opposite trend. Overall, we have successfully established the RIs of lymphocyte function in healthy adults in a simple way, which might be of important clinical value in the diagnosis, monitoring, and prognosis of immune-related diseases.

Background: With the abuse of antibiotics, the methicillin-resistant Staphylococcus aureus (MRSA) strain became prevalent. Furthermore, Staphylococcus aureus with a character of vancomycin intermediate-resistance (VISA) has been found globally since the first report in Japan. The main objectives of this study were to report a case of VISA isolated from a Chinese patient who had never undergone Vancomycin treatment, and to determine its molecular character. Methods: A total of 9 strains were recovered from a patient during the therapeutic process. Antimicrobial susceptibility testing was performed to determine their antibiotic susceptibility patterns. To detect the VISA strain's molecular epidemiological features, growth and morphological characters, we used multilocus sequence typing, autolysis assay and transmission electric microscope tests. Pulsed-field gel electrophoresis (PFGE) was performed to characterize the heterogeneities of all isolates. Results: One isolate was found to exhibit vancomycin intermediated-resistant with MIC of 8 μg/ml. It was ST239-T030-agr-1, had thickened cell wall, and displayed a slower growth rate and reduced susceptibility to Triton X-100-induced autolysis than other strains. All 9 strains exhibited the same PFGE pattern. Conclusion: This is the first report of VISA found in central China from a patient who had never received vancomycin treatment.

Objectives: Sequence type 1193 is emerging as a new, virulent and resistant lineage among fluoroquinolone resistant Escherichia coli (FQrE. coli). In this study, we investigated the prevalence and molecular characteristics of this clone isolated from a Chinese university hospital.Methods: 73 phylogenetic group B2-FQr-non-ST131 isolates were collected from August 2014 and August 2015 at a Chinese university hospital. Isolates were screened for ST1193 by multilocus sequence typing. E. coli ST1193 then underwent lactose fermentation determination, susceptibility testing, virulence genotyping, PCR-based O typing, pulsed-field gel electrophoresis (PFGE) and FQr mechanism analysis.Results: Of 73 B2-FQr-non ST131 E. coli isolates, 69.9% (n = 51) were ST1193. 90.2% (46/51) of ST1193 isolates were O75 serotype and 96.1% (49/51) of the ST1193 isolates were lactose non-fermenters. 35 clusters were identified by PFGE. ST1193 isolates exhibited a set of 3 conserved mutations defining quinolone-resistance determining region substitutions (gyrA S83L, D87N, and parC S80I). The most frequent VF genes detected in these E. coli ST1193 isolates were fyuA (yersiniabactin, 96.1%), fimH (type 1 fimbriae, 94.1%), iutA (iron uptake gene, 90.2%), kpsMT II (group II capsule, 90.2%), kpsK1 (K1 capsule, 86.3%) and PAI.Conclusion: ST1193 lineage accounts for the majority of group B2-FQr-non-ST131 E. coli clinical isolates. Most of the ST1193 are serotype O75 and lactose non-fermenting. Strategic surveillance and control schemes are needed in the future for this newly emerging clone of E. coli: B2-FQr-ST1193.

Sepsis is an exaggerated inflammatory condition response to different microorganisms with high mortality rates and extremely poor prognosis. Natural killer (NK) cells have been reported to be the major producers of IFN-γ and key players in promoting systematic inflammation in lipopolysaccharide (LPS)-induced endotoxic shock. T-cell immunoglobulin and mucin domain (Tim)-3 pathway has been demonstrated to play an important role in the process of sepsis, however, the effect of Tim-3 on NK cell function remains largely unknown. In this study, we observed a dynamic inverse correlation between Tim-3 expression and IFN-γ production in NK cells from LPS-induced septic mice. Blockade of the Tim-3 pathway could increase IFN-γ production and decrease apoptosis of NK cells in vitro, but had no effect on the expression of CD107a. Furthermore, NK cell cytotoxicity against K562 target cells was enhanced after blocking Tim-3 pathway. In conclusion, our results suggest that Tim-3 pathway plays an inhibitory role in NK cell function, which might be a potential target in modulating the excessive inflammatory response of LPS-induced endotoxic shock.

