Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of dexmedetomidine on the median effect concentration(EC50)of ropivacaine during sciatic nerve block combined with femoral nerve block in patients undergoing lower extremity surgery.Methods Patients with sciatic nerve block combined with femoral nerve block anesthesia who underwent lower extremity surgery from November 2021 to November 2023 were selected as the study objects.They were randomly divided into control group(0.9％saline),group D1(0.50 μg·kg-1 dexmedetomidine),group D2(0.75 μg·kg-1 dexmedetomidine)and group D3(1.00 μg·kg-1 dexmedetomidine).The stress response,serum pain mediators,vital signs and visual analogue scale(VAS)of patients at different time points during operation were analyzed by repeated measures ANOVA.ropivacaine EC50 was measured by sequential method,and the relationship between dexmedetomidine dose and ropivacaine EC50 was analyzed by Logistic regression.Results A total of 208 patients were include and each group was 52 patients.Compared with the same group before surgery,the stress response level of the 4 groups after surgery and 1 h after surgery was significantly decreased,and the serum pain mediators level was significantly increased(P＜0.05).Compared with the control group,the stress response and serum pain mediators levels in groups D1,D2 and D3 were more normal after surgery and 1 h after surgery,among them,group D3 was most close to the normal value(P＜0.05).There were no significant differences in blood oxygen saturation and bifrequency index of EEG among the four groups at each time point(P＞0.05).At T1 and T2,the heart rate(HR)of the control group was significantly higher than that of the group D2 and D3(P＜0.05).At T1,the control group had a significantly higher mean arterial pressure(MAP)than the other three groups,at T2,the control group had a significantly higher MAP than the group D2 and D3,and at T3,the control group had a significantly higher MAP than the group D3(P＜0.05).VAS scores in 4 groups were significantly lower after surgery and 1 h after surgery than before surgery(P＜0.05).The VAS score in group D3 was significantly lower than that in group D1 and D2(P＜0.05).Repeated measurement ANOVA showed that the effects of time on stress response and serum pain mediators were different with different anesthesia methods.The influence of time on HR,MAP and VAS scores varied with different anesthesia methods.Sequential assay results showed that the EC50 of ropivacaine in control group,group D1,group D2 and group D3 was 5.985,5.631,5.329 and 5.125 μg·mL-1,respectively.Logistic results showed that the dose of dexmedetomide was a protective factor for ropivacaine EC50 in sciatic nerve block combined with femoral nerve block in limb surgery patients(P＜0.05).Conclusion The ropivacaine EC50 can be significantly reduced by 1.00 μg·kg-1 dexmedetomidine.This is a protective factor for sciatic nerve block combined with femoral nerve block in patients undergoing lower limb surgery,and it can be applied clinically.

Objective:To investigate the effects and potential mechanisms of melatonin on cognitive dysfunction induced by long-term anesthesia with isoflurane.Methods:Male C57BL/6J mice aged 2 months were divided into control group, isoflurane group, melatonin group, and isoflurane+ melatonin group by random number table, with 6 mice in each group.Three days after anesthesia, cognitive function of mice was assessed by Y-maze and fear conditioning (FC) tests. ATP content in the hippocampus was measured by an ATP assay kit. Western blot was used to detect the expression of DRP1, pDRP1, MFN2, pAMPK and SIRT1 proteins in the hippocampus. Cultured HT-22 cells derived from mouse hippocampal neurons in vitro were divided into control group, isoflurane group, melatonin group, and isoflurane + melatonin group, and the levels of reactive oxygen species (ROS) in each group were detected by flow cytometry after intervention. Statistical analysis was performed by SPSS 22.0 software, and one-way ANOVA was used for comparisons among multiple groups.Results:(1) There was a statistically significant difference in the percentage of freezing behavior in contextual fear memory among the four groups of mice ( F=39.09, P<0.05). The percentage of freezing behavior in the isoflurane group was lower than that in the control group ((44.23±8.88)% vs (75.87±5.90)%, P<0.05), while the percentage of freezing behavior in the isoflurane+ melatonin group((67.45±14.89)%)was higher than that in the isoflurane group ( P<0.05). There was also a statistically significant difference in the percentage of exploration in the novel arm among the