Membrane P-glycoprotein expression in lymphocytes from adult patients with refractory glomerulonephritis.

OBJECTIVES: To investigate the expression of P-glycoprotein in T-cell subpopulations of lymphocytes from adult patients with refractory glomerulonephritis (GN). MATERIALS AND METHODS: Flow cytometry was used to analyze the T-cell subpopulations of lymphocytes from adult patients with refractory GN and healthy individuals. The CD243 antibody marked the membrane P-glycoprotein of immune cells. RESULTS: The mean ± standard deviation (SD) values of percentages of CD3+, CD3+CD4+, CD3+CD8+ cells in lymphocytes from patients with refractory GN were 63.94 ± 26.98, 55.16 ± 4.78, and 37.79 ± 6.01%, respectively. These values in healthy individuals were 74.88 ± 3.75, 56.60 ± 9.22, and 34.20 ± 5.21%, respectively. No significant differences were observed between the patients with refractory GN and healthy individuals. The mean ± SD values of percentages of CD3+CD4+CD243+ and CD3+CD8+CD243+ cells in the lymphocytes of patients with refractory GN were 0.14 ± 0.11 and 0.11 ± 0.07%, respectively. These values in healthy individuals were 0.05 ± 0.02 and 0.04 ± 0.02%, respectively. The difference in CD3+CD8+CD243+ percentage between patients with refractory GN and healthy individuals was significant (p = 0.0216). CONCLUSION: These findings suggest that P-glycoprotein expression on CD3+CD8+ T cells is a promising marker and a suitable target of drug resistance in patients with refractory GN.

Effects of soluble Klotho and Wnt/ß-catenin signaling pathway in vascular calcification in chronic kidney disease model rats and the intervention of Shenyuan granules.

OBJECTIVE: This study aimed to investigate the effect of the soluble Klotho (sKlotho)/Wnt/ß-catenin signaling pathway on vascular calcification in rat models of chronic kidney disease (CKD) and the intervention effect of Shenyuan granules. METHODS: Rats with 5/6 nephrectomy and high phosphorus feeding were used to establish the vascular calcification model. The rats were given gradient doses of Shenyuan granules aqueous solution and calcitriol solution by gavage for 8 weeks, which were divided into experimental group and positive control group. RESULTS: The 5/6 nephrectomy combined with high phosphorus feeding induced thoracic aortic calcification in rats. Shenyuan granules intervention increased the serum sKlotho level, inhibited the mRNA and protein expression of Wnt1, ß-catenin, and Runx2 in the thoracic aorta, and alleviated thoracic aortic media calcification in rats. CONCLUSION: Shenyuan granules may partially regulate the Wnt/ß-catenin signaling pathway via serum sKl to interfere with the expression of Runx2, thereby improving vascular calcification in CKD.

A robust NIR fluorescence-activated probe for peroxynitrite imaging in cells and mice osteoarthritis models.

Osteoarthritis (OA) is the most common type of joint disease, which is difficult to treat, but early standardized diagnosis and treatment can effectively alleviate the pain and symptoms of patients. Therefore, it is important to construct an effective tool to assist in the early diagnosis and evaluation of the therapeutic effect of OA. In this work, a near-infrared (NIR) fluorescence-activated fluorescent probe, YB-1, was constructed for the evaluation of the diagnostic and therapeutic efficacy of OA via detection and imaging of the biomarker of ONOO- in inflammatory cells and mice osteoarthritis models. YB-1 exhibited high selectivity, high sensitivity, and a high ratio yield (I668/I0) fluorescence increasing (∼30 folds). Besides, YB-1 can be used effectively to image endogenous and exogenous ONOO- in living human chondrocytes cells (TC28a2), as well as to evaluate the effect of drug (Chrysosplenol D, CD) treatment in IL-1ß-induced inflammatory cells model. Interestingly, YB-1 was available for OONO- imaging analysis in the collagenase-induced mice OA models and assessment of the effect of CD treatment in mice OA models, with good results. Thus, the newly constructed YB-1 is a powerful molecular tool for the diagnosis and treatment of OA-related diseases.

FGF2 isoforms play distinct roles in tubular epithelial-to-mesenchymal transition in diabetic nephropathy.