Introduction: Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatininduced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Methods: To investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques. Results: Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Discussion: Our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Aims and Objectives: The aim of this study was to explore the mental health of transplant recipients, especially psychological integration and the donor‐recipient relationship. Background: Psychological integration and the donor‐recipient relationship are unique psychological perception of recipients with transplantation, which have important effects on their mental health and recovery. However, few studies have focused on the feelings and attitudes of cadaveric liver transplant recipients. Design: A qualitative descriptive design was used. Methods: Individual semi‐structured interviews were conducted face‐to‐face with 30 recipients after liver transplantation. Qualitative content analysis was used and data saturation was achieved. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) were used. Results: Three themes and eight subthemes were identified. (1) Psychological integration—acknowledging the transplanted liver was a part of their own body and attaching great importance to the liver; (2) Attitudes towards the donor—gratitude to the donor, being inspired by the dedication of the donor and mourning the donor's misfortune; and (3) Living in the moment—health behaviours of self‐care, emotional regulation and positive attitude about life. Conclusion: The psychological integration of recipients of cadaveric liver transplants is smooth, and the attitudes towards the donor are positive. From the perspective of positive psychology, we observed the important role of post‐traumatic growth of the recipient and positive emotions in promoting the recipient's health behaviours for self‐care, emotion regulation and attitudes towards life. Relevance for Clinical Practice Medical staff should help recipients to deal with these issues about the organ and its donor constructively and guide them to focus on postoperative inner growth and positive emotion. [ABSTRACT FROM AUTHOR]

Introduction: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. Methods: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. Results: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. Conclusion: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.

This study examines how multicomponent exercise nursing interventions affect the state of frailty, daily activities, and quality of life in elderly stroke patients with frailty. A total of 125 elderly stroke patients with frailty were randomly assigned to either a control group (n = 62) or an intervention group (n = 63). The control group received standard nursing care, while the intervention group received a multicomponent exercise nursing intervention in addition to standard care. Patients were assessed using the FRAIL Frailty Scale, Modified Barthel Index (MBI), and Short Form Health Survey (SF-36) before the intervention, 4 weeks after the intervention, and 12 weeks after the intervention. Significant differences were observed between the two groups in terms of frailty status, activities of daily living, and quality of life (p

ObjectiveTo assess the efficacy and safety of iguratimod (IGU) in the treatment of inflammatory arthritis and degenerative arthritis.MethodsInitially, randomized controlled trials (RCTs) on using IGU in treating inflammatory arthritis and degenerative arthritis were systematically gathered from various databases up to February 2024. Subsequently, two researchers independently screened the literature, extracted data, assessed the risk of bias in included studies, and conducted a meta-analysis using RevMan 5.4 software.ResultsFifty-four RCTs involving three inflammatory arthritis were included, including ankylosing spondylitis (AS), osteoarthritis (OA), and rheumatoid arthritis (RA). For AS, the meta-analysis results showed that IGU may decrease BASDAI (SMD −1.68 [−2.32, −1.03], P < 0.00001) and BASFI (WMD −1.29 [−1.47, −1.11], P < 0.00001); IGU may also decrease inflammatory factor [ESR: (WMD −10.33 [−14.96, −5.70], P < 0.0001); CRP: (WMD −10.11 [−14.55, −5.66], P < 0.00001); TNF-α: (WMD −6.22 [−7.97, −4.47], P < 0.00001)]. For OA, the meta-analysis results showed that IGU may decrease VAS (WMD −2.20 [−2.38, −2.01], P < 0.00001) and WOMAC (WMD −7.27 [−12.31, −2.24], P = 0.005); IGU may also decrease IL-6 (WMD −8.72 [−10.00, −7.45], P < 0.00001). For RA, the meta-analysis results showed that IGU may improve RA remission rate [ACR20: (RR 1.18 [1.02, 1.35], P = 0.02); ACR50: (RR 1.32 [1.05, 1.64], P = 0.02); ACR70: (RR 1.44 [1.02, 2.04], P = 0.04)] and decrease DAS28 (WMD −0.92 [−1.20, −0.63], P < 0.00001); IGU may also decrease inflammatory factors [CRP: (SMD −1.36 [−1.75, −0.96], P < 0.00001); ESR: (WMD −9.09 [−11.80, −6.38], P < 0.00001); RF: (SMD −1.21 [−1.69, −0.73], P < 0.00001)]. Regarding safety, adding IGU will not increase the incidence of adverse events.ConclusionIGU might emerge as a promising and secure therapeutic modality for addressing AS, OA, and RA.Systematic Review RegistrationIdentifier PROSPERO: CRD42021289249

