ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism， so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking， the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system"， and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions， including the Third Affiliated Hospital of Beijing University of Chinese Medicine， Peking Union Medical College Hospital， Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital， from May 1， 2020 to December 31， 2021， were selected in the system. It included 60 patients treated with Osteoking and joint injection， and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score， visual analogue （VAS） pain score， individual types of pain symptoms （cold pain， hot pain， tingling， dull pain， soreness） and other TCM symptoms were observed and compared between the two groups， and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission， this study used the "Bone Injury Cross Database （http：//bone-xtrans.com/database，BX-Data）" to collect the gene set of knee osteoarthritis disease， the traditional Chinese medicinal materials， chemical composition， material base， candidate target， candidate target， sodium hyaluronate candidate target data for screening， and constructed an interaction network of "disease target". ResultsAmong the 105 patients with knee osteoarthritis enrolled， 15.24% （16/105） were in the episodic period， 84.76% （89/105） were in remission， and there were no convalescent patients. There were 72 cases （68.57%） in women， 33 cases （31.43%） more than men， 60 cases in the observation group and 45 cases in the control group in 105 patients. There were 20 patients with a VAS score of 5 and 19 patients with a score of 6 in the observation group， accounting for 65.00% of the observation group. The comparative results of VAS scores between groups before and after treatment showed that the scores of the two groups were （4.42±1.01） scores， （5.00±1.02） scores.4 weeks after treatment， and （3.12±1.04） scores and （3.56±1.08） scores，8 weeks after treatment， respectively， which were lower than those before treatment （6.23±1.28） scores，（ 6.02±1.22） scores （P<0.05）， and the comparative results of the pain properties of the two groups showed that the improvement rates before and after thermal pain and tingling in the observation group were 3.3%（2/60） and 16.7%（10/60）， respectively. The control group was 2.2% （1/45）and 15.6%（7/45）［（χ²=4.034、13.583，P<0.05）］， respectively， and the improvement rate of cold pain and soreness in the observation group was 5.0%（3/60） and 3.3%（2/60）， which was higher than that of the control group . The results of comparing the WOMAC scores before and after treatment of the two groups showed that the difference between the stiffness score before and after treatment in the observation group was （1.68±1.42） scores， the difference between the score before and after treatment in the control group was （1.20±1.60） scores （P<0.05）， and the pain score before and after treatment was （3.43±2.88） scores， the difference before and after daily activity score was （12.37±10.21） scores， and the total score before and after treatment was （17.48±12.76） scores， which were also higher than those in the control group （2.82±3.29）， （10.80±9.63），（14.82±12.62） scores. The results of comparing the improvement of other symptoms before and after treatment showed that the improvement rate of less sleep and more dreams in the observation group was 28.3%（17/60）， which was significantly higher than that of the control group of 2.2%（1/45）（χ²=5.914，P<0.05）， and the improvement rates of the five symptoms of thirst and drinking， irritability， dry mouth and pharynx， dull complexion and hand， foot and mouth fever in the observation group were 3.3%（2/60）， 10.0%（6/60）， 8.3%（5/60）， 10.0%（6/60） and 5.0%（3/60）， respectively， which were higher than those in the control group -2.2%（1/45）， 2.2%（1/45）， 2.2%（1/45）， 4.5%（2/45）， -6.7%（3/45）. Through network analysis， it was found that the enrichment pathway of Henggu bone wound healing agent mainly acted on the three mechanisms of bone improvement， energy metabolism and anti-inflammatory and analgesic， and the sodium hyaluronate enrichment pathway mainly acted on the anti-inflammatory and analgesic mechanism. ConclusionThe efficacy of Osteoking combined with intra-articular injection of sodium hyaluronate in the treatment of patients with knee osteoarthritis in attack and remission is better than that of sodium hyaluronate alone， especially in anti-inflammatory and analgesic， and the two drugs have synergistic effect. Osteoking may play its role in relieving the symptoms of joint stiffness， tingling， heat pain， and less sleep and more dreams by improving bone quality and regulating the body's energy metabolism pathways， which is worthy of clinical promotion.

