Primary membranous nephropathy (PMN) is one of the common causes of nephrotic syndrome in adults and is characterized by the deposition of immune complexes, resulting in thickening of basement membrane. With the identification of more autoantibodies, the understanding of the pathogenesis of PMN has expanded. Currently, supportive therapy and immunosuppressive therapy are the primary treatments for PMN, which mainly consists of cyclophosphamide, calcineurin inhibitors, rituximab, and so on. With the advent and application of an increasing number of biological agents, a subset of refractory or drug-resistant PMN patients can be effectively treated and achieve remission. This article reviews recent advances in the management of PMN. It covers pretreatment assessment, immunosuppressive therapy, complement- targeted therapy, and anticoagulant therapy and deliberates on the management of rituximab- resistant patients. The review aims to provide clinicians with an up-to-date basis for individualized clinical decision-making.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

Primary membranous nephropathy (PMN) is one of the common causes of nephrotic syndrome in adults and is characterized by the deposition of immune complexes, resulting in thickening of basement membrane. With the identification of more autoantibodies, the understanding of the pathogenesis of PMN has expanded. Currently, supportive therapy and immunosuppressive therapy are the primary treatments for PMN, which mainly consists of cyclophosphamide, calcineurin inhibitors, rituximab, and so on. With the advent and application of an increasing number of biological agents, a subset of refractory or drug-resistant PMN patients can be effectively treated and achieve remission. This article reviews recent advances in the management of PMN. It covers pretreatment assessment, immunosuppressive therapy, complement- targeted therapy, and anticoagulant therapy and deliberates on the management of rituximab- resistant patients. The review aims to provide clinicians with an up-to-date basis for individualized clinical decision-making.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

ObjectiveTo investigate the effect of Mashao Pingchuan decoction （MSPC） on lipopolysaccharides （LPS）-induced autophagy in human bronchial airway epithelial cells （16HBE） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method16HBE cells were selected for the study， and cell counting kit-8 （CCK-8） was used to detect the activity of of LPS-induced 16HBE cells and the effect of MSPC-containing serum on the cells. Suitable LPS-induced 16HBE cells were screened by the CCK-8 method， and the content of tumor necrosis factor-α （TNF-α） was measured to identify the established model. And MSPC-containing serum was prepared. The cells were divided into normal group， LPS group， LPS+MSPC group， LY294002+LPS group and LY294002+LPS+MSPC group. Transmission electron microscopy was performed to observe the changes in autophagic vesicles and ultrastructure of the cells. Western blot was performed to detect the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， mTOR， phosphorylated mTOR （p-mTOR） and microtubule-associated protein 1 light chain 3B （LC3B）， and enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of inflammatory factors interleukin-5 （IL-5）， IL-6， TNF-α and IL-10 in the five groups. ResultLPS inhibited the 16HBE cells in a dose-dependent manner. Compared with the normal group， the LPS group （150 mg·L^-1 of LPS） increased the expression of pro-inflammatory factor TNF-α after 24 h of treatment （P<0.05） and facilitated the autophagosome formation， and MSPC-containing serum exerted a concentration-dependent promotion effect on the 16HBE cells， inhibited the autophagy to a certain degree and enhanced the cell status. Western blot revealed that the protein expressions of p-PI3K， p-Akt and p-mTOR in the model group were lower （P<0.05） and the protein expression of LC3B was higher （P<0.01） than those in the normal group. Compared with the conditions in the LPS group， the protein expressions of p-PI3K， p-Akt and p-mTOR in the LPS+MSPC group were elevated （P<0.05） and that of LC3B was reduced （P<0.05）. Compared with the LPS+LY294002 group， the LY294002+LPS+MSCP group had up-regulated protein expressions of p-PI3K， p-Akt and p-mTOR （P<0.05） and down-regulated protein expression of LC3B （P<0.05）. ELISA showed that the LPS group had higher levels of IL-5， IL-6， TNF-α and IL-10 than the normal group， while the levels of TNF-α， IL-6 and IL-8 were decreased （P<0.01） and the level of IL-10 was increased （P<0.01） after treatment with MSCP. ConclusionMSCP may lower the LPS-induced autophagy in 16HBE cells and improve the inflammatory response through activating the PI3K/Akt/mTOR signaling pathway.

The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td),

Based on the three delivery forms of CRISPR/Cas9 system at the levels of DNA, RNA and protein, this paper mainly approaches the development and new strategies of CRISPR/Cas9 delivery systems, as well as their application in the biomedical field and the clinical treatment of gene-related diseases. By summarizing and elaborating the CRISPR/Cas9 system delivery and gene therapy strategy, new ideas are provided for the discovery of innovative drugs and the development of gene therapy.

Objective: To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods: Ninety children with HFMD were classified into three groups with 30 in each group: critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase (NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results: The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups (P<0.01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0.01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0.01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0.01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0.01). The levels of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE (P<0.01). Serum BNIP3 had the highest Youden value at the cut-off value of 3.015 μg/L, with a sensitivity of 83.33% and a specificity of 90.00%, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1.735 μg/L, with a sensitivity of 73.33% and a specificity of 93.33%, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.

Objective To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods Ninety children with HFMD were classified into three groups with 30 in each group:critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase ( NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic ( ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups ( P<0. 01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0. 01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0. 01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0. 01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0. 01). The lev-els of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE ( P<0. 01). Serum BNIP3 had the highest Youden value at the cut-off value of 3. 015μg/L, with a sensitivity of 83. 33％ and a specificity of 90. 00％, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1. 735 μg/L, with a sensitivity of 73. 33％ and a specificity of 93.33％, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.