Objective:To investigate the early and middle term clinical efficacies of 3D-printed metal prostheses in the reconstruction of bone defects after osteotomy in malignant bone tumors.Methods:A total of 34 patients with malignant bone tumors of lower extremity femur and tibia who underwent 3D printing individualized metal prosthesis replacement surgery in the Department of Bone and Soft Tissue of Affiliated Cancer Hospital of Zhengzhou University from March 2019 to March 2022 were retrospectively analyzed. There were 23 males and 11 females, with an average age of 19.1±15.2 years (range, 7-80 years). There were 22 children and adolescents younger than 18 years old. There were 3 cases in the proximal femur, 15 cases in the middle and distal femur, 10 cases in the proximal tibia and 6 cases in the distal tibia. According to the final pathological diagnosis, 24 cases of osteosarcoma, 6 cases of Ewing's sarcoma, 2 cases of undifferentiated sarcoma, 1 case of osteosarcoma, and 1 case of malignant giant cell tumor of bone were enrolled in this study. Postoperative complications, wound healing, periprosthetic fracture and aseptic loosening, tumor outcome (evaluated by tumor control evaluation criteria), and length difference of lower limbs were recorded. Response evaluation criteria in solid tumor (RECIST) was used to evaluate tumor outcomes. Prosthetic-bone interface healing was evaluated postoperatively, and the function was evaluated based on Musculoskeletal Oncology Society (MSTS) 93.Results:The length of lesions was 70-240 mm in 34 patients, with an average of 125.5±35.4 mm. The length of osteotomy was 80-275 mm, with an average of 160.2±33.9 mm. No tumor was found on the osteotomy surface. The customized prosthesis was firmly installed and closely matched with the side of the preserved articular surface. There were 2 patients with local incision fat liquefaction and 4 patients with superficial wound infection, which healed after debridement and antibiotic treatment. One distal tibia osteosarcoma case developed severe periprosthetic infection 2 months after surgery, resulting in prosthesis implantation failure, limb movement pain and poor ankle function. After removal of the prosthesis, infection control and osteogenesis with the Ilizarov technique, the infection was completely controlled and local osteogenesis was possible. The remaining 33 patients had a good prosthetic-bone interface union. One case was found to have localized bone resorption on the contact surface of the prosthesis 7 months after operation, but the metal prosthesis and screws were not loose. The incisions healed well in other patients, without infection, prosthesis loosening, fracture or other complications. All patients survived and were followed up for 13.8±5.6 months (range, 7-27 months). During the follow-up, there was no recurrence of tumor at the osteotomy end in all patients, but 5 patients developed lung metastasis. At the end of the last follow-up, all patients survived. Among them, 16 patients had unequal length of lower limbs, including 10 cases within 2 cm, 3 cases between 2-5 cm, and 3 cases over 5 cm. With the exception of one patient whose prosthesis was removed due to infection, the MSTS 93 of the other patients was 24.9±2.2 (range, 19-28), and were rated as excellent in 26 cases and good in 7 cases. According to the RECIST evaluation criteria, 26 of 34 patients had complete response, 5 had disease progression, and 3 had stable disease.Conclusion:3D printed metal prosthesis is one of the effective methods for the treatment of bone defects after resection of malignant bone tumors in lower limbs, which is safe, reliable and has satisfactory early curative effect.

