In recent years,the incidence of end-stage kidney disease(ESKD)in China has been increasing annually.Dialysis patients often experience various complications,and they are also a high-risk population for psychological disorders such as anxiety and depression.The choice of dialysis method and the dialysis process are closely related to the daily lives of the patients and their families.All these patients require a patient-centric treat-ment strategy.Before entering end-stage renal disease(ESRD)and preparing for renal replacement therapy,it is crucial for patients and their families to understand the characteristics of each renal replacement therapy.Considering clinical treatment needs,as well as the patient's living environment,work and study requirements,social reinte-gration,psychological needs,and personalized preferences,a collaborative decision-making approach is essential to choose an appropriate renal replacement therapy.With the growing preference for shared decision-making,more patients wish to undergo home dialysis treatment.Currently,due to limitations in equipment technology,economic costs,and human resources,home hemodialysis is challenging to widely adopt.Peritoneal dialysis,as a primary form of home dialysis,faces issues such as improper patient operation,poor treatment compliance,delayed prescription adjustments,and intervention for complications due to problems related to training and follow-up management.This article focuses on elucidating the shared decision-making process for ESRD patients,the prescription settings and remote patient follow-up management of automated peritoneal dialysis,which may help to collectively improve the treatment quality and social reintegration of home peritoneal dialysis patients.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

Objective To explore the relationship between serum thrombospondin-1(TSP-1),cathepsin S(Cat S),and Visfatin in patients with acute myocardial infarction(AMI)and myocardial microcirculation dis-orders after PCI and their clinical prognostic value.Methods A total of 90 AMI patients who underwent PCI treatment in the hospital from June 2021 to June 2023 were enrolled in the study.They were grouped into a microcirculation disorder group(62 cases)and a normal group(28 cases)based on their myocardial microcir-culation status.According to their postoperative prognosis,they were grouped into a good prognosis group(50 cases)and a poor prognosis group(40 cases).The risk factors of poor prognosis were analyzed by Logistic re-gression,and the predictive value of serum TSP-1,Cat S and Visfatin was analyzed by receiver operating char-acteristic(ROC)curve.Results The serum levels of TSP-1,Cat S,and Visfatin in the microcirculation disor-ders group were higher than those in the normal group,and those in the poor prognosis group were higher than those in the good prognosis group,and the differences were statistically significant(P＜0.05).Elevated levels of serum TSP-1,Cat S,and Visfatin were risk factors for poor prognosis in AMI patients after PCI(P＜0.05).The efficacy of combined detection of serum TSP-1,Cat S,and Visfatin levels for predicting the prog-nosis of AMI patients after PCI was higher than that of single detection(Zcombinedprediction-TSP-1=2.245,P=0.025,Z combined prediction-Cat S=2.101,P=0.036,Z combined prediction-Visfatin=2.252,P=0.024).Conclusion The serum levels of TSP-1,Cat S and Visfatin are obviously increased in AMI patients with myocardial microcirculation disorders after PCI,and the combination of the three has relatively high efficacy in predicting the prognosis of AMI pa-tients after PCI.

Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective:To assess the bacterial profiles and antimicrobial susceptibility patterns in uropathogens, and help to inform the empiric treatment decisions for urinary tract infection in outpatient settings.Methods:A single institutional retrospective analysis was performed on positive urine cultures from outpatient settings between January 1998 and December 2018. To analyze changes over time, trends analysis were undertaken on bacterial profiles, antimicrobial susceptibility and resistance.Results:A total of 1.172 pathogenic bacteria were isolated after exclusion of duplicate strains originated from the same patient, including 991(84.6%) Gram-negative bacterial strains and 181(15.4%) Gram-positive strains. The most common Gram-negative uropathogens were Escherichia coli (60.8%) and Klebsiella pneumonia (8.1%). Enterococcus faecalis (4.6%) was the predominant Gram-positive strain. The detection rate of Escherichia coli increased significantly, from 50.8% to 63.2% ( χ2=7.978, P=0.046), and no significant difference was observed in the distribution of major uropathogenic bacteria over the 20 years (all P>0.05). The proportion of extended-spectrum β-lactamase (ESBLs) producing strains increased significantly across the 20 years ( P<0.05). The resistance rates of Escherichia coli to amoxicillin and clavulanate potassium, aztreonam, ceftazidime, ciprofloxacin and sulbactam + cefoperazone increased significantly (all P<0.05). All the isolates sustained high susceptibility to tazobactam + piperacillin, amikacin, imipenem and nitrofurantoin (95.0%, 95.7%, 97.9% and 91.1%). Similar to those of Escherichia coli, Klebsiella pneumoniae remained a high and stable sensitivity to tazobactam+piperacillin, amikacin and imipenem during the 20 years (79.1%, 88.0% and 80.3%). However, the proportion of ESBLs producing strains increased significantly ( P<0.05). Among Gram-positive bacteria isolates, the sensitivity rates of Enterococcus faecalis to ampicillin, nitrofurantoin and penicillin G were 100.0%. No vancomycin resistant strain was detected in Gram-positive bacteria. Conclusions:From 1998 to 2018, Escherichia coli and Klebsiella pneumoniae are the most common Gram-negative bacteria uropathogens obtained in outpatient settings. Significant increases of resistance to some antimicrobial agents such as second- and third-generation cephalosporins and fluoroquinolones are observed during the 20 years and high susceptibilities to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin sustain over time. Local treatment strategies of urinary tract infections on outpatient basis should be made according to epidemiology of drug resistance and individual characteristics to control the spread and curb the prevalence of drug resistant.

Objective: To explore the clinicopathological features and the renal biopsy process of a case of IgG4-related chronic interstitial nephritis with perirenal capsule involved and review associated literature to improve the clinician's understanding for this disease and to perform a better renal biopsy. Methods: The onset, diagnosis and treatment course of the disease were described and associated literature were reviewed to summary the clinicopathologic features and key points in renal biopsy. Results: The data of the patient showed that the urine specific gravity was 1.011, with urine protein ± and urine sugar 3+. The concentration of hemoglobin was 53 g/L, serum creatinine was 1665 μmol/L, and IgG4 was 9.39 g/L. Computed tomography showed that both kidneys enlarged slightly with decreased density and low density shadow around the kidneys. On contrast-enhanced scan, irregular low-density enhancement areas were found in both kidneys, and the edge of the boundary was not clear. For the first renal biopsy, no renal parenchyma was found except mainly hyaline collagen fibrils. At the second time, 3 pieces of tissues were obtained, which showed chronic interstitial glomerulonephritis. The IgG4 positive plasma cells were about 60/HPF and the IgG4⁺/IgG⁺cells ratio was more than 40%. The diagnosis of IgG4-related chronic interstitial glomerulonephritis was confirmed. After corticosteroid treatment, the serum creatinine decreased to 502 μmol/L after the patient got rid of dialysis. Conclusions There are various manifestations of renal damage caused by IgG4-related disease. It is necessary to pay attention to the involvement of the perirenal capsule, and to balance the risk of bleeding and poor sampling in renal biopsy.

Objective:To explore the protective effect of curcumin on type 2 diabetic nephropathy rats and the possible mechanism.Methods:30 Wistar rats were randomly divided into control group,the DN group and curcumin group,10 cases in each group,rats in DN and curcumin group were fed with high fat,after that they were used the streptozotocin injection to set up DN model.In addition,rats in curcumin group were given 200 mg/kg curcumin once a day,other two group were given sodium carboxymethylcellulose half-and-half.After 12 weeks,the 24 h urine were collected at the last delivery,the blood glucose(BG),total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),serum creatinine(Scr),microalbu minuria(mAlb) were tested,the urinary albumin excretion rate(UAER) was calculated.Furthermore,rats were sacrificed,kidney mass weighed,and the kidney index(KI) was calculated.Renal cortical was fixed with polymers cresol for hematoxylin-eosin(HE) staining,renal cortical was also made renal cortex homogenate and the SOD activity,MDA were detected,the expression of nuclear factor related factor 2(Nrf2) and heme oxygenase 1(HO-1) protein in the kidney tissues was detected with Western blot detection.Results:BG,TC,TG,KI,BUN,Scr,UAER,MDA of DN group and curcumin group were significantly higher than control group,and BM,KM,SOD was significantly lower than the control group,the amplitude raising or reducing in curcumin group were less than DN group,the difference had statistical significance(P<0.05);HE staining results showed that,compared with DN group,renal tubule degeneration in curcumin group was obviously reduced,inflammatory cells infiltration was decreased significantly;Western blot results showed that expression of Nrf2 and HO-1 protein in control group were significantly lower than DN group and curcumin group,and curcumin group was significantly higher than the DN group,the differences were statistically significant(P<0.05).Conclusion:Curcumin may play a role of kidney protection through the activation of Nrf2/ARE signaling pathway to reduce oxidative stress in diabetic nephropathy rats.

