FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway.

Aerobic glycolysis accelerates tumor proliferation and progression, and inhibitors or drugs targeting abnormal cancer metabolism have been developing. Cancer stem-like cells (CSCs) significantly contribute to tumor initiation, metastasis, therapy resistance, and recurrence. Formyl peptide receptor 3 (FPR3), a member of FPR family, involves in inflammation, tissue repair, and angiogenesis. However, studies in exploring the regulatory mechanisms of aerobic glycolysis and CSCs by FPR3 in gastric cancer (GC) remain unknown. Here, we demonstrated that overexpressed FPR3 suppressed glycolytic capacity and stemness of tumor cells, then inhibited GC cells proliferation. Mechanistically, FPR3 impeded cytoplasmic calcium ion flux and hindered nuclear factor of activated T cells 1 (NFATc1) nuclear translocation, leading to the transcriptional inactivation of NFATc1-binding neurogenic locus notch homolog protein 3 (NOTCH3) promoter, subsequently obstructing NOTCH3 expression and the AKT/mTORC1 signaling pathway, and ultimately downregulating glycolysis. Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.

[Research progress on risk prediction of cardiac arrest].

Cardiac arrest (CA) is a serious cardiac event, which has a high incidence and low survival rate at home and abroad. In order to predict the risk of CA in advance, a large number of studies have been conducted by relevant researchers. This paper mainly summarizes the characteristics and research status of the existing analysis and prediction of CA from three aspects: the risk prediction factors of CA, the evaluation index of risk prediction of CA and the early warning scoring system of CA. We hope it can help medical staff to understand the current progress in this field, and provide new ways and methods for predicting the risk of CA.

Manipulating the Properties of Polymer Vitrimer Nanocomposites by Designing Dual Dynamic Covalent Bonds.

Polymer vitrimer is a novel material that contains dynamic covalent bonds (DCBs) allowing it to combine the desirable characteristics of both thermoplastics and thermosets. Similar to the traditional polymer nanocomposites, introducing nanoparticles into polymer vitrimer is also an effective strategy to further enhance its properties. However, a comprehensive understanding of matrix and interfacial bond exchange reactions (BERs) to tailor the properties of polymer vitrimer nanocomposites (PVNs) is still lacking. Herein, we utilized coarse-grained molecular dynamics simulations to investigate model PVNs in which there are two different kinds of DCBs in the vitrimer matrix and at the interface. Our results show that the normalized bond autocorrelation function (Csw) confirms the independence of BERs in the vitrimer matrix and in the interface. By varying the bond swap energy barrier (ΔEsw) in the matrix ΔEswmat or in the interface ΔEswint, or in both ΔEswall, a maximum mechanical property is observed at the moderate value of ΔEswmat, ΔEswint, orΔEswall. Meanwhile, the effect of ΔEsw on the stress relaxation and the bond orientation as a function of the time under a fixed strain is well probed, which both decay more slowly at greater ΔEsw. We simulated the tension-recovery curve to examine the effect of ΔEsw on the hysteresis loss and permanent deformation of PVNs, finding an optimal value to achieve its minimum energy dissipation and maximum recovery ratio. Lastly, we investigated the efficiency of self-healing by building and removing walls from the system. Interestingly, a maximum self-healing efficiency of the stress-strain behavior is observed at moderate ΔEsw. Overall, this study provides valuable insights into the relationship between the structure and properties of PVNs, offering implications for the manipulation of their mechanical properties and enhancement of their self-healing capabilities.

Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway.

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

Gut microbiota modulate CD8+ T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX.

The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A-/-mice resulted in fewer tumors and more IFN-γ+ CD8+ T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8+ T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.

Minor protopanaxadiol type sapogenins from the alkali hydrolysate of stems-leaves of Panax notoginseng.

Two new protopanaxadiol type sapogenins, (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-al (1) and (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-oic acid (2), were isolated from the alkali hydrolysate of stems-leaves of Panax notoginseng, along with seven known analogues (3-9). Their structures were elucidated by spectroscopic analyses and single-crystal X-ray diffraction. Compound 2 and the known sapogenins 5-8 displayed weak to moderate inhibition of NO production in LPS-induced RAW264.7 macrophages with IC50 values from 44.5 to 143.6 µM, respectively.

Discovery of Natural Ah Receptor Antagonists from Salvia miltiorrhiza Bunge and Synthesis of Analogs for Tumor Immunotherapy.

