The bone morphogenetic protein(BMP),as a member of the transforming growth factor beta(TGF-?) family,plays a pivotal role in the formation,induction,maintenance and repair of the bone.The expression level of BMPs has a direct influence on the differentiation of mesenchymal osteoprogenitors and the regulation of osteoblastic features.Among BMPs,BMP-2 is the most widely studied and has the strongest activity in inducing bone formation.This article reviews the current advances in researches on BMP-2 for bone repair.

Objective To investigate the value of one-stage lymphatics-venous anastomosis in radical mastectomy of breast cancer to prevent post-mastectomy upper limb lymphedema.Methods Ninety patients requiring radical mastectomy of breast cancer in Tangshan Tumor Hospital Affiliated to North China University of Science and Technology from March 2010 to May 2013 were collected as the objects.They were divided into the control group (45 cases) and the treatment group (45 cases) using block randomized grouping (concealment of allocation).Both groups underwent radical mastectomy of breast cancer, and the treatment group was treated with one-stage lymphatics-venous anastomosis on the basis of radical mastectomy.The operation times, amount of bleeding, hospitalization times, postoperative complications and the numbers of axillary lymph node dissection of the patients in the two groups were compared, and the postoperative upper limb lymphedema incidence rates of the patients in the two groups were compared.Results The operative times of the patients in the treatment group and the control group were (152.82 ± 18.76) min and (78.92 ± 10.33) min respectively, and amount of bleeding were (416.64 ± 94.65) ml and (250.84 ± 63.17) ml, with statistical significances (t =-20.39, P =0.00;t =-4.48, P =0.00).The average hospitalization times of the patients in the treatment group and the control group were (14.91 ± 5.44) d and (13.45 ± 2.36) d respectively, the numbers of axillary lymph node dissection were 14.63 ± 3.37 and 14.37 ± 3.18, the numbers of postoperative complications occurred were 9 cases (20.00％) and 5 cases (11.11％), with no statistical significances (t =-0.47, P =0.64;t =0.75, P =0.46;x2 =1.35, P =0.38).Compared with the control group, the treatment group has lower incidence of upper extremity lymphedema (13.95％ vs.40.91％) and lower swelling degree, with statistical significance (x2 =8.48, P =0.03).Conclusion One-stage lymphatics-venous anastomosis in radical masteetomy of breast cancer can effectively transfer lymph diversion to the venous circulation and reduce the incidence of limb lymphedema, which has significant preventive effect.

Objective:To explore the clinical efficacy of radical resection for lung metastasis from colorectal cancer and the prognostic factors.Methods:The retrospective cohort study was conducted. The clinicopathological data of 63 colorectal cancer patients with lung metastasis who were admitted to Peking University Cancer Hospital from January 2004 to December 2015 were collected. There were 35 males and 28 females, aged (57±12)years. Patients underwent radical resection for primary lesion and lung metastasis from colorectal cancer. Observation indicators: (1) diagnosis and treatment; (2) follow-up and survival; (3) prognostic factors analysis. Follow-up was conducte by outpatient examination and telephone interview to detect the survival of patients after operation up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-rank test was used for univariate analysis and COX proportional hazard model was used for multivariate analysis. Results:(1) Diagnosis and treatment: of 63 patients with lung metastasis from colorectal cancer, 6 had synchronous lung metastasis and 57 had metachronous lung metastasis. Eighteen cases of suspected lung metastasis were initially detected by chest X-ray, and further confirmed by computed tomography (CT). Forty-five cases of suspected lung metastasis were initially detected by chest CT. All the 63 patients underwent radical resection for primary and metastatic lesions. Two of 22 cases undergoing mediastinal lymph nodes dissection were detected one positive lymph node, respectively. All patients recovered well after operation, without severe complications. There were 57 of 63 patients receiving more than 6 months of postoperative adjuvant chemotherapy and targeted therapy based on fluorouracils. (2) Follow-up and survival: 63 patients were followed up for 8-143 months, with a median follow-up time of 58 months. During the follow-up, 19 of 63 patients died, 24 patients had secondary recurrence with a 5-year recurrence rate of 38.1%(24/63) and a recurrence interval of 18 months(range, 3-58 months). Of 24 patients with secondary recurrence, 19 had lung metastasis, 3 had brain metastasis, 2 had bone metastasis, 2 had liver metastasis; some patients had multiple metastases. Of 24 patients with secondary recurrence, 5 underwent reoperation and 19 underwent chemotherapy and radiochemotherapy. The 5-year overall survival rate of 63 patients was 62.7%. (3) Prognostic factors analysis: results of univariate analysis showed that location of primary lesion, the number of lung metastases and carcinoembryonic antigen (CEA) level before resection of lung metastasis were related factors for prognosis of patients with lung metastasis from colorectal cancer ( χ2=4.162, 7.175, 6.725, P<0.05). Results of multivariate analysis showed that the number of lung metastases and CEA level before resection of lung metastasis were independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer ( hazard ratio=2.725, 2.778, 95% confidence interval as 1.051-7.064, 1.072-7.021, P<0.05). Conclusions:Radical resection for lung metastasis from colorectal cancer is safe and feasible. The number of lung metastases and CEA level before resection for lung metastasis are independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer.

