Anti-angiogenic drugs (AADs), which mainly target the vascular endothelial growth factor-A signaling pathway, have become a therapeutic option for cancer patients for two decades. During this period, tremendous clinical experience of anti-angiogenic therapy has been acquired, new AADs have been developed, and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy. However, improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required. This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development. We revisit the history of concept initiation and AAD discovery, and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.

Objective To construct risk prediction models of death or readmission in patients with acute heart failure(AHF)during the vulnerable phase based on machine learning algorithms and screen the optimal model.Methods A total of 651 AHF patients with admitted to Department of Cardiology of the Second Affiliated Hospital of Army Medical University from October 2019 to July 2021 were included.The clinical data consisting of admission vital signs,comorbidities and laboratory results were collected from electronic medical records.The composite endpoint was defined as all-cause death or readmission for worsening heart failure within 3 months after discharge.The patients were divided into a training set(521 patients)and a test set(130 patients)in a ratio of 8:2 through the simple random sampling.Six machine learning models were developed,including logistic regression(LR),random forest(RF),decision tree(DT),light gradient boosting machine(LGBM),extreme gradient boosting(XGBoost)and neural networks(NN).Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical benefit of the models.Shapley additive explanation(SHAP)was used to explain and evaluate the effect of different clinical characteristics on the models.Results A total of 651 AHF patients were included,of whom 203 patients(31.2%)died or were readmitted during the vulnerable phase.ROC curve analysis showed that the AUC values of the LR,RF,DT,LGBM,XGBoost and NN model were 0.707,0.756,0.616,0.677,0.768 and 0.681,respectively.The XGBoost model had the highest AUC value.DCA showed that the XGBoost model exhibited greater clinical net benefit compared with other models,with the best predictive performance.SHAP algorithm analysis showed that the clinical features that had the greatest impact on the output of the model were serum uric acid,D-dimer,mean arterial pressure,B-type natriuretic peptide,left atrial diameter,body mass index,and New York Heart Association(NYHA)classification.Conclusion The XGBoost model has the best predictive performance in predicting the risk of death or readmission of AHF patients during the vulnerable phase.

Objective:To investigate the application of therapeutic grade ionization chamber to rapid measurement of short pulsed and high-dose-rate X-ray.Methods:The half-value layer of pulsed X-ray caused by an electron accelerator was measured by interpolation method and its equivalent energy was estimated. The cumulative doses from a certain amount of pulsed radiation at different distances in the same direction around the equipment were compared using the therapeutic grade ionization chamber and thermoluminescence measurement method . The relationship between the measurement result by using ionization chamber dosimeter and the distances away from source was analyzed. The cumulative doses from a certain amount of pulsed radiation at the same location at different frequencies were compared.Results:In working condition, 100 pulses of radiation were received accumulatively at 1 to 12 meters away from the outer wall of the equipment. The range of air Kerma was 0.08-9.65 mGy measured by using thermoluminescence dometers and 0.08 - 9.85 mGy using the ionization chamber dosimeters, respectively. The difference between both is within 10%. At different frequencies (1-10 Hz), there was no significant difference in X-ray air Kerma from 100 pulses measured by ionization chamber dosimeter at 2 m away from the front of the equipment ( P>0.05). Conclusions:The therapeutic grade ionization chamber dosimeter can be used for the rapid measurement of short pulsed X-ray radiation dose in the range of dose rates and pulse frequencies involved in the experimental accelerator device.

