This paper summarized the experience of Professor FANG Dingya in staged treatment of Sjögren's syndrome from the perspective of dryness toxin. It is believed that the cause of Sjögren's syndrome is externally-contracted dryness， consumption of essence and fluid， congenital and acquired essence deficiency， depleted essence and insufficient blood， and the core mechanism is internal accumulation of dryness toxin. The treatment can be divided into three stages， that is dryness toxin transforming into fire-heat， damp-heat and phlegm-stasis， from the perspective of dryness metal qi transformation. It is emphasized to dispel pathogen mainly， to clear and moisten with yin-nourishing medicinals in supplementation， and to treat by stages based on syndrome differentiation. For dryness toxin with fire-heat， it is suggested to moisten dryness， resolve toxins and subdue fire， with self-made Runzao Jiedu Decoction （润燥解毒汤） in modification. For dryness toxin with damp-heat， the method of nourishing yin， clearing heat and draining dampness should be used， and Chunze Decoction （春泽汤） in modification is suggested. For dryness toxin with phlegm-stasis， it is recommended to unblock collaterals， disperse phlegm and dissipate stasis， with self-made Sanyu Xiaotan Decoction （散瘀消痰汤） in modification.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.

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 explore the application effect of evidence-based clinical practice of enhanced recovery after surgery multiple discrepancies theory (ERAS-MDT) in perioperative nursing of patients with hepatectomy.Methods:From January to December 2018, 62 patients with hepatectomy who received perioperative care of ERAS-MDT in the Department of Hepatobiliary and Pancreatic Surgery of Ningbo First Hospital of Zhejiang Province were selected as the control group. We reviewed the implementation effect, searched the clinical practice guidelines, systematic reviews and evidence summary related to ERAS-MDT, carried out field investigation and expert consultation, summarized the obstacle factors, formulated countermeasures, and built a standardized operation mode of ERAS-MDT. From January to December 2019, a total of 66 patients with hepatectomy who received standardized ERAS-MDT perioperative nursing were selected as the observation group. The first exhaust time, defecation time, first ambulation time, first oral feeding time, hospitalization time, nutritional status and pain score were compared between the two groups.Results:The first exhaust time, defecation time, first ambulation time, first oral feeding time, hospitalization time of the observation group were earlier than those of the control group, and the differences were statistically significant ( P<0.05) . The albumin level of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The pain scores of the observation group on the operation day was lower than those of the control group, and the difference between the two groups was statistically significant ( P<0.05) . Conclusions:A standardized management model of ERSA-MDT based on evidence-based clinical practice exhibits positive effect on the perioperative recovery of hepatectomy patients, which can further improve the clinical outcome of patients.

OBJECTIVE：To investigate the intervention effect of Shenfu i njection（SFI）on the nuclear translocation of high mobility group box 1（HMGB1） in lipopolysaccharide （LPS）-induced RAW 264.7 cells. METHODS ： Using LPS-induced RAW264.7 cells as objects ，the histone deacetylase inhibitor RGFP 966 as positive control ，CCK-8 assay was used to screen drug dosage，and the effects of low ，medium and high doses （3，6，12 μL/mL）of SFI on HMGB 1 nuclear translocation in RAW 264.7 cells were observed by immunofluorescence method ；mRNA expression of HMGB 1 in RAW 264.7 cells were detected by real time fluorescent PCR. Western blotting assay was used to determine protein expression of HMGB 1 and Toll-like receptor 4（TLR4）；the expression of HMGB 1 were compared between nucleus and cytoplasm. The levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were detected by ELISA. RESULTS ：In blank control group ，HMGB1 was mainly located in the nucleus ；after LPS induction， HMGB1 migrated from nucleus to cytoplasm. Compared with blank control group ， mRNA and protein （No.81760738） expression of HMGB 1， protein expression of TLR 4 in RAW264.7 cells as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were increased significantly in LPS group （P＜0.01）. The protein expression of HMGB 1 was decreased significantly in nucleus while was in creased significantly in cytoplasm （P＜0.01）. After SFI treatment ，the nuclear translocation and secretion of HMGB 1 were inhibited in different degrees ；compared with LPS group ，mRNA and protein expression of HMGB 1 in administration groups ，protein expression of TLR 4 in RAW 264.7 cells of positive control group ，SFI medium- and high-dose groups as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells in administration groups were decreased significantly （P＜0.01）. In positive control group ，SFI medium- and high-dose groups ，the protein expressions of HMGB1 in nucleus were increased significantly ，while protein expressions of HMGB 1 in cytoplasm were decreased significantly （P＜0.01）. CONCLUSIONS ：SFI may inhibit the nuclear translocation and secretion of HMGB 1 in RAW 264.7 cells，thus avoiding the activation of inflammatory pathways and the production of inflammatory factors ，so as to reduce the inflammatory response induced by LPS.

Objective: To explore the cumulative effects of unintentional injury among children in rural area, in order to provide information for early intervention of unintentional injury. Methods: Through multistage clustering sampling method, 2 109 primary caregivers of students from 8 rural primary and elementary schools of Heilongjiang Province were recruited. Strengths and Difficulties Questionnaire (SDQ), Injury Behavior Checklist (IBC), Perceptions of Risks and Hazards were used to collect as the risk factors, while Perceptions of Risks and Hazards (PSAPQ), Home Observation for Measurement of the Environment (HOME) and Knowledge, Attitude and Practice for Children Unintentional Injury (KAP) were also used as the protective factors. Risk factors index (RFI) and protective factors index (PFI) were computed in the study. Results: The severity of unintentional injury were positively correlated with SDQ, IBC and perceptions of risks and hazards(r=0.15, 0.23, 0.12, P<0.01), and were negatively correlated with HOME, PSAPQ and KAP(r=-0.25, -0.14, -0.09, P<0.01). Hierarchical linear regression showed that the total scores of SDQ, IBC and environmental of HOME predicted the severity of unintentional injury which could explain 34% variant of unintentional injury. It also indicated that the severity of unintentional injury were positively correlated with RFI (β=0.21) and negatively correlated with PFI(β=-0.18), the interaction was significant(β=-0.11,R2=0.31)(P<0.01). Conclusion Both risk and protective factors of unintentional injury have cumulative effects on the severity of injury among rural children. The relationship between risk factors and injury could be mediated by protective factors.

