Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome elements in type 2 diabetes mellitus （T2DM） patients based on maximum body mass index （maxBMI） and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients， extracting age， gender， smoking history， alcohol consumption history， duration of disease， HbA1c level， complications， and TCM syndromes， and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight； patients with maxBMI ≥24 kg/m² were classified into spleen-heat syndrome group， and those with maxBMI ＜24 kg/m² were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients， syndrome elements in spleen-heat patients （1034 cases） were primarily located in the spleen （351 cases， 33.95%）， liver （240 cases， 23.21%）， and stomach （139 cases， 13.44%）， while in consumptive-heat patients （144 cases）， they were concentrated in the spleen （57 cases， 39.58%）， liver （34 cases， 23.61%）， and kidneys （17 cases， 11.81%）； regarding syndrome elements of disease nature， spleen-heat patients were predominantly characterized by qi deficiency （481 cases， 46.52%）， phlegm （353 cases， 22.73%）， and dampness （241 cases， 23.31%）， whereas consumptive-heat patients showed more qi deficiency （84 cases， 58.33%） and yin deficiency （44 cases， 30.56%）. After propensity score matching， 132 cases were included in each group， and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups （P＞0.05）， but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients （P = 0.006）. Regarding the risk of complications， spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients （OR=2.04， P=0.010）， while no significant differences were found between groups in the occurrence of microvascular complications （P＞0.05）. ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm， and a higher risk of developing macrovascular complications compared to consumptive-heat patients.

In order to establish the isolation,culture and identification method of cow bone marrow-derived macrophages,three different media(RPMI-1640,DMEM,DMEM/F12)were added with 20％fetal bovine serum(FBS),2.4％chlorine-streptomycin,1.2％glutamine(Gln),and M-CSF(20 ng/mL),respectively,to induce the monocytes extracted from the bone marrow of dairy cows to become macrophages.The induced M0 macrophages were polarized into M1-type macrophages by adding lipopolysaccharide(LPS).The morphology of macrophages was observed by optical mi-croscope at day 1,4 and 7,and the differences of differentiated macrophages between the three media were compared.The effects of prostaglandin D2(PGD2)-DP2 receptor pathway on the secre-tion of cytokines(IL-6,TNF-α)induced by Escherichia coli and phagocytosis of macrophages were also investigated.The results showed that the morphological changes of cells cultured in the medium of RPMI-1640 were the most obvious and the number was large.A large number of char-acteristic markers of mononuclear macrophages were detected(M0 markers:CD1 1b,CD14;M1 markers:CD11b,CD80)expression,M0 and M1 macrophage purity were 79.9％and 93.5％,re-spectively.COX-2 and H-PGDS gene expressions were significantly increased in E.coli group com-pared with the blank control group.The secretion of PGD2also increased significantly(P＜0.000 1).DP2 receptor inhibitors(CAY10471,CAY10595)could significantly inhibit the secretion of E.coli in-duced pro-inflammatory cytokines(IL-6,TNF-α)and significantly enhance the killing effect of macrophages on E.coli.The above results showed that the induced cells had the characteristic mor-phology and immunophenotype of macrophages.E.coli can induce the production of PGD2 in mac-rophages,and the PGD2-DP2 pathway regulates the secretion of cytokines in E.coli infected macro-phages.

Objective To systematically evaluate the risk prediction model for central venous catheter-related bloodstream infections and provide references for clinical practice.Methods Databases such as CNKI,Wanfang,CBM,VIP,PubMed,Web of Science,Cochrane Library,etc.were retrieved.The search period is from database establishment to June 2,2023.There are 2 researchers who independently screened and extracted the literature,and evaluated the quality of the literature using bias assessment tools of predictive model risk.Results A total of 9 articles were included,including 9 risk prediction models for catheter-related bloodstream infections.The total sample size was 80～11 901 cases;the number of outcome events was 19～403 cases;the C index of the included model was 0.81～0.93.The area under the curve of the subjects ranged from 0.73～0.90.The predictors that appear more frequently in the model mainly included the history of diabetes,albumin value,the number of days of catheterization,the location of catheterization.The evaluation results of the bias assessment tool of predictive model risk for research show that the overall applicability of the included risk prediction models is good,but the bias risk is high.The reasons are related to the improper source of research sample data,inappropriate processing of continuous variable methods,failure to process missing data,insufficient model performance evaluation,and non-standard evaluation indicators.Conclusion There are still some shortcomings in the risk prediction model for central venous catheter-related bloodstream infections.In the future,the quality of related model research should be further improved,especially in terms of predictive factor analysis,model evaluation indicators,etc.,which should be further standardized.

Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's disease(AD).Methods GSE132903 was selected from GEO database as the analysis dataset.The differential expressed genes(DEGs)of AD were screened,and visualized with volcano and heat map.Aging and senescence-associated genes(ASAGs)were downloaded from MsigDB,Aging Altas and CellAge databases.WGCNA screened the gene modules with the highest correlation with AD,and genes of key modules subsequently performed with gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.Protein-protein interaction(PPI)network analysis was performed using the STRING database to find key node genes.The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database.The key genes were validated in Alzdata database.Results 226 DEGs,606 ASAGs and 8 ARDEGs were obtained.The top 5 key genes selected by PPI were SYP,STXBP1,VAMP2,CPLX1 and STX1A.Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated,except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex,as well as no expression of CPLX1 in frontal cortex.The differential expression of VAMP2,STXBP1 and STX1A appeared in the early stage of AD,and CPLX1 was related to the pathological process of Tau.SYP and STXBP1 were related to the pathological processes of amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.

Objective To investigate the improvement effect and mechanism of Modified Kongsheng Zhenzhong Dan medicated serum on mitochondrial function of PC12 cells injured by oxygen-glucose deprivation/reperfusion(OGD/R)based on the SIRT1/PGC-1α pathway.Methods PC12 cells were used to construct OGD/R cell model in vitro.Cell grouping:normal group(10%FBS),model group(10%FBS),10%drug-containing serum group,5%drug-containing serum group(5%drug-containing serum+5%blank serum),10%blank serum group(control group).CCK-8 method was used to detect the cell survival rate,and the appropriate oxygen glucose deprivation time(2,4,6,8 hours)was screened.MTT assay was used to detect cell activity;mitochondrial stress test(MST)was used to detect the oxygen consumption rate(OCR).Apoptosis was detected by flow cytometry(Annexin V-PE/7-AAD double staining).The protein expression levels of SIRT1 and PGC-1α in PC12 cells were detected by Western Blot.Results Compared with the normal group,the activity of PC12 cells decreased significantly after oxygen-glucose deprivation for 2,4,6 and 8 hours(P＜0.05),and 6 hours of oxygen-glucose deprivation was selected as the time of subsequent experimental modeling.Compared with the normal group,the cell activity of the model group was significantly decreased(P＜0.05).The OCR values of basic respiration value,maximum respiration value,proton leakage,ATP production and standby respiration ability were significantly decreased(P＜0.05).The apoptosis rate was significantly increased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly decreased(P＜0.05).Compared with the model group,the cell activity of the Modified Kongsheng Zhenzhong Dan 10%and 5%drug-containing serum groups was significantly increased(P＜0.05).The OCR values of basal respiration value,maximum respiration value,proton leakage,ATP production and spare breathing ability were significantly increased(P＜0.05).The apoptosis rate was significantly decreased(P＜0.05).The protein expression levels of SIRT1 and PGC-1α in cells were significantly increased(P＜0.05).Conclusion The Modified Kongsheng Zhenzhong Dan medicated serum can improve mitochondrial dysfunction,inhibit neuronal apoptosis and promote neuronal survival in OGD/R-injured PC12 cells.The mechanism may be related to the activation of SIRT1/PGC-1α signaling pathway.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Objective:To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis.Methods:The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group ( n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group ( n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results:The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group ( P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group ( P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively ( P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively ( P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively ( P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% ( P=0.565), 34.0% and 35.7% ( P=0.859), 43.4% and 33.3% ( P=0.318), and 20.8% and 50.0% ( P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group ( P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively ( P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively ( P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively ( P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation ( HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant ( HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion:allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Case 1: A 27-year-old female with ALK-positive anaplastic large cell lymphoma/leukemia; Case 2: A 27-year-old male with acute myeloid leukemia; Case 3: A 56-year-old male with myelodysplastic syndrome. These three patients underwent haploid hematopoietic stem cell transplantation and experienced severe oral mucosal inflammation, nausea, vomiting, diarrhea, and other symptoms over a long period, which significantly restricted eating. Neurological and psychiatric symptoms appeared at 50, 38, and 50 days following transplantation, respectively. The diagnosis of Wernicke encephalopathy was made by head magnetic resonance imaging, whereas the condition improved significantly after intravenous infusion of vitamin B 1.