Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis.

Background: Membranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive. Methods: In this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer. Results: We conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers. Conclusion: This evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.

Comprehensive single-cell and bulk RNA-seq analyses reveal a novel CD8+ T cell-associated prognostic signature in ovarian cancer.

CD8+ T cells play pivotal roles in combating intracellular pathogens and eliminating malignant cells in cancer. However, the prognostic role of CD8+ T cells in ovarian carcinoma is insufficiently exploited. Herein, through univariate Cox regression along with least absolute shrinkage and selection operator (LASSO) regression analyses, we developed a novel prognostic model based on CD8+ T cell markers identified by single-cell sequencing (scRNA-seq) analyses. Patient grouping by the median risk score reveals an excellent prognostic efficacy of this model in both training and validation cohorts. Of note, patients classified as low-risk group exhibit a dramatically improved prognosis. In addition, higher enrichment level of immune-related pathways and increased infiltration level of multiple immune cells are found in patients with lower risk score. Importantly, low-risk patients also exhibited higher response rate to immunotherapies. Summarily, this developed CD8+ T cell-associated prognostic model serves as an excellent predictor for clinical outcomes and aids in guiding therapeutic strategy choices for ovarian cancer patients.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy: A case report.

BACKGROUND: About 70%-80% of patients with primary membranous nephropathy (MN) have phospholipase A2 receptor (PLA2R) in renal tissue. Systemic light-chain (AL) amyloidosis is the most common type of amyloidosis. MN complicated with amyloidosis is rare. CASE SUMMARY: A 48-year-old Chinese male presented with nephrotic syndrome, positive serum PLA2R antibody, and positive serum and urine IgG-lambda type M-protein, with a normal ratio of serum-free light-chain level. The patient was diagnosed with MN accompanied by AL amyloidosis. He was treated with rituximab with glucocorticoids and CyBorD regimen of chemotherapy. After 21 mo of follow-up, the patient achieved complete remission regarding nephrotic syndrome without adverse effects of chemotherapy. CONCLUSION: We report a case of PLA2R-related MN complicated with primary AL amyloidosis only with renal involvement and successfully treated with rituximab, glucocorticoids and chemotherapy.

Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes.

BACKGROUND: The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. METHODS: We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. RESULTS: We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. CONCLUSION: Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future.

Neutrophil extracellular trap is an important connection between hemodialysis and acute myocardial infarction.

The incidence of acute myocardial infarction (AMI) in hemodialysis (HD) patients is high and the prognosis is extremely poor. However, the potential connection between HD and AMI, and its regulatory mechanisms remain unclear. In this study, the gene expression profiles of HD (GSE15072) and AMI (GSE66360) were downloaded from the Gene Expression Omnibus database, common differentially expressed genes (DEGs) were obtained using the limma R package, the biological functions were analyzed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, machine learning was conducted to identify hub genes. Receiver operating characteristic curves and gene set enrichment analyses were used to explore the characters and biological function of hub genes, networks were used for candidate identification of transcription factor (TF), microRNA (miRNA), and drug. After a total of 255 common DEGs were selected, GO and KEGG analyses indicated that neutrophil extracellular trap (NET) may be a potential connection between HD and AMI, LILRB2, S100A12, CYBB, ITGAM, and PPIF were finally identified as hub genes. The area under curve of LILRB2, S100A12, and PPIF was higher than 0.8 in both datasets. Networks show the relationship between hub genes, TF, and miRNA, also the relationship between potential drugs and protein. In conclusion, NETs may be the potential connection between AMI and HD. The potential hub gene, signaling pathways, and drugs provided by this study may contribute to future AMI prevention and intervention in HD patients.

Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients / Características clínicas de la nefropatía membranosa con remisión espontánea: análisis de 24 pacientes

Purpose To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).Patients and methods Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up. Results Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30–77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8μmol/L. During the follow-up of 33.9±19.1 months (range, 6–73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases. ConclusionsMost patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse. (AU)