Objective:To investigate the clinical therapy of one-stage internal and external fixation combined with early perforator fiap for treatment of ankle fracture dislocation with soft tissue defects of Gustilo types Ⅲ.Methods:A retrospective study was conducted of the 20 patients with ankle fracture dislocation of Gustilo type Ⅲ who had been treated from May 2014 to July 2017 at Deparment of Traumatic Orthopaedics, the Second Hospital of Tangshan. There were 14 males and 6 famales among the patients, aged from 18 to 58 years (average, 40 years). There were 5 cases of Gustilo type ⅢA, 12 cases of type ⅢB, and 3 cases of type ⅢC; AO classification of ankle fractures: 4 cases of type A, 7 cases of type B, and 9 cases of type C; The wound size ranged from 4 cm×3 cm to 20 cm×9 cm. All patients were treated by primary internal and external fixation plus secondary transfer with a perforator flap. The times from injury to initial surgery ranged from 1 to 8 h (average, 5.5 h), the period from injury to secondary flap transfer ranged from 7 to 21days (average, 12 days). Among them, 11 cases of posterior tibial artery perforator flap, 5 cases of fibular artery perforator flap, 1 case of anterior ankle flap, and 3 cases of posterior tibial artery perforator flap combined with fibular artery perforator flap.Results:All 20 cases of limb preservation were successful, and there were no amputees. 9 patients showed superficial infection, no deep infection and osteomyelitis occurred. All 19 cases of flap survived, 1 case of distal part of posterior tibial artery perforator flap was necrosis, and the skin graft was cured later. All patients were followed up for 6 to 18 months (average, 12 months). The flap healed well. There was no sinus tract and bone exposure. The sensory recovery was S1 in 2 fiaps, S2 in 12 flaps, S3 in 6 flaps. The fracture healing time vanged from 4 to 10 months (average, 6.5 months), no bone disunion in patients. According to the American foot ankle surgery scoring system, the efficacy was assessed: 4 excellent cases, 11 good cases, 3 fair cases, 2 poor cases, yielding an excellent to good rate of 75%.Conclusions:One-stage internal and external fixation combined with early perforator fiap transfer is an effective strategy for treatment of ankle fracture dislocation with soft tissue defects of Gustilo types Ⅲ, due to its advantages of shortened treatment period, possibility for early rehabilitation, decreased complications and satisfactory functional recovery.