INTRODUCTION: The role of different isoforms of Fibroblast growth factor-2 (FGF2) in tubular epithelial-to-mesenchymal transition (EMT) in diabetic nephropathy remains unknown. We aimed to evaluate the role of FGF2 isoforms in the pathogenesis of EMT. MATERIALS AND METHODS: Western blot and immunofluorescence were used to assess the expression of FGF2 isoforms in db/db mice and high glucose-stimulated HK2 cells. The effects of specific FGF2 isoforms on EMT were explored via overexpression or knockdown of the corresponding isoform in HK2 cells cultivated in high glucose. RESULTS: Expression of low molecular weight (LMW) FGF2 was up-regulated while high molecular weight (HMW) FGF2 was down-regulated in the kidney of db/db mice and HK2 cells cultured in high glucose that underwent EMT. Overexpression of the LMW FGF2 enhanced EMT changes, while overexpression of the HMW FGF2 attenuated EMT. Knockdown of HMW FGF2 in HK2 cells promoted the EMT process. CONCLUSIONS: The expression and function of LMW and HMW FGF2 differed in the process of EMT in tubular cells. LMW FGF2 contributed to EMT, while HMW FGF2 played a protective role in the EMT process.

Imbalanced Th17/Treg in peripheral blood of adult patients with immunoglobulin A vasculitis nephritis.

INTRODUCTION: Adult immunoglobulin A vasculitis nephritis (IgAVN) was observed to be more severe than the disease in children because it tended to result in a poor prognosis. The present study analyzed the Th17/Treg cell axis in peripheral blood of adult IgAVN patients, aiming to provide new immunological viewpoints for the pathogenesis of adult IgAVN. MATERIAL AND METHODS: Th17 cell and Treg cell frequencies in peripheral blood of healthy subjects (n = 13) and adult IgAVN patients (n = 12) were analyzed by flow cytometry. Foxp3 mRNA in peripheral blood of healthy subjects and adult IgAVN patients was detected by RT-PCR. Interleukin (IL)-17 and IL-10 in peripheral blood serum of healthy subjects and adult IgAVN patients were examined by ELISA. RESULTS: The percentages of CD4+ Th17+ cells in peripheral blood of healthy subjects and adult IgAVN patients were 2.65 ±1.55% and 4.37 ±1.68% respectively. The percentages of Treg cells in peripheral blood of healthy subjects and adult IgAVN patients were 6.44 ±2.90% and 3.91 ±1.94% respectively. The ratio of Th17/Treg in adult IgAVN patients was significantly higher than that of healthy subjects (p = 0.0030). Meanwhile, the Foxp3 mRNA expression of adult IgAVN patients was significantly lower than that of healthy subjects. There was a significant difference in the ratio of IL-17/IL-10 between healthy subjects and adult IgAVN patients (p < 0.0001). A significant correlation between red blood cell distribution width (RDW) and the ratio of Th17/Treg in adult IgAVN patients was observed in Spearman correlation analysis (r = 0.6970, p = 0.0145). CONCLUSIONS: Imbalanced Th17/Treg contributed to the complex pathogenesis of adult IgAVN.

Thinner Average Choroidal Thickness Is a Risk Factor for the Onset of Diabetic Retinopathy.

PURPOSE: To analyze the relationships between choroidal thickness (CT) and diabetes mellitus (DM), diabetic retinopathy (DR), and DR severity in community residents diagnosed with type 2 DM, and to explore whether CT can improve the discriminatory ability of other risk factors to predict the incidence of DR. METHODS: A total of 1,250 type 2 DM residents and 1,027 healthy controls in Xinjing community of Shanghai participated a cross-sectional survey of eye diseases in 2016. CT was measured using swept-source optical coherence tomography. DR was classified according to the 2002 international clinical classification of DR. A total of 537 subjects with type 2 DM without DR at the 2016 survey were followed up in 2018 to investigate the 2-year incidence of DR. Receiver operating characteristic curve analysis was used to test the accuracy of different indicators in predicting the onset of DR. RESULTS: The central CT of the control, no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and PDR groups were 223.40, 216.22, 213.57, 211.91, 178.47, and 168.15 µm, respectively (p for trend <0.001), and the average CT (ACT) were 197.83, 186.94, 182.03, 178.00, 156.91, and 136.72 µm respectively (p for trend <0.001). Body mass index (BMI), DM duration, fasting blood glucose, glycosylated hemoglobin (HbA1C), and ACT were risk factors for 2-year DR incidence. For the onset of DR, as predicted by ACT, after tenfold cross validation the average area under the curve was 0.55 (p = 0.048). Addition of ACT did not improve the discriminatory ability of DM duration, BMI, glucose and HbA1C on the incidence of DR (Z = 0.48; p = 0.63). CONCLUSIONS: As the severity of DR increased, the CT of community type 2 DM patients showed a significant downward trend compared with the healthy controls. Thinner ACT was found to be a risk factor for DR incidence, but it did not improve the discriminatory ability of other risk factors to predict the incidence of DR.

