Association between serum 25-hydroxyvitamin D level and inflammatory markers in hemodialysis-treated patients.

OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level with novel inflammatory markers in hemodialysis-treated patients. METHODS: A total of 167 maintenance hemodialysis-treated patients were enrolled in this cross-sectional study. The patients were divided into vitamin D deficiency (a serum 25(OH)D level <20 ng/mL) and nondeficiency (a serum 25(OH)D level ≥20 ng/mL) groups. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) were calculated by the complete blood cell count. The relationship between 25(OH)D level with other parameters was assessed by bivariate correlation analysis and linear regression analysis. RESULTS: There were significant differences between the two groups in terms of age, diabetes, levels of albumin, creatinine, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as NLR and MLR (p = .004, p = .031, p < .001, p = .043, p = .008, p = .006, p = .002, and p < .001, respectively). There exist negative correlations between serum 25(OH)D level with age, diabetes, alkaline phosphatase level, NLR, PLR, and MLR (p = .002, p = .002, p = .037, p = .001, p = .041, and p < .001, respectively) and positive correlations between serum 25(OH)D level with albumin level, creatinine level, phosphorus level, HDL-C, and LDL-C (p < .001, p < .001, p = .013, p = .02, p = .002, respectively). Multiple analysis results showed that sex, diabetes, albumin level and NLR were independently associated with serum 25(OH)D level (p = .021, p = .015, p = .033, and p = .041, respectively). High values of NLR and MLR were associated with patients with serum 25(OH)D deficiency. There were negative interplays between serum 25(OH) D level with NLR, PLR, and MLR and also an independent association between serum 25(OH) D level with NLR. CONCLUSION: Collectively, serum 25(OH)D level has a negative correlation with inflammatory markers.

Recent advances in cotton fabric-based photocatalytic composites for the degradation of organic contaminants.

Cotton is one of the oldest and most widely used natural fibers in the world. It enables a wide range of applications due to its excellent moisture absorption, thermal insulation, heat resistance, and durability. Benefiting from current developments in textile technology and materials science, people are constantly seeking more comfortable, more beautiful and more versatile cotton fabrics. As the second skin of body, clothing not only provides the basic needs of wear but also increases the protection of body against different environmental stimuli. In this article, a comprehensive review is proposed regarding research activities of systematically summarise the development and research of cotton fabric-based photocatalytic composites for the degradation of organic contaminants in the area of self-cleaning, degradation of gaseous contaminants, pathogenic bacteria or viruses, and chemical warfare agents. Specifically, we begin with a brief exposition of the background and significance of cotton fabric-based photocatalytic composites. Next, a systematical review on cotton fabric-based photocatalytic composites is provided according to their mechanisms and advanced applications. Finally, a simple summary and analysis concludes the current limitations and future directions in these composites for the degradation of organic contaminants.

Effect of Neoadjuvant Immunotherapy Combined with Chemotherapy on Pulmonary Function and Postoperative Pulmonary Complications in Esophageal Cancer: A Retrospective Study.

BACKGROUND: Neoadjuvant immunotherapy, targeting the PD-1 or PD-L1, combined with chemotherapy (NICT), can improve the radical resection and survival rates for locally advanced EC. However, it may impair pulmonary function, and the effect of NICT on pulmonary function and postoperative pulmonary complications in EC patients remains unknown. This study aimed to investigate whether NICT can affect pulmonary functions and postoperative pulmonary complications in EC patients. METHODS: The study retrospectively recruited 220 EC patients who received NICT at the Department of Esophageal Cancer in Tianjin Medical University Cancer Institute & Hospital from January 2021 to June 2022. Changes in pulmonary function before and after NICT were compared. Logistic regression analysis was performed to analyze the correlations of pulmonary functions and clinical characteristics with postoperative pulmonary complications, respectively. RESULTS: The FEV1% pred, FVC, FVC% pred, and FEV1/FVC% significantly increased after NICT, with a P-value of 0.018, 0.005, 0.001, and 0.036, respectively. In contrast, there was a significant decline in the DLCO (8.92 ± 2.34 L before NICT vs. 7.79 ± 2.30 L after NICT; P < 0.05) and DLCO% pred (102.97 ± 26.22% before NICT vs. 90.18 ± 25.04% after NICT; P < 0.05). High DLCO and DLCO% pred at baseline levels were risk factors for DLCO reduction in EC patients after NICT. Advanced age, smoking history, FEV1% pred after NICT, and FVC% pred baseline and after therapy were risk factors for postoperative pulmonary complications, with a P-value of 0.043, 0.038, 0.048, 0.034, and 0.004, respectively. Although the DLCO level decreased after NICT, it did not increase the incidence of postoperative pulmonary complications. CONCLUSION: NICT may improve pulmonary ventilation function but also lead to a decrease in DLCO and DLCO% pred in EC patients. Nevertheless, the decreased DLCO after NICT did not increase the risk of postoperative pulmonary complications.

Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation.

OBJECTIVE: The exosomal cargo mainly comprises proteins, lipids, and microRNAs (miRNAs). Among these, miRNAs undertake multiple biological effects of exosomes (Exos). Some stem cell-derived exosomal miRNAs have shown the potential to treat diabetic nephropathy (DN). However, there is little research into the therapeutic effects of adipose-derived stem cell (ADSC)-derived exosomal miRNAs on DN. We aimed to explore the potential of miR-204-modified ADSC-derived Exos to mitigate DN. METHODS: Exos were extracted and identified from ADSCs. Histopathological injury, oxidative stress (OS), mitochondrial function, cell viability, and apoptosis were assessed to explore the effects of ADSC-derived Exos on DN. For mechanism exploration, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure miR-204, methyltransferase (METTL3, METTL14, and METTL7A), and CIDEC. Also, CIDEC m6A methylation and miR-204-METTL7A, and METTL7A-CIDEC interactions were determined. RESULTS: Initially, OS-induced mitochondrial dysfunction was observed in DN rats. ADSC-derived Exos inhibited histopathological injury, cell apoptosis, OS, and mitochondrial dysfunction in DN rats. The similar therapeutic effects of ADSC-derived Exos were detected in the in vitro model. Intriguingly, miR-204 was released by ADSC-derived Exos and its upregulation enhanced the anti-DN effects of Exos. Mechanically, miR-204 reduced METTL7A expression to CIDEC m6A methylation, thus suppressing OS and mitochondrial dysfunction. CONCLUSIONS: ADSC-derived exosomal miR-204 rescued OS-induced mitochondrial dysfunction by inhibiting METTL7A-mediated CIDEC m6A methylation. This study first revealed the significant role of ADSC-derived exosomal miR-204 in DN, paving the way for the development of novel therapeutic strategies to improve the clinical outcomes of DN patients.

Applications of waste polyethylene terephthalate (PET) based nanostructured materials: A review.

While polyethylene terephthalate (PET) has enjoyed widespread use, a large volume of plastic waste has also been produced as a result, which is detrimental to the environment. Traditional treatment of plastic waste, such as landfilling and incinerating waste, causes environmental pollution and poses risks to public health. Recycling PET waste into useful chemicals or upcycling the waste into high value-added materials can be remedies. This review first provides a brief introduction of the synthesis, structure, properties, and applications of virgin PET. Then the conversion process of waste PET into high value-added materials for different applications are introduced. The conversion mechanisms (including degradation, recycling and upcycling) are detailed. The advanced applications of these upgraded materials in energy storage devices (supercapacitors, lithium-ion batteries, and microbial fuel cells), and for water treatment (to remove dyes, heavy metals, and antibiotics), environmental remediation (for air filtration, CO2 adsorption, and oil removal) and catalysis (to produce H2, photoreduce CO2, and remove toxic chemicals) are discussed at length. In general, this review details the exploration of advanced technologies for the transformation of waste PET into nanostructured materials for various applications, and provides insights into the role of high value-added waste products in sustainability and economic development.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

A nomogram predicting the histologic activity of lupus nephritis from clinical parameters.

BACKGROUND: The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN. METHODS: The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2. CONCLUSIONS: The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.

Clinical Predictive Value of Phospholipase A2 Receptor Gene Polymorphism Combined with Subclass of Immunoglobulin G in Renal Tissues for Membranous Nephropathy.