Objective:To explore the clinical and CT imaging features of immune checkpoint inhibitor-associated pneumonia (CIP) and to improve the early diagnostic ability of CIP.Methods:From June 1, 2020 to October 31, 2021, the clinical data and chest CT images of 2 067 patients with advanced malignant tumor treated with immune checkpoint inhibitor (ICI) in the First Medical Center, Chinese PLA General Hospital were retrospectively analyzed. Patients with CIP were enrolled according to the guidelines for CIP diagnosis, and the incidence, time from the start of medication to the onset of CIP, medication cycle, imaging features, imaging patterns, CT grade and outcomes were analyzed. χ 2 test was used to compare the incidence of CIP in patients with or without basic lung disease. Results:Among 2 067 patients with malignant tumors treated with ICI, 67 patients developed CIP, the incidence of CIP was 3.2%. The incidence of CIP was significantly different between 386 patients with basic lung disease (7.00%, 27/386) and 1 681 patients without basic lung disease (2.4%, 40/1 681) (χ 2=21.32, P<0.001). The time from the start of medication to the onset of CIP was 7-367 d (median 52 days), and the duration of medication was 1-12 cycles (median 2 cycles). The imaging features of CIP presented as ground glass opacities in 54 cases (80.6%), solid nodules in 26 cases (38.8%), consolidations in 25 cases (37.3%) and irregular reticular opacities in 24 cases (35.8%). The main radiologic pattern was organizing pneumonia (OP, 34 cases, 50.7%), and followed by diffuse alveolar damage (DAD) pattern (14 cases, 20.9%). According to CT grading, there were 26 cases in low risk grade, 17 cases in moderate risk grade and 24 cases in high risk grade. Of 43 low-and medium-risk grade cases, 25 were OP pattern, accounting for 58.1%, and among 24 high-risk grade patients, 13 were DAD pattern, accounting for 54.2%. Forty-three of the 52 patients were initially untreated, of which 23 patients progressed, 17 had lesion shrinkage, and 3 had resolution, and relapsed in 8 cases after resolution or drug withdrawal. Conclusions:The imaging manifestations of CIP are mainly ground glass opacities, nodules, consolidations, and irregular reticular opacities. The radiologic patterns are mainly OP and DAD. OP is the most common pattern in low-moderate risk grade CIP and DAD is the most common pattern in high risk grade CIP. Patients with basic lung disease are more likely to get CIP.

OBJECTIVETo study the effects of acupuncture combined with rat nerve growth factor (NGF) on the cerebral palsy infant rats and the proteins which associated with growth, apoptosis and metabolism.

METHODSSeventy infant rats were selected, Fifty infant rats of which were made the cerebral palsy infant model by the ligation of unilateral carotid artery for cerebral ischemia and oxygen-deficient environment, then the 30 model rats were randomly divided into a model group, a NGF group and a combined group, 10 rats in each group. Twenty infant rats were used in the sham-operated group and the blank control group, 10 rats in each group. The treatment was not given in the blank control group. The rats in the sham-operated group were cut the neck skin and separated the left carotid artery, and then sutured and disinfected the wound. The intraperitoneal injection of NGF (2000 U•kg•d) was used in the NGF group. Based on the injection in the NGF group, acupuncture was used in the combined group, once a day, and the acupoints were "Baihui" (GV 20), left "nieⅠ" (extra), "Dazhui" (GV 14), "Jizhong" (extra), "Quchi" (LI 11), "Yongquan" (KI 1), "Hegu" (LI 4), "Zhoujie" (extra) and "Xiqianxue" (extra). The same volume of saline was intraperitoneally injected in the model group for continuous 14 days. Neurobehavioral ability score was evaluated after treatment. TUNEL were conducted to detect the brain cell apoptosis rate and the expressions of apoptosis associated gene Bax, Bcl-2 and Casp3 were detected by PCR. The level of nerve growth associated protein (GAP-43) and energy metabolism-related protein monocarboxylate transporter protien 1(MCT 1) were detected by Western blot.

