Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Background and aims:Radiofrequency ablation(RFA)is the first-line treatment for early-stage hepato-cellular carcinoma(HCC).However,recurrence after curative RFA remains a significant challenge for HCC patients.Although RFA induces an immune response,the anti-tumor effect is often limited by the immunosuppressive tumor microenvironment.Enhancing anti-tumor immunity is essential to improve treatment efficacy and prevent recurrence.In this study,we explore the efficacy and underlying mechanisms of the combination of RFA and anti-PD-1 in suppressing abscopal and recurrent tumors.Methods:We established a bilateral subcutaneous HCC mouse model and performed complete RFA on the right-flank tumor.Anti-PD-1 or anti-IgG was administered post-RFA.Tumor growth,immune cell profiles,and molecular pathways were assessed using flow cytometry,immunohistochemistry staining,RNA-sequencing,and Western blot.Chemokines released by the tumor were detected by ELISA.An in vivo tumor rechallenge experiment was performed after a complete tumor regression to evaluate the immune memory induced by the RFA+anti-PD-1 treatment.Results:RFA combined with anti-PD-1 significantly suppressed abscopal tumor growth and prolonged survival.Compared with RFA monotherapy,the infiltration of CD8+T cells and dendritic cells was sig-nificantly increased in the combined treatment group,while PMN-MDSCs were markedly reduced.Mechanistically,the chemokine signaling pathway and JAK-STAT signaling pathway were activated in the tumor of the RFA+anti-PD-1 group with upregulation of CXCL10 to recruit CD8+T cells.In addition,the combination therapy induced durable immune memory that inhibited rechallenge tumor outgrowth.Conclusions:Our study discovered that RFA combined with anti-PD-1 induced anti-tumor immunity to inhibit abscopal tumors and durable immune memory to prevent recurrence,suggesting RFA+anti-PD-1 as a potential therapeutic strategy for multifocal HCC and preventing recurrence.

This article reviews the benifits and challenges of nano-microspheres (NPs) in the treatment of osteoarthritis (OA). OA is a degenerative disease associated with aging, trauma, and excessive loading, with treatment strategies including basic therapy, drug therapy, reparative therapy, and reconstructive surgery. As emerging nanomaterials, NPs offer unique advantages in promoting cartilage repair due to their high surface area, excellent drug-loading capacity, and good biocompatibility. These advantages include facilitating chondrocyte generation through magnetic-mechanical control of mesenchymal stem cell microspheres and enhancing antioxidant levels using biomimetic liposomal NPs combined with glucosamine. Additionally, NPs can effectively modulate inflammatory responses, such as by inhibiting the formation of M1 macrophages and promoting their polarization to the M2 type to alleviate inflammation. Some NPs also enhance joint lubrication and relieve pain, such as hyaluronic acid-based NPs modified with choline phosphate groups. However, the application of NPs faces challenges such as high production costs, poor biocompatibility for certain types, and unknown long-term safety. Despite these challenges, with advancements in nanotechnology and a deeper understanding of the pathological mechanisms of OA, NPs are expected to provide new therapeutic approaches and more comprehensive and effective treatment options for OA patients in the future.

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

This article reviews the benifits and challenges of nano-microspheres (NPs) in the treatment of osteoarthritis (OA). OA is a degenerative disease associated with aging, trauma, and excessive loading, with treatment strategies including basic therapy, drug therapy, reparative therapy, and reconstructive surgery. As emerging nanomaterials, NPs offer unique advantages in promoting cartilage repair due to their high surface area, excellent drug-loading capacity, and good biocompatibility. These advantages include facilitating chondrocyte generation through magnetic-mechanical control of mesenchymal stem cell microspheres and enhancing antioxidant levels using biomimetic liposomal NPs combined with glucosamine. Additionally, NPs can effectively modulate inflammatory responses, such as by inhibiting the formation of M1 macrophages and promoting their polarization to the M2 type to alleviate inflammation. Some NPs also enhance joint lubrication and relieve pain, such as hyaluronic acid-based NPs modified with choline phosphate groups. However, the application of NPs faces challenges such as high production costs, poor biocompatibility for certain types, and unknown long-term safety. Despite these challenges, with advancements in nanotechnology and a deeper understanding of the pathological mechanisms of OA, NPs are expected to provide new therapeutic approaches and more comprehensive and effective treatment options for OA patients in the future.

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.

