Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO₂) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO₂ exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO₂ group, 15 rats in each group. Rats in the SiO₂ group were given 1 mL of 50 mg·L⁻¹ SiO₂ suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO₂ exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO₂ group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO₂ group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO₂ group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO₂ group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO₂ group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO₂ exposure.

Objective:To probe into the potential prognostic value of lymphocyte subsets in gastric cancer.Methods:This study included patients who underwent radical gastrectomy for gastric cancer from Aug 2014 to Dec 2016. The immunological differences was analyzed in different infiltration patterns. The overall survival of patients was analyzed by Kaplan-Meier method and Log-rank test. COX regression was performed to assess independent prognostic factors of the patients, and finally constructed nomogram.Results:The median number of peripheral CD4 and CD19 cells in infiltration pattern c was 750 (94-2 504) cells/μl and 186 (17-820) cells/μl; the median number of peripheral CD4 and CD19 cells in infiltration pattern a was 802 (203-2 071) cells/μl and 213 (5-948) cells/μl, the number of peripheral CD4,CD19 cells in infiltration pattern c was lower than that in infiltration pattern a, with statistically significant differences (CD4: Z=-3.061, P=0.002; CD19: Z=-2.016 , P=0.044). CD19 lymphocytes ( P=0.023) were associated with infiltration pattern a, CD8 lymphocytes ( P=0.027) were associated with infiltration pattern b, and CD4 lymphocytes ( P=0.026) were independent risk factors associated with the prognosis of infiltration pattern c. A nomogram can be constructed to evaluate the prognosis of patients. Conclusion:There are differences in the number of peripheral lymphocyte subsets in patients with different INF types. A nomogram can be constructed from lymphocyte subsets and clinicopathological features to assess patient prognosis.

Objective:To construct a double-line mixed teaching mode and to explore its application effect on the practice teaching of medical students in the department of surgical oncology.Methods:A total of 80 clinical medicine students were selected and randomly divided into a routine group and a research group, with 40 students in each group. The routine group implemented regular teaching, and the research group developed "double-line mixed teaching" mode. After teaching, the students' theoretical and practical skills assessment results, changes in medical students' abilities and their satisfaction with teaching were compared between the two groups. SPSS 19.0 was used for t test and chi-square test. Results:The theoretical and practical skill assessment scores of the research group were significantly higher than those of the routine group [(91.59±3.65) score vs. (84.67±4.34) scores, (86.05±4.16) scores vs. (74.73± 4.69) scores] ( P<0.05). The scores of medical humanistic spirit, clinical thinking ability, scientific research thinking ability, critical thinking and innovation ability of the two groups after teaching were all higher than those before teaching, and the above-mentioned ability scores of the research group were all higher than those of the routine group after teaching ( P<0.05). The satisfaction rates of the students in the research group regarding teaching content and form, improving self-study ability, strengthening understanding and mastering of knowledge, deepening practical experience, and improving collaboration ability were all higher than those of students in the routine group (87.50% vs. 67.50%; 82.50% vs. 60.00%; 90.00% vs. 67.50%; 92.50% vs. 75.00%; 95.00% vs. 77.50%), and the differences were statistically significant ( P<0.05). Conclusion:Constructing double-line mixed teaching mode in the practice teaching of medical students in the department of surgical oncology can improve the performance of theoretical and practical skills assessment, as well as improve the various abilities of medical students, and can obtain high satisfaction with the teaching mode.

Objective:To investigate any anti-aging effect of repeated transcranial magnetic stimulation (rTMS) and explore the relationship between the effect and relief of clinical symptoms in patients with Parkinson′s disease (PD).Methods:A total of 108 PD patients were randomly divided into an rTMS group and a control group, each of 54, while another 54 healthy counterparts were selected to form a normal group. In addition to anti-PD drug therapy, the rTMS group was given daily rTMS treatment, 5 days a week for 4 weeks, while the control group received sham rTMS treatment, with no treatment of the normal group. Before the treatment and after 4 weeks of treatment as well as and 1 month after the ending of the treatment, the subjects′ clinical exercise symptoms were evaluated using the Unified Parkinson′s Disease Rating Scale (UPDRS), a timed exercise test and the 10m re-entry exercise test. Non-exercise symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Mini-mental State Examination (MMSE). Fasting venous blood samples were analyzed to quantify the serum levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1β (IL-1β) and matrix metalloproteinase-3 (MMP-3).Results:Four weeks and 1 month after the treatment, the average UPDRS scores, exercise test times and 10m re-entry exercise test results of the rTMS group were significantly better than those before treatment and significantly better than those of the control group at the same time point. The rTMS group′s average HAMA, HAMD and MMSE scores, as well as its average P300 latency and amplitude were also significantly better than those of the control group at the same time point and significantly better than those before treatment. After 4 weeks, the average MMP-3 content in the rTMS group was significantly lower than the control group′s average, and after a month the average levels of TNF, IL-6, IL-1β and MMP-3 of the rTMS group were all significantly different from those before treatment and those of the control group. The TNF, IL-6, IL-1β and MMP-3 levels were all positively correlated with the average UPDRS total score.Conclusion:High-frequency rTMS therapy can change the phenotypes related to cell senescence, and thus has good therapeutic effect on motor and non-motor symptoms of PD.

