Objective To explore the mediating effect of community elderly care service on the influence of social isolation on cognitive function of the elderly.Methods Based on the data of China Health and Retirement Longitudinal Study in 2018,mini mental status examination(MMSE)was used to assess the cognitive function of the elderly.Multivariate Logistic regression was used to analyze the influence of individual characteristics and social isolation on cognitive function of the elderly,and the correlation among social isolation,community elderly care service and cognitive function was analyzed through mediating effect.Results A total of 6615 elderly individuals were included,among whom 2906 cases(43.93％)had cognitive impairment.The results of multivariate Logistic regression analysis indicated that social isolation,age,gender,educational level,place of residence,marital status,activities of daily living ability,smoking,sleep duration,loneliness,community elderly care service,social interaction,and less than one contact with children per week were all influencing factors for the occurrence of cognitive impairment in the elderly(P＜0.05).Community elderly care service exerted a partial mediating effect in the impact of social isolation on the cognitive function of the elderly.Conclusion Social isolation is a risk factor for cognitive impairment in the elderly,and community elderly care service is a protective factor for cognitive impairment in the elderly.It is necessary to improve the coverage and utilization rate of community elderly care service support,improve the social isolation of the elderly,and protect the cognitive function of the elderly.

Objective To explore the mechanism of Gandou Fumu Decoction(GDFMD)for improving Wilson's disease(WD)in tx-J mice.Methods With 6 syngeneic wild-type mice as the control group,30 tx-J mice were randomized into WD model group,low-,medium-and high-dose GDFMD treatment groups,and Fer-1 treatment group.Saline(in control and model groups)and GDFMD(3.48,6.96 or 13.92 g/kg)were administered by gavage,and Fer-1 was injected intraperitoneally once daily for 14 days.Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue;ALT,AST,albumin,AKP levels were determined to assess liver function of the mice.Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4,ACSL4,ALOX15,FTH1,FLT,TFR1,FAS,SCD1,and ACOX1,and Fe2+,MDA,ROS,SOD,GSH and 4-HNE levels were analyzed to assess oxidative stress.Results The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT,AST and AKP,decreased albumin level,increased Fe2+,MDA,ROS,4-HNE levels,decreased SOD and GSH levels(P<0.05),lowered protein expressions of ACOX1,GPX4,FTH1,FLT,FAS,and SCD1,and increased protein contents of TFR1,ACSL4 and ALOX15 in the liver.Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models,decreased the levels of Fe2+,MDA and ROS,increased SOD and GSH levels,and reversed the changes in hepatic protein expressions.Conclusion GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male

ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease（AD） using bioinformatics and machine learning methods， validate them at the clinical specimen level， and predict potential traditional Chinese medicine（TCM）. MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus （GEO） database， and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected， and the relative gene expression was clinically verified by real-time polymerase chain reaction（Real-time PCR）. Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained， mainly involved in pathways of tricarboxylic acid cycle， 2-oxocarboxylic acid metabolism， and carbon metabolism. Five core cuproptosis-related genes， dihydrolipoamide dehydrogenase （DLD）， glutaminase （GLS）， pyruvate dehydrogenase E1 subunit beta （PDHB）， full name nuclear factor （erythroid-derived 2）-related factor 2 （NFE2L2）， and dihydrolipoamide branched-chain transacylase E2 （DBT） were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group， minimum mental state examination （MMSE） and Montreal cognitive assessment （MoCA） were significantly decreased in the AD group （P<0.01）， Homocysteine（Hcy）， interleukin（IL）-6， C-reactive protein（CRP） ， and β amyloid protein（Aβ） indexes were significantly increased （P<0.01）， and malondialdehyde（MDA） indexes were decreased （P<0.05）. Superoxide dismutase（SOD） levels were significantly decreased （P<0.01）. The mRNA relative expressions of NFE2L2 and DBT were up-regulated （P<0.05）， and those of DLD， GLS， and PDHB were significantly down-regulated （P<0.01）. The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth， calmness， and cold， and the five flavors including bitterness， sweetness， and pungency， and it was attributed to the meridians of the liver， spleen， stomach， and kidney， with the efficacy of tonifying Qi， activating blood， eliminating phlegm， and resoling dampness. ConclusionDLD， GLS， NFE2L2， PDHB， and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes， and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.

