Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Objective : To examine the association between prediabetes and the risk of cancer, so as to provide insights into precision cancer prevention. Methods: Based on the project of Early Screening and Comprehensive Interventions among Population at A High Risk of Cardiovascular Diseases in Changning District, Shanghai Municipality, baseline data were captured from permanent community residents at ages of 35 to 75 years from 2016 to 2019, including demographics, physical examinations, previous medical history and used of medications. The development of cancers was used as a outcome measure, and the follow-up was terminated by May 2021. The development of cancer was collected through the Changning Cancer Registration System, and the association between prediabetes and the risk of cancer was examined using a multivariable logistic regression model. Results: A total of 9 503 participants were finally included, with a mean age of (57.12±10.89) years. The participants included 2 167 cases with prediabetes (22.80%) and 7 336 individuals with normal glucose (77.20%), and included 3 713 men (39.07%) and 5 790 women (60.93%). A total of 114 new cases with cancers were diagnosed until the final follow-up, including 37 cases among prediabetic patients (1.71%) and 77 cases among participants with normal blood glucose (1.05%). Multivariable logistic regression analysis showed that after adjustment for age, gender, marital status, educational level, family annual income, smoking, alcohol consumption, body mass index, hypertension, administration of antihypertensive agents, dyslipidemia, administration of lipid-lowering agents and medical history of cardio-cerebrovascular diseases, a higher risk of cancers was detected among prediabetic patients than among participants with normal blood glucose (OR=1.528, 95%CI: 1.025-2.277), and prediabetes had no significant interactions with age, gender, smoking or alcohol consumption (all P>0.05). Conclusion Prediabetes is statistically associated with the risk of cancer.

This article reviewed the effect of transitional care on the readmission rate of chronic obstructive pulmonary disease (COPD) patients, and summarized the intervention methods and contents of transitional care, aiming to provide references and basis for establishing strategies and plans to reduce readmission rate of COPD patients.

Objective To investigate the effect of phenformin combined with hexokinase inhibitor 2-deoxyglucose (2-DG) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with phenformin, 2-DG or phenformin combined with 2-DG on 4T1 and MDA-MB-231 cells for 48 h, the cell proliferation in each group was detected by SRB and the apoptosis of cells was detected by flow cytometry. The concentration of glucose and lactic acid in cell culture supernatant was detected by ELISA. The activity of mitochondrial respiratory chain complex Ⅰ was detected by FlexStation3 and the mitochondrial oxygen consumption (OCR) was assayed with the Seahorse X Fe Analyzer. Results The hexokinase expression (4.6±0.17,3.73±0.21), glucose consumption (356±31，397±42) μg/10⁵ cells , Lactic acid concentration (5.59±0.52, 7.83±0.78) μmol/L in the supernatant of 4T1 and MDA-MB-231 cells in Phenformin group were higher than that in control group ( 1±0.15，1±0.12 ) , ( 289±25，301±32) μg/10⁵cells , ( 2.37±0.18，4.01±0.45) μmol/L (P < 0.01). Even if the dose was reduced by 90%, the cell viability of phenformin combined with 2-DG group (64.63±2.28, 51.97±2.29) % was still higher than that of phenformin group (86.70±1.83, 85.53±1.46) % (P<0.001). The combination of the two drugs significantly promoted the apoptosis of 4T1 and MDA-MB-231. In addition, compared with the phenformin group (5.59±0.52, 7.83±0.78) μmol/L, the phenformin combined with 2-DG group (3.46±0.37, 5.18±0.62) μmol/L cell lactic acid production also greatly reduced (P<0.01). Compared with the phenformin or 2-DG single-drug group, the phenformin combined with 2-DG group can significantly inhibit the growth rate of tumors in tumor-bearing mice (P<0.01). The median survival time of tumor-bearing mice in the phenformin combined with 2-DG group was 72.5 d, which was higher than that in the phenformin group 57 d and 2-DG group 55.5 d (P<0.01). Conclusion Hexokinase inhibitor 2-DG significantly enhances the therapeutic effects of phenformin on triple-negative breast cancer cells.

Objective:To observe any effect of repeated unilateral high frequency transcranial magnetic stimulation (rTMS) on the swallowing function and functional magnetic resonance images of dysphagic stroke survivors.Methods:Twenty stroke survivors with dysphagia were randomly divided into a treatment group ( n=10) and a control group ( n=10). Both groups received traditional swallowing rehabilitation training, while the treatment group was additionally provided with high frequency rTMS over the cortical area of the suprahyoid muscle group of the healthy contralateral cerebral hemisphere. The stimulation frequency was 5Hz and the stimulation intensity was 80% of the resting movement threshold. During the 20-minute treatment, there was a 20-second interval between each 2-second dose of stimulation. Before and after the treatment, both groups were evaluated using the Eating Assessment Tool-10 (EAT-10), a swallowing functional communication measurement (FCM) and the modified Mann Assessment of Swallowing Ability (MMASA). In addition, functional magnetic resonance imaging was used to observe any changes in the relevant brain regions. Results:After the treatment the average EAT-10, FCM and MMASA scores of both groups were significantly better than those before the treatment, with the treatment group′s averages significantly superior to those of the control group. After the treatment, the activation range of the parietal lobe, the superior parietal lobule, the BA7 region and the BA40 area in the treatment group was significantly larger than before the treatment and larger than the control group′s ranges.Conclusions:Repeated high-frequency transcranial magnetic stimulation of the cortical area of the suprahyoid muscles in the contralateral cerebral hemisphere can improve dysphagia and promote the activation of brain areas related to swallowing after a stroke.