Phenome-wide association study (PheWAS) is a reverse genetic analysis method to identify the potential phenotypes associated with genetic variations. With the increasing availability of biomedical databases and electronic medical records (EMR), PheWAS has gradually become an effective tool to unveil the relationships between exposure and a broad range of health phenotypes. The unique advantage of this method is that it can simultaneously explore the associations of a specific exposure with a variety of disease outcomes, thus helping to reveal multiple causal relationships and the shared pathogenic mechanisms among diseases. However, PheWAS has limitations, including selecting instrumental variables and the heavy burden of various corrections. In addition, how to interpret the biological mechanisms underlying significant findings is another crucial issue of PheWAS. This review will focus on the methodology and application of PheWAS to provide meaningful suggestions and insights for future studies.

Objective To study the relationship between preoperative serum ALT and clinicopathological factors in patients with gastric cancer after radical gastrectomy.Methods At the Department of Gastrointestinal Surgery,Tumor Hospital of Harbin Medical University from Jan 2008 to Dec 2010,491 patients were grouped according to ROC curve cut-off point of serum ALT.The relationship between ALT and clinical factors was analyzed,and single-factor and multi-factor survival analysis was performed.Results There were 201 patients with ALT ≤ 20.05 U/L,and 290 patients with ALT ＞ 20.05 U/L Serum ALT was associated with age (x2 =11.231,P ＜ 0.001),depth of tumor invasion (x2 =23.178,P＜0.001),GGT(x2 =19.190,P＜0.001) and AST(x2 =30.771,P＜0.001).The 1-,3-,and 5-year survival rates of patients with ALT ≤ 20.05U/L and ALT ＞ 20.05U/L were 83.5％,51.4％,42.1％ and 66.2％,27.4％,15.7％.There was significant difference between the two groups (x2 =41.711,P＜0.001).Muhivariate analysis showed that tumor TNM stage(HR =1.882,95％ CI:1.468-2.413,P ＜0.001),tumor infiltration depth (HR =1.161,95％ CI:1.020-1.322,P =0.024),lymph node metastasis (HR =1.177,95％ CI:1.042-1.329,P =0.009),Hb (HR =0.726,95％ CI:0.579-0.909,P =0.005),neutrophil to lymphocyte rate(HR =1.275,95％ CI:1.002-1.623,P =0.048) and ALT(HR =2.191,95％ CI:1.754-2.738,P ＜ 0.001) were independent risk factors for the prognosis.Conclusions Serum ALT is an independent risk factor for the prognosis of gastric cancer patients after radical gastrectomy.

