Objective:To discuss the effect of acupuncture on the differentiation and apoptosis of quadriceps muscle satellite cells in model rats with knee osteoarthritis(KOA),and to clarify its related mechanism.Methods:A total of 40 SPF-grade rats were selected and randomly divided into control group,model group,celecoxib group,and acupuncture group,with 10 rats in each group.The rats in control group only underwent joint cavity incision followed by suturing,while the rats in model group,celecoxib group,and acupuncture group were used to replicate the KOA models.The maximum circumference of the femoral segment of the affected limb,rat body mass,and quadriceps wet weight of the rats in various groups were measured;the quadriceps wet weight maintenance rate and quadriceps wet weight/body mass ratio of the rats in various groups were calculated.HE staining was used to observe the pathomorphology of articular cartilage and quadriceps muscle tissue of the rats in various groups;terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of interleukin-6(IL-6),Janus kinase(JAK),and signal transducer and activator of transcription 3(STAT3)in quadriceps muscle tissue of the rats in various groups;Western blotting method was used to detect the expression levels of IL-6/JAK/STAT3 signaling pathway proteins,and muscle satellite cells,and apoptosis-related proteins in quadriceps muscle tissue of the rats in various groups.Results:Compared with control group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in model group were significantly decreased(P<0.05);compared with model group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in acupuncture group were significantly increased(P<0.05).The HE staining results showed that the knee articular cartilage of the rats in control group remained intact,chondrocytes were aggregated and horizontally arranged with smooth edges,and quadriceps muscle cells were long cylindrical,orderly arranged,and regular in shape;in model group,the knee articular cartilage was thinner with rough edges,reduced number of cartilage layers,and disordered arrangement,and the quadriceps muscle fibers were disorganized,with some muscle fiber dissolution and muscle cell membrane damage,accompanied by muscle fiber fragments and a large amount of inflammatory exudate;in celecoxib group,the morphology of knee articular cartilage was generally normal,occasionally with irregular cartilage arrangement and reduced thickness,sporadically visible necrotic chondrocytes,quadriceps muscle fibers and sarcolemma were relatively intact,new muscle fibers appeared,some muscle fiber edges were blurred,accompanied by a small amount of cell debris and mild inflammatory infiltration;in acupuncture group,the knee articular cartilage structure remained intact with smooth edges,occasionally rough edges,and chondrocytes were aggregated and orderly arranged.The TUNEL assay results showed that compared with control group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly decreased(P<0.05);compared with celecoxib group,the apoptosis index in articular cartilage and quadriceps muscle tissue of the rats in acupuncture group were significantly decreased(P<0.05).The immunofluorescence assay results showed that compared with control group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of IL-6,JAK,STAT3,paired box transcription factor 7(Pax7),Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).Compared with control group,the expression levels of B-cell lymphoma 2(Bcl-2),B-cell lymphoma-xl(Bcl-xl),and myeloid cell leukemia 1(MCL1)proteins in quadriceps muscle tissue in model group were significantly decreased(P<0.05),and the expression levels of Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)proteins were significantly increased(P<0.05);compared with model group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05);compared with celecoxib group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05).Conclusion:Acupuncture can promote the differentiation of quadriceps muscle satellite cells and inhibit muscle cell apoptosis in the model rats with KOA,and the mechanism may be related to the up-regulation of expressions of IL-6,JAK,and STAT3 proteins in the quadriceps muscle tissue.

Due to the long pathological process of Alzheimer disease(AD),this paper begins with the time-line of classical pathological events in AD and uses anomalous microglia activation as a starting point to elucidate the role of abnormal lipid metabolism in the pathological process of AD.This includes its influence on microglial pathology and its interactions with the two primary nodes of AD,namely,Amyloid-β and the microtubule-associated protein tau.Using this as a foundation,the paper briefly describes the effects of abnormal lipid metabolism caused by short-term and long-term high-fat diets on the pathological progression of AD and its potential mechanisms,aiming to provide a reference framework for the early intervention of AD.

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism* ; Flavonoids/metabolism* ; Molecular Docking Simulation ; Prenylation ; Saccharomyces cerevisiae/metabolism* ; Sophora/metabolism*

Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.

Objective:To evaluate the efficacy of splenic artery ligation on liver function recovery and hypersplenism in liver transplant patients with end-stage liver disease complicating portal hypertension and hypersplenism.Methods:From Jan 2016 to Jan 2019, the clinical data of patients undergoing liver transplantation at our hospital were analyzed retrospectively, among which 53 patients were enrolled in the study with end-stage liver disease complicated with portal hypertension and hypersplenism. Patients were divided into ligation group( n=23) and no ligation group( n=30). The serum liver function and white blood cells, platelets and postoperative complications were compared. Results:20 pairs of patients were successfully matched by PSM method. All patients were followed up for over 6 months.There was no statistically significant difference between the two groups in all the observation points within 2 weeks after operation; Within 6 months, there was no statistically significant difference in WBC, platelet and Hgb.Statistically significant differences in postoperative complications such as infection, gastrointestinal bleeding, and splenic artery stealing syndrome were also not found between these two groups.Conclusions:Splenic artery ligation during liver transplantation does not accelerate liver function recovery nor ameliorate hypersplenism.