four groups of mice ( F=13.87, P<0.05). The percentage of exploration in the novel arm in the isoflurane group was lower than that in the control group((33.64±6.53)% vs (47.13±3.87)%, P<0.05), while the percentage of exploration in the novel arm in the isoflurane+ melatonin group((43.05±1.64)%)was higher than that in the isoflurane group ( P<0.05). (2) Statistically significant difference in the levels of ATP in the hippocampus was found among the four groups of mice ( F=49.22, P<0.05). The level of ATP in the hippocampus in the isoflurane group was lower than that in the control group((2.29±0.15)nmol/mg vs (3.58±0.12)nmol/mg, P<0.05), while the level of ATP in the hippocampus in the isoflurane+ melatonin group ((3.02±0.27)nmol/mg)was higher than that in the isoflurane group ( P<0.05). There was a statistically significant difference in the levels of ROS in HT-22 cells among the four groups ( F=18.36, P<0.05). The level of ROS in HT-22 cells in the isoflurane group was higher than that in the control group after anesthesia ( P<0.05), while the level of ROS in HT-22 cells in the isoflurane+ melatonin group was lower than that in the isoflurane group after anesthesia ( P<0.05). (3) There were statistically significant difference in the levels of pDRP1, pAMPK and SIRT1 protein in the hippocampus among the four groups of mice ( F=19.87, 21.20, 25.65, all P<0.05). The levels of pDRP1 and SIRT1 protein in the hippocampus in the isoflurane group were both lower than those in the control group (both P<0.05), while the levels of pDRP1 and SIRT1 protein in the hippocampus in the isoflurane+ melatonin group were both higher than those in the isoflurane group (both P<0.05). In the isoflurane group, the expression of pAMPK protein in the hippocampal region was higher than that in the control group ( P<0.05), while the expression of pAMPK protein in the isoflurane+ melatonin group was lower than that in the isoflurane group ( P<0.05). Conclusion:Melatonin improves long-term isoflurane anesthesia-induced cognitive dysfunction by regulating mitochondrial homeostasis through the AMPK/SIRT1 signaling pathway.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Objective With the intensification of population aging,the incidence of aging-related neurodegenerative diseases continues to rise,however,their pathogenesis remains elusive and therapeutic options are limited.This study used bioinformatics approaches to explore brain cell-type-specific changes in gene expression during brain aging and their impacts,to provide further insights into the biological mechanisms of brain aging.Methods We analyzed single-cell sequencing datasets(GSE169606)from young and old mouse brains,including integration,quality control,normalization,conduct cell-type annotation and differential gene expression analysis to identify differentially expressed genes(DEGs)across various cell types,using the Seurat package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation and enrichment analyses,and interactions between DEGs were analyzed by protein-protein interaction(PPI)networks.The hub genes in each cell type were identified using the MCC,MNC,DMNC,and Dgree algorithms in the cyto Hubba plugin.Results A total of 13 cell types were identified through cell annotation.After comparing the aged and young groups,we focused on in-depth analyses of the DEGs screened from four major cell types:neurons,microglia,astrocytes,and endothelia.GO analysis revealed that DEGs in neurons,astrocytes,and endothelial cells were significantly enriched in biological pathways related to circadian rhythm,and KEGG analysis indicated that DEGs in microglia and endothelial cells were enriched in circadian rhythm-related signaling pathways.PPI analysis also demonstrated that the biological networks of DEGs in neurons,microglia,and endothelial cells were significantly enriched in circadian rhythm functional clustering modules.Furthermore,based on the intersection of the four algorithms,we identified core genes within these cell types and also identified specific variations in circadian rhythm genes in microglia,astrocytes,and endothelial cells.Conclusions This study employed single-cell transcriptomics technology to reveal the differential expression of genes in neurons,microglia,astrocytes,and endothelial cells during aging.The identification of hub genes in microglia,astrocytes,and endothelial cells indicated specific changes in circadian rhythm genes across these three cell types.These findings provide a foundation for further studies of the molecular mechanisms involved in brain aging and for the development of related intervention strategies.