Objective To investigate the clinical features and treatment of solid pseudopapillary neoplasm (SPN) of the pancreas.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 69 patients with SPN of the pancreas who were admitted to the Qilu Hospital of Shandong University from January 2012 to July 2017 were collected.Serum tumor markers detection,enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of abdomen were carried out preoperatively for all the patients,and a part of the patients received endoscopic ultrasonography (EUS).Surgery plans were formulated after completion of examinations.Observation indicators:(1) clinical features;(2) treatment situation;(3) results of pathological examination;(4)follow-up.All the patients were followed up via outpatient examination and telephone interview to detect the survival and tumor recurrence and metastasis till July 2017.Measurement data with normal distribution were presented by (x)±s and were compared by Student's t test.Count data were compared by chi-square test.Results (1) Clinical features:① epidemiologic features:the ratio of male to female was 1∶5.9;patients were aged between 9 and 65 years,including 40 under 30 years and 29 above or equal to 30 years.The onset age was (34± 15)years for male patients and (28 ± 11)years for female patients,respectively,with no statistically significant difference (t=1.364,P＞0.05).Of 69 patients,SPN was located at pancreatic uncinate process in 25 patients,at neck of pancreas in 12 patients,body and tail of pancreas in 32 patients.② Medical history:history of acute or chronic pancreatitis and abdominal trauma were denied by all the 69 patients.③ Clinical manifestation:26 patients had no obvious symptoms and were detected by physical examination;31 patients had discomfort in upper abdomen,nausea and vomiting;other patients were admitted to the hospital because of upper abdominal mass (10 patients),jaundice (1 patient) or nausea,constipation (1 patient).④ Laboratory examination:the levels of preoperative carcinoembryonic antigen (CEA) and CA19-9 were normal.⑤ Imaging examination:plane scan of the CT examination showed round or round-like low-density shadows in the 69 patients,including 51 of cystic solid lesion,13 of solid lesion and 5 of cystic lesion.Complete capsules were observed in 64 patients,blurred boundary between pancreas and adjacent viscera in 5 patients,calcified foci in the pancreatic parenchyma and capsules in 14 patients.Ten patients received MRI examination,and the T1-weighted images showed equal or slightly lower signal,T2-weighted images showed slightly higher signal in the plane scan,and T1-weighted and T2-weighted images of the tumor capsule showed continuous or non-continuous ring-like signal.The results of enhanced scan showed slightly heterogeneous enhancement of the capsule and the parenchyma of the pancreas in the arterial phase,and progressive enhancement in the venous and delayed phase,while the enhancement degree was lower than that of the normal pancreas parenchyma.The parenchyma was cloud-,papillaor mural nodule-like enhanced.Obvious enhancement was observed in capsule while not in the cystic components.The boundaries of the tumors in 5 patients were clear under EUS.Hypo-,iso-and hyperechoic regions were found in the masses,and the masses were confirmed as cyst-solidary type.Obvious calcified foci were found in 1 patient.(2) Treatment outcome:twenty-seven patients received laparoscopic surgery,including tumor expiration in 13 patients,distal pancreatectomy with preservation of spleen in 8 patients,distal pancreatectomy combined with splenectomy in 2 patients,middle pancreatectomy in 2 patients,pancreaticoduodenectomy with preservation of pylorus in 1 patient,pancreatic head resection with preservation of duodenum under the assistance of laparoscopy in 1 patient.Forty-two patients received open surgery,including tumor expiration in 12 patients,distal pancreateetomy with preservation of spleen in 10 patients,distal pancreatectomy combined with spleneetomy in 6 patients,middle pancreatectomy in 5 patients,pancreaticoduodenectomy in 7 patients (with preservation of pylorus in 2 patients) and pancreatic head resection combined with preservation of duodenum in 1 patient.One patient with SPN + hepatic metastasis received distal pancreatectomy+ metastatic foci resection in the lesser omental bursa,and then followed by radiofrequency ablation in the hepatic metastatic foci.Postoperative complications:21 of 69patients had postoperative complications,including 17 intestinal fistulas,2 abdominal bleedings,1 incomplete obstruction,1 pleural effusion + atelectasis,and all of them were cured by symptomatic treatment.(3)Pathological examination:the resection margins of 69 patients were negative.The mean diameter of the tumor was (7±4) cm (21 patients with tumor diameter ＜ 5 cm,and 48 with tumor diameter ≥5 cm).The tumor diameters of 4 in 10 male patients were above or equal to 5 cm,and the number was 44 in 59 female patients,with statistically significant difference (x2 =4.828,P＜0.05).The tumor diameters of 32 in 40 patients who aged under 30 years were above or equal to 5 cm,and the number was 16 in 29 patients who were aged above or equal to 30 years,with statistically significant difference (x2=4.895,P＜0.05).Solid,pseudo-papillary and cystic regions in the SPN tissues were seen under the light microscope.Tumor cells were surrounded the blood vessels and were arranged in the nest or sheet shape in the solid region;blood vessels were surrounded by one or multiple layers of tumor cells in the axis or pseudopapillary shape in the pseudopapillary region;large amount of mucus and clusters of blood cells were seen in the cystic regions.The result of immunohistochemistry showed that the positive rates of α1-antitrypsin,vimentin,β-catenin,progesterone receptor,CD10,synaptophysin and chromogranin A were 100.0％ (39/39),96.6％ (28/29),95.7％ (45/47),94.4％ (51/54),92.5％ (49/53),72.9％ (35/48) and 5.6％ (3/54),respectively.(4) Follow-up:63 of 69 patients were followed up for 1-68 months,with median time of 29 months.No SPN recurrence or metastasis was detected.One patient died of lung cancer at postoperative month 35 and other patients survived well.Conclusions SPN of pancreas is mostly detected in young female patients,and it could be solid or cystic.Abdominal enhanced CT or MRI examination could clarify the diagnosis.EUS-fine needle aspiration examination could provide pathological evidence for definitive diagnosis.Typical cellular morphology and pseudopapillary regions may provide hints for the diagnosis of SPN,and the diagnosis could be clarified when combined with the detection of vimentin,α 1-antitrypsin or other indexes.Complete resection of SPN and ensure negative resection margin are fundamental principles of treatment.

Objective:To evaluate the biological characters of C57-TgN(HBV adr2.0)SMMU transgenic mice. Methods: Integration,expression,replication and histology change of hepatitis B virus gene in F6 transgenic mice were estimated by ge-nomic DNA PCR,Western blotting,ELISA,immunohistochemistry,serum DNA PCR,transmission electron microscopy and H-E staining. Results: Hepatitis B virus gene was integrated into F6 C57-TgN(HBV adr2. 0)SMMU transgenic mice and expressed HBsAg,HBcAg and X protein in liver tissue. HBsAg and HBeAg were expressed in serum of 19. 54% and 3. 39% F6 transgenic mice. Hepatitis B virus were replicated in serum and liver tissue of transgenic mice. Long-term integration,expression and replication of hepatitis B virus gene induced pathological lesion of transgenic mice liver and lung. Conclusion: C57-TgNCHBV adr2. 0)SMMU transgenic mice line has the biological characters including integration of hepatitis B virus gene into genomic DNA,expression and replication of hepatitis B virus gene in serum and liver, and histological change in liver and lung. It is a valuable animal system to study pathogenesis, treatment and prevention of hepatitis B virus.