Objective To investigate the expression of metastasis associated gene-1 (mag-1) and mammalian target of rapamycin (mTOR) in rectal cancer, and its correlation with clinical pathology. Methods The expressions of mag-1 and mTOR in 60 rectal cancer tissue, 30 adenoma tissues and 10 normal rectal tissues were detected by immunohistochemical method, and the correlation between the expression levels and rectal cancer clinical pathologic characteristics was discussed. Results The positive expression rates of mag-1 and mTOR in rectal cancer tissue were significantly higher than those in normal rectal tissue and adenoma tissue:55%(33/60) vs. 1/10 and 27%(8/30), 58%(35/60) vs. 2/10 and 30% (9/30), and there were statistical differences (P<0.05). The expression levels of mag-1 and mTOR in rectal cancer tissue were correlated with carcinoembryonic antigen on admission, degree of cell differentiation, TNM stage, lymph node metastasis and distant metastasis (P<0.01 or<0.05), but had no correlation with age, gender, neoplasm location and neoplasm appearance (P > 0.05). The correlation analysis result showed that the expressions of mag-1 and mTOR were positively correlated in rectal cancer tissue (r=0.730, P<0.01). Conclusions The mag-1 and mTOR may correlate with invasion and metastasis in rectal cancer, and monitoring mag-1 and mTOR expression has a certain value for determining biological behavior of rectal cancer.

Objective:To explore the driving mechanism contributing to doctors′ turnover intention in public hospitals based on the grounded theory.Methods:" Willingness or intention for doctors to quit public hospitals" was used as the theme word, and the literature was retrieved from CNKI published from January 1, 2017 to January 1, 2022. Based on the grounded theory, NVivo 11.0 software was used for a qualitative analysis of the literature. The three-level coding method of open coding, axial coding and selective coding was used to identify the main categories affecting the willingness of doctors to quit public hospitals. On this basis, the driving mechanism model was integrated. In-depth interviews with hospital managers were used to test the theoretical saturation.Results:When 31 papers were coded, four level-1 influencing factors of the formation of doctors′ turnover intention in public hospitals were summarized: career selection deviation, practice reality, perceived experience and external opportunity. Among them, perceived experience was the direct driving factor; career selection deviation was the initial driving factor, and the practice reality was the key driving factor, both of them affected the perceived experience; external opportunity was the possible driving factor.Conclusions:In order to prevent doctors from willing to leave, the following measures are expected: the hospital management should improve both its recruitment evaluation indexes and recruitment effectiveness; pay attention to doctors′ psychological capital management and cultivate positive perception; promote the reform of performance pay, emphasize fairness and value; pay attention to employee relationship management and build a supportive hospital culture.

Objective To observe the expression levels of serum osteopontin (OPN),adenosine kinase 1 (TK1) and secretory protein Dikkopf 1 (DKK1) in patients with lung cancer and their clinical significances.Methods Lung cancer patients treated in the First Affiliated Hospital of Xi'an Medical University from February 2017 to April 2018 were selected as the lung cancer group (60 cases),and 60 healthy adults who received physical examination in the same period were selected as the control group.The differences of serum OPN,TK1 and DKK1 levels between the lung cancer group and the control group and lung cancer patients with different characteristics were compared.Measurement data were compared by using t test.Results The levels of serum OPN,TK1 and DKK1 in lung cancer patients were (38.56±3.18) μg/L,(4.69±1.03) pmol/L and (3.76±0.89) ng/ml,respectively,which were higher than those in the control group [(15.98±2.06) μg/L,(1.01±0.22)pmol/L,(1.21±0.24) ng/ml;t =-46.162,-27.064,-21.428,all P ＜ 0.01].The levels of serum OPN,TK1 and DKK1 in lung cancer patients of different ages and gender had no statistical differences (all P ＞ 0.05).The levels of serum OPN,TK 1 and DKK1 in stage Ⅲ-Ⅳ lung cancer patients were (57.18 ±3.12) μg/L,(6.26±1.28) pmol/L and (4.98±1.03) ng/ml,respectively,which were higher than those in stage Ⅰ-Ⅱ lung cancer patients [(30.35±2.96) μg/L,(3.49±0.67) pmol/L,(3.01±0.96) ng/ml;t =-34.156,-10.690,-7.665,all P ＜ 0.01].The levels of serum OPN,TK 1 and DKK1 in non-small cell lung cancer (NSCLC) patients were (55.13±5.02) μg/L,(5.96±1.11) pmol/L and (5.02±1.32) ng/ml,respectively,which were higher than those in small cell lung cancer (SCLC) patients [(29.68±3.16) μg/L,(3.13±0.98) pmol/L,(2.86±0.56) ng/ml;t =-22.353,-10.213,-7.688,all P ＜ 0.01].Conclusion The levels of serum OPN,TK1 and DKK1 in patients with lung cancer are higher,which are related to the type and stage of lung cancer.