RESULTSAfter intervention, the neurobehavioral ability of baby rats in the blank control and sham-operated group was normal, but there was various degrees of abnormity in the model group, NGF group and combined group. The scores of neurobehavioral ability of the combined group and NGF group were better than those of the model control (all <0.05), and the scores in the combined group was better than those in the NGF group (all <0.05). The left brain cell apoptosis rate, expressions of Bax and Casp3 in the combined group and NGF group were lower and the expressions of Bcl-2 were higher than those of the model group (all <0.05), with more obvious results of Bax and Gasp3 in the combined group than those in the NGF group (all <0.05). The protein levels of GAP-43 and MCT 1 in the combined group and NGF group were higher than those in the model group (all <0.05), with higher expressions in the combined group compared with those in the NGF group (both <0.05).

CONCLUSIONAcupuncture combined with NGF could improve the neurobehavioral ability of cerebral palsy infant rats, inhibit the nerve cell apoptosis and improve the brain tissue injure and energy metabolism by up-regulating the expressions of GAP-43 and MCT 1.

In order to build an "Internet +" innovation and entrepreneurship education practice platform, 3,752 undergraduates from 5 medical colleges and universities were investigated by questionnaire. The results showed that there was a gap between the expectation of the students and the setting of entrepreneurship and innovation courses, project guidance and so on. In view of the contradiction between the supply of educational resources and the needs of students in medical colleges and universities, we have developed the "Internet +" innovation and entrepreneurship education practice platform, that including five main functions and three layers of framework based on cloud computing and open source technology. The platform integrates various resources of medical colleges and universities to make useful exploration for cultivating students' innovation and entrepreneurship ability, accelerating the implementation of projects, and promoting the connotation development of innovation.

Objective:To investigate the CT features of lepidic predominant adenocarcinoma (LPA) and other pathological subtypes in early-stage invasive pulmonary adenocarcinoma appearing as ground glass nodule (GGN); and to provide imaging-derived information for the clinical management of GGN.Methods:The clinical and CT data of patients with early-stage invasive pulmonary adenocarcinoma in the First Medical Center of PLA General Hospital from January to December 2019 were retrospectively reviewed. All patients presented with pure GGNs or mixed GGNs with a consolidation-to-tumor ratio (CTR)<0.5, with the pathological results confirmed by surgery. GGNs were divided into LPA and non-LPA (n-LPA) groups according to pathological subtypes. Univariate analysis was used to compare the clinical data and CT characteristics between the two groups. The multivariate analysis was performed for the indicators with statistically significant differences and a multivariate model was generated using the reverse elimination method. The area under the ROC curve (AUC) was used to evaluate the discriminatory power of this model for differentiation of LPA from n-LPA.Results:A total of 630 GGNs from 589 patients were analyzed, with 367 GGNs in LPA group and 263 GGNs in n-LPA group. In univariate analysis, the diameter [(14±5) mm], CT value [(-566±98) HU], and CTR [13.9% (0, 27.3%)] in the LPA group were significantly smaller than those in the n-LPA group [(15±5) mm, (-499±111) HU, 27.8%(7.7%, 40%)], respectively, P<0.05]. The frequency of mGGN, deep lobulation sign, burrs, vascular changes, bronchial changes, and clear tumor-lung interface were significantly higher in the n-LPA group than those in the LPA group ( P<0.05). Multivariate analysis results showed that mean CT values, CTR, deep lobulation sign, burr, vascular changes, and bronchial changes were independent predictors for predicting n-LPA ( P<0.05), which were included in the logistic model. Using the optimal cutoff value of 3.958, the logistic regression model for differentiate LPA from n-LPA had a sensitivity of 76.4%, a specificity of 78.7%, and an area under the curve of 0.840. Conclusion:The CT features are helpful for differentiating lepidic predominant subtype from other subtypes in early-stage invasive pulmonary adenocarcinoma presenting as a GGN.