Objective To explore the mediating effect of community elderly care service on the influence of social isolation on cognitive function of the elderly.Methods Based on the data of China Health and Retirement Longitudinal Study in 2018,mini mental status examination(MMSE)was used to assess the cognitive function of the elderly.Multivariate Logistic regression was used to analyze the influence of individual characteristics and social isolation on cognitive function of the elderly,and the correlation among social isolation,community elderly care service and cognitive function was analyzed through mediating effect.Results A total of 6615 elderly individuals were included,among whom 2906 cases(43.93％)had cognitive impairment.The results of multivariate Logistic regression analysis indicated that social isolation,age,gender,educational level,place of residence,marital status,activities of daily living ability,smoking,sleep duration,loneliness,community elderly care service,social interaction,and less than one contact with children per week were all influencing factors for the occurrence of cognitive impairment in the elderly(P＜0.05).Community elderly care service exerted a partial mediating effect in the impact of social isolation on the cognitive function of the elderly.Conclusion Social isolation is a risk factor for cognitive impairment in the elderly,and community elderly care service is a protective factor for cognitive impairment in the elderly.It is necessary to improve the coverage and utilization rate of community elderly care service support,improve the social isolation of the elderly,and protect the cognitive function of the elderly.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.

Oral and maxillofacial space infections (OMSI) are common diseases of the facial region involving fascial spaces. Recently, OMSI shows trends of multi drug-resistance, severe symptoms, and increased mortality. OMSI treatment principles need to be updated to improve the cure rate. Based on the clinical experiences of Chinese experts and with the incorporation of international counterparts′ expertise, the principles of preoperative checklist, interpretation of examination results, empirical medication principles, surgical treatment principles, postoperative drainage principles, prevention strategies of wisdom teeth pericoronitis-related OMSI, blood glucose management, physiotherapy principles, Ludwig′s angina treatment and perioperative care were systematically summarized and an expert consensus on the diagnosis and treatment of OMSI was reached. The consensus aims to provide criteria for the diagnosis and treatment of OMSI in China so as to improve the level of OMSI treatment.

Objective: To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance. Methods: Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1). Results: Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (P<0.01). Positive FERMT2 expression was different in tumors at different tumor stages: 11/17 at stage Ⅰ, 16/20(80.0%)at stage Ⅱ, 17/20(85.0%)at stage Ⅲ, and 15/15 at stage Ⅳ, and there was a significant difference between each stage (P<0.01). By real-time PCR and Western blot, the expression of FERMT2 in non-small cell lung cancer tissues was significantly higher than that of para-cancerous tissue (P<0.01). The expression levels of integrin related proteins (integrin β1, VCAM1 and MRP1) in tumor tissues were significantly higher than those in para-cancerous tissues, and positively correlated with the expression of FERMT2 (r=0.531, P<0.01; r=0.483, P<0.01; r=0.612, P<0.01). Conclusions FERMT2 is highly expressed in non-small cell lung carcinomas. Its expression is closely correlated with the tumor clinical stage. It is hypothesized that FERMT2 may promote tumor metastasis through interactions with integrin-like protein.

Objective To investigate the effect of blood glucose levels at admission on the outcomes and hemorrhagic transformation in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From December 2013 to January 2017, patients with AIS treated with intravenous thrombolysis at the Department of Neurology, Xuzhou Central Hospital were enrolled retrospectively. According to the blood glucose levels on admission, they were divided into non-hyperglycemic group ( ≤8 mmol/L ) and hyperglycemic group ( > 8 mmol/L). The functional outcome was assessed with the modified Rankin Scale score at 90 d after onset, and 0-2 was defined as good outcome and > 2 was defined as poor outcome. From 24 h to 7 d after treatment, CT scan was performed again to determine whether there was intracranial hemorrhage or not. Multivariate logistic regression analysis was used to identify the independent influencing factors of outcomes after intravenous thrombolysis. Results A total of 323 patients with AIS were enrolled, including 237 (73. 4％) in the non-hyperglycemic group and 86 (26. 6％) in the hyperglycemic group; 238 (73. 7％) in the good outcome group, and 85 (26. 3％) in the poor outcome group; 25 (7. 7％) in the hemorrhagic transformation group, and 298 (92. 3％) in the non-hemorrhagic transformation group. Univariate analysis showed that there were significant differences in the proportions of patients with ischemic heart disease, atrial fibrillation, past history of stroke or TIA, as well as age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose between the poor outcome group and the good outcome group (all P < 0. 05). There were significant differences in the proportion of hypertensive patients and baseline NIHSS score between the hemorrhagic transformation group and the non- hemorrhagic transformation group ( all P < 0. 05 ). Multivariate logistic regression analysis showed that hyperglycemia at admission (odds ratio [OR] 2. 239, 95％ confidence interval [CI] 1. 210-4. 143; P = 0. 010)and baseline NIHSS score (OR 3. 528, 95％ CI 2. 451-5. 078; P < 0. 001) were the independent influencing factors of poor outcome; hypertension (OR 0. 410, 95％ CI 0. 173-0. 972; P = 0. 043 ) and baseline NIHSS score (OR 2. 283, 95％ CI 1. 382-3. 772, P = 0. 001 ) were the independent influencing factors of hemorrhagic transformation. Conclusion Hyperglycemia at admission was an independent risk factor for poor outcome in patients with AIS after intravenous thrombolytic therapy, but it was not associated with the risk of hemorrhagic transformation.