ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Objective:To obtain fucose-free anti-West Nile virus nonstructural protein 1 (NS1) antibody and evaluate its antibody-dependent cell-mediated cytotoxicity (ADCC).Methods:The guanosine diphosphate-fucose transporter SLC35C1 in CHO cells was knocked out using CRISPR/Cas9 gene editing technology to obtain the fucose-free cell line CHO SLC35C1 -/-. CHO SLC35C1 -/- cells were used to produce fucose-free anti-West Nile virus NS1 antibodies. The binding abilities of the antibodies to the target antigen of West Nile virus NS1 protein and the human high-affinity IgG Fc receptor hFcγRⅠ (hCD64) were detected by ELISA and flow cytometry, respectively. The ADCC activity of the antibodies was detected by ADCC reporter gene assay. One-way analysis of variance was used for statistical analysis. Results:CHO SLC35C1 -/- cells expressed green fluorescent protein but not Lens culinaris agglutinin. The anti-West Nile virus NS1 antibodies produced by CHO SLC35C1 -/- cells with a fucose content of 0.22% could bind to West Nile virus NS1 protein in a concentration-dependent manner. Compared with the wild-type antibodies, the fucose-free anti-West Nile virus NS1 antibodies showed a stronger binding ability to hFcγRⅠ(hCD64), as indicated by a significant increase in fluorescence intensity. The ADCC reporter gene assay showed that the fucose-free anti-West Nile virus NS1 antibodies had increased activity as compared with the wild-type antibodies ( P<0.001). Conclusion:The fucose-free anti-West Nile virus NS1 antibodies may be used to protect against West Nile virus infection.

MRI is a non-invasive imaging technique with high soft tissue contrast,multi sequences and multi parameters imaging capabilities,which has been widely used in researches of lung diseases in recent years.However,MRI application still faces certain challenges due to the unique physiological structure of lung and respiratory motion artifacts on images.The advances of MRI in pulmonary diseases were reviewed in this article.

Monkeypox,caused by the monkeypox virus(MPXV),is a zoonotic infectious disease characterized clinically by fever,rash,and lymphadenopathy.In September 2024,the outbreak of a novel MPXV Clade Ib variant in the Democratic Republic of the Congo was designated by the World Health Organization as a public health emergency of international concern,highlighting deficiencies in current prevention and control systems.Although modified attenuated smallpox vaccines exhibit cross-protective efficacy against MPXV infection,their adverse effects still limit clinical applications.Further-more,the therapeutic efficacy of tecovirimat—the FDA emergency-authorized antiviral drug for Smallpox—is limited.Recent studies have shown that tecovirimat does not significantly improve lesion healing time or reduce overall mortality in patients infected with MPXV CladeⅠ.Monoclonal antibodies,which neutralize viral activity by targeting critical membrane proteins,have emerged as a pivotal strategy to overcome current therapeutic bottlenecks by integrating therapeutic,diagnostic and prophylactic functions.This article reviews the epidemiological and virological characteristics of MPXV,along with functional characteristics of MPXV major membrane proteins,including A29L,A35R,B6R,E8L,M1R and H3L,focusing on the research progress in monoclonal antibodies against these key targets.Their protective effects in vitro/in vivo are explored while such as strategies monoclonal antibody combina-tion therapy are recommended to enhance efficacy and overcome drug resistance.

Objective:To obtain fucose-free anti-West Nile virus nonstructural protein 1 (NS1) antibody and evaluate its antibody-dependent cell-mediated cytotoxicity (ADCC).Methods:The guanosine diphosphate-fucose transporter SLC35C1 in CHO cells was knocked out using CRISPR/Cas9 gene editing technology to obtain the fucose-free cell line CHO SLC35C1 -/-. CHO SLC35C1 -/- cells were used to produce fucose-free anti-West Nile virus NS1 antibodies. The binding abilities of the antibodies to the target antigen of West Nile virus NS1 protein and the human high-affinity IgG Fc receptor hFcγRⅠ (hCD64) were detected by ELISA and flow cytometry, respectively. The ADCC activity of the antibodies was detected by ADCC reporter gene assay. One-way analysis of variance was used for statistical analysis. Results:CHO SLC35C1 -/- cells expressed green fluorescent protein but not Lens culinaris agglutinin. The anti-West Nile virus NS1 antibodies produced by CHO SLC35C1 -/- cells with a fucose content of 0.22% could bind to West Nile virus NS1 protein in a concentration-dependent manner. Compared with the wild-type antibodies, the fucose-free anti-West Nile virus NS1 antibodies showed a stronger binding ability to hFcγRⅠ(hCD64), as indicated by a significant increase in fluorescence intensity. The ADCC reporter gene assay showed that the fucose-free anti-West Nile virus NS1 antibodies had increased activity as compared with the wild-type antibodies ( P<0.001). Conclusion:The fucose-free anti-West Nile virus NS1 antibodies may be used to protect against West Nile virus infection.

MRI is a non-invasive imaging technique with high soft tissue contrast,multi sequences and multi parameters imaging capabilities,which has been widely used in researches of lung diseases in recent years.However,MRI application still faces certain challenges due to the unique physiological structure of lung and respiratory motion artifacts on images.The advances of MRI in pulmonary diseases were reviewed in this article.

Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.
Humans ; Neurodegenerative Diseases/metabolism* ; alpha-Synuclein/metabolism* ; Amyloid beta-Peptides/metabolism* ; tau Proteins/metabolism* ; Protein Aggregation, Pathological/metabolism* ; DNA-Binding Proteins/metabolism* ; Animals ; Protein Aggregates/physiology*

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.