Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

ObjectiveTo investigate the clinical efficacy of Gandouling tablet （GDL） on abnormal lipid metabolism in Wilson's disease （WD） and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD. MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， serum triglyceride （TG）， total cholesterol （TC）， apolipoprotein B （ApoB）， low density lipoprotein cholesterol （LDL-C）， bile acid （BA）， γ-glutamyl transferase （GGT）， prediction model of hepatic steatosis ［hepatic steatosis index （HSI） and Zhejiang University index （ZJU index）］， ultrasonic attenuation coefficient imaging （ATT）， and traditional Chinese medicine （TCM） syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG， TC， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome score， ATT， and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method， with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate （DMPS）， while the control group was only treated with DMPS as a control. After six courses of treatment， 24-hour urine copper， TC， TG， LDL-C， ApoB， HSI， ZJU， ATT， TCM syndrome score， and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC， TG， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome scores， and ATT was analyzed. ResultPearson correlation analysis showed that serum TC （r = 0.811）， TG （r = 0.826）， LDL-C （r = 0.802）， ApoB （r = 0.820）， ALT （r = 0.497）， ALT/AST （r = 0.826）， TCM syndrome score （r = 0.716）， and ATT （r = 0.736） were positively correlated with HSI （P<0.01）， while AST， BA， and GGT had no significant correlation with HSI. TC （r = 0.718）， TG （r = 0.765）， LDL-C （r = 0.667）， ApoB （r = 0.699）， ALT/AST （r = 0.403）， TCM syndrome score （r = 0.666）， and ATT （r = 0.684） were positively correlated with ZJU （P<0.01）. ALT， AST， BA， and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 （37/43）， and that of the control group was 72.09% （31/43）. The total effective rate of the observation group was higher than that of the control group （Z = -2.301， P<0.05）. After treatment， the 24-hour urine copper of the two groups increased significantly. The levels of TC， TG， LDL-C， and ApoB were significantly decreased， and the HSI， ZJU， and ATT were significantly decreased （P<0.01）. Compared with those in the control group after treatment， the above indexes improved better in the observation group （P<0.05， P<0.01）. ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD， with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective:To translate the Cumulated Ambulation Score (CAS) into Chinese and test its reliability and validity in elderly inpatients, to provide a basis for assessing elderly inpatients′ basic mobility during hospitalization.Methods:This was a cross-sectional study. After obtaining the authorization of the original author, the Chinese version of CAS was formed by WHO′s cross-cultural translation process. A total of 414 hospitalized elderly inpatients from Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and Shanghai Yangpu District Kongjiang Hospital were selected between March and September 2021. Cronbach′s α coefficient was used to test internal consistency, linear weighted Kappa was employed to assess inter-rater reliability, and concurrent validity was examined using items related to mobility of Barthel Index scores as a reference standard.Results:Of the 414 patients, 221 were males and 193 were females, and the patients aged (76.67 ± 9.98) years old; 122 cases (29.5%) had a perfect score of 6 with normal basic mobility, 89 cases (21.5%) had a score of 0 with complete loss of mobility, and the remaining 203 patients had a score of 1-5 with varying degrees of reduced mobility. The Chinese version of CAS demonstrated good assessment performance for basic mobility in elderly inpatients with a Cronbach′s α coefficient of 0.952. Weighted Kappa values for individual items and total scores showed excellent agreement among raters (>0.85), while concurrent validity yielded a value of 0.935 ( P<0.01) when compared with Barthel Index scores.Total score of CAS was significantly correlated with item scores and total score of Barthel index ( r values were 0.423 to 0.944, all P<0.01). Conclusions:The Chinese version of CAS has good reliability and validity. The items are concise, clear and easy to understand. It is suitable as a preliminary screening tool for clinical departments to evaluate the basic mobility of elderly inpatients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.