Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

Objective To systematically review the influencing factors of social isolation among the elderly in China.Methods Studies on social isolation of the elderly in China were searched in Chinese and English databases from database construction to July 2024.Fifteen studies were included,with a total sample size of 13 799.Meta-analysis were performed.Results Meta-analysis results showed that age,depression,impaired activities of daily living,cognitive impairment and loneliness were risk factors for social isolation in elderly in China.Social support,moderate social support,education level(junior high school or above),good self-rated health status,and high family care were protective factors.Conclusion There are many influencing factors of social isolation among elderly in China,and early intervention should be carried out to reduce the occurrence and development of social isolation of elderly in China.

Objective To compare the safety and adverse effects of esketamine alone or fentanyl combined with propofol for interventional occlusion of congenital heart disease in children,so as to provide a more suitable sedation and analgesia plan for these patients.Methods A prospective randomized controlled study was adopted.A total of 104 cases of congenital heart disease,including 53 cases of atrial septal defect(ASD),31 cases of ventricular septal defect(VSD),and 20 cases of patent ductus arteriosus(PDA),who underwent interventional occlusion under general anesthesia while preserving spontaneous breathing from January to March 2025,were taken as the research subjects.The children were divided into two groups by random number table method:esketamine group(group ES)and fentanyl+propofol group(group AP),with 52 cases in each group.The children in the group ES and the group AP were anesthetized by esketamine 0.5 mg/kg and fentanyl 2 ug/kg+propofol 2.5 mg/kg,respectively,and sevoflurane inhalation anesthesia was maintained during the operation.The mean arterial pressure(MAP),heart rate(HR),respiratory rate(RR)and pulse oxygen saturation(SpO2)were recorded at the time of entry(T0),1 min after induction of general anesthesia(T1),femoral artery puncture(T2),occluder insertion(T3),recovery(T4),and 10 min after recovery(T5).The operation time,dosage of sevoflurane,anesthesia induction time and recovery time of the two groups were recorded.The occurrence of adverse events during general anesthesia was recorded,including hypoxemia after general anesthesia induction,respiratory depression and intraoperative body movement,restlessness during the recovery period,and increased secretion during the recovery period.Results There were significant differences in MAP,HR,SpO2 and RR in time points within each group,between two groups,and across the time×group interaction(P<0.05).There was no significant difference in operation time,dosage of sevoflurane,anesthesia induction time,and recovery time between the two groups(P>0.05).The incidence of hypoxemia in the group ES was significantly lower than that in the group AP[1.9%(1/52)vs.28.9%(15/52),χ2=14.477,P=0.000],the incidence of respiratory depression in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027],and the incidence of intraoperative body movement in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027].Conclusions During the three interventional occlusion procedures for congenital heart disease in children,compared with fentanyl combined with propofol injection,esketamine can better maintain the stability of respiratory circulation,and has a lower incidence of adverse events such as intraoperative hypoxemia,respiratory depression and intraoperative body movement.Compared with traditional anesthetic drugs,eketamine can be used as a better choice for sedation and analgesia during interventional occlusion for the three types of congenital heart diseases in children.

Objective To investigate the effects of Yitangkang on renal ectopic lipid deposition and the PPAR-α/PGC-1α signaling pathway in db/db mice;To explore its mechanism in improving renal injury.Methods Totally 30 db/db mice were divided into model group,Yitangkang group and losartan potassium group(10 mice in each group)using a random number table method.An additional 10 db/m mice were assigned as the blank group.The mice received corresponding interventions for 8 weeks.Body mass,fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),and 24-hour urinary protein content were measured,renal morphology and injury were observed using HE,PAS and Masson staining,lipid deposition in renal tissue was observed by oil red O staining,renal ultrastructure was observed by transmission electron microscopy,immunofluorescence staining was used to detect the expressions of CPT1A and Nrf2 in renal tissue,RT-qPCR was performed to assess the mRNA expressions of PPAR-α and PGC-1α,Western blot was used to detect the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.05),and the contents of SCr,BUN and 24-hour urinary protein significantly increased(P<0.05);histopathology revealed glomerular hypertrophy,mesangial cell and matrix proliferation,thickened basement membrane,abnormal deposition of interstitial collagen fibers,increased lipid deposition in renal tissue,widespread foot process effacement,reduced foot process density(P<0.05),blurred mitochondrial outer membranes,swollen morphology,and indistinct cristae;mRNA expressions of PPAR-α and PGC-1α significantly decreased(P<0.05),and protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM significantly decreased(P<0.05).Compared with the model group,the body mass and FBG of mice in Yitangkang group significantly decreased(P<0.05),but there was no significant difference in the above indexes in losartan potassium group(P>0.05);the contents of SCr,BUN and 24-hour urinary protein in Yitangkang group and losartan potassium group significantly decreased(P<0.05);the pathological damage and lipid deposition of renal tissue was alleviated,the ultrastructure of podocytes was improved,and the density of podocytes significantly increased(P<0.05);the mRNA expressions of PPAR-α and PGC-1α in renal tissue increased,and the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM increased,with statistical significance(P<0.05).Conclusion Yitangkang can effectively alleviate renal injury in diabetic nephropathy mice.The mechanism may be related to the activation of PPAR-α/PGC-1α signaling pathway and the reduction of renal lipid deposition and mitochondrial biogenesis.

Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

Objective To systematically review the influencing factors of social isolation among the elderly in China.Methods Studies on social isolation of the elderly in China were searched in Chinese and English databases from database construction to July 2024.Fifteen studies were included,with a total sample size of 13 799.Meta-analysis were performed.Results Meta-analysis results showed that age,depression,impaired activities of daily living,cognitive impairment and loneliness were risk factors for social isolation in elderly in China.Social support,moderate social support,education level(junior high school or above),good self-rated health status,and high family care were protective factors.Conclusion There are many influencing factors of social isolation among elderly in China,and early intervention should be carried out to reduce the occurrence and development of social isolation of elderly in China.

Objective To compare the safety and adverse effects of esketamine alone or fentanyl combined with propofol for interventional occlusion of congenital heart disease in children,so as to provide a more suitable sedation and analgesia plan for these patients.Methods A prospective randomized controlled study was adopted.A total of 104 cases of congenital heart disease,including 53 cases of atrial septal defect(ASD),31 cases of ventricular septal defect(VSD),and 20 cases of patent ductus arteriosus(PDA),who underwent interventional occlusion under general anesthesia while preserving spontaneous breathing from January to March 2025,were taken as the research subjects.The children were divided into two groups by random number table method:esketamine group(group ES)and fentanyl+propofol group(group AP),with 52 cases in each group.The children in the group ES and the group AP were anesthetized by esketamine 0.5 mg/kg and fentanyl 2 ug/kg+propofol 2.5 mg/kg,respectively,and sevoflurane inhalation anesthesia was maintained during the operation.The mean arterial pressure(MAP),heart rate(HR),respiratory rate(RR)and pulse oxygen saturation(SpO2)were recorded at the time of entry(T0),1 min after induction of general anesthesia(T1),femoral artery puncture(T2),occluder insertion(T3),recovery(T4),and 10 min after recovery(T5).The operation time,dosage of sevoflurane,anesthesia induction time and recovery time of the two groups were recorded.The occurrence of adverse events during general anesthesia was recorded,including hypoxemia after general anesthesia induction,respiratory depression and intraoperative body movement,restlessness during the recovery period,and increased secretion during the recovery period.Results There were significant differences in MAP,HR,SpO2 and RR in time points within each group,between two groups,and across the time×group interaction(P<0.05).There was no significant difference in operation time,dosage of sevoflurane,anesthesia induction time,and recovery time between the two groups(P>0.05).The incidence of hypoxemia in the group ES was significantly lower than that in the group AP[1.9%(1/52)vs.28.9%(15/52),χ2=14.477,P=0.000],the incidence of respiratory depression in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027],and the incidence of intraoperative body movement in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027].Conclusions During the three interventional occlusion procedures for congenital heart disease in children,compared with fentanyl combined with propofol injection,esketamine can better maintain the stability of respiratory circulation,and has a lower incidence of adverse events such as intraoperative hypoxemia,respiratory depression and intraoperative body movement.Compared with traditional anesthetic drugs,eketamine can be used as a better choice for sedation and analgesia during interventional occlusion for the three types of congenital heart diseases in children.

Objective To investigate the effects of Yitangkang on renal ectopic lipid deposition and the PPAR-α/PGC-1α signaling pathway in db/db mice;To explore its mechanism in improving renal injury.Methods Totally 30 db/db mice were divided into model group,Yitangkang group and losartan potassium group(10 mice in each group)using a random number table method.An additional 10 db/m mice were assigned as the blank group.The mice received corresponding interventions for 8 weeks.Body mass,fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),and 24-hour urinary protein content were measured,renal morphology and injury were observed using HE,PAS and Masson staining,lipid deposition in renal tissue was observed by oil red O staining,renal ultrastructure was observed by transmission electron microscopy,immunofluorescence staining was used to detect the expressions of CPT1A and Nrf2 in renal tissue,RT-qPCR was performed to assess the mRNA expressions of PPAR-α and PGC-1α,Western blot was used to detect the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.05),and the contents of SCr,BUN and 24-hour urinary protein significantly increased(P<0.05);histopathology revealed glomerular hypertrophy,mesangial cell and matrix proliferation,thickened basement membrane,abnormal deposition of interstitial collagen fibers,increased lipid deposition in renal tissue,widespread foot process effacement,reduced foot process density(P<0.05),blurred mitochondrial outer membranes,swollen morphology,and indistinct cristae;mRNA expressions of PPAR-α and PGC-1α significantly decreased(P<0.05),and protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM significantly decreased(P<0.05).Compared with the model group,the body mass and FBG of mice in Yitangkang group significantly decreased(P<0.05),but there was no significant difference in the above indexes in losartan potassium group(P>0.05);the contents of SCr,BUN and 24-hour urinary protein in Yitangkang group and losartan potassium group significantly decreased(P<0.05);the pathological damage and lipid deposition of renal tissue was alleviated,the ultrastructure of podocytes was improved,and the density of podocytes significantly increased(P<0.05);the mRNA expressions of PPAR-α and PGC-1α in renal tissue increased,and the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM increased,with statistical significance(P<0.05).Conclusion Yitangkang can effectively alleviate renal injury in diabetic nephropathy mice.The mechanism may be related to the activation of PPAR-α/PGC-1α signaling pathway and the reduction of renal lipid deposition and mitochondrial biogenesis.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.