Objective:To investigate the effects and potential mechanisms of melatonin on cognitive dysfunction induced by long-term anesthesia with isoflurane.Methods:Male C57BL/6J mice aged 2 months were divided into control group, isoflurane group, melatonin group, and isoflurane+ melatonin group by random number table, with 6 mice in each group.Three days after anesthesia, cognitive function of mice was assessed by Y-maze and fear conditioning (FC) tests. ATP content in the hippocampus was measured by an ATP assay kit. Western blot was used to detect the expression of DRP1, pDRP1, MFN2, pAMPK and SIRT1 proteins in the hippocampus. Cultured HT-22 cells derived from mouse hippocampal neurons in vitro were divided into control group, isoflurane group, melatonin group, and isoflurane + melatonin group, and the levels of reactive oxygen species (ROS) in each group were detected by flow cytometry after intervention. Statistical analysis was performed by SPSS 22.0 software, and one-way ANOVA was used for comparisons among multiple groups.Results:(1) There was a statistically significant difference in the percentage of freezing behavior in contextual fear memory among the four groups of mice ( F=39.09, P<0.05). The percentage of freezing behavior in the isoflurane group was lower than that in the control group ((44.23±8.88)% vs (75.87±5.90)%, P<0.05), while the percentage of freezing behavior in the isoflurane+ melatonin group((67.45±14.89)%)was higher than that in the isoflurane group ( P<0.05). There was also a statistically significant difference in the percentage of exploration in the novel arm among the four groups of mice ( F=13.87, P<0.05). The percentage of exploration in the novel arm in the isoflurane group was lower than that in the control group((33.64±6.53)% vs (47.13±3.87)%, P<0.05), while the percentage of exploration in the novel arm in the isoflurane+ melatonin group((43.05±1.64)%)was higher than that in the isoflurane group ( P<0.05). (2) Statistically significant difference in the levels of ATP in the hippocampus was found among the four groups of mice ( F=49.22, P<0.05). The level of ATP in the hippocampus in the isoflurane group was lower than that in the control group((2.29±0.15)nmol/mg vs (3.58±0.12)nmol/mg, P<0.05), while the level of ATP in the hippocampus in the isoflurane+ melatonin group ((3.02±0.27)nmol/mg)was higher than that in the isoflurane group ( P<0.05). There was a statistically significant difference in the levels of ROS in HT-22 cells among the four groups ( F=18.36, P<0.05). The level of ROS in HT-22 cells in the isoflurane group was higher than that in the control group after anesthesia ( P<0.05), while the level of ROS in HT-22 cells in the isoflurane+ melatonin group was lower than that in the isoflurane group after anesthesia ( P<0.05). (3) There were statistically significant difference in the levels of pDRP1, pAMPK and SIRT1 protein in the hippocampus among the four groups of mice ( F=19.87, 21.20, 25.65, all P<0.05). The levels of pDRP1 and SIRT1 protein in the hippocampus in the isoflurane group were both lower than those in the control group (both P<0.05), while the levels of pDRP1 and SIRT1 protein in the hippocampus in the isoflurane+ melatonin group were both higher than those in the isoflurane group (both P<0.05). In the isoflurane group, the expression of pAMPK protein in the hippocampal region was higher than that in the control group ( P<0.05), while the expression of pAMPK protein in the isoflurane+ melatonin group was lower than that in the isoflurane group ( P<0.05). Conclusion:Melatonin improves long-term isoflurane anesthesia-induced cognitive dysfunction by regulating mitochondrial homeostasis through the AMPK/SIRT1 signaling pathway.