IDO/TDO/Kyn/AhR signaling plays a crucial role in regulating innate and adaptive immunity, and targeting Ah receptor (AhR) inhibition can potentially redirect immune cells toward an antitumoral phenotype. Therefore, AhR is an attractive drug target for novel small molecule cancer immunotherapies. In this study, natural products tanshinolic A-D (1-4), the first adducts composed of ortho-naphthoquinone-type tanshinone and phenolic acid featuring a unique 1,4-benzodioxan hemiacetal structure, were isolated and characterized from the roots of Salvia miltiorrhiza Bunge. Luciferase reporter gene assay revealed that these adducts exhibited significant AhR inhibitory activity. A linear strategy was developed to construct a cis-3,4-disubstituted 1,4-benzodioxan hemiacetal structure. Encouragingly, in both in vitro and in vivo experiments, (±)-13e demonstrated the ability to inhibit tumor cell proliferation, promote INF-γ secretion in CD8+ T cells, and inhibit PD-1/PD-L1 signal transduction, which could exert tumor inhibition properties by inhibiting AhR activity, positioning it as a promising candidate for tumor immunotherapy.

Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes.

AIM: This study aimed to assess the pharmacokinetics of henagliflozin in dialysis patients with diabetes. METHODS: In this prospective, randomized, open-label study where 10 hemodialysis and 10 peritoneal dialysis patients with diabetes were randomized in a 1:1:1:1 ratio to oral administration of henagliflozin in doses of 5 and 10 mg/day. The pharmacokinetics of a single dose of henagliflozin on Days 1 and 2, the minimum plasma concentration (Cmin) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured. RESULTS: The mean values of Cmax were 70.2-77.0 ng/mL and 105-143 ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively; the mean values of AUCinf were 777-811 h*ng/mL and 1290-1730 h*ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively. The median Tmax values ranged from 1 to 3 h across the dose range. The mean values of T1/2 of henagliflozin were 14.1-14.5 and 16.2-21.0 h in the 5 mg and 10 mg groups, respectively. The Cmin values of the steady state in dialysis patients taking 5 mg and 10 mg of henagliflozin were 15.0 ± 4.4 ng/mL and 26.8 ± 16.3 ng/mL, respectively, which were 123.8% and 131.0% higher than those in diabetic patients with normal renal function, respectively. Henagliflozin concentration was decreased by 1.1% after hemodialysis treatment. No treatment-related serious adverse events or discontinuations occurred. CONCLUSIONS: Henagliflozin at the current recommended dosage may be safe, although it is possible to result in slight accumulation in patients on dialysis. REGISTRATION: Chinese Clinical Trial Registry number ChiCTR2200062872. The date of registration: August 22, 2022.

HOXA11 promotes lymphatic metastasis of gastric cancer via transcriptional activation of TGFß1.

Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFß1 expression and activates the TGFß1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.

Paxlovid for hospitalized COVID-19 patients with chronic kidney disease.

BACKGROUND: COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited. METHODS: A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022. The association of Paxlovid treatment with early (within 5 days post diagnosis) or late (5 days or later post diagnosis) initiation time with clinical outcomes was assessed by Cox proportional hazards regression model with time-dependent covariates. RESULT: 1279 of 2387 enrollees were included in the study. Patients with early initiation of Paxlovid had a lower all-cause death rate compared to those with late initiation or without Paxlovid treatment (P = 0.046). For the CKD patients with Charlson comorbidity index (CCI) > 7, the early initiation of Paxlovid was associated with a lower all-cause death rate compared to the later initiation or the lack of Paxlovid treatment (P = 0.041). Cox regression analyses revealed that eGFR (HR 4.21 [95%, CI 1.62-10.99]), Paxlovid treatment (0.32 [0.13-0.77]), CCI (4.32 [1.64-11.40]), ICU admission (2.65 [1.09-6.49]), hsCRP (3.88 [1.46-7.80]), chronic liver disease (4.02 [1.09-14.85]) were the independent risk factors for all-cause death for CKD patients after adjusting for demographics and biochemical indexes. CONCLUSIONS: All-cause death, invasive ventilation, and ICU admission were all significantly lowered by an early initiation of Paxlovid treatment in COVID-19 patients with severe CKD.

Cancer Immunotherapy Based on Cell Membrane-Coated Nanocomposites Augmenting cGAS/STING Activation by Efferocytosis Blockade.

Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.

Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19.

Background: Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety. Objectives: Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients. Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (p = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (p = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.

Piceatannol-3'-O-ß-d-glucopyranoside alleviates nephropathy via regulation of High mobility group B-1 (HMGB1)/Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) signalling pathway.

OBJECTIVES: Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3'-O-ß-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. METHODS: In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. KEY FINDINGS: The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKß and yet up-regulated IκBα expression by western blot analysis. CONCLUSIONS: Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS.

Clusterin regulates TRPM2 to protect against myocardial injury induced by acute myocardial infarction injury.

BACKGROUND: Clusterin and transient receptor potential melastatin 2 (TRPM2) play significant roles in acute myocardial infarction (AMI), but their interactions in AMI are unclear. METHODS: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in wild-type C57BL/6J male mice. Infarct size and myocardium pathology were evaluated after 6, 12, and 24 h of ischemia. The expression levels of clusterin and TRPM2 were measured in the myocardium. Furthermore, myocardial infarction was induced in TRPM2 knockout (TRPM2-/-) C57BL/6J male mice to evaluate the expression of clusterin. H9C2 cells with various levels of TRPM2 expression were used to analyze the effects of clusterin under hypoxic conditions. RESULTS: Following AMI, myocardial hypertrophy and TRPM2 expression increased in a time-dependent manner. In contrast, the expression of clusterin decreased in an infarct time-dependent manner. Knockout of TRPM2 protected against myocardial injury and resulted in upregulation of clusterin. In the H9C2 cells, cultured under hypoxic conditions treatment with clusterin or silencing of TRPM2 significantly increased cell viability and decreased TRPM2 expression. Treatment with clusterin protected against TRPM2 overexpression-induced damage in hypoxia-treated H9C2 cells. CONCLUSION: This study characterized the effects of clusterin on TRPM2 in AMI, which may guide development of new treatment strategies for AMI.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

Automated peritoneal dialysis in urgent-start dialysis ESRD patients: Safety and dialysis adequacy.

BACKGROUND: Recent evidence suggests that automated peritoneal dialysis (APD) might be a feasible alternative to hemodialysis (HD) in urgent-start peritoneal dialysis. METHODS: This prospective study enrolled end-stage renal disease (ESRD) patients who had started APD as an urgent-start dialysis modality at a single center. Dialysis-related complications were recorded. Dialysis adequacy and electrolytes imbalance were compared between baseline, 14 and 42 days after catheter insertion. Technique survival and patient survival were also recorded. RESULTS: A total of 36 patients were included in the study. Mean follow-up duration was 22 months. During the follow-up, 11 PD patients (30.6%) developed dialysis-related complications. Only two patients (5.6%) required re-insertion and one patients (2.8%) transfer to HD. The 2-year technique survival rate and patient survival rate were 94.4% and 97.2%, respectively. CONCLUSION: In considering safety and dialysis adequacy, APD could be a feasible dialysis modality for urgent-start dialysis in ESRD patients, using a standard procedure.

Non-clinical safety evaluation of salvianolic acid A: acute, 4-week intravenous toxicities and genotoxicity evaluations.

BACKGROUND: Toxicological problem associated with herbal medicine is a significant public health problem. Hence, it is necessary to elaborate on the safety of herbal medicine. Salvianolic acid A (SAA) is a major active compound isolated from Danshen, a popular herbal drug and medicinal food plant in China. The aim of the present study was to explore the toxicological profile of SAA. METHODS: The acute toxicity studies were performed in mice and Beagle dogs with single administration with SAA. A 4-week subchronic toxicity was test in dogs. SAA was intravenously administered at doses of 20, 80 and 300 mg/kg. Clinical observation, laboratory testing and necropsy and histopathological examination were performed. The genotoxic potential of SAA was evaluated by 2 types of genotoxicity tests: a reverse mutation test in bacteria and bone marrow micronucleus test in mice. RESULTS: In acute toxicities, the LD50 of SAA is 1161.2 mg/kg in mice. The minimum lethal dose (MLD) and maximal non-lethal dose (MNLD) of SAA were 682 mg/kg and 455 mg/kg in dogs, respectively. The approximate lethal dose range was 455-682 mg/kg. In the study of 4-week repeated-dose toxicity in dogs, focal necrosis in liver and renal tubular epithelial cell, the decrease in relative thymus weight, as well as abnormal changes in biochemical parameters, were observed in SAA 80 or 300 mg/kg group. The no observed adverse effect level (NOAEL) of SAA was 20 mg/kg. Thymus, liver and kidneys were the toxic targets. These toxic effects were transient and reversible. These results indicated that it should note examination of liver and kidney function during the administration of SAA in clinic. Furthermore, SAA had no mutagenic effect at any tested doses. CONCLUSION: These results provide new toxicological information of SAA for its clinical application and functional food consumption.

