Objective To analyze the characteristics of adverse events of disposable hemoperfusion devices in real-world clinical practice using multicenter data,and to investigate the influencing factors of hypotension,providing evidence for the safe clinical use of these devices.Methods An observational study was conducted involving patients who received disposable hemoperfusion therapy across 17 sentinel hospitals in China from June 2022 to July 2024.Device-related adverse events were monitored and analyzed.Descriptive statistics,Firth's Logistic regression model,and balanced random forest model were applied to systematically evaluate the manifestations of adverse events and the risk factors for the occurrence of hypotension.Results A total of 17,824 usage records were included.In the sentinel hospital data,hypotension[0.19％,95％CI(0.14％,0.27％)]and hemoperfusion occlusion[0.13％,95％CI(0.09％,0.19％)]occupied the highest incidence rate.The Firth's Logistic regression analysis revealed that end-stage renal disease with comorbidities significantly increased hypotension risk(OR=77.324),while no prior medical history was protective(OR=0.061).Stepwise blood purification modalities(hemoperfusion alone or sequential hemoperfusion-hemodialysis)significantly reduced the hypotension risk compared with simultaneous hemoperfusion and hemodialysis(OR=0.003).The random forest model further confirmed that blood purification modality was the strongest influencing factor for hypotension.Conclusion In real-world clinical settings,hypotension and device occlusion were the predominant adverse events,with blood purification modality critically influencing hypotension risk.Stepwise blood purification is recommended to mitigate this risk.Enhancing clinical operating procedures and device design is essential to improve overall treatment safety.

Objective To analyze the characteristics of adverse events of disposable hemoperfusion devices in real-world clinical practice using multicenter data,and to investigate the influencing factors of hypotension,providing evidence for the safe clinical use of these devices.Methods An observational study was conducted involving patients who received disposable hemoperfusion therapy across 17 sentinel hospitals in China from June 2022 to July 2024.Device-related adverse events were monitored and analyzed.Descriptive statistics,Firth's Logistic regression model,and balanced random forest model were applied to systematically evaluate the manifestations of adverse events and the risk factors for the occurrence of hypotension.Results A total of 17,824 usage records were included.In the sentinel hospital data,hypotension[0.19％,95％CI(0.14％,0.27％)]and hemoperfusion occlusion[0.13％,95％CI(0.09％,0.19％)]occupied the highest incidence rate.The Firth's Logistic regression analysis revealed that end-stage renal disease with comorbidities significantly increased hypotension risk(OR=77.324),while no prior medical history was protective(OR=0.061).Stepwise blood purification modalities(hemoperfusion alone or sequential hemoperfusion-hemodialysis)significantly reduced the hypotension risk compared with simultaneous hemoperfusion and hemodialysis(OR=0.003).The random forest model further confirmed that blood purification modality was the strongest influencing factor for hypotension.Conclusion In real-world clinical settings,hypotension and device occlusion were the predominant adverse events,with blood purification modality critically influencing hypotension risk.Stepwise blood purification is recommended to mitigate this risk.Enhancing clinical operating procedures and device design is essential to improve overall treatment safety.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Objective:To investigate the clinical features and prognosis of patients with pancreatic metastasis from clear cell renal cell carcinoma(CCRCC).Methods:From Jan 2000 to May 2020, the clinical data of patients pathologically diagnosed as CCRCC with pancreatic metastasis and admitted in Cancer Institute and Hospital of Tianjin Medical University were analyzed retrospectively. The gender, age, metastasis time, relapse time, metastatic sites, numbers of metastatic lesions and whether metastatic pancreatic lesions should be surgerically removed were recorded and the influencing factors were analyzed.Results:Among the 20 patients, there were 12 males and 8 females. The median age of diagnosis was 50 years. There were 12 patients(60%) of left renal carcinoma and 8 patients(40%)of the other side. 12 cases(60%) had single pancreatic metastatic lesion and the other 8 cases(40%) had multiple metastatic lesions. Seven patients(35%) had other organs metastasis besides pancreatic metastasis. Two patients(10%) had simultaneous pancreatic metastasis and renal cancer, and the other eighteen patients(90%) had pancreatic metachronous metastasis after being diagnosed as renal cancer. The median time from the diagnosis of CCRCC to pancreatic metastasis was 102 months. Thirteen patients(65%)had recurrences within 10 years and the other seven patients(35%)had recurrences after 10 years. Pancreatectomy was performed in nine patients(45%) and targeted therapy was conducted in thirteen patients. The mean follow-up was 122.9 months (1-256 months). Three patients (15%) died and 17 patients (85%) survived. The median overall survival was 75.9 months, and the 5 year-survival rate was 66.7%. Simultaneous metastasis and extra-pancreatic metastasis were prognostic factors in patients with CCRCC with pancreatic metastasis.Conclusions:Pancreatic metastases from renal clear cell carcinoma were rare, but the prognosis was good, especially in patients with only pancreatic metastases several years after renal carcinoma was diagnosed.