OBJECTIVE: To observe the correlated serum inflammatory factor and cytokine changes in patients with coronary stent implantation, and to explore the significance of these changes.METHODS: Chinese Journal Full-Text Database was retrieved with search terms of coronary artery disease, percutaneous coronary interventions, inflammation, intimal hyperplasia, apoptosis and platelet-derived growth factor from 1995 to 2008. The language was restrained Chinese. A total of 17 literatures were collected, which concerns the changes of correlated inflammatory factor and cytokine levels and its significance. The literatures were sorted according to research object, experimental grouping,sample collection, assay method, experimental result, as well as experimental conclusion. Simultaneously, the patients received coronary stent implantation was analyzed to explore the significance of inflammatory factor and cytokine changes.RESULTS: The dynamic changed serum inflammatory factor and cytokine in patients with coronary stent implantation may be associated with the following mechanisms:①Endothelial cells were easily damaged in the balloon dilatation or stent implantation,therefore, inflammatory mediators or inflammatory factors were exposed to blood circulation, which stimulating neutrophilic granulocytes and up-regulating leukocyte adhesion molecule CD11b expression. ②Many stimulus could arise nuclear factor induced inflammatory reaction, produce interleukin 6, and stimulate C-reactive protein generation. ③The level of angiotensin Ⅱ increased at several days following stent implantation, and heightened with time prolonged, the proliferation of angiotensin Ⅱ was regulated by platelet-derived growth factor. By increasing the expression of endothelin, the synthesis of endothelin was accelerated, the proliferation and migration of vascular smooth muscle cells was promoted, which ultimately resulted in atherogenesis, balloon damage also involved in this process, which may be one of the mechanisms of restenosis.CONCLUSION: The changes of correlated inflammatory factor and cytokine can be served as inflammatory reaction indexes;moreover, soluble CD40 ligand, C-reactive protein and matrix metalloproteinase 9 may be associated with in-stent restenosis.

We immobilized carbonic anhydrase (CA) onto the surface of membrane oxygenator of polymethyl pentene (PMP) to enhance the removal of carbon dioxide in blood by two steps. We first introduced hydroxyl groups onto PMP surface by water plasma treatment, and then coupled CA onto PMP surface by using cyanate bromide (CNBr) as a crosslinker. After plasma treatment, the contact angle with water and chemical composition of PMP surface were characterized by analysis system of surface contact angle and XPS. Using p-nitrophenyl acetate (p-NPA) as a substrate, the activity, concentration, storage stability and re-usability of immobilized CA on PMP hollow fibers were studied by ultraviolet spectrophotometer. The preliminary data showed that hydroxyl groups could be introduced on the surface of PMP by water plasma treatment, and CA with catalysis activity could be successfully introduced onto PMP surface in high immobilization efficiency. The activity of covalently immobilized CA increased with the increase of concentration of CNBr, and the maximum was 73% of the theoretical activity of CA spread on PMP surface in monolayer in studied range. Covalently immobilized CA showed higher reusability compared to physically adsorbed CA, and higher storage stability compared to free CA in solution at 37 degrees C. The method would be used potentially in the membrane oxygenator to improve the capacity of removal of carbon dioxide in blood in the future.
Carbonic Anhydrases ; chemistry ; metabolism ; Enzymes, Immobilized ; Membranes, Artificial ; Oxygenators, Membrane ; Polyenes ; chemistry