Objective: To explore the effects of vitamin D₃ on intestinal mucosal barrier of mice with severe burns. Methods: Forty-two C57BL/6C male mice aged eight to twelve weeks were divided into vitamin D₃ vehicle+ sham injury group of seven mice, vitamin D₃ vehicle+ burn injury group of fourteen mice, vitamin D₃+ sham injury group of seven mice, and vitamin D₃+ burn injury group of fourteen mice according to random number table. Mice in vitamin D₃ vehicle+ sham injury group and vitamin D₃ vehicle+ burn injury group were injected with vehicle of vitamin D₃ at a dose of 0.1 mL intraperitoneally at 1, 24, and 48 h before burn experiment. Mice in vitamin D₃+ sham injury group and vitamin D₃+ burn injury group were injected with vitamin D₃ at a dose of 100 ng/kg dissolved in 0.1 mL vehicle intraperitoneally at the same time points. Mice in vitamin D₃ vehicle+ burn injury group and vitamin D₃+ burn injury group were inflicted with 30% total body surface area full-thickness dermal scald (hereinafter referred to as burn) on the back by 98 ℃ hot water for 3 to 4 seconds. And mice in vitamin D₃ vehicle+ sham injury group and vitamin D₃+ sham injury were treated with 37 ℃ water on the back for 3 to 4 seconds to simulate injury. Seven mice in vitamin D₃ vehicle+ sham injury group and seven mice in vitamin D₃+ sham injury group at post injury hour (PIH) 24, and seven mice in vitamin D₃ vehicle+ burn injury group and seven mice in vitamin D₃+ burn injury group at PIH 6 and 24 were sacrificed respectively to collect mesentery lymph nodes, spleens, livers, and intestinal tissue. The mesentery lymph nodes, spleens, and livers of mice in each group were collected to observe growth of bacteria, and number of bacteria was counted. Intestinal tissue of mice in each group was collected to detect protein expressions of zonal occludin 1 (ZO-1) and occludin by immunohistochemistry staining method, distribution of ZO-1 by immunofluorescence staining method, and expression of occludin by Western blotting. Data were processed with Kruskal-Wallis H test, Nemenyi test, one-way analysis of variance, t test, and Bonferroni correction. Results: (1) At PIH 6 and 24, bacterial counts of mesentery lymph nodes, livers, and spleens of mice in vitamin D₃ vehicle+ burn injury group were significantly higher than those of mice in vitamin D₃ vehicle+ sham injury group (P<0.05). At PIH 6, bacterial counts of livers and spleens of mice in vitamin D₃+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ burn injury group (P<0.05). At PIH 24, bacterial counts of mesentery lymph nodes and livers of mice in vitamin D₃+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ burn injury group (P<0.05). (2) At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ sham injury group, and expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were close to those of mice in vitamin D₃+ sham injury group. At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were significantly higher than those of mice in vitamin D₃ vehicle+ burn injury group. (3) At PIH 6 and 24, compared with that of mice in vitamin D₃ vehicle+ sham injury group, distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃ vehicle+ burn injury group was discontinuous. Distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃+ sham injury group was normal, and the distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃+ burn injury group was with good continuity. (4) At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were 0.720±0.003, 0.638±0.052 respectively, significantly lower than 0.918±0.003 of mice in vitamin D₃ vehicle+ sham injury group (t=57.33, 5.36, P<0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were 0.994±0.058, 1.064±0.060, close to 0.938±0.023 of mice in vitamin D₃+ sham injury group (t=0.91, 1.96, P>0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were significantly lower than those of mice in vitamin D₃+ burn injury group (t=4.75, 5.35, P<0.05). Conclusions Intestinal bacterial translocation can occur in the early stage of severe burn. And vitamin D₃ plays a protective role in the intestinal mucosal barrier post severe burn to reduce the bacterial translocation by protecting tight junction proteins of intestinal epithelium.

Objective: To investigate the curative effect and prognostic factors of radical radiotherapy for cervical cancer. Methods: A total of 211 patients with stage Ⅰ_A-Ⅲ_B cervical cancer who underwent therapy in department of radiotherapy, Tumor Hospital of Jilin province between June 2014 and February 2017, were analyzed retrospectively. All patients received radical radiotherapy with or without concurrent chemotherapy. Short-term and long-term efficacy and related prognostic factors were observed. Kaplan-Meier method was used for survival analysis, Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Results: The 2-year overall survival (OS) and disease free survival (DFS) were 83.4% and 72.5%, respectively. During the follow-up periods, 46 patients (21.8%) died, including two from non-tumor-related diseases, and one from second primary colon cancer. Totally 57 patients (27%) had recurrence and metastasis, including 16 (28.1%) with local recurrence, 27 (47.4%) with distant metastasis, and 14 with local recurrence and distant metastasis(24.6%). Univariate analysis showed that 2-year OS and DFS were significantly correlated with pathological type, pre-treatment squamous cell carcinoma antigen (SCC) value and FIGO stage (OS: χ²=7.123, 6.014, 8.398, P<0.05; DFS: χ²=11.832, 8.003, 7.731, P<0.05). In addition to the above factors, 2-year DFS was also associated with pelvic lymph node metastasis (χ²=9.286, P<0.05). Multivariate analysis showed that pathological type, pre-treatment SCC value and FIGO stage were independent prognostic factors of OS(HR=2.963, 2.473, 2.574, P<0.05). The independent prognosis factors affecting DFS included pathological type, pre-treatment SCC value and pelvic lymph node metastasis (HR =3.014, 1.988, 1.914, P<0.05). Conclusions By means of radical radiotherapy, cervical cancer patients with adenocarcinoma, pre-treatment SCC levels ≥30 ng/ml and advanced stage have poor prognosis, so more active treatment strategy should be adopted.

