Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

Vascular dementia(VD)is a chronic progressive cognitive impairment caused by cerebrovascular diseases.Its pathogenesis is complex,primarily involving brain tissue damage due to factors such as neuronal apoptosis,oxidative stress response,inflammatory reaction,ferroptosis,and mitochondrial damage.Among these,oxidative stress plays a crucial role in the development of VD.It leads to the accumulation of free radicals,disrupts cellular structures,and is closely related to inflammatory reactions,mitochondrial damage,ferroptosis,and neuronal apoptosis,together forming a complex pathogenic network.In recent years,monomeric compounds from traditional Chinese medicine(TCM)have shown significant therapeutic effects on VD through the regulation of oxidative stress.This article reviews the relevant research progress and explores the mechanisms of oxidative stress in VD.Oxidative stress regulates inflammatory reactions through factors such as Nrf2,NLRP3,and NF-κB;mediates mitochondrial damage by disrupting mitochondrial function and dynamics through excessive reactive oxygen species(ROS);induces ferroptosis through lipid peroxidation,iron metabolism,and glutathione metabolism;and activates apoptotic proteins via pathways such as protein denaturation,DNA modification,endoplasmic reticulum stress,and death receptors,thereby inducing neuronal apoptosis.Additionally,this article summarizes the therapeutic approaches of TCM monomers in treating VD through the regulation of oxidative stress and its related mechanisms.For example,curcumin reduces ROS levels and enhances antioxidant and anti-inflammatory capacities;gastrodin alleviates mitochondrial damage mediated by oxidative stress,improves energy metabolism,and inhibits ferroptosis;dendrobium polysaccharides mitigate oxidative stress and subsequently inhibit ferroptosis;and triptolide enhances antioxidant capacity,reduces cell apoptosis,and slows the progression of VD.It is hoped that this review will provide insights for future experimental mechanism studies and clinical applications of TCM monomers targeting oxidative stress in the treatment of VD.

Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

Vascular dementia(VD)is a neurodegenerative disease caused by brain injury.Research on the processes leading to its occurrence is lacking depth.In recent years,it has been proposed that regulatory cell death(RCD)mechanisms,including apoptosis,pyroptosis,autophagy,ferroptosis,and cuproptosis,are related to the pathological mechanisms of VD.Therefore,studies aiming to explain the links between the mechanisms of regulatory death and the pathology of VD would be beneficial to our understanding of VD.This article provides a review of the roles of five mechanisms of RCD in VD and summarizes the recent progress made in researching the treatment of VD with traditional Chinese medicine,providing a resource for the development of new traditional Chinese medicine drugs.

As the global population continues to age,the incidence of neurodegenerative diseases has seen a constant increase in the elderly.Research indicates that neuroinflammation is a significant pathological mechanism in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,multiple sclerosis and Huntington's disease.Astrocytes are key glial cells involved in the regulation of neuroinflammation.More studies have revealed that astrocytes closely interact with other glial cells,neurons and peripheral immune cells to regulate synaptic plasticity,neuronal function,glutamate cycling and energy metabolism in the central nervous system,which shows notable therapeutic effects on neurodegenerative diseases.This paper aims to further explore specific manifestations and potential molecular mechanisms of astrocyte-mediated inflammatory processes in neurodegenerative diseases through interactions of astrocytes and other cells,therefore to identify new therapeutic targets from the perspective of astrocytes and then improve the symptoms.