Context: Idiopathic membranous nephropathy (IMN) is a common pathologic type of nephrotic syndrome, and the level of the M-type phospholipase A2 receptor (PLA2R) antibody can serve as one index for predicting its progression and prognosis. However, patients with the same level can show great differences in their responses and prognoses. Objectives: The study aimed to explore the relationship between a PLA2R gene polymorphism combined with an immunoglobulin G (IgG) subclass in renal tissues and patients' responses to immunosuppressive therapy, to determine the clinical prognosis for IMN patients. Design: This is a prospective study. Patients with new onset membranous nephropathy who need treatment were selected and grouped according to the curative effect after 6 months of treatment. Setting: The study took place at the First Affiliated Hospital of Ningbo University, Ningbo, China. Participants: Participants were 60 patients with IMN, who had been admitted in the hospital between January 1, 2021 and June 30, 2022. Intervention: Participants first received standard immunosuppressive therapy for six months. The research team then clinically divided participants into two groups: (1) a remission group with 32 participants and (2) a nonremission group with 28 participants. Outcome Measures: The research team: (1) compared the groups, summarizing the demographic and clinical differences between the groups, (2) compared the PLA2R antibody titers at baseline and postintervention between the groups, (3) analyzed the genotyping of the PLA2R single nucleotide polymorphisms (SNPs) rs35771982 and rs4664308 loci as well as the human leukocyte antigen (HLA)-DQA1 SNP rs2187668 locus, and (4) compared the subclass IgG and PLA2R depositions in the renal tissues between the groups. Results: Compared with the remission group, the nonremission group included significantly more males (P < .05), was significantly older (P < .05), had significantly more participants with a BMI of >25 (P < .05), and included significantly more participants with a positive IgG3 (P < .01) than the remission group. The remission group's PLA2R antibody titers at baseline and postintervention weren't significantly different from those of the nonremission group. Postintervention, 24 participants in the remission group had a negative conversion of PLA2R antibodies, and 22 in the nonremission group had a negative conversion. The genotyping of the PLA2R SNP rs4664308 and the HLA-DQA1 SNP rs2187668 loci showed no relationship to the remission rate. The GC genotype on the PLA2R SNPrs35771982 locus may be a risk factor for a poor prognosis for IMN patients. Moreover, the patients with a positive IgG3 in the renal tissues and the GC genotype on the PLA2R SNPrs35771982 locus exhibited a poor response to immunosuppressive therapy and could need intensive treatment. Conclusions: The PLA2R gene polymorphism combined with the IgG subclass can predict the sensitivity of IMN patients to immunosuppressive therapy.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

The efficacy and safety of an improved percutaneous peritoneal dialysis catheter placement technique in urgent-start peritoneal dialysis patients: a retrospective cohort study.

BACKGROUND: Urgent-start peritoneal dialysis has high catheterization skill requirements and that early complications. The optimal catheter placement method remains debatable in urgent-start peritoneal dialysis patients. Safe and effective peritoneal dialysis catheterization is needed in clinical work. METHODS: We retrospectively analyzed the data of 34 patients diagnosed with end-stage renal disease who opt for peritoneal dialysis, 19 males and 15 females, with an average age of 62.3±14.7 years, peritoneal dialysis catheter implantation was completed by the improved percutaneous catheterization technique. They were followed for 6 months, early and late complications were observed and the survival rate of the catheter technique was calculated. RESULTS: All 34 patients diagnosed with end-stage renal disease successfully underwent catheter placement using the improved percutaneous technique; the catheterization success rate was 100%. No severe organ injuries, such as intestinal perforation and bladder perforation, occurred intraoperatively. Peritoneal dialysis was started immediately after surgery. The early complications included one case of leakage, one case of omental wrapping, and six cases of rectus abdominis hemorrhage. The late complications included one case of pleuro-abdominal fistula and two cases of peritonitis. The 6-month technical survival rate for the catheter was 94.1% (32/34). Compared to previously reported studies, this technique may reduce leakage and early catheter dysfunction, and improve the technical survival of catheters. CONCLUSIONS: The improved percutaneous peritoneal dialysis catheter placement technique might be an effective and safe method for urgent­start peritoneal dialysis patients.

The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice.

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

The safety and urate-lowering efficacy of febuxostat in patients undergoing peritoneal dialysis: a retrospective single-arm cohort study of 84 patients.

BACKGROUND: Studies have shown that hyperuricemia (HUA) is an independent risk factor for all-cause death and residual kidney function loss in peritoneal dialysis (PD) patients. The control of blood uric acid (UA) is an important link to improve the prognosis of end-stage renal disease (ESRD). As a therapeutic drug for HUA, febuxostat is rarely studied in PD patients. The purpose of our study is to investigate the safety, efficacy, and effect on residual renal function (RRF) of febuxostat in patients undergoing PD. METHODS: This is a retrospective single-arm cohort study. During the study period which from September 2016 to November 2020, 191 patients underwent PD at this hospital. Among these patients, 84 were administrated for over a period of 3 months and were eventually included. These 84 patients (51 males and 33 females; average age: 55.18 years) were undergoing PD complicated with HUA or gout who received febuxostat during a regular follow-up from January 2018 to November 2020. Serum UA (sUA) levels, blood routine, liver function, and RRF were compared before and after febuxostat administration. Adverse events (AEs) resulting from febuxostat treatment were collected from medical records. RESULTS: All 84 patients were administered febuxostat for over 3 months, including 39 for over 6 months and 26 for over 12 months. Some 60 patients were treated with febuxostat dose of 20 mg/day and the remaining 24 patients received 40 mg/day. Compared with pretreatment level, the mean sUA level was observed to be markedly reduced at 1 month after febuxostat administration (320.2±87.27 vs. 498.8±81.47 µmol/L, P<0.0001) and at 3 months (291.6±82.66 vs. 498.8±81.47 µmol/L, P<0.0001) and subsequently remained at a significantly low level for 12 months. Only 5 patients stopped febuxostat because of its associated AEs. An initial dose of 40 mg/day was associated with a higher rate of AEs compared with dose of 20 mg/day (25% vs. 18.33%, respectively). After febuxostat treatment, no significant differences were observed between RRF in the two groups. CONCLUSIONS: Febuxostat may be safe and efficient in patients undergoing PD and may not impair RRF. Febuxostat administration at dose of 20 mg/day may be an appropriate dose for patients undergoing PD.

The Effect of Hydroxychloroquine on Residual Proteinuria in Patients With Immunoglobulin A Nephropathy: A Retrospective Study Based on Propensity Score Matching.

Background: There is insufficient evidence to support the use of hydroxychloroquine (HCQ) in Immunoglobulin A nephropathy (IgAN) patients with high residual proteinuria in spite of 6-month supportive treatment combined with corticosteroids (P) and/or immunosuppressives (IM). This study aims to explore the effect of HCQ on residual proteinuria in IgAN. Materials and Methods: This is a retrospective study. IgAN patients who had residual proteinuria ≥0.3 g/24 h after 6-month treatment by renin-angiotensin system inhibitors (RASI) + P ± IM were included. Groups were divided based on the different regimens and then matched by the propensity score matching method. The primary outcome was defined as the cumulative frequency of residual proteinuria reduction ≥30%. Results: RASI (n = 183), HCQ + RASI (n = 59), RASI + P ± IM (n = 145), and HCQ + RASI + P ± IM (n = 38) groups were included. HCQ + RASI group had a higher level of residual proteinuria and a worse renal function than those in the RASI group. The renal function was worse in the HCQ + RASI + P ± IM group than that in the control group, but residual proteinuria levels were similar. After matching, there were 40 patients in the first two groups and 29 patients in the latter two groups, respectively. The cumulative frequency of residual proteinuria reduction ≥30% in HCQ + RASI + P ± IM group was higher than that in control group (86.2% vs. 62.1%, χ2 = 6.397, p = 0.011). HCQ combination treatment was one of independent factors. Conclusion: The addition of HCQ treatment can effectively reduce the residual proteinuria in IgAN patients previously treated with supportive treatment combined with P and IM treatment and the cumulative frequency of effective reduction of residual proteinuria can reach 86.2%.

Long-term efficacy, safety, and medication compliance of roxadustat on peritoneal dialysis patients with renal anemia affected by the COVID-19 pandemic: a retrospective study.

BACKGROUND: Current studies have limited data on long-term treatment safety and medication compliance of roxadustat for renal anemia in peritoneal dialysis (PD) patients. We aimed to analyze the long-term efficacy, safety, and medication compliance of roxadustat in the treatment of renal anemia in patients with PD who discontinued recombinant human erythropoietin (rhEPO) treatment due to the corona virus disease 2019 (COVID-19) outbreak. METHODS: We retrospectively collected patients who were switched from rhEPO to roxadustat in our hospital due to the pandemic. The criteria for subject inclusion: aged >18 years with a dialysis vintage >3 months, without malignant tumor, no severe cardiovascular and cerebrovascular diseases, and not combined hemodialysis. Patients were followed up until the end of December 2021. Hemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) were recorded at baseline, month 1-12 and month 20, and iron parameters at baseline, 3, 6, 9, 12, and 20 months were collected. The Morisky Medication Adherence Scale-8 (MMAS-8) was used to score medication compliance during rhEPO treatment and roxadustat treatment, and adverse reactions occurred during treatment were collected. The efficacy and medication compliance of roxadustat were analyzed using Wilcoxon rank sum test or t-test. RESULTS: The median follow-up time was 21.1 (20.6, 21.7) months. After 1 month of treatment, the Hb level was significantly increased by 9.4 g/L (95% CI: 6.0-12.8 g/L) compared with the baseline, follow up at 20 months showed the Hb level had remained stable, increased by 20.7 g/L (95% CI: 15.9-25.4 g/L) compared with before treatment. At the beginning of treatment, total iron binding capacity increased, transferrin saturation and serum ferritin decreased, serum iron remained stable during treatment. During roxadustat treatment, no patient discontinued treatment due to the pandemic, and the Morisky score was improved compared with that during rhEPO treatment [5.75 (4.25, 6.00) vs. 6.75 (5.75, 7.00), P=0.000]. There were no serious adverse events associated with roxadustat were observed. CONCLUSIONS: Roxadustat can effectively improve anemia and had good tolerance in patients undergoing PD who have difficult using rhEPO, and the medication compliance was better than rhEPO during the COVID-19.

The clinical application of metagenomic next-generation sequencing in infectious diseases at a tertiary hospital in China.

Background: Compared with traditional diagnostic methods (TDMs), rapid diagnostic methods for infectious diseases (IDs) are urgently needed. Metagenomic next-generation sequencing (mNGS) has emerged as a promising diagnostic technology for clinical infections. Methods: This retrospective observational study was performed at a tertiary hospital in China between May 2019 and August 2022. The chi-square test was used to compare the sensitivity and specificity of mNGS and TDMs. We also performed a subgroup analysis of the different pathogens and samples. Results: A total of 435 patients with clinical suspicion of infection were enrolled and 372 (85.5%) patients were finally categorized as the ID group. The overall sensitivity of mNGS was significantly higher than that of the TDMs (59.7% vs. 30.1%, P < 0.05). However, there was no significant difference in the overall specificity between the two methods (83.3% vs. 89.6%, P = 0.37). In patients with identified pathogens, the positive rates of mNGS for detecting bacteria (88.7%), fungi (87.9%), viruses (96.9%), and Nontuberculous mycobacteria (NTM; 100%) were significantly higher than those of TDMs (P < 0.05). The positive rate of mNGS for detecting Mycobacterium tuberculosis was not superior to that of TDMs (77.3% vs. 54.5%, P = 0.11). The sensitivity rates of mNGS for pathogen identification in bronchoalveolar lavage fluid, blood, cerebrospinal fluid, pleural fluid, and tissue were 72.6%, 39.3%, 37.5%, 35.0% and 80.0%, respectively. Conclusion: With the potential for screening multiple clinical samples, mNGS has an overall advantage over TDMs. It can effectively identify pathogens, especially those that are difficult to identify using TDMs, such as NTM, chlamydia, and parasites.

From "feeling" to "seeing": modification of the percutaneous peritoneal dialysis catheter insertion with an optical puncture system.

PURPOSE: Blind insertion limits the application of percutaneous peritoneal dialysis (PD) catheter placement. In this study, we first described the use of an optical puncture system in the PD catheter insertion, and investigated the feasibility and advantages of this modified technique. METHODS: This retrospective study included 65 patients with chronic kidney disease stage 5 (CKD5) who received ultrasound-guided percutaneous PD catheter insertion with or without optical puncture system assistance between June 2018 and July 2019. The patients' characteristics as well as the surgical outcomes and complications were compared between the modified group and the routine percutaneous insertion group. RESULTS: Twenty-five patients underwent optical puncture system assistant insertion, whereas 40 patients received routine percutaneous insertion. More patients had previous abdominal surgical histories in the modified group than those in the routine group (24.0% vs. 5.0%, p = 0.047). The time of accessing to the abdominal cavity was significantly shorter in the modified group (median [IQR]; 1.1 min [0.8-1.3] vs. 5.0 min [4.0-6.0]; p < 0.001). Meanwhile, the time of the whole procedure was also significantly shorter in the modified group (median [IQR]; 26.0 min [25.0-29.0] vs. 33.0 min [29.0-35.0]; p < 0.001). None of the patient in the modified group, while two patients (5.0%) in the routine group converted to open procedure. There were no significant differences in the short and long postoperative complications between the two groups. CONCLUSIONS: The operation of ultrasound-guided PD catheter placement with the optical puncture system is easy, safe, fast and accurate, whereby the PD catheter can be implanted percutaneously and visually under local anesthesia with minimal procedure-related complications. The visible puncture of the optical puncture system may facilitate ultrasound-guided percutaneous PD catheter insertion in patients with obesity and previous abdominal surgeries.

Perturbations in mitochondrial dynamics by p66Shc lead to renal tubular oxidative injury in human diabetic nephropathy.

Renal tubular injury is increasingly being recognized as an early characteristic of diabetic nephropathy (DN). Mitochondrial dynamic alterations and redox protein p66Shc-mediated oxidative stress are both critical for ensuing diabetic tubular cell injury and apoptosis; whether these two processes are interlinked remains unclear. In the present study, we observed changes in mitochondrial morphology and expression of associated proteins in tubules of patients with DN. We demonstrated mitochondrial fragmentation as an important pathogenic feature of tubular cell injury that is linked to oxidative stress and p66Shc up-regulation. In renal proximal tubular cells, alterations in mitochondrial dynamics and expression of fission-fusion proteins were observed under high glucose (HG) ambience, along with p66Shc Ser36 phosphorylation. Gene ablation of p66Shc alleviated HG-induced mitochondrial fragmentation, down-regulated Fis1 and reduced p66Shc-Fis1 binding, increased Mfn1 expression, and disrupted interactions between Mfn1 and proapoptotic Bak. Overexpression of p66Shc exacerbated these changes, whereas overexpression of dominant-negative p66Shc Ser36 mutant had a marginal effect under HG, indicating that p66Shc phosphorylation as a prerequisite in the modulation of mitochondrial dynamics. Disrupted mitochondrial dynamics and enhanced Mfn1-Bak interactions modulated by p66Shc led to loss of mitochondrial voltage potential, cytochrome C release, excessive ROS generation, and apoptosis. Taken together, these results link p66Shc to mitochondrial dynamic alterations in the pathogenesis of DN and unveil a novel mechanism by which p66Shc mediates HG-induced mitochondrial fragmentation and proapoptotic signaling that results in oxidative injury and apoptosis in the tubular compartment in human diabetic nephropathy.

STIM1 and TRPV4 regulate fluid flow-induced calcium oscillation at early and late stages of osteoclast differentiation.

Bone resorption is mainly mediated by osteoclasts (OCs), whose formation and function are regulated by intracellular Ca2+ oscillation. Our previous studies demonstrated that fluid shear stress (FSS) lead to Ca2+ oscillation through mechanosensitive cation-selective channels. However, the specific channels responsible for this FSS-induced Ca2+ oscillation remain unknown. In the present study, we examined the expression of several Ca2+ channels in OCs, including STIM1, ORAI1, TRPV1, TRPV4, TRPV5, and TRPV6, by western blotting and reverse transcription-polymerase chain reaction. The results showed that STIM1 was highly expressed in early stage OCs, while TRPV4 was highly expressed in late stage OCs. We observed intracellular Ca2+ responses in OCs that were mechanically stimulated by FSS. When we blocked STIM1-dependent store-operated Ca2+ entry or inhibited TRPV4 using siRNA or drug inhibition, FSS-induced Ca2+ oscillations were almost undetectable in early and late stage OCs, respectively. These results indicate that STIM1 and TRPV4 act as mechanical transduction channels for OCs during the early and late differentiation stages, respectively, suggesting that these calcium channel could serve as markers of osteoclastogenesis or bone resorption.

Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma.

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.