Objective:This study aims to summarize the theoretical basis and practical effect of interdisciplinary team building in the National Clinical Medical Research Center for Aging and Medicine, Huashan Hospital.Methods:Interactive memory was employed as the theoretical basis for building cross-disciplinary teams, and the work was carried out in three dimensions of specialization, credibility, and coordination.Results:The center had shaped a coordinative team atmosphere and strengthened its integrity in five dimensions, including discipline construction, open platform, innovation curation, science popularization, and technology transfer. The center also promoted the implementation of research tasks in the three core areas.Conclusions:As the aging healthcare issues are highly diversified, complex, and systematic, the center needs to continuously improve its ability to build interdisciplinary teams and provide a platform for integrating various types of resources into the solution of healthcare problems of the elderly.

OBJECTIVE To explore the effect of acupuncture on the learning and memory ability and intestinal flora structure of senescence-accelerated mouse prone 8(SAMP8)mice.METHODS Eighteen 6-month-old SAMP8 mice were randomly divided in-to model group and acupuncture group,with 9 mice in each group,and 9 senescence-accelerated mouse resistant strain 1(SAMR1)mice of the same month as the normal group.The acupuncture group selected Baihui and Yongquan points for acupuncture,5 times a week,20 min each time,for 8 consecutive weeks.Morris water maze was used to detect the learning and memory ability of mice in each group,immunofluorescence method was used to detect β-amyloid protein(Aβ)expression in the cerebral cortex,and 16S rDNA technology was used to detect changes in intestinal flora.RESULTS The results of the water maze experiment showed that compared with the normal group,the learning and memory abilities of the mice in the model group were significantly reduced(P<0.05),and the learning and memory abilities of the mice in the acupuncture group were significantly improved compared with the model group(P<0.05).Immunofluorescence results showed that compared with the normal group,the model group had increased positive expression of Aβ in the cerebral cortex,and obvious Aβ plaque deposition could be seen;the acupuncture group had fewer Aβ plaques than the model group.Alpha diversity index showed that compared with the normal group,the Ace and Simpson values of the model group de-creased(P<0.05)and the Shannon value increased(P<0.05);compared with the model group,the Ace and Chao values of the acu-puncture group increased(P<0.05,P<0.01).In the beta diversity analysis,the results of principal component analysis(PCA)and principal coordinate analysis(PCoA)showed that the samples in each group were relatively clustered,and the distance between sam-ples in each group was far away.The Venn diagram showed that there were 664,689,and 649 OTUs in the normal group,model group,and acupuncture group,respectively.Results of intestinal flora structure analysis showed that compared with the normal group,the abundance of Bacteroidetes,Ruminococcaceae,and Eubacterium xylanophilum in the model group increased(P<0.05),and the abundance of Fusobacterium,unclassified Fusobacterium,and Porphyromonas decreased(P<0.05);compared with the model group,the abundance of Bacteroidetes and Eubacterium xylanophilum decreased in the acupuncture group(P<0.05),and the abundance of Fusobacterium,unclassified Fusobacterium,and Porphyromonas increased(P<0.05).CONCLUSION Acupuncture can reduce cortical Aβ deposition and improve learning and memory abilities in SAMP8 mice,which may be related to regulating the structure of intestinal flora and increasing species diversity.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective To establish a quantitative and visual prediction model for spontaneous hemorrhagic transformation(sHT)after acute ischemic stroke(AIS)and validate the efficacy by nomogram.Methods A total of 240 patients with AIS were selected,and the general data,serological tests and imaging findings were collected.The patients were randomly divided into modeling group(175 cases)and validation group(65 cases).The patients were also divided into non-HT group and HT group according to the imaging results.The R 4.1.1 software and the rms package were used to build the column line graph model,while Bootstrap method was applied to repeat sampling 1000 times for internal and external validation,and the H-L goodness-of-fit test,clinical decision curve and ROC curve were used to assess the calibration and discrimination of the column line graph model,respectively.Results Among 240 patients with AIS,bleeding conversion occurred