Objetivo Investigar el pronóstico de los pacientes con remisión espontánea en la nefropatía membranosa (MN, por sus siglas en inglés) asociada al receptor fosfolipasa A2 (PLA2R). Pacientes y métodos Pacientes con MN diagnosticados por biopsia renal en el Departamento Renal del China-Japan Friendship Hospital entre enero de 2015 y septiembre de 2021. Entre ellos, 24 pacientes con remisión espontánea fueron reclutados y seguidos. Resultados Se reclutaron 24 pacientes con MN en remisión espontánea asociada a PLA2R; 11 varones y 13 mujeres, con una edad media de 49,5±14,5 años (rango: 30-77 años) en el momento del diagnóstico. La proteína total y la albúmina sérica en orina de 24h iniciales fueron de 0,29±0,14 y 37,5±4,4g/l, respectivamente; la creatinina sérica inicial fue de 65,0±15,8μmol/l. Durante el seguimiento de 33,9±19,1 (rango: 6-73) meses, 22 pacientes (91,7%) mantienen la remisión. Un paciente presentó insuficiencia renal por síndrome coronario agudo y angiografía coronaria. Otro paciente tuvo una recaída causada por una infección del tracto respiratorio 2 veces, a los 50 y 70 meses. Se realizó una revisión sistemática de la literatura. Los pacientes con MN asociada con PLA2R en remisión espontánea se recuperaron en 16 informes o series de casos, de 97 casos en total. ConclusionesLa mayoría de los pacientes con MN en remisión espontánea tuvieron un pronóstico prometedor a largo plazo, mientras que solo unos pocos casos tuvieron recaída. (AU)

Application of a core genome sequence typing (cgMLST) pipeline for surveillance of Clostridioides difficile in China.

Introduction: Clostridioides difficile (C. difficile) is a nosocomial bacterial pathogen that causes antibiotic-associated diarrhea mediated by cellular exotoxins secreted into the intestine during bacterial growth. Multilocus sequence typing (MLST) and PCR ribotyping are the main molecular typing for C. difficile. Whole genome sequencing (WGS) core genome multilocus sequence typing (cgMLST) was developed for genetic evolution and outbreak investigation of C. difficile with higher precision and accuracy. Methods: A total of 699 whole (complete and draft) genome sequences of distinct C. difficile strains were used in this study to identify core gene set (2469 core genes) and the cgMLST scheme for the phylogeny analysis of C. difficile. This cgMLST pipeline was then carried the Chinese Pathogen Identification Net (China PIN) for surveillance of C. difficile in China. Within the China PIN, 195 WGS of C. difficile and an outbreak of CDI with 12 WGS of C. difficile were used to evaluate the cgMLST pipeline. Results: The result displayed that mostly tested C. difficile isolates could be successfully divided into 5 classic clades and the outbreak event was also successfully identified. Discussion: The results are meaningful and offer a practicable pipeline for a national-wide surveillance of C. difficile in China.

Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients.

PURPOSE: To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). PATIENTS AND METHODS: Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up. RESULTS: Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30-77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8µmol/L. During the follow-up of 33.9±19.1 months (range, 6-73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases. CONCLUSIONS: Most patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse.

A rapid multiplex real-time PCR detection of toxigenic Clostridioides difficile directly from fecal samples.

This study developed a new single-tube multiplex real-time PCR method for detecting toxigenic C. difficile directly from fecal samples using tcdA, tcdB, cdtB, and internal gene tpi as targets, which could be performed on kinds of polymerase chain reaction device including point-of-care testing (POCT), with improved detection efficiency. The specificity, sensitivity, and repeatability of each gene was evaluated using 69 C. difficile isolates and 74 fecal samples. Results were compared with established PCR, qPCR, and ELISA methods. Interspecies specificity was 100% based on six common intestinal pathogens (Escherichia coli, Enterococcus Faecium, Enterococcus faecalis, Clostridium perfringens, Bacteroides fragilis, Clostridium botulinum). The lower detection limit (LDL) for tcdA, tcdB, and cdtB with pure C. difficile DNA was 101,100, and 100 copies/µL, respectively, the coefficients of variation among different experimental batches and within each experimental batch were both less than 3%, which shows that this method has strong repeatability. And the LDL of fecal DNA was 5 × 100, 5 × 103, and 5 × 102 colony-forming units (CFU)/g, respectively. In addition, the efficiency for detection of tcdA was compared with established PCR and real-time PCR methods, demonstrating high consistency (98.4%) and similar sensitivity. ELISA was used to confirm inconsistent results, which were identical with our method. The sensitivity and specificity for detecting toxigenic C. difficile in fecal samples were 96.49% and 94.12% compared with the toxigenic culture (TC). This method effectively identified the toxigenic and non-toxigenic strains with high specificity, sensitivity, and repeatability, and could reduce the false positive rate of tcdA, and accurately identify the typical Asian strain RT017, making it potentially contribute to the surveillance of CDI in China. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03434-6.