Objective: To study the relationship of liver function index alanine aminotransferase and aspartate aminotransferase ratio (LSR) with clinicopathological factors in patients with gastric cancer and its clinical significance in predicting the survival of patients. Methods: A retrospective case-control study was used. Retrospective analysis was conducted on 891 patients with advanced gastric cancer who underwent gastric cancer surgery at the Gastrointestinal Surgery Department of Harbin Medical University Cancer Hospital from January 2007 to December 2010, having complete postoperative clinicopathological and follow-up data. Case inclusion criteria: (1) preoperative definite diagnosis of gastric cancer, residual gastric cancer and other gastric tumors were excluded; (2) no neoadjuvant therapy before surgery; (3) no other serious diseases such as acute coronary heart disease, cirrhosis, chronic renal failure, etc.; (4) radical gastrectomy was performed, palliative treatment or open laparotomy cases were excluded; (5) complete postoperative pathological data, complete follow-up information; (6) cause of death was associated with gastric cancer. Blood examination was performed during hospitalization. The best cut-off points of LSR, hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were obtained by using receiver operating characteristic curve(ROC). Patients were divided into two groups according to best LSR cut-off points. The relationship between LSR and clinicopathological factors was analyzed, and the overall survival rate of different LSR groups was compared. Relevant clinical factors and LSR were included in the univariate and multivariate survival analysis using the Cox method. Results: The best cut-off point of LSR in ROC curve was 1.43, and 682 cases in LSR<1.43 group, 209 cases in LSR≥1.43 group. The best cut-off points of hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were 130.2 g/L, 18.0%, 4.75 cm, 68.1 U/L, 16.55 U/L, 5.58 μmol/L and 135.8 U/L, respectively. Between patients with LSR<1.43 and LSR≥1.43, age (χ²=4.412, P=0.036), depth of tumor invasion (χ²=64.306, P<0.001), histological type (χ²=8.026, P=0.005), alkaline phosphatase (χ²=8.217, P=0.004), glutamyl transpeptidase (χ²=33.207, P<0.001), total bilirubin (χ²=14.012, P<0.001) and lactate dehydrogenase (χ²=63.630, P<0.001) were significantly different. The 1-, 3- and 5-year survival rates of LSR<1.43 group and LSR≥1.43 group were 70.8%, 31.3%, 25.0% and 64.9%, 24.4%, 11.3% respectively, whose difference was significant (χ²=10.140, P=0.001). Univariate analysis showed that age, hemoglobin, TNM stage, depth of invasion, lymph node metastasis rate, lymph node metastasis, histological type, maximum diameter of tumors, glutamyl transferase, total bilirubin and LSR were associated with overall survival of gastric cancer (all P<0.05). Multivariate analysis showed that tumor TNM stage (HR=1.605, 95%CI: 1.332 to 1.936, P<0.001), tumor invasion depth (HR=1.299, 95%CI: 1.168 to 1.445, P<0.001), lymph node metastasis rate (HR=2.400, 95%CI:1.873 to 3.076, P<0.001), lymph node metastasis (HR=1.263, 95%CI: 1.106 to 1.478, P=0.007), maximum tumor diameter (HR=1.375, 95%CI: 1.134 to 1.669, P=0.001), and LSR (HR=1.427, 95%CI: 1.190 to 1.711, P<0.001) were independent risk factors for the prognosis of patients with gastric cancer. Conclusions LSR is an independent risk factor for the prognosis of gastric cancer patients, and the detection is simple and easy. It is a potential marker for the prognosis of gastric cancer. Therefore, in the preoperative comprehensive management stage, it should be possible to restore and improve the liver function in order to obtain a better prognosis of gastric cancer and prolong the survival time of patients.

Objective:To compare the ability of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in evaluating the prognosis of patients with TNM stageⅠto Ⅲ gastric cancer.Methods:From May 2001 to December 2013, the clinicopathological data of 645 patients with gastric cancer treated at Harbin Medical University Cancer Hospital were retrospectively analyzed. Chi-square test was used to analyze the differences between NLR, and PLR and clinicopathological characteristics of patients. Kaplan-Meier method and log-rank test were performed to compare the overall survival of patients. Cox proportional hazards regression model was performed to analyze the prognosis of gastric cancer patients. The ability of NLR and PLR to evaluate the prognosis of gastric cancer was compared by receiver operating characteristic curve.Results:The cutoff values of PLR and NLR were 141.50 and 1.94, respectively. PLR was associated with gender, resection method, maximum diameter of tumor, whether chemotherapy, T-stage, N-stage, TNM stage, tumor location, white blood cell, hemoglobin, albumin, and whether total gastrectomy ( χ2=9.224, 10.577, 28.825, 6.831, 29.059, 28.637, 30.748, 18.023, 24.320, 77.274, 9.021 and 10.745, all P<0.05). NLR were associated with resection method, maximum diameter of tumor, T-stage, N-stage and TNM stage, white blood cell, hemoglobin and albumin ( χ2=14.563, 12.092, 22.697, 44.735, 34.151, 7.949, 9.611 and 7.498, all P<0.05). The results of multivariate analysis showed that resection method, whether chemotherapy, T-stage, N-stage, PLR and whether total gastrectomy were all independent risk factors for gastric cancer patients ( χ2=23.653, 22.023, 16.697, 24.038, 4.110 and 22.364, all P<0.05). The five-year cumulative survival rate of the patients with PLR<141.50 was higher than that of patients with PLR≥141.50 (55.4% vs. 30.5%), and the difference was statistically significant ( χ2=47.968, P<0.01). The AUC value of PLR in prognostic evaluation of gastric cancer was 0.629, which was higher than that of NLR (0.596, P<0.01). Conclusion:PLR is better than NLR in the prognostic evaluation of gastric cancer patients.

Objective:To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism.Methods:From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10 6 cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results:High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-β1, TIMP-1 levels in serum were significantly higher in PQ group ( P<0.05) , while TNF-α and MMP-9 had no significant difference ( P>0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-β1 in BMSC-A and BMSC-B groups were lower than those in PQ group ( P<0.05) . The Lung organ coefficients, TGF-β1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference ( P>0.05) . Conclusion:Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-β1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .