OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Objective To explore the regulation of DIRAS2 gene expression by acetylated STAT3 and its involvement in the proliferation of triple-negative breast cancer(TNBC)cells.Methods The expression levels of DIRAS2 and acetylated STAT3 in TNBC tissues and cells were analyzed by database query,Western blotting,and qRT-PCR.TNBC cell lines MDA-MB-231 and SUM159 were selected,and lentivirus or plasmid was used to construct DIRAS2 overexpression and STAT3 wild or Lys685 mutation cell lines.The CCK-8 assay was used to evaluate the effect of DIRAS2 and STAT3 acetylation on the proliferation of TNBC cells.Western blotting,pyrosequencing,ChIP and IP were employed to investigate the regulatory effect and mechanism of acetylated STAT3 on DIRAS2 expression.Results The expression of DIRAS2 was decreased in TNBC tissues and cells.Pyrosequencing analysis found that the methylation level of CpG islands in the DIRAS2 promoter was increased in TNBC cells compared with normal breast epithelial cells,which promoted the growth of cancer cells.Furthermore,TNBC cells showed an increase in STAT3 acetylation,which was accompanied by a shift in the methylation status of the DIRAS2 promoter.ChIP and IP experiments showed that acetylated STAT3 could bind to the DIRAS2 promoter,and the STAT3 Lys685 mutation disrupted the interaction between STAT3 and DNMT1.Conclusion Acetylated STAT3 induces DIRAS2 promoter methylation by recruiting DNMT1,leading to loss of DIRAS2 expression and cancer cell proliferation in TNBC.

Objective:To investigate the risk factors of restenosis after dilation of anastomotic stenosis in patients with esophageal cancer surgery.Methods:Clinical data of 997 patients who underwent endoscopic dilation due to anastomotic stenosis after esophageal cancer radical surgery in the Affiliated Huai′an First Hospital of Nanjing Medical University from June 2015 to July 2021, were retrospectively analyzed. There were 486 cases receiving single dilation (single dilation group) and 511 cases receiving more than two dilations (multiple dilation group). The risk factors of restenosis were explored using univariate and multivariate logistic regression analysis.Results:There were 682 males and 315 females with a median age of 65 years, the median distance between the stenosis and incisor was 20 (20, 22) cm, the median stenosis diameter was 4 (3, 5) mm, and the median stenosis diameter after dilation was 11 (11, 13) mm. Univariate analysis showed that there were significant differences in the distance of the stenosis and incisor ( Z=-2.303, P<0.05), stenosis diameter ( Z=-4.637, P<0.05) and stenosis diameter after dilation ( Z=-5.773, P<0.05) between single and multiple dilation groups. Stratified multivariate logistic regression showed that for male patients, risk of multiple dilations dropped by approximately 3% for every 1-mm increase in the distance between the stenosis and incisor ( OR=0.97, 95% CI:0.93-1.00, P=0.047); the risk of multiple dilations decreased by about 15%, for every 1-mm increase in stenosis diameter ( OR=0.85, 95% CI:0.76-0.94, P=0.004); the risk of multiple dilations decreased by about 13% for every 1-mm increase in stenosis diameter after dilation ( OR=0.87, 95% CI:0.78-0.96, P=0.007). For females patients under 60 years old, the risk of multiple dilations decreased by about 31%, for every 1-mm increase in stenosis diameter after dilation ( OR=0.69, 95% CI:0.47-0.98, P=0.049); for female patients≥60 years old, the risk decreased by about 5%, for every 1-year increase in age ( OR=0.95, 95% CI:0.91-1.00, P=0.037), risk of multiple dilations dropped by 17%( OR=0.83, 95% CI:0.70-0.99, P=0.039) for every 1 mm increase in stenosis diameter after dilation. Stratified smooth curve fitting indicated that the distance between the stenosis and incisor≤23 mm, stenosis diameter≤4.5 mm, stenosis diameter after dilation≤12 mm were risk factors for multiple dilations. Conclusions:The study indicates that patients with the distance between the stenosis and incisor≤23 mm, stenosis diameter≤4.5 mm, stenosis diameter after dilation≤12 mm may need multiple dilations; and the first dilation should expand the stenosis diameter to 12 mm or above as far as possible to reduce the risk of restenosis in patients receiving esophageal cancer radical surgery.

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

The increasing incidence of chronic kidney disease (CKD) has become a major global public health problem. Hypertension and CKD can cause and effect each other and often coexist. Controlling blood pressure is one of the core tasks in the treatment of CKD. Over the past 10 years, many large clinical studies have provided evidence-based medical evidence for the updating and revision of hypertension management guidelines, but there remains controversies in targets of blood pressure in hypertensive patients with CKD. Personalized and evidence-based management is the key to achieve effective control of blood pressure and slow the progression of CKD. This review will summary the epidemiological status of hypertensive patients with CKD and the progress related to the targets of controlling blood pressure in CKD.

In case of ischemic stroke(IS),thrombus in the vascular system can cause ischemia and hypoxia in brain tissue,produce inflammatory cytokines and cause brain tissue damage,while reactive oxygen species during ischemia-reperfusion cause stress injury.Conventional drug administra-tion is limited by the selective permeability of the blood-brain barrier and the low bioavailability of the drug itself,and its therapeutic effect against IS is unsatisfactory.Nanomedicine is expected to bring hope in that it has a unique mechanism of action and can cross the blood-brain barrier to reach the periphery of the infarct,release drugs or therapeutic genes,and exert a therapeutic effect.Nanomedi-cine inhibits platelet aggregation,enhances the efficacy of thrombolytic drugs,dissolves thrombus,increases blood supply to ischemic areas,eliminates reactive oxygen species and weakens injury response by fighting inflammatory cytokines.Loaded therapeutic genes regulate the differentiation pro-cess of neural stem cells,increase the number of neurons,induce the occurrence of blood vessels,and enhance the repair function of brain tissue.Nanomedicines can not only improve pharmacokinetics and pharmacodynamics to achieve more effective drug treatment,but also use nanoimaging technology to achieve real-time monitoring and condition assessment of therapy.

China’s chronic disease management suffers from problems such as unclear institutional function， insufficient information technology application， and weak regulation support. On the basis of current chronic disease management condition in China， this paper proposes to apply the concept of “people-centered” integrated health management to community chronic disease management and discusses the content and procedure of establishing an integrated community-based chronic disease management model driven by massive databases. The model innovatively combines technology integration， data integration and service integration， and can accurately and efficiently realize the "people-centered" full-course health management of various chronic diseases. Shanghai has provided integrated community-based chronic disease management service for 1.98 million citizens through applying this model. The model warrants further effectiveness and economic evaluation. This study provides precious experience for the development of chronic disease prevention and treatment in China.

The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.
Aged ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Neurodegenerative Diseases ; Parkinson Disease/therapy*

Objective:To investigate the expression of four cancer stem cell (CSC) markers (EpCAM, CD133, CD90 and CD24) in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells (CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods:A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM, CD133, CD90 and CD24. The clinical data of patients were collected, including tumor size, tumor number, satellite lesions, vascular invasion, Edmondson stage, BCLC stage and liver cirrhosis, etc. The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results:The positive expression rates of EpCAM, CD133, CD90 and CD24 in hepatocellular carcinoma tissues were 66% (33/50), 18% (9/50), 60% (30/50) and 56% (28/50); the positive expression rates in CTC were 55% (16/29), 38% (11/29), 31% (9/29) and 59% (17/29). CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis ( P<0.05), while CD133 expression was negatively correlated with the 5-year survival rate of patients ( P<0.05). The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage ( P<0.05). The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression ( P<0.05); the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression ( P<0.05). The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepatocellular carcinoma tissue and negative in peripheral blood ( P<0.01). Conclusion:Different expression characteristics of four markers in cancer tissues and peripheral blood CTC might provide useful information about predicting prognosis of hepatocellular carcinoma. The expression of CD133 in tissues can be used as an important survival predictor of hepatocellular carcinoma patients. The differential expression of cancer markers in tissue samples and blood samples can provide more clinical prognostic information.