Objective To observe effects of different extracts of Jianpi Huogu Formula (JPHGF) on proliferation and differentiation of bone marrow mesenchymal stem cell (BMSCs). Methods Whole bone marrow adherent was used to screen, culture, and isolate BMSCs. Extracts from different parts (water, chloroform, ethyl acetate and n-butanol parts) of JPHGF were administrated for a certain time. MTS was used to detent cell proliferation;ALP staining was used to detect ALP activity;ARS staining was used to detect the formation of calcium nodules;oil red O staining was used to detect fat cell formation. Results Extracts from different parts of JPHGF could promote cell proliferation of BMSCs in different levels, followed by its strength in water, chloroform, ethyl acetate, and n-butanol parts;ALP staining results showed that the intensity of ALP expression of the order is water, acetic acid ethyl, chloroform and n-butanol parts;in promoting the formation of calcium nodules, ARS staining results showed that its intensity were water, chloroform, ethyl acetate, and n-butanol parts;oil red O staining results showed that inhibition intensity of fat cells interaction strength was formed from ethyl acetate, water, chloroform to n-butanol parts. Conclusion Extracts from different parts of JPHGF have different effects on BMSCs proliferation and differentiation. Water extraction has the strongest osteogenic differentiation and proliferation, and ethyl acetate has the best effect on the inhibition of cell formation.

BACKGROUND:The majority of people do not believe that the femoral component flexion in total knee arthroplasty affect or affect little postoperative function and it is the only that the radiographic films is not satisfactory.So it has not caused people's enollgh attention.But the femoral component flexion affects the results of total knee arthroplasty obviously.OnJECTIVE:To investigate the curative effects of femoral component installed in the position of flexion during the operative procedure of total knee arthroplasty(123 knees)on the follow up results in 78 patients.DESIGN:Grouping contrast observation.SETTlNG:First Department of Bone and Joint,Wangjing Hospital of China Academy of Traditional Cllinese Medicine.PARTlCIPANTS:123 knees(78 patients)were given total knee arthroplasty in the First Department of Bone and Joint,Wangjing Hospital of China Academy of Traditional Chinese Medicine from October 2001 to June 2004.Seventeen(13.8%,15 patients)knees were found with femoral component flexion(FCF),in which there were 5 male cases and 10 female cases,aged from 47 to 81 years old.106(63 patients)knees were found without FCF,in which there were 22 male cases and 41 female cases,aged from 47 to 79 years old.METHODS:Total knee arthroplasties about their HSS rating scores,ranges of motion and flexion contractures werecompared in the two groups before operation and after operation,and the degrees of the FCF angle and the distances of femoral component flexion were measured.MAIN OUTCOME MEASURES:①Femoral Drostllesis flexion measurement;②HSS scores and activity:③femoral prosthesis flexion angle and distance buckling;④adverse events and side effects.RESULTS:Follow up lasted for one year above.①The degrees of flexion of femoral components were from 7°to 19°(average 11.3°)and the distance of flexion was from 2 mm to 4 mm(average 2.6 mln)in those 17 knees of total knee arthroplasty.②Differences in HSS rating scores and range of motion were not statistically significant(P＞0.05)before operations between the group of femoral component flexion and the group of femoral component plane.However,after operations the above aspects in the group of femoral component flexion were less than that in the group of femoral component plane significantly(P=0.01,P＜0.01),and were statistically significant(P=0.02,P＜0.01)between post-operations and pre-operations in HSS rating scores and range of motion respectively in the two groups.③The statistic differences in cases and angles of flexion contractures of postperations between the group of femoral component flexion and the group of femoral component plane were significant(P＜0.01),the situation in the group of femornl component flexion were more bad than that in the group of femoral component plane,but were all improved significantly in cases and angles of flexion contractures after operations in the two groups(P＜0.05,P＜0.01).④There was one case with the right deep venous thrombosis and one case with myositis ossifican in non-FCF group,and there was one case in FCF group with impingement sign between patellar and component.CONCLUSION:The findings show that femoral component flexion will increase the incidence of knee flexion contracture and result in knee extension dysfunction after total knee arthroplasty surgery.

Objective To observe the dynamic characteristics of protein kinase ,casein kinase II α (CK2α) ,expression during hepatic fibrogenesis in rats ;and the effects of a matrine derivative ,13-methylamino-18-thione-matrine (M ASM ) ,on CK2αexpression when it is used for anti-fibrotic treatment .Methods Hepatic fibrosis model was established in SD rats by dimethylnitrosamine (DMN) injection or by bile duct ligation (BDL) .The established fibrotic rats were given 50 mg/kg MASM or saline as a control by gavage for three weeks .The level of hepatic fibrosis was evaluated by histopathology examina-tion using hematoxylin-eosin staining ,and using the sirius red and Masson's trichrome staining for collagen determination in fi-brosis .The expressions of CK2αandα-smooth muscle actin (α-SMA) in hepatic tissues were detected by immunohistochemis-ry .Results CK2α is mainly expressed in the stellate cells of fibrotic livers induced by DM N or BDL comparing the control group .Along with the development of hepatic fibrosis as evidenced by α-SMA expression ,increased CK2α-positive cells in liver were detected while injecting DMN in the rats for one to four weeks .MASM treatment significantly inhibited the hepatic fibro-sis and suppressed the expression of CK2αcomparing the model group .Conclusion The expression level of CK2α,and hepatic fibrosis formation are positively correlated .The matrine derivative ,MASM ,can significantly inhibit hepatic fibrosis and sup-press the CK2αexpression .These results suggest CK2αmay be a potential target for hepatic fibrosis therapy .

Objective To establish the animal model of comorbidity of knee osteoarthritis(KOA)and hypertension with pattern of liver and kidney deficiency and evaluate its characteristics of comorbidity and pattern.Methods Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)were assigned to the WKY control group(control group),hypertension combined with KOA sham-operation group(sham-operation group),hypertension combined with KOA group(model group),hypertension combined with KOA and liver-kidney deficiency pattern group(LKD group).The animal model of KOA combined with hypertension was prepared by anterior cruciate ligament transection(ACLT)in spontaneously hypertensive rats.ACLT combined with intramuscular injection of hydrocortisone was performed to prepare an animal model of KOA with liver-kidney deficiency(LKD)pattern type,combined with hypertension.Then,the related indexes of LKD syndrome were detected in turn,including the contents of thyroid stimulating hormone(TSH),testosterone(T),corticosterone(CORT),adrenocorticotropic hormone(ACTH)in serum,and enzyme activities of alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP)in serum,the mass ratio of liver,kidney,spleen,thymus to the brain,body weight,anal temperature,activity situation,and emotion.Systolic blood pressure,diastolic blood pressure,and other blood pressure-related indices were also detected.The levels of serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),plantar mechanical pain sensitivity threshold,weight difference score of both hind limbs,hind limb joint swelling,and quadruped gait parameters were also measured.Furthermore,hematoxylin-eosin,safranine-fast green,and Masson staining were performed to observe pathological changes,cartilage degeneration,and bone destruction of the knee joint,and the microstructure parameters of the tibia were detected by Micro-CT imaging.Results Compared to the model group,the contents of serum TSH,ACTH,T,CORT and the mass ratio of the kidney,spleen,and thymus to the brain in the LKD group decreased(P<0.05).Compared to the control group,the systolic blood pressure and diastolic blood pressure of the other three groups increased significantly(P<0.05).Compared to the sham-operation group,serum TNF-α and IL-1β levels increased,plantar mechanical pain threshold decreased,weight difference score of both hind limbs and joint swelling of the affected limb increased(P<0.05),and gait parameters(e.g.,gait length and standing time of the affected limbs)became abnormal in the model and LKD groups.Simultaneously,the cartilage surface defect of the rat knee joint was severe,the arrangement of the surface chondrocytes was altered,the cartilage layer became thinner,the muscle fibers increased,and the cartilage ossification was severe.Furthermore,the relative volume,thickness,and number of trabeculae of the knee joint decreased significantly(P<0.05).Conclusion The rat model established in this study is consistent with the clinical characteristics of integrated traditional Chinese and Western medicine in patients with comorbidities of hypertension and KOA with liver and kidney deficiency pattern.This rat model can characterize the typical symptoms of liver and kidney deficiency pattern.It has typical pathological changes in knee cartilage and subchondral bone tissues and can maintain a stable range of high systolic and diastolic blood pressure.It also explore the scientific connotation of simultaneous treatment of different diseases in traditional Chinese medicine,revealing the therapeutic mechanism and developing new drugs.

Objective To find small molecules binding specifically to signal transducer and activator of transcription3 (STAT3) based on surface plasmon resonance (SPR) technology and confirm their inhibitory activities to STAT3. Methods The biomolecular interaction analysis T200 system based on SPR technology was used to couple the purified protein STAT3 to CM5 chip under the optimal pH conditions. The compounds with high binding response value were screened out from 50 candidate compounds derived from traditional Chinese medicines and the binding specificity was then confirmed. Biological experiments were performed to confirm the inhibitory effects of the screened compounds on STAT3. The binding pattern of STAT3 and the compound was fitted by molecular docking technique. Results More than 10 candidate molecules exhibited binding activities to STAT3 and kinetics assays revealed that only one candidate molecule, apigenin, showed specific binding. Western-blot analysis exhibited that apigenin inhibited the phosphorylation of STAT3 dose-dependently. Luciferase reporter gene assays demonstrated that apigenin also inhibited IL-6-induced STAT3 transcriptional activity in a dose-dependent manner. Molecular docking results showed that apigenin binds to the SH2 domain of STAT3, and interacts with key residues Glu638, Gln644, Gly656 and Lys658 by hydrogen bonds and with Tyr657 through π-π interactions. Conclusion Apigenin was a direct inhibitor of STAT3.