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

【Objective】 To establish a method to determine the content of the effective ingredient PCA (p-coumaric acid) in Shuang Bailian mixture and to investigate its anti-cancer mechanism. 【Methods】 High performance liquid chromatography (HPLC) was used to determine the content of PCA in Shuang Bailian mixture. The CCK8 method was used to detect the antitumor activity of PCA on esophageal cancer cells and the semi-inhibitory concentration of PCA on esophageal cancer cells. Moreover, the nude mice were used to investigate the anticancer effect of PCA. Western blotting was used to detect the expressions of apoptosis-related proteins (cleaved caspase 3, cleaved PARP, Bad, Bcl-2, PI3K, AKT, p-PI3K and p-AKT) in esophageal cancer cells and tumor tissues of nude mice. 【Results】 The concentration of PCA in Shuang Bailian mixture was 16.84 μg/mL. The linear regression equation of PCA was y=204 402x +360 904 (15-40 μg/mL), the RSD of the precision experiment was 2.66%, the RSD of the stability experiment was 2.35%, 3.22%, 1.58%, and 4.08%, respectively. The RSD of the repeatability experiment was 4.01%. The mean value of the recovery rate was 97.83% and the RSD value was 6.16%. CCK8 results showed that the half maximal inhibitory concentration (IC50) of PCA in KYSE30 and KYSE140 cells was 36 μg/mL and 55 μg/mL, respectively. The results of nude mice tumor experiments showed that after 30 days of administration, the tumor xenograft in control mice continued to increase in size, while the cisplatin group, PCA group, and PCA combined with cisplatin administration could effectively inhibit the growth of transplanted tumors in tumor-bearing mice. In addition, Western blotting results showed that compared with the control group, the cisplatin group, PCA group, and PCA combined with cisplatin group could effectively increase the protein expressions of cleaved caspase 3, cleaved PARP, and Bad, but decrease the protein expressions of Bcl-2, p-PI3K, and p-AKT in tumor tissues and KYSE30 and KYSE140 esophageal cancer cells. 【Conclusion】 The concentration of PCA in Shuang Bailian mixture was 16.84 μg/mL, and the HPLC content determination method conditions were sensitive and stable. PCA may have an active anti-tumor effect by regulating the PI3K/AKT/Bcl-2 signaling pathway and inducing apoptosis in esophageal cancer cells.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Lung distension belongs to chronic obstructive pulmonary disease (COPD) in modern medicine.In recent years,its disease incidence and mortality have increased year by year.Supported by the traditional Chinese medicine (TCM) standardization of the State Administration of TCM project-TCM preventive treatment practice guidelines-prevention of lung distension recrudescence,the first draft of the TCM Preventive Treatment Practice Guideline on Prevention of Lung Distension Recrudescence was formulated on the basis of preventive treatment theory,evidences from both ancient and modern literatures,and through the Delphi method as well as expert consensus conference.And then,peer review comments were collected,which laid the foundation for the further improvement of this guideline.This guideline was aimed to achieve the industry consensus,to improve the quality of life (QoL) in patients of the stable period,to reduce the economic burden of patients,as well as to improve both the theoretical connotation and practical value of preventive treatment in TCM.

OBJECTIVE:To provide reference for standardizing the clinical use of carbapenem antibiotics and controlling drug-resistant bacteria infection. METHODS:The detection of 3 kinds of carbapenems-resistant Gram-negative bacillus in our hospi-tal during 2011-2016 were analyzed retrospectively. The consumption,target cure rate and treatment course of carbapenem antibiot-ics were analyzed statistically. The correlation between detection rate of drug-resistant bacteria with the consumption of carbapenem antibiotics was investigated by Pearson test. RESULTS:During 2011-2016,1222 strains of carbapenems-resistant Acinetobacter bauman (CRAB),655 strains of carbapenems-resistant Pseudomonas aeruginosa (CRPA) and 53 strains of carbapenem-resistant Escherichia coli (CRE) were detected in our hospital. The detection rates increased from 23.88%,8.92%,0.09% in 2011 to 80.34%,35.74%,0.97% in 2016. The types of carbapenem antibiotics in our hospital were mainly imipenem and meropenem. The consumption of them increased from 4222,145 g in 2011 to 7218,4387 g in 2016. The both target cure rates were all lower than 60%,and the proportion of the patients with treatment course >14 d was more than 65%. The detection rates of CRAB,CR-PA and CRE were positively correlated with the consumption of carbapenem antibiotics (r>0.9,P<0.05). CONCLUSIONS:The detection rate of carbapenems-resistant Gram-negative bacillus and drug consumption increase year by year in our hospital,and they have certain correlation. The target cure rate of carbapenem antibiotics in our hospital is in low level,and there is a long treatment course. They are should be standardized in the clinic. The selection of carbapenem antibiotics should be strictly followed clinical in-dications so as to reduce the generation of drug-resistant strains.

Objective To investigate the expression and significance of FoxM1 in esophageal squamous cell carcinoma ( ESCC) cell lines and tissues.Methods Western blot assay was used to detect the expression of FoxM1in human esophageal epithelial cells and esophageal squamous cell cancer cell lines TE1, TE10, TE11 and Eca109 cells.To determine whether down-regulation of FoxM1 expression could inhibit the aggressive phenotype of ESCC cells, we knocked down the expression of FoxM1 by using FoxM1-shRNA in TE1 cells.Then we detected the cell proliferation, migration and invasion of TE1 cells by MTT assay, scratch assay and transwell assay.Furthermore, the effect of FoxM1 knockdown on tumorigenicity in nude mice was evaluated.Finally, immunohistochemical staining was used to detect the expression of FoxM1 in 99 cases of ESCC tissues and adjacent normal esophageal tissues.χ2 test was used to analyze the correlations between the expression of FoxM1 and clinicopathologic characteristics and prognosis of ESCC patients.Results Western blot data showed that FoxM1 expression was lower in normal esophageal epithelial cells and highly expressed in four esophageal cancer cell lines, especially in TE1 cells.Knockdown of FoxM1 inhibited the growth, invasion and migration of TE1 cells and reduced their tumorigenicity in nude mice.The positive expression rate of FoxM1 in ESCC was 61.6%(61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05).The positive expression rate of FoxM1 in ESCC tissues was 61.6%( 61/99 ) , significantly higher than that in the paired adjacent normal tissues ( 24.2%, 24/99) ( P<0.05) .FoxM1 expression was significantly and positively correlated with lymph node metastasis, clinical stage and invasive depth ( P<0.05).The median survival time was 42.3 months in 38 cases of patients with negative FoxM1 expression, and 33.0 months in 61 cases of positive FoxM1 expression, and the difference was statistically significant (P=0.036).Conclusions FoxM1 is highly expressed in ESCC, and significantly correlated with the initiation, development and prognosis of esophageal cancer. FOXM1 might be an indicator to predict the prognosis and serve as a potential target for therapy in esophageal cancer.

Objective To investigate the expression and significance of FoxM1 in esophageal squamous cell carcinoma ( ESCC) cell lines and tissues.Methods Western blot assay was used to detect the expression of FoxM1in human esophageal epithelial cells and esophageal squamous cell cancer cell lines TE1, TE10, TE11 and Eca109 cells.To determine whether down-regulation of FoxM1 expression could inhibit the aggressive phenotype of ESCC cells, we knocked down the expression of FoxM1 by using FoxM1-shRNA in TE1 cells.Then we detected the cell proliferation, migration and invasion of TE1 cells by MTT assay, scratch assay and transwell assay.Furthermore, the effect of FoxM1 knockdown on tumorigenicity in nude mice was evaluated.Finally, immunohistochemical staining was used to detect the expression of FoxM1 in 99 cases of ESCC tissues and adjacent normal esophageal tissues.χ2 test was used to analyze the correlations between the expression of FoxM1 and clinicopathologic characteristics and prognosis of ESCC patients.Results Western blot data showed that FoxM1 expression was lower in normal esophageal epithelial cells and highly expressed in four esophageal cancer cell lines, especially in TE1 cells.Knockdown of FoxM1 inhibited the growth, invasion and migration of TE1 cells and reduced their tumorigenicity in nude mice.The positive expression rate of FoxM1 in ESCC was 61.6%(61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05).The positive expression rate of FoxM1 in ESCC tissues was 61.6%( 61/99 ) , significantly higher than that in the paired adjacent normal tissues ( 24.2%, 24/99) ( P<0.05) .FoxM1 expression was significantly and positively correlated with lymph node metastasis, clinical stage and invasive depth ( P<0.05).The median survival time was 42.3 months in 38 cases of patients with negative FoxM1 expression, and 33.0 months in 61 cases of positive FoxM1 expression, and the difference was statistically significant (P=0.036).Conclusions FoxM1 is highly expressed in ESCC, and significantly correlated with the initiation, development and prognosis of esophageal cancer. FOXM1 might be an indicator to predict the prognosis and serve as a potential target for therapy in esophageal cancer.

Objective To observe the effect of treating asthma in remission stage(Latent phlegm in lung syndrome) withJinlong-Gubenmixture.Methods 108 patients of asthma on remission stage were randomized into a control group and a treatment group. The treatment group was givenJinLong-GuBen mixture. The control group was given nothing for treatment. Both groups were treated for 120 days and follow-up period were 360 days. The change of ACT scores and FEV1 was observed.Results After treatment, ACT scores(t=2.931, 2.618) and FEV1(t=2.011, 2.680) of treatment groups were markedly increased than before the treatment(P<0.05), and the effect of the treatment group was better than the control group(P<0.01). After treatment, the effective rate of treatment group was 93.75%(45/48), and the effective rate of control group was 78.72%(37/47),there existed statistical significance between the two groups(U=-0.4531,P<0.01). Conclusion The theory of latent phlegm in lung has a good guiding function in treating asthma in remission stage(Latent phlegm in lung syndrome).

Objective To explore the expression of HCCR, pERK and pELK1 in gastric cancer tissue and para-carci-noma tissue, and to explove its correlations. Methods In 60 human gastric cancers and their corresponding paraneo-plastic tissuses,the expression of HCCR, pERK and pELK1 were detected by immunohistochemistry. Results The ex-pression of HCCR was 75.0%(45/60), pERK, and pELK1 were 73.3%(44/60) and 71.7%(43/60), respectively, and the expression of proteins in gastric tumor were higher than that in paraneoplastic tissues (P<0.05). Conclusion The HCCR, pERK and pELK1 are higher expressed in tumor tissues, availably as a auxiliary index for clinical immunohis-tochemistry in gastric cancer.