ObjectiveTo explore the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis based on real-world data and provide a basis for clinical medication. MethodFrom May 2020 to December 2021， the data of a total of 1 002 patients with knee osteoarthritis who did not undergo knee joint replacement surgery was collected through the registration method. 952 patients were ultimately included， including 133 cases orally taking Osteoking combined with non-steroidal anti-inflammatory drugs as the observation group and 73 cases orally taking non-steroidal anti-inflammatory drugs alone as the control group. Statistical analysis was conducted on the baseline data， VAS scores， WOMAC scores， and other items. The visit point is the 4^th and 8^th weeks after registration. In order to further elucidate the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis， the effective components of Osteoking and the relevant gene sets of non-steroidal anti-inflammatory drugs and knee osteoarthritis were obtained through network pharmacology methods and retrieval in bone injury cross database， TCMSP， and other databases. Venn analysis was performed on the relevant gene sets， and a PPI network diagram was constructed. Then key core targets were screened out， and enrichment GO and KEGG enrichment analyses were conducted. ResultThe VAS score of the observation group decreases by an average of （-2.79±1.206） scores in the 4^th week， which is better than the control group ［（-2.73±1.575） scores， P<0.05］. The VAS score of the observation group decreases by an average of （-3.97±1.308） scores in the 8^th week， which is better than the control group ［（-3.89±1.822） scores， P<0.05］. The total WOMAC score of the observation group decreases by an average of （-52.07±21.677） scores points in the 8^th week， which is significantly better than the control group ［（-46.75±25.368） scores， P<0.05］. The observation group has an average decrease of （-10.99±4.229） scores in WOMAC （pain） score in the 8^th week， which is better than the control group ［（-10.03±5.535） scores， P<0.05］. The observation group has an average decrease of （-1.49±2.901） in WOMAC （stiffness） score in the 4^th week， which is better than the control group ［（-0.92±1.998） scores， P<0.05］， and the observation group has an average decrease of （-1.90±3.200） scores in WOMAC （stiffness） score in the 8^th week， which is better than the control group ［（-1.26±2.230） scores， P<0.05］. The observation group shows an average decrease of （-39.17±16.562） scores in WOMAC （joint function） score in the 8^th week， which is significantly better than the control group ［（-35.47±20.098） scores， P<0.05］. According to network pharmacology analysis， the core network target of Osteoking in treating knee osteoarthritis is manifested as regulating signal pathways such as signal transduction transcription activator 3（STAT3）， vascular endothelial growth factor A（VEGFA）， tumor necrosis factor （TNF） to regulate cell signaling， angiogenesis， chondrocyte proliferation and migration， and inflammatory cells， thereby inhibiting inflammatory reactions， reducing damage， and delaying the development of the disease. ConclusionAfter a 4-week and 8-week course of treatment for knee osteoarthritis with Osteoking combined with non-steroidal anti-inflammatory drugs， there is a significant therapeutic effect on relieving pain and joint stiffness and improving joint function. In network pharmacology， Osteoking is involved in regulating inflammatory factors， metabolic response-related biological processes， the proliferation and apoptosis of chondrocytes， etc. in the treatment of knee osteoarthritis， resulting in anti-inflammatory and analgesic effects and improving joint mobility and joint stiffness. Therefore， it is worthy of clinical promotion and application.