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.

Annexin A3（ANXA3）is a member of the membrane associated protein family. It has two subtypes of 36 kDa and 33 kDa. Its gene is located on the fourth chromosome of human. ANXA3, widely expressed in human bone marrow, lung, placenta, prostate and thyroid, is closely related to several biological processes such as exoplasmosis, vascular production, fat cell maturity, and white blood cell migration. Studies have found that ANXA3 is abnormally expressed in various diseases including cancer, cardiovascular disease and inflammation. It can regulate multiple signaling pathways such as JNK, NF-κB, PI3K/AKT, and may become a potential drug target for treatment of related diseases. The structure, functions, the link with diseases and related mechanisms of ANXA3 were summarized in this paper, which could provide reference for ANXA3 related research.

ObjectiveTo elucidate the mechanism of Osteoking against fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation by integrating heterogeneous information network mining and experimental validation. MethodOn the basis of the disease-related database and transcriptome expression profiling dataset， as well as the ETCM database， the gene sets related to four target diseases and the candidate target spectrum of Osteoking were obtained through the integration and analysis of bioinformatics data， and a "disease-syndrome-formula-target-pathway-effect" heterogeneous information network was constructed. In addition， by functional enrichment analysis， the core targets of Osteoking in interfering with the imbalance network of four kinds of bone injury diseases， the biological pathways involved， and the corresponding clinical symptoms were screened， and they were verified in animal experiments. ResultHeterogeneous information network mining indicates that Osteoking may commonly reverse the imbalance networks of fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation via regulating cell function and activity， inhibiting inflammatory response， reducing bone destruction， and improving the immune function of the body by modulating relevant core candidate targets such as RAC-alpha serine/threonine-protein kinase （Akt1）， catenin beta-1 （CTNNB1）， epidermal growth factor receptor （EGFR）， heat shock protein 90-alpha （HSP90AA1）， and phosphatidylinositol 3-kinase catalytic subunit alpha isoform （PI3KCA）， as well as related biological pathways such as phosphatidylinositide 3-kinases/protein kinase B （PI3K/Akt）， janus kinase/signal transducer and activator of transcription （JAK/STAT）， tumor necrosis factor （TNF）， nuclear factor kappa-B （NF-κB）， and Toll-like receptors. In particular， Osteoking may improve the blood supply of the fracture end by regulating blood circulation at the target site of the disease， and it may maintain the balance of bone metabolism by regulating hormone-related pathways to promote fracture healing. In addition， Osteoking may relieve lipid metabolism disorders by targeting and regulating lipid-related pathways， accelerate bone formation and bone repair， and delay the progression of femoral head necrosis. Osteoking may relieve the symptoms of pain by acting on neurological pathways to reduce local nociceptive stimulation in patients with osteoarthritis and lumbar disc herniation. Further experimental validation demonstrates that the PI3K/Akt signaling pathway is the most significantly enriched pathway for the key network targets of Osteoking for the four diseases. The candidate target of Osteoking may have the strongest association with the network of fracture-related genes. Therefore， this study chooses fracture as the target disease to verify the efficacy of Osteoking. The results show that Osteoking can accelerate bone formation and promote fracture healing by inhibiting the activation of the PI3K/Akt signaling axis. ConclusionThe study shows that the main mechanism of "treating different diseases with an identical treatment" of four bone injury diseases with Osteoking involves cell function regulation and immune inflammation-related signaling pathways. Further experimental validation identifies that the PI3K/Akt signaling axis may be one of the key pathways of Osteoking to promote bone regeneration， bone reconstruction， and bone metabolism homeostasis.

Sophora alopecuroides, a plant of the family Leguminosae, is one of the Daodi herbs in Ningxia. The active constituents of Sophora alopecuroides are abundant and complex, including alkaloids, flavonoids, volatile oils, steroids, polysaccharides, fatty acids and so on. In recent decades, a great number of domestic and overseas studies have been carried out on Sophora alopecuroides alkaloids, which have anti-hepatitis, anti-liver fibrosis, anti-cirrhosis, anti-liver failure and anti-liver cancer and other pharmacological effects. Clinically, Matrine-related drugs are used to treat hepatitis B virus infection and other diseases. This review aims to summarize the main active ingredients of Sophora alopecuroides, mainly focusing on the research progress in their treatment activities for liver diseases.

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.