Tolvaptan ameliorated kidney function for one elderly autosomal dominant polycystic kidney disease patient: A case report.

BACKGROUND: Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts within the kidneys. Disease progress of some patients often occurs at the early stage. Thus, managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders. CASE SUMMARY: One 80-year-old male autosomal dominant polycystic kidney disease (ADPKD) patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban. Estimated glomerular filtration rate, creatinine and uric acid were monitored during the treatment. In addition, the whole exome sequencing was performed to screen ADPKD genetic variants. The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime, a venous thromboembolism was removed and leg and pedal edema were alleviated. One mutation c.10102G>A /p.D3368N in the PKD1 gene was identified. CONCLUSION: Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.

Acute kidney injuries induced by thrombotic microangiopathy following severe hemorrhage in puerperants: a case series and literature review.

BACKGROUND: Acute kidney injury in puerperants is generally caused by acute tubular necrosis and occasionally by thrombotic microangiopathy (TMA) following post-partum hemorrhage. However, TMA leads to worse clinical outcomes and is rarely reported in the literature. Therefore, this study aimed to evaluate the pathological mechanism behind the development of TMA in puerperants to improve the diagnosis and treatment of this condition. METHODS: Three patients diagnosed with severe postpartum hemorrhage and TMA from 2014 to 2017 at a nephrology center were retrospectively investigated. RESULTS: All patients had severe hemorrhage during delivery with a mean blood loss, 4.0 L (range, 2.7-5.0 L). AKI developed rapidly in these patients and was treated with hemodialysis. Following treatment, the mean volume of packed red blood cells was 2.3 L (range, 1.2-3.6 L), and the mean volume of resuscitation fluid was 3.7 L (range, 3.5-4.0 L). All patients had renal biopsy specimens with typical TMA and ATN changes on light microscopy. Two patients required a hysterectomy while another two patients received respiratory support. Only one patient received plasma exchange. None of the patients had recovered normal kidney function by the final follow-up (26-61 months), with two patients having stage 3 chronic kidney disease, and one patient having an end-stage renal disease requiring maintenance hemodialysis. CONCLUSION: Severe postpartum hemorrhage could lead to TMA, in addition to the common finding of ATN. Renal histology revealed that poor renal outcomes could be attributed to TMA coexisting with ATN. The potential mechanism was ischemia-reperfusion, which was followed by endothelial cell injury and activation of the alternative complement pathway.

A novel method to rapidly calculate the urea clearance index and urea reduction rate based on parameters obtained during hemodialysis.

BACKGROUND: The efficacy of hemodialysis (HD) is closely associated with patient survival time and quality of life. The classical method (CLM) to calculate the urea clearance index (Kt/V) and urea reduction rate (URR) requires multiple blood tests. A novel method that may be used as a noninvasive alternative to CLM is required. METHODS: Based on the urea kinetic model, a new method, named the "assessment method" (ASM), was established to calculate blood urea nitrogen after HD, based on parameters obtained during HD. The consistency of the Kt/V and URR values between the ASM and CLM was evaluated in 41 patients from the China-Japan Friendship Hospital between September 2017 and December 2018. RESULTS: Forty-one patients (24 males and 17 females; mean age, 55.7 ± 14.2 years) undergoing regular HD in our hospital were randomly selected for this study. The blood flow rate was 244.5 ± 19.6 mL/min and the dialysate flow rate was 500 mL/min. We obtained Kt/V (CLM = 1.40 ± 0.06, ASM = 1.37 ± 0.07) and URR (CLM = 68.6 ± 6.4%, ASM = 67.7 ± 7.2%) values. Paired t-test indicated no significant differences between the ASM- and CLM-derived values. The intraclass correlation coefficients were 0.907 and 0.916 for Kt/V and URR, respectively. Similarly, Bland-Altman plots suggested good concordance between the 2 methods. CONCLUSIONS: The Kt/V and URR values calculated using the ASM and CLM were in significant agreement, and both can be used to effectively assess the adequacy of HD in patients undergoing maintenance HD. The ASM is an effective, rapid, inexpensive, and noninvasive alternative to the CLM for obtaining Kt/V and URR values. The ASM has good potential for clinical application, particularly for patients in areas of low socioeconomic status.

Enhancing gonorrhea surveillance in China by testing females in gynecology clinics: Lessons learned from a pilot survey.