Two-Year Incidence and Associated Factors of Dry Eye Among Residents in Shanghai Communities With Type 2 Diabetes Mellitus.

OBJECTIVE: To evaluate the 2-year incidence and associated factors of dry eye (DE) among community residents with type 2 diabetes mellitus (DM). METHODS: For confirmed type 2 DM residents in the Xinjing community of Shanghai in China, 2 surveys on DE and related factors were performed in 2016 and 2018. The survey content included general information, subjective symptom questionnaires, tear-film break-up time test, Schirmer I test, corneal fluorescence staining (FL), slit-lamp examination, and examination of blood and urine samples. Symptoms of depression were evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. Dry eye was diagnosed based on the diagnostic standards developed by the Asia Dry Eye Society in 2016. RESULTS: The 2-year incidence of DE among 460 type 2 DM residents was 33.7% (95% confidence interval [CI]=29.6%-38.3%). The incidence of DE significantly increased with increasing age (P<0.01). The incidence among women (35.7%) was not statistically significant compared with that of men (31.0%). In the multivariate logistic regression model, age (odds ratio [OR]=1.03, 95% CI=1.01-1.06, P=0.04), corneal sensitivity (OR=0.97, 95% CI=0.94-0.99, P=0.03), and depressive symptom score (OR=1.04, 95% CI = 1.00-1.08, P=0.04) were associated factors for the incidence of DE. In the CES-D scale, two items, "I felt that everything I did was an effort" and "I felt sad," were significantly correlated with DE onset. CONCLUSION: The incidence of DE among community residents with type 2 DM was high. Screening for DE among DM residents, especially residents with advanced age, corneal hypoesthesia, and depression, should be strengthened.

Prevalence and clinical characteristics of dry eye disease in community-based type 2 diabetic patients: the Beixinjing eye study.

BACKGROUND: This study was performed to evaluate the prevalence and clinical characteristics of dry eye disease (DED) in community-based type 2 diabetic patients and to identify the associated factors related with DED. METHODS: A total of 1360 type 2 diabetic patients in the Beixinjing community were randomly selected. All participants were given a questionnaire that assessed basic information and subjective symptoms.DED was diagnosed using the revised Japanese DED diagnostic criteria. All subjects underwent a routine ophthalmic examination, corneal sensitivity test, tear film break-up time(BUT) test, Schirmer I test, fluorescein and lissamine green staining(FL) and fundus photography. Diabetic retinopathy (DR) was graded according to the International severity scale of diabetic retinopathy and diabetic macular edema. RESULTS: Of the 1360 subjects, 238 (17.5%) were diagnosed with DED. There was a significant association between the presence of DED and higher blood glucose (P < 0.001, OR1.240) as well as higher levels of glycosylated hemoglobin HbA1c (P < 0.001, OR1.108). Corneal sensitivity was negatively correlated with the prevalence of DED (P = 0.02, OR0.973). CONCLUSIONS: The prevalence of DED in this community-based study was 17.5%, which was lower than that observed in hospital-based studies. Diabetic patients with poor metabolic control were more likely to present with DED. A dry eye examination should be added to the routine screening of diabetes.

[Tripterygium glycosides in treatment of henoch-schonlein purpura nephritis: a systematic review of randomized controlled trials].

To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG for HSPN. Two researchers independently screened the literature according to inclusion criteria and exclusion criteria, extracted data, and evaluated the quality of the literature. After completion, cross-checking was performed and Meta-analysis was performed using RevMan 5.3 software. At the same time, different outcomes of the interventions were analyzed subgroupically. A total of 46 RCTs were included, with 1 659 in the experimental group and 1 596 in the control group. All the clinical studies showed a low quality. In terms of complete remission rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.82，95%CI[1.39，2.39];RR=2.03，95%CI[1.37，2.99]），the group with TG+GC performed better than the group with GC（RR=1.46，95%CI[1.32，1.60]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.35，95%CI[0.16，0.75]）. In terms of total effective rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.44，95%CI[1.19,1.74];RR=1.30，95%CI[1.16，1.46]），the group with TG+GC performed better than the group with GC（RR=1.27，95%CI[1.21，1.34]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.60，95%CI[0.43，0.85]）. No significant difference was found between the group with TG+GC and LEF+GC（RR=0.68，95%CI[0.30，1.53]）. In terms of urinary protein, urine occult blood negative time，the group with TG performed better than the group with conventional therapy（MD=-9.00，95% CI[-11.99，-6.01];MD=-12.00，95%CI[-16.13，-7.87]），the group with TG+GC performed better than the group with GC（MD=-8.86，95%CI[-10.08，-7.64];MD=-16.24，95%CI[-23.80，-8.67]）. In terms of recurrence rate, the group with TG+GC was lower than the group with GC（RR=0.13，95%CI[0.06，0.25]）, but there were no significant difference between the group with TG and conventional therapy（RR=0.43，95%CI[0.15，1.19]）. In adverse reactions, the common adverse effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and the adverse reactions are relatively safe. Due to the generally low methodological quality of the included studies, which affected the accuracy and reliability of the result. Therefore, more high-quality, large samples and multi-center randomized controlled trials are necessary for further evidence.

Prevalence and risk factors for cardiovascular disease among chronic kidney disease patients: results from the Chinese cohort study of chronic kidney disease (C-STRIDE).

BACKGROUND: Although a high incidence of cardiovascular disease (CVD) is observed among chronic kidney disease (CKD) patients in developed countries, limited information is available about CVD prevalence and risk factors in the Chinese CKD population. The Chinese Cohort of Chronic Kidney Disease (C-STRIDE) was established to investigate the prevalence and risk factors of CVD among Chinese CKD patients. METHODS: Participants with stage 1-4 CKD (18-74 years of age) were recruited at 39 clinical centers located in 28 cities from 22 provinces of China. At entry, the socio-demographic status, medical history, anthropometric measurements and lifestyle behaviors were documented, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI creatinine equation. CVD diagnosis was based on patient self-report and review of medical records by trained staff. A multivariable logistic regression model was used to estimate the association between risk factors and CVD. RESULTS: Three thousand four hundred fifty-nine Chinese patients with pre-stage 5 CKD were enrolled, and 3168 finished all required examinations and were included in the study. In total, 40.8% of the cohort was female, with a mean age of 48.21 ± 13.70 years. The prevalence of CVD was 9.8%, and in 69.1% of the CVD cases cerebrovascular disease was observed. Multivariable analysis showed that increasing age, lower eGFR, presence of hypertension, abdominal aorta calcification and diabetes were associated with comorbid CVD among CKD patients. The odds ratios and 95% confidence intervals for these risk factors were 3.78 (2.55-5.59) for age 45-64 years and 6.07 (3.89-9.47) for age ≥65 years compared with age <45 years; 2.07 (1.28-3.34) for CKD stage 3a, 1.66 (1.00-2.62) for stage 3b, and 2.74 (1.72-4.36) for stage 4 compared with stages 1 and 2; 2.57 (1.50-4.41) for hypertension, 1.82 (1.23-2.70) for abdominal aorta calcification, and 1.70 (1.30-2.23) for diabetes, respectively. CONCLUSIONS: We reported the CVD prevalence among a CKD patient cohort and found age, hypertension, diabetes, abdominal aorta calcification and lower eGFR were independently associated with higher CVD prevalence. Prospective follow-up and longitudinal evaluations of CVD risk among CKD patients are warranted.

Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K.