Tumor-Targeted Polydopamine-Based Nanoparticles for Multimodal Mapping Following Photothermal Therapy of Metastatic Lymph Nodes.

Purpose: Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs. Materials and Methods: PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH2)2 for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvß3 integrin-mediated endocytosis. Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice. Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.

High intraperitoneal interleukin-6 levels predict ultrafiltration (UF) insufficiency in peritoneal dialysis patients: A prospective cohort study.

Introduction: UF insufficiency is a major limitation in PD efficiency and sustainability. Our study object to investigate the efficacy of intraperitoneal inflammation marker, IL-6 level as a predictor of UF insufficiency in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Stable prevalent CAPD patients were enrolled in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6 AR). Patients were divided into two groups according to the median of IL-6 AR and prospectively followed up until death, transfer to permanent HD, recovery of renal function, kidney transplantation, transfer to other centers, lost to follow-up or to the end of study (January 31, 2021). Factors associated with UF capacity as well as dialysate IL-6 AR were assessed by multivariable linear regression. Cox proportional hazards model was used to examine the association between dialysate IL-6 AR and UF insufficiency. Results: A total of 291 PD patients were enrolled, including 148 males (51%) with a mean age of 56.6 ± 14.1 years and a median PD duration of 33.4 (12.7-57.5) months. No correlation was found between dialysate IL-6 AR and UF capacity at baseline. PD duration was found positively correlated with baseline dialysate IL-6 AR, while 24h urine volume was negatively correlated with baseline dialysate IL-6 AR (P < 0.05). By the end of study, UF insufficiency was observed in 56 (19.2%) patients. Patients in the high IL-6 AR group showed a significantly inferior UF insufficiency-free survival when compared with their counterparts in the low IL-6 AR group (P = 0.001). In the multivariate Cox regression analysis, after adjusting for DM, previous peritonitis episode and 24h urine volume, higher baseline dialysate IL-6 AR (HR 3.639, 95% CI 1.776-7.456, P = 0.002) were associated with an increased risk of UF insufficiency. The area under the ROC curve (AUC) for baseline IL-6 AR to predict UF insufficiency was 0.663 (95% CI, 0.580-0.746; P < 0.001). Conclusion: Our study suggested that the dialysate IL-6 AR could be a potential predictor of UF insufficiency in patients undergoing PD.

Automated peritoneal dialysis as a cost-effective urgent-start dialysis option for ESRD patients: A prospective cohort study.

BACKGROUND: Several studies have reported the feasibility of urgent-start peritoneal dialysis (PD) as an alternative to hemodialysis (HD) using a central venous catheter (CVC). However, the cost-effectiveness of automated peritoneal dialysis (APD) as an urgent-start dialysis modality has not been directly evaluated, especially in China. METHODS: We prospectively enrolled patients with end-stage renal disease (ESRD) who required urgent-start dialysis at a single center from March 2019 to November 2020. Patients were grouped according to their urgent-start dialysis modality (APD and HD). Urgent-start dialysis conducted until 14 days after PD catheter insertion. Then, PD was maintained. Each patient was followed until July 2021 or death or loss to follow-up. The primary outcome was the incidence of short-term dialysis-related complications. The secondary outcome was the cost and duration of the initial hospitalization. Technique survival, peritonitis-free or bacteriamia-free survival and patient survival were also compared. RESULTS: Sixty-eight patients were included in the study, of whom 36 (52.9%) patients were in APD group. Mean follow-up duration was 20.1 months. Compared with the HD group, the APD group had significantly fewer short-term dialysis-related complications. The cost of initial hospitalization was also significantly lower in APD patients. There was no significant difference between APD and HD patients with respect to duration of the initial hospitalization, technique survival rate, peritonitis-free or bacteriemia-free survival rate, and patient survival rate. CONCLUSION: Among ESRD patients with an urgent need for dialysis, APD as urgent-start dialysis modality, compared with HD using a CVC, resulted in fewer short-term dialysis-related complications and lower cost.