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of nrhTNF combined with chemotherapy in the trial group and chemotherapy alone in the control group in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSNinety patients with NSCLC in multicenter were randomly devided into trial group and control group. Each group had 45 patients. Chemotherapy with CAP regimen was given for the patients in the trial group. Meanwhile, nrhTNF injection of 4×10⁶U/m ² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy course. Twenty-one days were as a cycle, 2 cycles were given each patients. Chemotherapy alone with CAP regimen was given in the control group. The chemothepeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSOf the 90 patients, 3 cases in each group were out of the trial because of economy. The other 84 cases (each group had 42 patients) could be used to analyze and evaluate the clinical effects and toxicity. The response rate of chemotherapy was 47.62% (20/42) in the trial group and 19.05% (8/42) in the control group (P=0.002) respectively. The KPS was 85.02±10.74 in the trial group, and 81.35±9.63 in the control group (P=0.038). No significant difference of degree III+IV toxicity was observed between the trial group and control group (P > 0.05). The side effects related to nrhTNF included slight fever, cold like symptoms, pain, and red and swelling in injection site. All of them were mild and didn't need any treatment and disappeared after the therapy.

CONCLUSIONSThe results demonstrate that the effects of domestic nrhTNF combined with chemotherapy can remarkably higher than that of chemotherapy alone in the treatment of NSCLC. It is able to increase the sensitivity to chemotherapy and improve the quality of life of the patients. The toxicity is also slight and is worth to expand clinical use, so as to further evaluate its effect and toxicity.

OBJECTIVE：To establish the method for the content determination of 7 components，such as puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin ，in Zhengxin jiangzhi tablets ，and conduct cluster heatmap analysis. METHODS ：HPLC method was adopted. The separation was performed on Kromasil C 18 column with mobile phase consisted of acetonitrile- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.8 mL/min. The detection wavelength was set at 280 nm，and the column temperature was 25 ℃. The sample size was 10 μL. Taking the content data as the object，the cluster heatmap was drawn by Hiplot scientific research mapping platform. RESULTS ：The linear range of puerarin ， 3′-methoxypuerarin，daidzein，rutin，hesperidin，salvianolic acid A and quercetin were 17.00-170.00（r＝0.999 9），5.14-51.40（r＝ 0.999 8），3.00-30.00（r＝0.999 8），153.00-1 530.00（r＝0.999 9），7.88-78.75（r＝0.999 8），2.85-28.50（r＝0.999 9）and 11.34-113.40 μg/mL（r＝0.999 8），respectively. RSDs of precision ，stability（24 h）and repeatability tests were all less than 2％； the average recoveries were 99.58％（RSD＝0.83％，n＝6），100.31％（RSD＝1.17％，n＝6），100.61％（RSD＝1.08％，n＝6）， 100.05％（RSD＝0.82％，n＝6），100.31％（RSD＝1.38％，n＝6），100.31％（RSD＝0.85％，n＝6），99.85％（RSD＝1.01％， n＝6），respectively. The contents of above components in 10 batches of samples were 7.262 5-8.941 5，2.464 9-3.068 9，1.478 9- 1.883 4，58.632 8-79.408 3，3.569 4-4.500 6，1.077 6-1.341 5，1.139 7-5.957 0 mg/g，respectively. Results of cluster heatmap analysis showed that 10 batches of samples could be divided into 4 categories，including S 1-S3 as one category ，S4 as one category，S5-S6 as one category and S 7-S10 as one category. CONCLUSIONS ：The established method is simple ，accurate and specific，which can be used for the quality control of Zhengxin jiangzhi tablets ，combined with cluster heatmap analysis. There are some differences in the quality of different batches of samples.

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Postnatal heart maturation is the basis of normal cardiac function and provides critical insights into heart repair and regenerative medicine. While static snapshots of the maturing heart have provided much insight into its molecular signatures, few key events during postnatal cardiomyocyte maturation have been uncovered. Here, we report that cardiomyocytes (CMs) experience epigenetic and transcriptional decline of cardiac gene expression immediately after birth, leading to a transition state of CMs at postnatal day 7 (P7) that was essential for CM subtype specification during heart maturation. Large-scale single-cell analysis and genetic lineage tracing confirm the presence of transition state CMs at P7 bridging immature state and mature states. Silencing of key transcription factor JUN in P1-hearts significantly repressed CM transition, resulting in perturbed CM subtype proportions and reduced cardiac function in mature hearts. In addition, transplantation of P7-CMs into infarcted hearts exhibited cardiac repair potential superior to P1-CMs. Collectively, our data uncover CM state transition as a key event in postnatal heart maturation, which not only provides insights into molecular foundations of heart maturation, but also opens an avenue for manipulation of cardiomyocyte fate in disease and regenerative medicine.
Gene Expression Regulation ; Heart ; Myocytes, Cardiac/metabolism* ; Single-Cell Analysis ; Transcription Factors/metabolism*