in 60 cases(25.0%).In the modeling group,the results of multifactorial Logistic regression showed that the presence or absence of previous history of atrial fibrillation,NIHSS score at the onset,Hb,high-density lipoprotein(HDL)and infarct area were significant influencing factors for sHT after AIS.The x2 values of the H-L goodness-of-fit test for the modeling and validation groups were 5.61 and 0.74,respectively,corresponding to P values of 0.13 and 0.69,indicating that the established column line graph model had good prediction accuracy;the area under the ROC curve for the column line graph prediction modeling group and validation group were 0.963(95%CI:0.926-1.000)and 0.977(95%CI:0.950-1.000),and the results suggested that the model had good discrimination.Conclusions Previous history of atrial fibrillation,NIHSS score size at onset,Hb,HDL and the size of infarct area are independent influencing factors of sHT after AIS.Establishing the visual nomogram model based on the above factors can effectively predict the risk of sHT after AIS.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Objective To investigate the expression level of receptor-interacting protein serine threonine kinase (RIP) 3 in macrophages/monocytes activation in autoimmune hepatitis (AIH) and its regulation on inflammatory cytokines.Methods The degree of macrophage infiltration and the expression of RIP3 in liver tissues from patients with AIH or hepatic cysts by double-immunofluorescence.After 24 hours treated with different concentrations (0,1,3,6,10 μg/mL) of lipopolysaccharide (LPS),Necrostatin-1,the specific inhibitor of RIP3 signaling pathway,and 6-thioguanine,the active metabolite of azathioprine,the expression levels of RIP1 (RIP3 upstream signal molecule),RIP3 and mixed-lineage kinase domain-like protein (MLKL,RIP3 downstream substrate) in RAW264.7 macrophages were detected by Western blotting.The expression of macrophage-associated cytokine at mRNA level of each treatment group was determined by real time quantitative polymerase chain reaction (PCR).Student's t test and sum rank test were performed for statistical analysis.Spearman analysis was performed for the correlation analysis.Results Compared with hepatic cysts adjacent liver tissues,the infiltration of CD68 positive macrophages in liver tissue of AIH patients was significantly increased (4.75 ± 0.96 vs 28.86 ± 6.23),and the difference was statistically significant (t =7.80,P＜0.05),and the expression level of RIP3 also was significantly increased (15,11 to 22 vs 0,0 to 1),and the difference was statistically significant (Z=-2.66,P＜0.05).In vitro,compared with those of control group,the expression levels of RIP1,RIP3 and MLKL stimulated by LPS at 0,1,3,6,10 μg/mL were significantly increased,and the differences were statistically significant (t=4.00,4.90,6.40,10.30;3.80,9.30,9.80,9.00;4.90,9.90,9.30 and 7.70;all P＜0.05),and were dose-dependent (r=0.91,0.86 and 0.79,all P＜0.05).Furthermore,compared with those of LPS-stimulated group,the expressions of RIP1,RIP3,MLKL of LPS+Necrostatin-1 group were significantly decreased (0.73±0.11 vs 0.47±0.13,0.60±0.07 vs 0.37 ± 0.05,0.65 ± 0.22 vs 0.38 ± 0.04,respectively),and the differences were statistically significant (t=2.60,4.50 and 2.10,all P＜0.05).And the expressions of interleukin (IL)-1β,IL-6and IL-10 at mRNA levels were also decreased (810.3±200.8 vs 463.7±118.1,1 504.4±482.7 vs 290.4±106.9,1 358.6 ± 559.2 vs 677.8 ± 297.6,respectively),and the differences were statistically significant (t=5.40,12.52,5.70,all P＜0.05).However,the expressions of IL-4 and TGF-β at mRNA levels up-regulated (0.3±0.2 vs 0.6±0.3,0.4±0.1 vs 0.9±0.4,respectively),and the differences were statistically significant (t=4.60 and 6.10,both P＜0.05).Compared with those of the LPS-stimulated group,the expressions of IL-1β,IL-6 and IL-10 at mRNA levels of LPS and 6-thiopurine stimulated group significantly down-regulated (810.3±200.8 vs 283.4±65.5,1 504.4±482.7 vs 354.4±73.8,1 358.6± 559.2 vs 625.6±336.3),and the differences were statistically significant (t=4.30,10.60 and 3.50,all P＜0.05);however,the expressions of IL-4 and TGF-β at mRNA levels significantly up-regulated (0.3±0.2 vs 0.6±0.1 and 0.4±0.1 vs 0.5±0.1),and the differences were statistically significant (t=5.20and 12.50,P＜0.05).Conclusions The regulation effects of 6-thiopurine on RIP3 signaling pathway and related cytokines are similar to those of Necrostatin-1.And the expression of RIP3 signaling protein increasing in activated macrophages of liver tissues from AIH patients is closely related to the regulation of IL-6.The RIP3 mediated inflammatory signaling pathway in macrophage may be involved in the genesis and development of AIH and may be a potential therapeutic target.

