Objective:To study the effects of hepatitis B virus(HBV)infection in vitro on differentiation of mesenchymal stem cells(MSCs)to liver cells.Methods:MSCs were isolated from human bone marrow by density gradient centrifugation,and expanded by adherent culture.MSCs were cultured under liver-stimulating condition,and different composition of serum was added to the induced medium:Group A:5% fetal bovine serum(FBS);Group B:2.5% FBS+2.5% HBV-containing serum;Group C:2.5% FBS+2.5% serum from healthy volunteers;Group D:the undifferentiated MSCs cultured in LG-DMEM+10% FBS.The expressions of a variety of hepatic lineage markers were analyzed by immunocytochemistry and immunofluorescence.The functionality of differentiated cells was assessed by their ablility to store glycogen.After 2 weeks of exposure to HBV infected serum,HBV-specific protein was also detected by immunocytochemistry.Results:As a result of our hepatic induction,the expressions of albumin(ALB)and alpha-fetoprotein(AFP)by MSCs were observed by immunocytochemical and immunofluorescence techniques.Moreover,MSCs had acquired the ability of glycogen storage which was characteristic of liver cells.Compared with the control group,the proliferation of MSCs was inhibited greatly by the virus-containing serum.After 2 weeks of exposure to HBV infected serum,the surface antigen(HBsAg)was detected in some induced MSCs.However,after immunocytochemical stain for ALB and AFP,there was not much difference between the Group B and C.The ability of glycogen storage of two groups were almost the same.Using confocal microscopy,we found the co-expressions of ALB and HBsAg in the same differentiated cells.Conclusion:The bone marrow MSCs have the ability to trans-differentiate into functional hepatocyte-like cells,hence may serve as a cell source for tissue engineering and cell therapy of hepatic diseases.HBV infected serum could inhibit the proliferation of MSCs in culture,but it seemed that the hepatic differentiation of the cell was unsuppressed.

Objective:To investigate the types of non-tumor diseases in patients with cancer, and to explore the effects of those dis-eases on the diagnosis and treatment of cancer patients. Methods:We collected the medical records of cancer patients from January 2013 to December 2017 in Peking University Cancer Hospital, and screened for non-tumor diseases. The clinical records of the patients in this group were analyzed retrospectively, and the effects of those diseases on the diagnosis and treatment of tumors were dis-cussed. Results:Of the 1,323 cases of inter-hospital consultation, 1,153 cases of non-tumor disease (87.2％) were selected. There were 773 men (67.0％) and 380 women (33.0％) included. The median age was 62 (14-90) years. The primary tumor types included lung can-cer, gastric cancer, lymphoma, colorectal cancer, esophageal cancer, breast cancer, malignant melanoma, liver cancer, cholangiocarci-noma/gallbladder cancer, pancreatic cancer, and other tumors. Non-neoplastic diseases included cardiovascular disease in 356 cases (30.9％), respiratory system disease (17.0％) in 196 cases, digestive system disease in 107 cases (9.3％), skin and venereal diseases in 81 cases (7.0％), nervous system lesions (6.4％) in 74 cases, urinary system disease in 72 cases (6.2％), blood disease in 70 cases (6.1％), en-docrine and metabolic diseases in 47 cases (4.1％), autoimmune disease in 23 cases (2.0％), and other diseases (11.0％) in 127 cases. Impact on tumor diagnosis and treatment was as follows:direct, 771 cases (66.9％);no influence, 313 cases (27.1％);and uncertain, 69 cases (6.0％). Conclusions:Cardiovascular disease is a major non-tumor disease associated with cancer. Non-neoplastic diseases are important factors affecting the diagnosis and treatment plans of cancer.

OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.

Background and objective Chemotherapy is a highly effcient primary treatment for extensive-stage small cell lung cancer (ES-SCLC). However, patients receiving such treatment are prone to develop drug resistance. Local treatment is palliative and thus can alleviate the local symptoms and improve quality of life, but limited evidence is available for prolonging survival. Hence, this study evaluated the role of local treatment in chemotherapy of patients with ES-SCLC. Methods A total of 302 ES-SCLC cases were enrolled in this retrospective study. Prognostic factors were analyzed by Kaplan-Meier and Cox multivariate proportional hazards model. Results Median progression-free survival (PFS) and median survival time (MST) of the patients were 4.4 and 10.4 months, respectively. 1-, 2-, and 3-year survival rates were 37.8%, 10.2%and 4.4%, correspondingly. hTe MST of the primary tumor radiotherapy plus chemotherapy group was 14.3 months, whereas that of the chemotherapy group was 8.2 months (P<0.01). hTe MSTs of multiple-site, single-site, and non-metastasis local treatments were 18.7, 12.3 and 8.9 months, respectively (P<0.01). hTe MSTs of initiative, passive, and non-metastasis local treatments were 16.0, 10.9 and 9.4 months, correspondingly (P<0.01). hTe MSTs of patients with prophylactic cranial irradiation (PCI) and those without PCI were 19.8 and 9.9 months, respectively (P<0.01). Primary tumor radiotherapy, metastasis local treat-ment, and PCI were independent prognostic factors for ES-SCLC. Conclusion Primary tumor radiotherapy, metastasis local treatment, and PCI can signiifcantly improve survival in patients with ES-SCLC.

Background and objective Lung cancer is currently the leading cause of cancer death, two thirds of patients are over the age of 65. Small cell lung cancer (SCLC) accounts for about15%-20%of all lung cancer. hTe objective of this study is to evaluate the survival of patients older than 65 with SCLC and analyze the independent prognostic factors in this group of patients. Methods A retrospective study has enrolled160 cases of lung cancer aged over 65. hTe prognostic factors were analyzed by Kaplan-Meier and Cox multivariate proportional hazards model. Results ①hTe median follow-up time was12 (2-109) months.1-, 3-, and 5-year survival rate was 47.1%,13.0%, 9.6%respectively, and 74.4%, 25.0%,19.7%for limited-stage (LD), and 36.8%, 8.7%, 5.8%for extensive-stage (ED). Median survival time (MST) of all the patients was12 months, 24 months for LD and11months for ED, respectively.②Multivariate analysis suggested that performance status (PS) pre-treatment, the change of PS atfer treatment, stage, liver metastases and thoracic radiotherapy were the independent prognostic factors in all patients.③For LD-SCLC patients, PS pre-treatment, thoracic radiotherapy were the independent prognostic fac-tors. hTe model of thoracic radiotherapy (concurrent chemoradiation vs sequential chemoradiation, early concurrent chemo-radiation vs late concurrent chemoradiation) and prophylactic cranial irradiation (PCI) did not show signiifcant difference.④For ED-SCLC patients, sex, the change of PS atfer treatment, chemotherapy, liver metastases, thoracic radiotherapy, PCI were the independent prognostic factors. Conclusion hTe survival time is related to PS and thoracic radiotherapy in eldly patients. Besides, it is also related to sex, chemotherapy, liver metastases and PCI for ED-SCLC.

Background and objective Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). hTe aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes.Methods Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemo-therapy or targeted therapy) were identiifed. hTe rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no signiifcant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease speciifc-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group.Results Me-dian overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 monthsvs 12.6 months;P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 monthsvs 3.0 months;P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy atfer the diagnosis of brain metastases as any line therapy improved the OS (20.0 monthsvs 10.7 months;P<0.01), whereas receiving TKI as ifrst line therapy did not (17.9 monthsvs 15.2 months;P=0.289).Conclusion Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospec-tive multi-central randomized study is imminently needed.

ObjectiveTo investigate the protective effect of Jianpi Huogu prescription （JPHGP） on the functional injury of vascular endothelial cells caused by alcohol and explore its mechanism based on protein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathway. MethodThrough chick embryo allantoic membrane， thoracic aortic ring， and migration， invasion， adhesion， and lumen formation of human umbilical vein endothelial cells （HUVEC）， the effect of JPHGP with different concentrations （8， 16 and 32 μg·L^-1） on angiogenesis was observed in the presence or absence of alcohol. The expression levels of phosphorylation of Akt， JNK， and p38 MAPK were determined by Western blot. ResultAs compared with the normal group， the number and length of capillaries around the arterial ring in the model group were decreased， and the migration， invasion， and lumen formation capacity of HUVEC were decreased （P<0.05， P<0.01）. After treatment with 16 and 32 μg·L^-1 JPHGP， the length of neovascularization in chick embryo allantoic membrane was significantly increased （P<0.05， P<0.01）. Compared with the model group， the 8， 16， and 32 μg·L^-1 JPHGP groups increased the number of capillaries around the thoracic aortic ring in a concentration-dependent manner （P<0.05， P<0.01）， and the 32 μg·L^-1 JPHGP group increased the length of capillaries around the thoracic aortic ring （P<0.05）. The 16 and 32 μg·L^-1 JPHGP groups enhanced the migration， invasion， and lumen formation capacity of HUVEC. The results of Western blot showed that， as compared with the normal group， the protein expression levels of p-JNK/JNK， p-p38 MAPK/p38 MAPK， and p-Akt/Akt were significantly decreased in the model group （P<0.01）， and as compared with the model group， the protein expression levels of p-p38 MAPK/p38 MAPK and p-Akt/Akt were significantly increased in the 8， 16， and 32 μg·L^-1 JPHGP groups （P<0.01） and the protein expression level of p-JNK/JNK was increased significantly in the 16 and 32 μg·L^-1 JPHGP groups （P<0.01）. ConclusionJPHGP has a protective effect on the functional injury of vascular endothelial cells caused by alcohol， and its mechanism may be related to the activation of Akt/JNK/p38 MAPK signaling pathway. Relevant research results will provide certain scientific basis for clarifying the effect of JPHGP on 'invigorating spleen and promoting blood circulation'.