ObjectiveThis study aims to evaluate whether radiomic features of pericoronary adipose tissue (PCAT) derived from coronary computed tomography angiography (CCTA) can better predict major adverse cardiovascular events (MACE) in patients with angina pectoris.MethodsA single-center retrospective study included 239 patients with angina pectoris who underwent coronary CT examinations. Participants were divided into MACE (n = 46) and non-MACE (n = 193) groups based on the occurrence of MACE during follow-up, and further allocated into a training cohort (n = 167) and a validation cohort (n = 72) at a 7:3 ratio. Automatic segmentation of PCAT surrounding the proximal segments of the left anterior descending artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA) was performed for all patients. Radiomic features of the coronary arteries were extracted, screened, and integrated while quantifying the fat attenuation index (FAI) for the three vessels. Univariate and multivariate logistic regression analyses were utilized to select clinical predictors of adverse cardiovascular events. Subsequently, machine learning techniques were employed to construct models based on FAI, clinical features, and radiomic characteristics. The predictive performance of each model was assessed and compared using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis for clinical utility.ResultsThe radiomics model demonstrated superior performance in predicting MACE in patients with angina pectoris within both the training and validation cohorts, yielding areas under the curve (AUC) of 0.83 and 0.71, respectively, which significantly outperformed the FAI model (AUC = 0.71, 0.54) and the clinical model (AUC = 0.81, 0.67), with statistically significant differences in AUC (p 0.05). Decision curve analysis indicated that the radiomics model provided higher clinical benefit than the traditional clinical and FAI models.ConclusionThe CCTA-based PCAT radiomics model is an effective tool for predicting MACE in patients with angina pectoris, assisting clinicians in optimizing risk stratification for individual patients. The CCTA-based radiomics model significantly surpasses traditional FAI and clinical models in predicting major adverse cardiovascular events in patients with angina pectoris.

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and is characterized by the accumulation of lipid peroxides to lethal levels. Ferroptosis involves multiple pathways including redox balance, iron regulation, mitochondrial function, and amino acid, lipid, and glycometabolism. Furthermore, various disease-related signaling pathways also play a role in regulating the process of iron oxidation. In recent years, with the emergence of the concept of ferroptosis and the in-depth study of its mechanisms, ferroptosis is closely associated with various biological conditions related to kidney diseases, including kidney organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanisms of ferroptosis (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, and MBOAT1/2 pathways), and the latest research progress on its involvement in kidney diseases. It summarizes research on ferroptosis in kidney diseases within the frameworks of metabolism, reactive oxygen biology, and iron biology. The article introduces key regulatory factors and mechanisms of ferroptosis in kidney diseases, as well as important concepts and major open questions in ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs can be made in understanding the regulation mechanism of ferroptosis and utilizing ferroptosis to promote treatments for kidney diseases, such as acute kidney injury(AKI), chronic kidney disease (CKD), diabetic nephropathy(DN), and renal cell carcinoma. This paves the way for a new approach to research, prevent, and treat clinical kidney diseases.