OBJECTIVE： To study the improvement and anti-inflammation mechanism of Shenfu injection on lung tissue of endotoxin shock model rats. METHODS： Totally 48 rats were randomized into control group，model group，dexamethasone group （positive control，1 mg/kg） and Shenfu injection low-dose，medium-dose and high-dose groups （5，10，15 mL/kg），with 8 rats in each group. Except for normal group， other groups were given intraperitoneal injection of lipopolysaccharide （LPS） to induce endotoxin shock model. After modeling， each group was given relevant medicine once intraperitoneally. 24 h after medication， HE staining was used to observe pathological changes of lung tissue in rats and pathological scoring was conducted. RT-PCR was used to determine mRNA levels of P65 and P50 proteins related to NF-κB signaling pathway. Western blot assay was used to determine the expression levels of P65 and P50 proteins in lung tissue， and the expression levels of P65 protein in nucleus and cytoplasm of lung tissue were also determined. The level of TNF-α in plasma in rats were determined by ELISA. RESULTS： Compared with control group， alveolar septum became thicker， obvious vascular engorgement was found， and a large number of neutrophils infiltrated the interstitium in model group. Histopathological score， mRNA and protein expression levels of P65 and P50 in lung tissues were increased significantly （P＜0.01 or P＜0.001）； the protein expression of levels P65 in nucleus and cytoplasm and level of TNF-α in plasma were increased significantly （P＜0.001）. Compared with model group， alveolar structure of rats in dexamethasone group and Shenfu injection medium-dose and high-dose groups was complete， no obvious bleeding was observed， and the degree of inflammatory cell infiltration was improved significantly. Histopathological score， mRNA and protein expression levels of P65 and P50 in lung tissue and level of TNF-α in plasma were decreased significantly （P＜0.05 or P＜0.01 or P＜0.001）. The protein expression level of P65 in nucleus and cytoplasm of lung tissue were decreased significantly in dexamethasone group and Shenfu injection low-dose and medium-dose groups were decreased significantly （P＜0.05 or P＜0.01 or P＜0.001）. CONCLUSIONS： Shenfu injection can decrease mRNA and protein expression levels of P65 and P50 in lung tissue， level of TNF-α in plasma， and protect lung tissue of endotoxin shock rats.

Four new limonoid-type nortriterpenoids, 1-detigloyl-1--methacryloylsalannin (), 28-deoxo-2,3-dihydronimbolide (), 12-acetoxy-3--acetyl-7--tigloylvilasinin () and 12-acetoxy-3--acetyl-7--methacryloylvilasinin (), along with five known ones, were isolated from seeds of A. Juss. Their structures were elucidated by various spectroscopic methods, including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation, as well as by comparison of their spectroscopic data with those reported. In the cytotoxic assay, showed inhibitory activity against human breast cancer MDA-MB-231 cell line with IC value of 7.68±1.74 μmol/L, and inhibited growth of human cervical cancer Hela cell line, melanoma A375 cell line and promyelocytic leukemia HL-60 cell line, with IC 12.00±2.08, 17.44±2.11, and 13.95±5.74 μmol/L, respectively.

Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.

Objective To explore the relationship between osteoporosis and serum total type Ⅰ amino terminal extension of the peptide,vitamin D3 and smoking index in the patients with chronic obstructive pulmonary disease (COPD).Methods One hundred and fifty patients with COPD (test group) and 150 healthy people (control group) were selected.The total type Ⅰ amino terminal extension of the peptide was measured by electrochemical luminescence,and enzyme-linked immunoassay was adopted to determine the vitamin D3.The 150 patients with COPD were divided into slight group (45 cases),moderate group (52 cases) and severe group (53 cases) according to the severity of COPD.In 150 patients with COPD,120 patients with smoking were divided into 3 groups according to smoking index:A group smoking index ＜ 360,36 cases;B group smoking index 360-400,34 cases;and C group smoking index 401-560,50 cases.The levels of serum total type Ⅰ amino terminal extension of the peptide and vitamin D3 were compared and correlation was analyzed.Results The vitamin D3 and the total type Ⅰ amino terminal extension of the peptide levels in test group were significandy lower than those in control group:(35.37 ± 12.11) mg/L vs.(45.88 ± 12.55) mg/L and (38.16 ± 11.12) mg/L vs.(45.23 ± 12.33) mg/L,and there were statistical differences (t =2.74 and 4.64,P＜ 0.01).The levels of vitamin D3 and the total type Ⅰ amino terminal extension of the peptide in slight,moderate and severe group were decreased in turn,and the levels of total type Ⅰ amino terminal extension of the peptide and the vitamin D3 were positively associated with the severity of COPD (r =0.185 and 0.257,P ＜ 0.05).The levels of vitamin D3 and total type Ⅰ amino terminal extension of the peptide in A,B and C group were decreased in turn,and the levels of total type Ⅰ amino terminal extension of the peptide and the vitamin D3 were positively associated with smoking index (r =0.159 and 0.172,P ＜ 0.05).Conclusion COPD patients are easier to suffer from osteoporosis compared with healthy population,and the serum vitamin D3 and total type Ⅰ amino terminal extension of the peptide can forecast the osteoporosis in COPD patients.