Objective: To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues. Methods: From August 2011 to May 2013, 73 patients with ESCC, who received radical resection in The First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospital, were enrolled. The expressions of ESCCAL-1 in esophageal tumor tissues and corresponding adjacent non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). T test, chi square test and multivariate analysis were performed for statistical analysis. Results: The expression of ESCCAL-1 was 28.03±9.37 in esophageal tumor tissues of patients with ESCC, which was higher than that in corresponding adjacent normal tissues (11.39±4.15), and the difference was statistically significant (t=2.964, P<0.01). However there were no statistically significant differences in the expressions of ESCCAL-1 among the patients with different age, gender, histological grade, classification of Union for International Cancer Control (UICC), T stage or lymph nodes metastasis (all P>0.05). The median disease-free survival (DFS) time and overall survival (OS) time of patients with low ESCCAL-1 expression were 39 months and 42 months, respectively, which were longer than those of patients with high ESCCAL-1 expression (30 months and 37 months), and the differences were statistically significant (χ²=9.049, P=0.003; χ²=10.165, P=0.001). The results of multivariate analysis showed that ESCCAL-1 expression was the independent risk factor of DFS and OS (high risk (HR)=2.45, 95% confidence interval (CI) 1.22 to 4.93, P=0.012; HR=2.29, 95%CI 1.14 to 4.59, P=0.019). Conclusions ESCCAL-1 may be involved the genesis and development of ESCC. The expression of ESCCAL-1 in esophageal tumor tissues may be a prognostic parameter for patients with ESCC receiving radical resection.

Objective To detect the down-regulation ofmiRNA-99b expression in cell invasion and its mechanism in human glioma cell line U251.Methods Glioma cell line U251 were routinely cultured in vitro.(1) U251 cells were divided into blank control group,negative control group and miRNA-99b inhibitor group;cells in the latter two groups were transfected with negative control sequences and miRNA-99b inhibitors,respectively;and cells in the blank control group did not give any treatment;mRNA expressions of miRNA-99b and mammalian target of rapamycin (mTOR) in U251 cells were measured by reverse transcription (RT)-PCR;the changes of mTOR,eIF4E-binding protein 1 (4E-BP1) andphosphorylated (p)-4E-BPl protein expressions in U251 cells were detected by Westem blotting;cell invasion was evaluated by Transwell assay.(2) U251 cells were divided into negative control group Ⅰ and mTOR siRNA group,and cells in the two groups were transfected with negative control sequences and mTOR siRNA,respectively;the miRNA-99b and mTOR mRNA expressions in U251 cells were measured by RT-PCR;the mTOR and p-4E-BP1 protein expressions in U251 cells were measured by Western blotting.(3) U251 cells were divided into miRNA-99b inhibitor+negative control group and miRNA-99b inhibitor+mTOR siRNA group,and cells in the two groups were transfected with miRNA-99b inhibitor+negative control sequences and miRNA-99b inhibitor+mTOR siRNA,respectively;the p-4E-BP1 protein expression in U251 cells was measured by Western blotting;cell invasion was evaluated by Transwell assay.Results (1) As compared with those in the blank control group and negative control group,the miRNA-99b rnRNA expression was significantly decreased,the mTOR mRNA and protein expressions and p-4E-BP1 protein expression were significantly increased,and the number of transmembrane cells was significantly larger in U251 cells of miRNA-99b inhibitor group (P＜0.05);there were no significant differences in 4E-BP1 protein expression among the three groups (P＞0.05).(2) As compared with those in the negative control group Ⅰ,the mTOR mRNA and protein expressions and p-4E-BP1 protein expression were significantly decreased in U251 cells of mTOR siRNA group (P＜0.05);there was no significant difference in miRNA-99b mRNA expression between the two groups (P＞0.05).(3) As compared with those in the miRNA-99b inhibitor+negative control group,the p-4E-BP1 protein expression and number of transmembrane cells were significantly decreased/smaller in U251 cells ofmiRNA-99b inhibitor+mTOR siRNA group (P＜0.05).Conclusions Down-regulation ofmiRNA-99b expression promotes glioma cell invasion,and its mechanism is related to the regulation of mTOR/4E-BP1 signaling pathway.