Objective:To explore the correlation of c-MET and CXCR4 proteins and microvessel density (MVD) with liver metastasis in colorectal cancer tissues.Methods:A total of 40 colorectal cancer tissue samples and 10 paracancerous (5 cm from the edge of the tumor) normal colorectal tissue samples were collected from March 2015 to December 2020 in Shanxi Traditional Chinese Medical Hospital. Among 40 patients with colorectal cancer, 15 patients had liver metastasis. Immunohistochemistry was used to detect c-MET protein, CXCR4 protein and CD34-labeled MVD in various tissues, and the relationships between them and liver metastasis and between the three were analyzed.Results:The positive rates of c-MET protein [72.5% (29/40) vs. 30.0% (3/10)], CXCR4 protein [47.5% (19/40) vs. 10.0% (1/10)] and MVD (20.1±5.2 vs. 11.5±4.3) in colorectal cancer tissues were higher than those in paracancerous tissues, and the differences were statistically significant (all P < 0.05). The positive rates of c-MET protein [86.7% (13/15) vs. 64.0% (16/25)] and CXCR4 protein [66.7% (10/15) vs. 36.0% (9/25)] in colorectal cancer liver metastasis group were significantly higher than those in non-liver metastasis group, and the differences were statistically significant (both P < 0.05). MVD in colorectal cancer liver metastasis group was significantly higher than that in non-liver metastasis group (21.5±5.3 vs. 12.4±5.7), and the difference was statistically significant ( P < 0.05). In colorectal cancer tissues, c-MET protein expression was positively correlated with CXCR4 protein expression ( r = 0.568, P < 0.05), and MVD in c-MET-positive patients or CXCR4-positive patients was higher than that in negative ones (both P < 0.05). Conclusions:The c-MET protein, CXCR4 protein and MVD may play important roles in the liver metastasis of colorectal cancer. The three indicators can provide a certain reference for the early diagnosis and prognosis prediction of liver metastasis of colorectal cancer.

Objective:To improve the understanding of adult primary hemophagocytic syndrome (HPS) with aggressive natural killer cell leukemia (ANKL).Methods:The clinicopathological data of one adult patient with suspected primary HPS complicated with ANKL in Huiqiao Medical Center, Nanfang Hospital of Southern Medical University in October 2017 were retrospectively analyzed, and literatures were reviewed.Results:A 21-year-old male patient presented with persistent fever, hemocytopenia, splenomegaly, low fibrinogen, a significant increase in ferritin, hemophagocytes in bone marrow, decreased natural killer (NK) cell activity, and increased soluble CD25. Flow cytometry detection showed that the expression of NK cells was abnormal, and there were familial lysosomal trafficking regulator (LYST) and UNC13D gene defects. He was suspected of primary HPS complicated with ANKL. The patient was given 4 courses of EPOCH+PEG-Asp (etoposide, dexamethasone, vindesine, cyclophosphamide, doxorubicin hydrochloride liposome, pegaspargase) regimen chemotherapy, 20 mg of citalopidine twice a week maintenance therapy and matched unrelated hematopoietic stem cell transplantation. After 35 months of follow-up, he got sustained remission.Conclusions:Even if there are secondary causes of adult HPS, it is necessary to screen out related genes to avoid misdiagnosis. HPS patients with ANKL progress rapidly, and the early mortality is high. EPOCH+ PEG-Asp regimen induction therapy and allogeneic hematopoietic stem cell transplantation should be used as early as possible after diagnosis.

Objective To explore the efficacy and safety of apatinib combined with S-1 in patients with advanced NSCLC without sensitive gene mutation or unknown mutation status.Methods One hundred and four patients with advanced NSCLC without sensitive gene mutation or unknown mutation status were selected from the oncology department of the First Hospital of Qinhuangdao City,Hebei Province from April 2015 to April 2017.All patients refused intravenous chemotherapy.One hundred and four patients were randomly divided into treatment group (apatinib combined with S-1 group) and control group (S-1 alone group) by 1:1 digital method.However,two patients in the treatment group transferred to the control group for personal reasons.There is 50 cases in apatinib combined with S-1 group and 54 cases in S-1 group.The efficacy and adverse reactions of the two groups were evaluated.Results The objective remission rate was 48.0％ (24/50) and 27.8％ (15/54) (x2=4.530,P =0.033),the disease control rate was 82.0％ (41/50) and 74.1％ (40/54) (x2=0.947,P=0.331),the median PFS was 6.6 months and 3.4 months (t=25.555,P =0.000),the median OS was 16.0 months and 10.5 months (t =59.439,P =0.000),respectively.The overall incidence of adverse reactions was 82.0％ (41/50) and 70.4％ (38/54) respectively (x2 =1.923,P=0.166),of which 18.0％ (9/50) and 13.0％ (7/54) were more than grade 3 respectively (x2 =0.506,P =0.477).There was no death caused by treatment-related adverse reactions in both groups.Conclusion Appatinib combined with S-1 capsule has good short-term and long-term efficacy in the treatment of advanced non-small cell lung cancer without gene mutation or unknown mutation.The adverse reactions are tolerable and can be used as first-line treatment for patients unwilling to receive intravenous chemotherapy.