Objective:To compare the efficacy of robot assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of pediatric renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 29 children with renal tumors admitted to Xinhua Hospital from March 2019 to March 2024. Among them, there were 10 cases in the RAPN group, including 6 males and 4 females; The median age is 7.5 (4, 12) years old, with a tumor diameter of (4.3±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size (tumor volume/contralateral kidney volume) of (34.0%±19.3%). There were 19 cases in the LPN group, 8 males and 11 females; the median age is 5.0(4, 11) years old, with a tumor diameter of (4.4±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size(37.7%±18.1%). There was no statistically significant difference in preoperative characteristics between the two groups ( P>0.05). Both groups underwent partial nephrectomy, with renal artery occlusion and then warm ischemia. Clinical data from both groups during and postoperatively were compared, and a simple linear regression analysis was utilized to assess the correlation between the relative size of the tumor and the duration of intraoperative warm ischemia. Results:All 29 cases underwent a successful surgery. Compared with the LPN group, the total surgery time in the RAPN group was (115.0±28.4) minutes versus (127.9±28.2) min( P=0.25); the warm ischemia time was (20.9±3.0) min versus (27.0±4.5) min, respectively( P<0.01); the intraoperative bleeding was (50.0±24.5) ml and (80.0±21.2) ml( P<0.01); the difference in hemoglobin level before and after surgery was (10.3±3.5) g/L versus (12.9±2.7) g/L( P<0.05), respectively; the median postoperative drainage time was 3.5 (3, 4) days versus 4.0(3, 6) days( P=0.17); the median postoperative hospital stay was 4.5 (4, 8) days versus 6.0(5, 10) days( P<0.05). There were 3 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of mixed epithelial and stromal tumors, and 2 cases of cystic nephroma by postoperative pathological examination in the RAPN group. There were 10 cases of nephroblastoma, 3 cases of teratoma, 2 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of metanephric adenoma, 1 case of unclassified renal cell carcinoma, and 1 case of cystic nephroma in the LPN group. Apart from one child in the LPN group who developed a postoperative fever over 39℃, no other severe complications occurred during or after the surgery in the remaining patients. Compared with preoperative parameters, eGFR decreased (8.9±18.9) ml/(min·1.73m 2) and (21.4±34.8) ml/(min·1.73m 2) in the RAPN group and LPN group, respectively, 1 month postoperatively( P=0.36); three months after surgery, eGFR was followed up, and the RAPN group and LPN group showed a decrease of (5.9±23.4) ml/(min·1.73m 2) and (13.9±20.1) ml/(min·1.73m 2) compared with preoperative levels, respectively( P=0.42). Linear regression analysis indicated that in the LPN group, intraoperative warm ischemia time exhibited a progressively increasing trend with the augmentation of the tumor's relative size, and warm ischemia time = 0.1688×tumor relative size+ 20.64, ( R2=0.46, P<0.01). Based on this, it is estimated that when the tumor's relative size exceeds 55.5%, the intraoperative warm ischemia time often surpassed 30 minutes. However, in the RAPN group, this trend is not statistically significant (P>0.05). Conclusions:Both LPN and RAPN are safe and feasible for the treatment of pediatric renal tumors. Compared with LPN, RAPN surgery has advantages of shortening warm ischemia time and reducing intraoperative bleeding, which helps patients recover early. RAPN is a better choice for children with a relative renal tumors size over 55.5%.

Objective:To compare the efficacy of robot assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of pediatric renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 29 children with renal tumors admitted to Xinhua Hospital from March 2019 to March 2024. Among them, there were 10 cases in the RAPN group, including 6 males and 4 females; The median age is 7.5 (4, 12) years old, with a tumor diameter of (4.3±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size (tumor volume/contralateral kidney volume) of (34.0%±19.3%). There were 19 cases in the LPN group, 8 males and 11 females; the median age is 5.0(4, 11) years old, with a tumor diameter of (4.4±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size(37.7%±18.1%). There was no statistically significant difference in preoperative characteristics between the two groups ( P>0.05). Both groups underwent partial nephrectomy, with renal artery occlusion and then warm ischemia. Clinical data from both groups during and postoperatively were compared, and a simple linear regression analysis was utilized to assess the correlation between the relative size of the tumor and the duration of intraoperative warm ischemia. Results:All 29 cases underwent a successful surgery. Compared with the LPN group, the total surgery time in the RAPN group was (115.0±28.4) minutes versus (127.9±28.2) min( P=0.25); the warm ischemia time was (20.9±3.0) min versus (27.0±4.5) min, respectively( P<0.01); the intraoperative bleeding was (50.0±24.5) ml and (80.0±21.2) ml( P<0.01); the difference in hemoglobin level before and after surgery was (10.3±3.5) g/L versus (12.9±2.7) g/L( P<0.05), respectively; the median postoperative drainage time was 3.5 (3, 4) days versus 4.0(3, 6) days( P=0.17); the median postoperative hospital stay was 4.5 (4, 8) days versus 6.0(5, 10) days( P<0.05). There were 3 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of mixed epithelial and stromal tumors, and 2 cases of cystic nephroma by postoperative pathological examination in the RAPN group. There were 10 cases of nephroblastoma, 3 cases of teratoma, 2 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of metanephric adenoma, 1 case of unclassified renal cell carcinoma, and 1 case of cystic nephroma in the LPN group. Apart from one child in the LPN group who developed a postoperative fever over 39℃, no other severe complications occurred during or after the surgery in the remaining patients. Compared with preoperative parameters, eGFR decreased (8.9±18.9) ml/(min·1.73m 2) and (21.4±34.8) ml/(min·1.73m 2) in the RAPN group and LPN group, respectively, 1 month postoperatively( P=0.36); three months after surgery, eGFR was followed up, and the RAPN group and LPN group showed a decrease of (5.9±23.4) ml/(min·1.73m 2) and (13.9±20.1) ml/(min·1.73m 2) compared with preoperative levels, respectively( P=0.42). Linear regression analysis indicated that in the LPN group, intraoperative warm ischemia time exhibited a progressively increasing trend with the augmentation of the tumor's relative size, and warm ischemia time = 0.1688×tumor relative size+ 20.64, ( R2=0.46, P<0.01). Based on this, it is estimated that when the tumor's relative size exceeds 55.5%, the intraoperative warm ischemia time often surpassed 30 minutes. However, in the RAPN group, this trend is not statistically significant (P>0.05). Conclusions:Both LPN and RAPN are safe and feasible for the treatment of pediatric renal tumors. Compared with LPN, RAPN surgery has advantages of shortening warm ischemia time and reducing intraoperative bleeding, which helps patients recover early. RAPN is a better choice for children with a relative renal tumors size over 55.5%.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.