OBJECTIVES: China has a high burden of gonorrhea, but an imbalanced male-to-female (M/F) ratio of reported cases. Therefore, the prevalence of gonorrhea in China may be underestimated due to inadequate testing of potentially infected females. The objective of this study is to investigate the cause of this imbalanced M/F ratio and develop strategies to enhance gonorrhea surveillance, particularly among females. METHODS: The national center for STD control (NCSTDC) of China CDC collected data in Zhongshan city over the year 2018 from the National Notifiable Disease Report System (NNDRS) and the Hospital and Laboratory Information Systems (HIS and LIS) that obtains information from 24 hospitals. RESULTS: Analysis of 1,542 reported cases of gonorrhea and the case distribution among different hospitals showed that most of the female cases (80.31%) were reported by gynecological clinics. The M/F ratio of reported cases varied between different hospitals and was dependent on the intensity of testing of females by their gynecological clinics. CONCLUSIONS: This study showed a significant correlation between M/F ratios and the relative contribution of female gonorrhea testing, especially in gynecology clinics. Enhancing gonorrhea testing among females should be advocated to improve surveillance in China.

Angiotensin II type 1 receptor blockers favorably affect renal angiotensin II and MAS receptor expression in patients with diabetic nephropathy.

INTRODUCTION: The aims of this study were to assess the renal expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor in human type 2 diabetic nephropathy (DN). MATERIALS AND METHODS: In total, 115 patients diagnosed with DN by renal biopsy were enrolled in this study. The protein expression levels of the AT1R, AT2R, and MAS receptors were assessed by immunohistochemistry. RESULTS: The protein expression levels of AT1R, AT2R, and MAS receptor in the renal biopsy tissue were correlated with the pathologic classification of DN. Tubulointerstitial AT1R expression in patients of class IIb was significantly stronger than control samples (p < 0.05). Expression of AT2R and MAS receptors were highest with class IIb DN patients. When DN patients were treated with AT1R blocker (ARB), the expression of AT1R was downregulated (p < 0.05), and the MAS receptor was upregulated in tubular interstitial (p < 0.05). CONCLUSIONS: Our results directly observed that renal expression levels of AT1R increase during the early stages of DN, ARB reducing AT1R while increasing MAS receptor. Therefore, ARB should be used as soon as possible in patients with DN.

Effects of adding tripterygium glycosides to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on albuminuria in patients with diabetic nephropathy.

INTRODUCTION: Tripterygium glycosides (TGs) have been widely used in China to treat diabetic nephropathy (DN); however, proof of their use is scarce. The present study aimed to evaluate the effectiveness and safety of adding TGs to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). METHODS: By searching Embase, MEDLINE, Cochrane Library, SINOMED, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases, we identified previous studies that met the specific selection criteria and included them in the meta-analysis. Analyses were performed using Review Manager (version 5.3). RESULTS: Nine randomized controlled trials were included in the final meta-analysis. Patients were compared before and after treatment with ACE inhibitors or ARBs plus TGs, or ACE inhibitors or ARBs alone. The results revealed that treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in 24-h urinary total protein (UTP) levels (trial duration <2 months, mean difference [MD]: -0.25; 95% confidence interval [CI]: -0.32, -0.18; trial duration between 2 and 6 months, MD: -0.39; 95% CI: -0.44, -0.33; trial duration >6 months, MD: -2.09; 95% CI: -2.89, -1.29) compared with treatment using ACE inhibitors or ARBs alone. Additionally, ACE inhibitors or ARBs plus TGs showed better results after long-term administration. Treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in serum creatinine (SCr) compared with ACE inhibitors or ARBs alone (MD: -9.87; 95% CI: -13.76, -5.97). CONCLUSION: In patients with DN, adding TGs to ACE inhibitors or ARBs significantly lowered both the 24-h UTP and SCr levels. Therefore, ACE inhibitors or ARBs plus TGs might improve the treatment of DN in patients.

The molecular characters and antibiotic resistance of Clostridioides difficile from economic animals in China.