BACKGROUND: Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model. METHODS: Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight). Rats were randomly divided into five groups: normal, high fat diet, diabetes mellitus, high fat diet plus RPFC prevention, and RPFC prevention before diabetes mellitus. RPFC was given to rats daily by intragastric gavage. The blood bio-chemical index and renal pathological changes were examined. The later includes hematoxylin and eosin staining, periodic acid schiff staining, and Masson trichrome staining. Protein levels of were determined by Western blot and immunohistochemical staining. mRNA levels were detected by RT-PCR. RESULTS: Rats prevented with RPFC resulted in decreasing blood glucose with corresponding vehicle treated rats. Glomerulus mesangial matrix expansion, renal capsule constriction, and renal tubular epithelial cell edema were less severe following RPFC prevention. Moreover, RPFC prevention reduced protein levels of PI3K, AKT, α-SMA and collagen IV in the kidney of diabetic rats. CONCLUSION: Combined prevention with RPFC may inhibit the PI3K/AKT pathway in the kidney, thereby prevent renal injury in diabetic rats.

Relationship between dry eye disease and myopia: A systematic review and meta-analysis.

Background/objectives: Dry eye disease (DED) and myopia are common ocular disorders. This systematic review and meta-analysis investigated the association between DED and myopia. Methods: PubMed and EMBASE were searched for articles published between 1984 and 2022. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and analysis was conducted using the DerSimonian-Laird random-effects model. Results: Of the 1,313 studies identified, 15 studies on DED and myopia were included. The meta-analysis revealed that the overall prevalence of subjective DED symptoms in the myopia population was 45.1 % (95 % confidence interval: 0.287-0.616). There was a significant association between DED and myopia. The myopia population had higher Ocular Surface Disease Index scores and shorter tear film breakup times than the non-myopia population. Additionally, the meta-regression analysis showed that spherical equivalent was significantly associated with the prevalence of DED symptoms in adults with myopia. Conclusion: Interventions to prevent DED are required in the myopia population. Enhancing patient awareness and self-management for DED, in addition to early screening and detection, is especially critical for younger populations who are at a higher risk of developing myopia.

Construction of a highly specific fluorescence "turn-on" probe for H2S detection and imaging in drug-induced live cells, zebrafish and mice arthritis models.

Quantitatively and selectively detecting the biomarker of hydrogen sulfide (H2S) in arthritis diseases is of great significance for the early diagnosis and treatment of arthritis. Modern medical studies show that H2S as a biomarker is involved in the development of inflammation. In this work, a new highly specific fluorescence "turn-on" probe JMD-H2S was tailored for H2S detection and imaging in drug-induced live cells, zebrafish and mice arthritis models, which utilized pyrazoline molecule as the fluorescence signal reporter group and 2,4-dinitrophenyl ether group (DNB) with strong intramolecular charge transfer (ICT) effect as the H2S recognition moiety and fluorescence quenching group. JMD-H2S showed a fast response time (<60 s), a large fluorescence response ratio (enhanced ∼20 folds) at I453/I0, excellent sensitivity toward H2S over other analytes, and an outstanding limit of detection (LOD) as low as 25.3 nM. In addition, JMD-H2S has been successfully applied for detecting and imaging H2S in drug-induced live cells, zebrafish, and mice arthritis models with satisfactory results, suggesting it can be used as a robust molecular tool for investigating the occurrence and development of H2S and arthritis.

Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1ß signalling pathway and gut-bone axis.

AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1ß signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.

Optimal cutoff value of the dry eye-related quality-of-life score for diagnosing dry eye disease.

This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.

Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

Ocular surface microbiota in patients with varying degrees of dry eye severity.

AIM: To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye (DE). METHODS: The single-center, prospective, case-control, observational study categorized all participants into three distinct groups: 1) control group (n=61), 2) mild DE group (n=56), and 3) moderate-to-severe DE group (n=82). Schirmer's tear secretion strips were used, and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing. RESULTS: The three groups had significant differences in alpha diversity: the control group had the highest richness (Chao1, Faith's phylogenetic diversity), the mild DE group showed the highest diversity (Shannon, Simpson), and the moderate-to-severe DE group had the lowest of the above-mentioned indices. DE severity was positively correlated with a reduction in beta diversity of the microbial community, with the moderate-to-severe DE group exhibiting the lowest beta diversity. Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each. Furthermore, the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria, as determined by random forest analysis. CONCLUSION: As DE severity worsens, microbial community diversity tends to decrease. DE development corresponds with changes in microbial constituents, primarily characterized by reduced microbial diversity and a more homogenous species composition.