One case of COVID-19 infection secondary to pulmonary mucormycosis in a recipient of simultaneous pancreas-kidney transplantation was described. Early identification of the pathogen was achieved by metagenomic next-generation sequencing. On the basis of disease status and liver function changes, targeted treatments included intravenous amphotericin B liposome, amphotericin B nebulization& gargling and subsequently a maintenance therapy of oral posaconazole. This regimen resulted in the absorption of lung infection, stabilization of transplanted pancreas function and reduced levels of creatinine and urea as compared to pre-infection period. The therapeutic efficacy was decent.

Purpose: Reports showed that some of intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM) may also gain survival benefit undergone resection. However, the effect of the extent of LNM on prognosis and surgical indication is barely discussed. Methods: From September 1994 to November 2018, primary ICC patients undergone initial curable surgery were enrolled. Based on the extent of LNM, we divided these patients into 4 groups, including patients with no LNM (group N0), LNM to hepatoduodenal ligament or common hepatic artery (region A, group A), LNM to gastrohepatic lymph nodes for left liver ICC and periduodenal and peripancreatic lymph node for right liver ICC (region B, group B), or LNM beyond these regions (region C, group C). Multivariable Cox regression analysis was performed to identify the prognostic factors for recurrencefree survival (RFS) and overall survival (OS) in all groups. Results: A total of 133 patients were enrolled. There were 56, 21, 17, and 39 patients in groups N0, A, B, and C, respectively. There was significant difference between groups N0 and C in RFS (P < 0.001) and OS (P = 0.002). When we compared group N0 + A + B with group C, we also found that RFS (P < 0.001) and OS (P = 0.007) were significantly different. In multivariable analysis, the extent of LNM was an independent risk factor for RFS (P < 0.050). Conclusion ICC patients with the LNM to regions A and B could still achieve good prognosis with resection. Surgery should be carefully considered when LNM to region C.

Objective To investigate the distribution and drug resistance characteristics of pathogens in donors and recipients undergoing simultaneous pancreas-kidney transplantation (SPK). Methods Clinical data of 231 pairs of donors and recipients undergoing SPK were analyzed retrospectively. The pathogens of samples from donors and recipients were identified by VITEK-2 analyzer, and drug sensitivity test was performed by K-B method. The source distribution and composition ratio of pathogens in donor and recipient samples, distribution characteristics of multi-drug resistant organism, infection of recipients and drug resistance characteristics of pathogens were analyzed. Results A total of 395 strains of pathogens were cultured from 1 294 donor samples, and the detection rate was 30.53%. Gram-negative bacteria mainly consisted of klebsiella pneumoniae, Gram-positive bacteria mainly comprised staphylococcus aureus, and fungi primarily included candida albicans, respectively. In total, 2 690 strains of pathogens were cultured from 10 507 recipient samples, and the detection rate was 25.60%. Gram-negative bacteria mainly consisted of pseudomonas maltophilia, Gram-positive bacteria primarily comprised enterococcus faecalis, and fungi mainly included candida albicans, respectively. Among 395 pathogens of donors, 15 strains of methicillin-resistant staphylococcus aureus (MRSA), 16 strains of extended-spectrum β-lactamase (ESBL) positive drug-resistant bacteria, 8 strains of carbapenem-resistant pseudomonas aeruginosa (CR-PA), 21 strains of carbapenem-resistant acinetobacter baumannii (CR-AB), 2 strains of carbapenem-resistant enterobacteriaceae (CRE) and 1 strain of multiple-drug/pan-drug resistant pseudomonas aeruginosa (MDR/PDR-PA) were identified. Among 2 690 strains of recipient pathogens, 73 strains of ESBL positive drug-resistant bacteria, 44 strains of CR-PA, 31 strains of CR-AB and 3 strains of MDR/PDR-PA were detected. One recipient developed donor-derived infection, 69 cases of pneumonia, 52 cases of urinary tract infection, 35 cases of abdominal infection and 2 cases of hematogenous infection were reported within postoperative 1 year. Gram-negative bacteria were resistant to certain antibiotics. Gram-positive bacteria were sensitive to vancomycin. Fungi were sensitive to amphotericin B. Conclusions Gram-negative bacteria are the main pathogens of SPK recipients, which are resistant to certain antibiotics. Empirical use of antibiotics can be delivered before culture results are obtained. Subsequently, sensitive antibiotics should be chosen according to the culture results to improve the survival rate of SPK recipients.