Hepatocellular carcinoma is one of the most common malignancies of liver cancer.Partial hepatectomy and liver transplantation are potentially curative treatments in patients with hepatocellular carcinoma.However,the postoperative tumor recurrence rate is high with poor long-term survival outcome.Studies have shown that the presence of microvascular invasion is an independent risk factor of post-resection prognosis.Therefore it draws attention that whether postoperative TACE can prevent the recurrence of liver cancer.This article reviews the research progress postoperative TACE effect on hepatocellular carcinoma patients with microvascular invasion,in order to provide the reference for selection of further treatment.

Objective To observe the effects of associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) on liver regeneration of the unligated lobe with cirrhosis.Methods 60 liver cirrhosis SD rats were randomly divided into three groups:C-ALPPS group (n =20,liver cirrhosis + ALPPS),C-PVL group (n =20,liver cirrhosis + PVL) and C-Sham group (n =20,liver cirrhosis + sham operation).60 normal SD rats were randomly divided into three groups:N-ALPPS group (n =20,normal liver + PVL),N-PVL group (n =20,normal liver + PVL) and N-Sham group (n =20,normal liver + sham operation).The weight ratio of unligated lobes/total liver,proliferating cell nuclear antigen (Ki-67) and liver function were compared before operation and 2,4 and 7 days after operation.Results Except for sham operation group,liver weight ratios of unligated livers on the 4th and 7th days after operation were lower than those in the normal group (P ＜ 0.05).The weight ratios of unligated lobes/total liver in C-ALPSS group and N-ALPPS group on 4th and 7th day postoperation were (54.3 ± 3.1)％ vs.(61.2 ± 2.1)％,(65.0 ± 4.1) ％ vs.(79.2 ± 1.1) ％.The weight ratio unligated lobes/total liver in group C-PVL and group N-PVL at 4th and 7th day postoperation were (52.4 ± 1.8) ％ vs.(56.6 ± 2.0) ％,(63.8 ± 3.1) ％ vs.(70.0 ± 2.5) ％.There was no significant difference on weight ratio of unligated lobes/total liver between C-ALPPS group and C-PVL group at each time point (P ＜ 0.05).There was significant difference on the alanine transaminase (ALT),aspartate aminotransferase (AST) and albumin (ALB) levels between cirrhosis group and normal group at 4 and 7 days after operation (P ＜ 0.05).The expression level of Ki-67 in cirrhosis group was significantly lower than that in normal group at each time point (P ＜ 0.05).The expression level of Ki-67 in group C-ALPSS and group N-ALPPS at 2nd,4th and 7th day after operation were (19.4 ± 4.8)％ vs.(84.1 ±8.9)％,(33.6±3.5)％ vs.(70.2±7.2)％,(20.2±2.5)％ vs.(50.7±4.4) ％,and the expression level of Ki-67 in group C-PVL and group N-PVL at 2nd,4th and 7th day postoperationwere (21.1±4.0)％ vs.(52.1 ±7.3)％,(32.4 ±5.9)％ vs.(35.6 ±5.3)％,(15.5± 4.6) ％ vs.(12.2 ±4.9) ％.There was no significant difference of Ki-67 levels between C-PVL group and C-ALPPS group at 2 and 4 days after operation (P ＜ 0.05).Conclusions In normal rats,the liver regeneration rate after ALPPS was significantly higher than that after PVL.The liver regeneration rate after ALPPS in cirrhotic rats was significantly lower than that in normal rats after ALPPS.There was no significant difference of the liver regeneration rate between ALPPS and PVL in cirrhotic rats.

Arsenic trioxide (ATO) has been identified as an effective treatment for acute promyelocytic leukemia (APL) but is much less effective against solid tumors such as hepatocellular carcinoma (HCC). In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yl)tryptophan methyl ester (ETME). Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP) in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.

Objective To explore stress response of government employees,businessmen and police officers.Methods A total of1547 government employees,8672 businessmen and1555 police officers were recruited and completed a questionnaire survey concerning psychological stress.t or F test was used for data analysis.Results There were significant differences of stress response among government employees,businessmen and police officers ( P ＜ 0.01).Male or female government employees showed different stress response,physiology,emotion and behavior (all P＜0.01).Government employees from various age group showed difference in emotion and behavior ( both P ＜ 0.01).Businessmen of various gender and age were found difference of stress response at all dimensions ( P ＜ 0.05 ).Police officers of different gender showed different behavior ( P ＜ 0.0l ).ConclusionIt may be necessary to carry out occupation-specific stress management for individuals.