Association between alkaline phosphatase/albumin ratio and the prognosis in patients with chronic kidney disease stages 1-4: results from a C-STRIDE prospective cohort study.

Background: The alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1-4 in China. Methods: Patients with CKD stages 1-4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted. Results: A total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068-1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260-2.810) but not in eGFR < 60 ml/min/1.73 m2. Conclusion: Higher APAR levels in patients with CKD stages 1-4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1-4.

Ocular Surface Microbiota in Diabetic Patients With Dry Eye Disease.

Purpose: To investigate the ocular surface (OS) commensal bacteria profiles of patients with diabetes mellitus (DM) and dry eye disease (DED). Methods: In the present study, subjects were assigned to four groups: 37 to the diabetic mellitus with dry eye disease (DM with DED) group, 22 to the diabetes mellitus (DM)-only group, 34 to the dry eye disease (DED)-only group, and 22 to the control group. Tear fluid was collected using Schirmer's tear secretion test paper. 16S ribosomal ribonucleic acid (rRNA) gene sequencing was used to analyze the bacterial microbiota. Results: The DM with DED group showed the highest operational taxonomic unit (OTU) numbers and alpha diversity and the most different beta diversity. The groups shared the four most abundant phyla, accounting for over 96% of the total abundance. At the genus level, there were 10 types of overlap in the core microbiota in the groups. They showed significant differences between the groups. Additionally, the DM with DED group and the control group showed four unique core genera, respectively. Unclassified Clostridiales and Lactobacillus were the core microbiota members of the DM with DED group, the DM-only group, and the DED-only group, but not the control group. Conclusions: In the present study, our results showed that the patients in the DM with DED group had a more complex and comprehensive ocular surface microbial composition. To the best of our knowledge, this is the first study to reveal the microbial profile of dry eye disease in patients with diabetes mellitus.

Prevalence and Correlates of Cardiovascular Calcification and Its Prognostic Effects Among Patients With Chronic Kidney Disease: Results From the C-STRIDE Study.

Background and Aims: The purpose of this study was to identify the characteristics and risk factors for cardiovascular calcification, and its relationship to prognosis, in patients with chronic kidney disease (CKD) stages 1-4. Methods: Cardiovascular calcification was evaluated at baseline by lateral abdominal radiography to detect abdominal aortic calcifications (AAC), and by echocardiogram to detect cardiac valvular calcifications (CVC), respectively. Demographic and laboratory data were collected and analyzed. Univariate and multivariable logistic regression model was used to explore the factors associated with the indicators of cardiovascular calcification, while Cox proportional hazards regression was used to examine the association between AAC/CVC and incidence of cardiovascular events and all-cause mortality. Results: A subgroup of 2,235 patients with measurement of AAC in the C-STRIDE study and a subgroup of 2,756 patients with CVC were included in the analysis. AAC was present in 206 patients (9.22%) and CVC was present in 163 patients (5.91%). Age, gender, history of cardiovascular diseases, smoking, hypertension, diabetes, levels of hemoglobin, low-density lipoprotein cholesterol, and uric acid were associated with prevalence of AAC, while only age, history of cardiovascular diseases, levels of serum albumin and low-density lipoprotein cholesterol were associated with prevalence of CVC (all p < 0.05).Survival analyses showed that cardiovascular events and all-cause mortality were significantly greater in patients with AACor with CVC (all p-values for log-rank tests <0.05). After adjustment for age, sex and estimated glomerular filtration rate (eGFR), AAC was associated with increased risk of all-cause mortality (hazard ratio = 1.67[95% confidence interval: 0.99, 2.79]), while CVC associated with that of cardiovascular events only among patients with comparatively normal eGFR (≥45 ml/min/1.73m2) (hazard ratio = 1.99 [0.98, 4.03]). Conclusion: Demographic and traditional cardiovascular risk factors were associated with cardiovascular calcification, especially AAC. AAC may be associated with risk of death for patients CKD of any severity, while CVC as a possible risk factor for cardiovascular disease only among those with mild to moderate CKD. Assessments of vascular calcification are need to be advanced to patients in the early and middle stages of chronic kidney disease and to initiate appropriate preventive measures earlier.