Objective With the intensification of population aging,the incidence of aging-related neurodegenerative diseases continues to rise,however,their pathogenesis remains elusive and therapeutic options are limited.This study used bioinformatics approaches to explore brain cell-type-specific changes in gene expression during brain aging and their impacts,to provide further insights into the biological mechanisms of brain aging.Methods We analyzed single-cell sequencing datasets(GSE169606)from young and old mouse brains,including integration,quality control,normalization,conduct cell-type annotation and differential gene expression analysis to identify differentially expressed genes(DEGs)across various cell types,using the Seurat package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation and enrichment analyses,and interactions between DEGs were analyzed by protein-protein interaction(PPI)networks.The hub genes in each cell type were identified using the MCC,MNC,DMNC,and Dgree algorithms in the cyto Hubba plugin.Results A total of 13 cell types were identified through cell annotation.After comparing the aged and young groups,we focused on in-depth analyses of the DEGs screened from four major cell types:neurons,microglia,astrocytes,and endothelia.GO analysis revealed that DEGs in neurons,astrocytes,and endothelial cells were significantly enriched in biological pathways related to circadian rhythm,and KEGG analysis indicated that DEGs in microglia and endothelial cells were enriched in circadian rhythm-related signaling pathways.PPI analysis also demonstrated that the biological networks of DEGs in neurons,microglia,and endothelial cells were significantly enriched in circadian rhythm functional clustering modules.Furthermore,based on the intersection of the four algorithms,we identified core genes within these cell types and also identified specific variations in circadian rhythm genes in microglia,astrocytes,and endothelial cells.Conclusions This study employed single-cell transcriptomics technology to reveal the differential expression of genes in neurons,microglia,astrocytes,and endothelial cells during aging.The identification of hub genes in microglia,astrocytes,and endothelial cells indicated specific changes in circadian rhythm genes across these three cell types.These findings provide a foundation for further studies of the molecular mechanisms involved in brain aging and for the development of related intervention strategies.

Objective To investigate the effect of dexmedetomidine on the median effect concentration(EC50)of ropivacaine during sciatic nerve block combined with femoral nerve block in patients undergoing lower extremity surgery.Methods Patients with sciatic nerve block combined with femoral nerve block anesthesia who underwent lower extremity surgery from November 2021 to November 2023 were selected as the study objects.They were randomly divided into control group(0.9％saline),group D1(0.50 μg·kg-1 dexmedetomidine),group D2(0.75 μg·kg-1 dexmedetomidine)and group D3(1.00 μg·kg-1 dexmedetomidine).The stress response,serum pain mediators,vital signs and visual analogue scale(VAS)of patients at different time points during operation were analyzed by repeated measures ANOVA.ropivacaine EC50 was measured by sequential method,and the relationship between dexmedetomidine dose and ropivacaine EC50 was analyzed by Logistic regression.Results A total of 208 patients were include and each group was 52 patients.Compared with the same group before surgery,the stress response level of the 4 groups after surgery and 1 h after surgery was significantly decreased,and the serum pain mediators level was significantly increased(P＜0.05).Compared with the control group,the stress response and serum pain mediators levels in groups D1,D2 and D3 were more normal after surgery and 1 h after surgery,among them,group D3 was most close to the normal value(P＜0.05).There were no significant differences in blood oxygen saturation and bifrequency index of EEG among the four groups at each time point(P＞0.05).At T1 and T2,the heart rate(HR)of the control group was significantly higher than that of the group D2 and D3(P＜0.05).At T1,the control group had a significantly higher mean arterial pressure(MAP)than the other three groups,at T2,the control group had a significantly higher MAP than the group D2 and D3,and at T3,the control group had a significantly higher MAP than the group D3(P＜0.05).VAS scores in 4 groups were significantly lower after surgery and 1 h after surgery than before surgery(P＜0.05).The VAS score in group D3 was significantly lower than that in group D1 and D2(P＜0.05).Repeated measurement ANOVA showed that the effects of time on stress response and serum pain mediators were different with different anesthesia methods.The influence of time on HR,MAP and VAS scores varied with different anesthesia methods.Sequential assay results showed that the EC50 of ropivacaine in control group,group D1,group D2 and group D3 was 5.985,5.631,5.329 and 5.125 μg·mL-1,respectively.Logistic results showed that the dose of dexmedetomide was a protective factor for ropivacaine EC50 in sciatic nerve block combined with femoral nerve block in limb surgery patients(P＜0.05).Conclusion The ropivacaine EC50 can be significantly reduced by 1.00 μg·kg-1 dexmedetomidine.This is a protective factor for sciatic nerve block combined with femoral nerve block in patients undergoing lower limb surgery,and it can be applied clinically.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.