Objective To evaluate the efficacy of one stage anterior debridement combined with posterior pedicle screw fixation in the treatment of cervical intervertebral space infection.Methods From June 2010 to June 2016,28 cases were fixed by anterior debridement combined with the posterior vertebral pedicle screws for the cervical intervertebral space infection,19 males and 9 females.The average age was 45-74 years (58±14.5 years old).21 cases (75％) were spontaneous infection,of which 6 cases were diabetes mellitus,15 cases were over 60 years old.The remaining 7 cases (25％) were intervertebral space infection after radiofrequency ablation of the cervical spine.All patients were excluded from tuberculosis and Brucella infection.All patients underwent hematological examination,with emphasis on WBC,ESP and CRP.All patients received JOA score before operation,applied antibiotic according to blood culture and drug sensitive test.All patients underwent one stage anterior debridement combined with posterior pedicle screw fixation,and the operative time and bleeding volume were recorded.After the operation,intravenous antibiotic therapy was continued,and the application of antibiotics was guided according to the results of ESP and CRP,and the time for the application of antibiotics was recorded.Follow up was performed at 3 months,6 months and 1 years after operation respectively.The JOA score and postoperative cervical lordosis Cobb angle were recorded.Results All operations were successfully completed in this group.The operation time was 130-225 min,with an average of 145.5±12.7 min.The intraoperative blood loss was 40-100 ml,with an average of 67±35.2 ml.The incision was healed in one stage.The time of application of antibiotics in 28 patients was 21-87 days,with an average of 30.8±8.7 days.The longest application time of antibiotics was 87 days,and no relapse was found during follow-up.The postoperative JOA score increased from 11.3± 1.2 to three months 14.9 ± 1.96 postoperatively and 6 months 15.1 ± 1.55 and 1 years 16.5±0.48 after operation.The JOA score was significantly higher than that before operation.No significant loss and change of the Cobb angle in the cervical spine surgery were found.All cases had good bone graft fusion at 1 years.Conclusion One stage anterior debridement combined with posterior pedicle screw fixation is a safe and effective method for the treatment of cervical vertebra instability and nerve function injury caused by cervical intervertebral space infection.It provides a new way for the treatment of cervical intervertebral space infection.

Objective To observe and explore the differentiation value of serum hepcidin level in iron defi-ciency anemia(IDA) and anemia of chronic disease(ACD) .Methods 40 cases of IDA in the hospital from Oc-tober 2015 to February 2017 and 40 cases of ACD were selected as the ACD group and in the same period 50 healthy people undergoing physical examination served as the control group .The ELISA method was adopted to detect serum hepcidin level in each group .The levels of serum iron and total iron binding capacity (TIBC) were detected by using the ferrous benzoxazines colorimetric method .Then the serum hepcidin levels were performed the contrastive analysis and statistical processing .Results The serum hepcidin level in the IDA group was lower than that in the control group ,the difference was statistically significant (P<0 .05) ,and ser-um hepcidin level in the ACD group was higher than that in control group ,the difference was statistically sig-nificant (P<0 .05) .The areas of under the receiver operating characteristic (ROC) curve for hepcidin ,serum iron ,TIBC in the differentiation diagnosis of ACD and IDA were 0 .98 ,0 .67 and 0 .86 respectively .Conclusion Serum hepcidin level is a simple and easy method for the differentiation diagnosis of IDA and ACD ,and its accuracy is superior to that of serum iron and TIBC levels .

According to the cognitive behavior theory and meta-cognitive theory of health anxiety, to examine the association between alexithymia, cognition factors or meta-cognition factors and health anxiety.
 Methods: A total of 1 164 medical students were investigated by the Short Health Anxiety Inventory, the Health Cognitions Questionnaire, the Meta-cognitions about Health Questionnaire and the Toronto Alexithymia Scale.
 Results: 1) Correlation analysis showed that alexithymia, dysfunctional beliefs, meta-cognition were significantly positively correlated with health anxiety (r=0.227-0.477, all P<0.01); 2) The results of structural equation model indicated that alexithymia could not exert effects on health anxiety directly (β=-0.05, 95% CI -0.123 to 0.021). The alexithymia could exert effects on health anxiety indirectly not only through dysfunctional beliefs (β=0.192, 95% CI 0.156 to 0.235), but also through the chain-mediated effect of dysfunctional beliefs and meta-cognitions (β=0.103, 95% CI 0.077 to 0.135). Dysfunctional beliefs fully mediated the relation between alexithymia and health anxiety (β=0.247, 95% CI 0.196 to 0.290).
 Conclusion: Alexithymia can affect health anxiety through the mediating effects of dysfunctional beliefs and meta-cognition.
Affective Symptoms ; complications ; Anxiety ; complications ; Culture ; Humans ; Metacognition ; Surveys and Questionnaires