Objective To study the safety of transfusion of itraconazole through PICC and to evaluate the effect of different amount of blood transfusion before and after the infusion. Methods Patients were recruited from January 1, 2014, until December 31, 2015, in the Hematology hematopoietic stem cell transplantation ward. Thiry-two patients were recruited in the control group. Ninety patients wererecruited in the experience group. They were randomly assigned to three groups with 30 cases each, extracting different amounts of itraconazole before infusion, back phlebotomize in group A, B, C respectively was 10.0, 0.5, 1.0 ml. Comparing the phlebitis and obstruction after ten days from the transfusion day on. Results Catheter obstruction was not observed in any case. There was a significant difference between control group (21.9%,7/32) and observation group (0) regarding the incidence of phlebitis (χ2=21.157,P < 0.05). No statistical difference was noted among the observation groups regarding the incidence of phlebitis (P>0.05). Conclusions Drawing a small amount of blood volume before itraconazole injection through PICC can effectively avoid the drug-induced catheterobstruction. What′s more, transfusion through PICC can significantly reduce the incidence of phlebitis compared with peripheral infusion.

We report two cases of rituximab (RTX)-induced interstitial pneumonia in two lymphoma patients receiving RTX treatment. Interstitial pneumonia was successfully managed in these two cases after a one-week-long intervention with corresponding treatments without affecting further treatment of the primary disease. RTX-induced interstitial pneumonia is characterized by a latent onset with an unclear pathological mechanism and absence of typical symptoms. High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-induced interstitial pneumonia, which might be attributed partially to an increased susceptibility to P. jirovecii and fungal infection due to prolonged RTX treatment.

We report two cases of rituximab (RTX)-induced interstitial pneumonia in two lymphoma patients receiving RTX treatment. Interstitial pneumonia was successfully managed in these two cases after a one-week-long intervention with corresponding treatments without affecting further treatment of the primary disease. RTX-induced interstitial pneumonia is characterized by a latent onset with an unclear pathological mechanism and absence of typical symptoms. High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-induced interstitial pneumonia, which might be attributed partially to an increased susceptibility to P. jirovecii and fungal infection due to prolonged RTX treatment.

Objective To investigate the effect of simulated microgravity on the proliferation and differentiation of the human megakaryocyte cells in vitro. Methods The fourth generation rotating cell culture system (RCCS-4) was used to generate the simulated microgravity environment. The cell viability was assessed by trypan blue staining method. The proliferation of cells was assessed by cell counting method and CCK8 method. The CD41+/CD61+ cells rate and the cells cycle were detected by flow cytometry. The expression levels of thrombopoietin receptor (c-mpl) and transcription factors were detected with RT-PCR. Results After 24, 48, 72 h, culture under simulated microgravity resulted in a significant decrease in the cell number , proliferative activity, cells in the G2/M phase and levels of c-mpl mRNA expression in comparison with that under the normal gravity (P < 0.05). After 48 h and 72 h culture, CD41+/CD61+ cells ratio decreased and RUNX-1 mRNA expression was down-regulated in cells of the group SMG compared with that of the group NG (P < 0.05). Conclusion Microgravity can inhibit the proliferation and differentiation of human megakaryocyte cells in vitro. The mechanism may be that TPO/c-mpl pathway was inhibited by down regulating the expression of c-mpl which transcriptional inhibition lead to.