Objective:To investigate the diagnostic and diagnostic values of plasma microRNA-21-3p (miR-21-3p) and miR-551-5p expression in patients with acute pancreatitis (AP).Methods:A prospective observational study was conducted. AP patients admitted to the Third People's Hospital of Hainan Province from January 1st 2017 to December 31st 2019 were enrolled. The patients were divided into mild acute pancreatitis (MAP) group, moderate severe acute pancreatitis (MSAP) group and severe acute pancreatitis (SAP) group according to their severity. Fasting venous blood was collected from all subjects the day after admission, and real-time quantitative polymerase chain reaction (PCR) as used to detect the expression levels of plasma miR-21-3p and miR-551-5p. Rehabilitation, discharge or death were end points of study. In addition, 50 healthy people in the same period were selected as the control group. The receiver operating characteristic (ROC) curve was used to analyze the value of the expression levels of plasma miR-21-3p and miR-551-5p for the diagnosis and prognosis of SAP. Pearson correlation was used to analyze the relationship between the expressions of miR-21-3p and miR-551-5p in SAP patients.Results:A total of 164 AP patients were enrolled, including 72 MAP patients, 47 MSAP patients and 45 SAP patients. Among the SAP patients, 27 cases survived and 18 cases died. There were no deaths in MAP group and MSAP group. The levels of plasma miR-21-3p and miR-551-5p in AP group were significantly higher than those in control group [miR-21-3p (2 -ΔΔCt): 2.17±0.90 vs. 0.65±0.12, miR-551-5p (2 -ΔΔCt): 1.80±0.73 vs. 0.42±0.08, both P < 0.01]. The expression levels of plasma miR-21-3p and miR-551-5p in AP patients increased gradually with the aggravation of the disease ( F values were 11.635, 10.204 respectively, both P < 0.01), and the expression levels of plasma miR-21-3p and miR-551-5p in SAP group were significantly higher than those in MSAP group and MAP group [miR-21-3p (2 -ΔΔCt): 3.16±1.08 vs. 1.85±0.71, 1.70±0.64; miR-551-5p (2 -ΔΔCt): 2.63±0.95 vs. 1.52±0.46, 1.36±0.40; all P < 0.01]. ROC curve analysis showed that the area under the ROC curve (AUC) and 95% confidence interval (95% CI) of the joint diagnosis of SAP with miR-21-3p and miR-551-5p were significantly higher than that of miR-21-3p or miR-551-5p alone [0.898 (0.841-0.960) vs. 0.820 (0.763-0.882), 0.806 (0.748-0.867), Z1 = 4.480, Z2 = 4.916, both P < 0.05], and the sensitivity was 90.7% and the specificity was 85.0%. The expression levels of plasma miR-21-3p and miR-551-5p in the death group of SAP patients were significantly higher than those in the survival group [miR-21-3p (2 -ΔΔCt): 3.75±1.17 vs. 2.66±0.87, miR-551-5p (2 -ΔΔCt): 3.17±1.04 vs. 2.24±0.83, both P < 0.01]. ROC curve analysis showed that the AUC and 95% CI of the combined prediction of death in SAP patients with miR-21-3p and miR-551-5p were significantly higher than that of miR-21-3p or miR-551-5p alone [0.933 (0.875-0.996) vs. 0.856 (0.794-0.917), 0.816 (0.759-0.874), Z1 = 4.395, Z2 = 5.520, both P < 0.05], and the sensitivity was 95.2% and the specificity was 87.5%. Correlation analysis showed a positive correlation between the expression level of plasma miR-21-3p and miR-551-5p in SAP patients ( r = 0.827, P < 0.001). Conclusions:The increased expression of plasma miR-21-3p and miR-551-5p are positively correlated with the severity of AP patients. The combination of the two items has a better value in the diagnosis and prognosis evaluation of SAP.

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Objective: To effectively reduce the concentration of poisons in cleanroom, protect the health of workers, realize the optimization and automatic control of the new return air device. And the influence of initial concentration, air volume, temperature and relative humidity of formaldehyde on the purification effect of the new return air device was explored. Methods: The purification effect of the new return air device installed with the activated carbon and the photocatalyst purification net or ordinary activated carbon purification network was tested in a 60 m³ simulated cleanroom. The concentration of formaldehyde was determined by solution absorption-phenol reagent spectrophotometry. Based on the single factor experiment to determine the combination of two purification nets. The effects of air volume, initial formaldehyde concentration, temperature and relative humidity on the purification effect of the new return air device were investigated by orthogonal test. Then, the performance parameters of the return air device to purify formaldehyde were determined. Results: The formaldehyde purification efficiency of the two types of purification nets in the new return air device was higher than that of the ordinary activated carbon purification network (P<0.05) . The combination of activated carbon and photocatalyst purification net has no effect on the formaldehyde purification efficiency of the return air device (P>0.05) . According to the direct analysis and variance analysis, air volume was the most sensitive factor (F value is 18.894, P<0.05) , followed by initial concentration (F value is 16.128, P<0.05) , while temperature and relative humidity have little effect (F value is 0.041 and 0.599, respectively, P>0.05) . LSD analysis showed that there was no significant difference in the purification efficiency of formaldehyde between 475 m³/h and 626 m³/h (P>0.05) . From the perspective of formaldehyde purification efficiency and energy saving, when the air volume is set to 475 m³/h, the new return air device has higher purification efficiency for high concentration of formaldehyde. Conclusion The new return air device consisting of activated carbon and photocatalyst purification net can play a good purification role in cleanroom with different temperatures and different humidity. Its formaldehyde purification efficiency is affected by air volume and initial concentration.

The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.