Objective To explore the expression and clinical significance of sodium borate transporter member 11 of solute carrier family 4 (SLC4A11) and tumor protein P53 (TP53) proteins in gastric cancer (GC).Methods From March 2004 to December 2009,a total of 415 patients with GC,who received operation at Department of General Surgery of Affiliated Hospital of Nantong University,were enrolled.The clinical data and gastric tissues samples of them were collected.At same period,64 patients with non-malignant gastric diseases,who underwent surgery at Department of General Surgery of Affiliated Hospital of Nantong University,were also recruited.The clinical data and gastric precancerous tissues were also collected.The tissues were maken into tissue microarray (TMA).The expression of SLC4A11 and TP53 protein in tissue microarrays was detected by immunohistochemical staining.The relationship between the two proteins and clinicopathological parameters and prognosis of patients were analyzed.Chi square test,and univariate and multivariate analyses were used for statistical analysis.Results The positive rates of protein expression of SLC4A11 and TP53 in GC tissues were 48.19％ (200/415) and 34.94％ (145/415),respectively,which were higher than 17.19％ (11/64) and 6.25％ (4/64) in gastric precancerous lesions,respectively,and the differences were statistically significant (x2 =24.150 and 59.345;both P＜0.01).The results of statistical analysis showed that the expression of SLC4A11 was correlated with human epidermal growth factor receptor 2(Her2) levels,depth of invasion,distant metastasis and TNM staging (x2 =28.056,11.300,8.880,24.943;all P＜0.05).Meanwhile,the expression of TP53 was related with depth of invasion,lymph node metastasis,distant metastasis,TNM staging and preoperative carcinoembryonic antigen (CEA;x2=12.333,7.875,9.347,20.307,10.678;all P＜0.05).The expression of TP53 was significantly positive correlated with SLC4A11 expression (x2 =6.237,P=0.013).The results of univariate analysis showed that SLC4A11,TP53,SLC4A11+/TP53+,Her2,preoperative CEA and cancer antigen 19-9 (CA19-9) levels were correlated with the poor prognosis of GC patients (hazard ratio (HR)=1.947,1.459,1.797,1.419,2.221,1.908;all P＜0.05),while the results of multivariate analysis indicated that positive SLC4A11 and TNM staging were the independent parameters for judging the prognosis of patients with GC (HR =1.954,1.468,both P＜0.05).Conclusions The high expression of SLC4A11 and TP53 is related to the occurrence and development of GC.Combined detection of their changes will contribute to the early diagnosis and prognostic evaluation of patients with GC.

Objective: To explore the mechanism of excessive senescence in bone marrow-derived mesenchymal stem cells (BM-MSC) of mouse model with severe aplastic anemia (SAA) . Methods: 40 BALB/c mice were randomly assigned to two groups of control (n=20) and AA (n=20) . SAA mouse model was induced by intraperitoneal injection with IFN-γ and intragastric infusion with busulfan. BM-MSC were isolated and cultured from bone marrow of SAA and healthy mice. The cell morphology was observed by inverted microscope and cell cytoskeleton was stained by Rhodamine-Phalloidin; The level of proliferation was analyzed by CCK-8 method, and cell cycle was tested by flow cytometry. Senescence-associated β-galactosidase (SA-β-gal) assay was used to detect senescent BM-MSC; The expression of mTOR protein was detected by Western blot method. Results: BM-MSC from normal mice presented spindle-shaped, clear boundaries and stress fibers were arranged in parallel, neat. while BM-MSCs from SAA mice presented cell volume increases, tiled, ill-shaped and the stress fiber appeared to be disordered. The decreased activity of proliferation [more cells restricted in G₀/G₁ phase [ (77.461±1.567) % vs (46.045±2.055) %, t=-34.384, P<0.001], increased percentage of SA-β-gal positive cells [ (75±11) % vs (28±8) %, t=15.454, P<0.001] and notably enhanced expression of mTOR of BM-MSC from SAA mice were observed when compared with those from normal mice. Conclusion This study clarified senescent BM-MSCs from SAA model mice, which could be caused by the excessive activation of mTOR pathway.

Scales are important tools to measure and evaluate the severity degree and treatment effect of anxiety, but objective index with high quality is insufficient. Clinical researches of anxiety treated with acupuncture and moxibustion from the domestic and the oversea in recent 10 years are retrieved. The applications of all kinds of scales for anxiety treated with acupuncture and moxibustion in clinical research are analyzed, and problems needed to be paid attention to about scales are further explored. The establishment of effect evaluation system combining clinical symptoms with the quality of life is raised, so as to provide reference to further research.
Acupuncture Therapy ; Anxiety Disorders ; psychology ; therapy ; Evaluation Studies as Topic ; Humans ; Moxibustion ; Quality of Life ; Surveys and Questionnaires ; Treatment Outcome