BACKGROUND: It has been performed worldwidely to explore the potential of animals that might be a reservoir for community associated human infections of Clostridioides difficile. Several genetically undistinguished PCR ribotypes of C. difficile from animals and human have been reported, illustrating potential transmission of C. difficile between them. Pig and calf were considered as the main origins of C. difficile with predominant RT078 and RT033, respectively. As more investigations involved, great diversity of molecular types from pig and calf were reported in Europe, North American and Australia. However, there were quite limited research on C. difficile isolates from meat animals in China, leading to non-comprehensive understanding of molecular epidemiology of C. difficile in China. RESULTS: A total of 55 C. difficile were isolated from 953 animal stool samples, within which 51 strains were from newborn dairy calf less than 7 days in Shandong Province. These isolates were divided into 3 STs and 6 RTs, of which ST11/RT126 was predominant type, and responsible for majority antibiotic resistance isolates. All the isolates were resistant to at least one tested antibiotics, however, only two multidrug resistant (MDR) isolates were identified. Furthermore, erythromycin (ERY) and clindamycin (CLI) were the two main resistant antibiotics. None of the isolates were resistant to vancomycin (VAN), metronidazole (MTZ), tetracycline (TET), and rifampin (RIF). CONCLUSIONS: In this study, we analyzed the prevalence, molecular characters and antibiotic resistance of C. difficile from calf, sheep, chicken, and pig in China. Some unique features were found here: first, RT126 not RT078 were the dominant type from baby calf, and none isolates were got from pig; second, on the whole, isolates from animals display relative lower resistant rate to these 11 tested antibiotics, compared with isolates from human in China in our previous report. Our study helps to deep understanding the situation of C. difficile from economic animals in China, and to further study the potential transmission of C. difficile between meat animals and human.

Direct Blood Culturing of Candida spp. on Solid Medium by a Rapid Enrichment Method with Magnetic Beads Coated with Recombinant Human Mannan-Binding Lectin.

A rapid and accurate method to identify the species and antibiotic resistance of Candida spp. in blood is vital to increase the survival rates of patients with bloodstream infections. However, the extremely low levels of Candida spp. in blood make rapid diagnosis by standard blood culture difficult. In this study, we constructed a direct blood culturing method (i.e., the M1 method) by a rapid enrichment method with magnetic beads coated with a recombined human mannan-binding lectin (rhMBL; i.e., M1 protein), which demonstrated much higher Candida sp.-binding capacity than that of full-length MBL expressed in vitro (i.e., M2). With the M1 method, individual colonies were obtained before the standard blood culture method for each species of Candida spp. tested at <1 CFU/ml (an average of 29 h earlier). Additionally, the clinical sensitivity of the M1 method was 90.5% compared with that of the standard blood culture method when detecting frozen plasma from patients. More significantly, the turnaround time of the M1 method for blood culture could be reduced by approximately 37 to 43 h compared with that of the standard blood culture method in clinical sample identification.

Microevolution within ST11 group Clostridioides difficile isolates through mobile genetic elements based on complete genome sequencing.

BACKGROUND: Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. RESULTS: Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. CONCLUSIONS: We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.

Antibiotic resistance of clinical isolates of Clostridioides difficile in China and its association with geographical regions and patient age.

It is known that antibiotic usage is associated with the development of Clostridioides difficile infection (CDI), especially clindamycin, third-generation cephalosporins, and fuoroquinolones. Antibiotic resistance rates to many antibiotics varies a lot by study. We performed a study focused on antibiotic resistance in clinical isolates of C. difficile from more widespread geographic regions across China. Of 319 C. difficile isolates tested against 11 antibiotics, 313 (98.1%) were resistant to at least one antibiotic. The highest rate of resistance was to ciprofloxacin, clindamycin, and erythromycin across all age groups, similar to previous studies. However, all isolates were susceptible to metronidazole and vancomycin. Overall the resistance rate to tested antibiotics was lower than other reports in China except for chloramphenicol and meropenem. Genotype ST37/RT017 in clade 4 was resistant to more antibiotics than other types. Unexpectedly, RT078 isolates in this study were susceptible to almost all tested antibiotics. In addition, the proportion of multi-drug resistant (MDR) isolates observed (17%) in this study was much lower than several European studies (up to 55%) and a previous study in China (78%). Although isolates from patients aged between 65 and 85 were more resistant to antibiotics in comparison to other age groups, MDR isolates were still detected in children below 2-years of age. The highest percentage of MDR isolates was determined in South China, an area that is most developed economically. The clade 4, RT017 (ST37) has been associated with outbreaks in Europe and North America and is responsible for most C. difficile infections (CDIs) in Asia. In addition, RT017 is often clindamycin and fluoroquinolone resistant. This study provided a relatively comprehensive description of antibiotic resistance of C. difficile in China, and further elucidates the epidemiology and antibiotic resistance of clinical isolates of C. difficile in China at a national level.