[The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation].

Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

[Application value of folate receptor-positive circulating tumor cells in the diagnosis of head and neck squamous cell carcinoma].

A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR+CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR+CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR+CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR+CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

[Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation].

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

Effects of miR-490-5p targeting CDK1 on proliferation and apoptosis of colon cancer cells via ERK signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effects of micro ribonucleic acid (miR)-490-5p on the proliferation and apoptosis of colon cancer cells, and to explore its potential mechanism. PATIENTS AND METHODS: The mRNA expression of miR-490-5p in 30 pairs of colon cancer tissues and adjacent normal tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). Human colon cancer SW480 cell lines were cultured in vitro and divided into Control group and miR-490-5p overexpression group (miR-490-5p mimic group). The nonsense sequence and miR-490-5p mimic were transfected using liposome transfection technique into colon cancer cells in control group and miR-490-5p mimic group, respectively. Cell proliferation and apoptosis in each group were then observed. At the same time, the effect of miR-490-5p on the growth of colon cancer in vivo was explored using subcutaneous tumorigenesis assay. The protein expressions of extracellular signal-regulated kinase (ERK)1/2 signaling pathway and cyclin-dependent kinase 1 (CDK1) were determined via Western blotting. Furthermore, immunohistochemical staining was performed to verify the protein expression of CDK1 in vivo. RESULTS: The expression of miR-490-5p in colon cancer tissues was significantly lower than that in adjacent normal tissues (p<0.05). After transfection with miR-490-5p mimic in vitro, EdU staining and colony formation assay showed that the proliferation ability of SW480 cells was significantly weakened (p<0.05). Meanwhile, the number of colonies in miR-490-5p mimic group was markedly less than that in Control group (p<0.05). The results of Western blotting revealed that overexpression of miR-490-5p remarkably up-regulated the Bax/Bcl-2 and C-Caspase3/T-Caspase3 ratios in cancer cells (p<0.05). Subsequent results indicated that the subcutaneous tumorigenesis of colon cancer cells was markedly inhibited by overexpression of miR-490-5p (p<0.05). According to the results of Western blotting, the activation of ERK signaling pathway and the protein expression of CDK1 were significantly suppressed by overexpression of miR-490-5p (p<0.05). In vivo experiments further revealed that the protein expression of CDK1 in colon cancer tissues increased significantly (p<0.05). CONCLUSIONS: MiR-490-5p was found lowly expressed in colon cancer patients. In addition, overexpression of miR-490-5p inhibited the proliferation and promoted the apoptosis of colon cancer cells via down-regulating CDK1 both in vitro and in vivo.

[The predictive value of ureteral wall area for impacted ureteral stones].

Objective: To investigate the clinical indicators for preoperative prediction of impacted ureteral stones and analyze the predictive value of ureteral wall area(UWA). Methods: A total of 197 patients who underwent ureteroscopic lithotripsy due to ureteral stones at our institution from January to December 2020 were retrospectively analyzed. Preoperative patient age, gender, body mass index (BMI), history of hypertension, diabetes mellitus, side of stone, location of stone, maximum diameter of stone, CT value of stone, C-reactive protein (CRP), creatinine, renal pelvis diameter, ureteral wall thickness and UWA were collected. Patients were divided into impacted and non-impacted groups according to whether the stones were impacted intraoperatively. Univariate analysis was used to compare the differences in each clinical indicator between the two groups, and multivariate logistic regression was performed to analyze the independent predictors of impacted stones for those with differences. The receiver operating characteristic (ROC) curve was used to analyze the predictive power of each independent predictor, and the Delong test was used to analyze whether the difference in the area under the curve (AUC) of each independent predictor was statistically significant. Results: All 197 patients successfully completed the operation, aged 51 (36, 56) years; 137 males and 60 females. According to the results of ureteroscopy, they were divided into 82 cases of impacted ureteral stones and 115 cases of non-impacted ureteral stones. Univariate analysis showed that there were significant differences in maximum stone diameter, stone CT value, renal pelvis diameter, ureteral wall thickness and ureteral wall area between the two groups (P<0.05); There was no significant difference in age, gender, BMI, history of hypertension, diabetes, stone side, location of stone, CRP and creatinine (P>0.05). Multivariate logistic regression analysis showed that stone CT value (P<0.01), ureteral wall thickness (P<0.001) and ureteral wall area were independent predictors of impacted ureteral stones (P<0.001). The ROC curve was used to compare the predictive efficacy of independent predictors of stone CT value, ureteral wall thickness and ureteral wall area. The area under the ureteral wall area curve was the largest (AUC = 0.901, 95%CI: 0.859-0.943, P<0.001), followed by ureteral wall thickness (AUC = 0.799, 95%CI: 0.736-0.862, P<0.001) and stone CT value (AUC = 0.700, 95%CI: 0.626-0.775, P<0.001). By Delong test, there were significant differences in AUC between ureteral wall area and stone CT value (Z=4.527, P<0.001) and ureteral wall thickness (Z=3.407, P<0.001). The best predictive value of ureteral wall area was 79.6 mm2. The sensitivity and specificity of this critical value for predicting ureteral incarcerated calculi were 80.1% and 89.5%. Conclusions: The UWA, ureteral wall thickness as well as the CT value of stones were all independent predictors of impacted ureteral stones, and UWA had a better predictive value.

MicroRNA-424-5p inhibits the development of non-small cell LCa by binding to ITGB1.

OBJECTIVE: The aim of this study was to explore the effect of microRNA-424-5p on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells, and to investigate its influence on the expression of ITGB1 and potential regulatory mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of microRNA-424-5p in 44 paired NSCLC tissues and adjacent tissues. The relation between microRNA-424-5p expression and NSCLC clinical indicators was analyzed. Subsequently, microRNA-424-5p mimics and inhibitors were transfected into NSCLC cells to construct microRNA-424-5p overexpression or knockdown models, respectively. QRT-PCR was used to further verify the transfection efficiency. A series of experiments, including cell counting kit-8 (CCK-8) assay, colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze the effect of microRNA-424-5p on the biological function of NSCLC A549 and H358 cells. Finally, the potential association between microRNA-424-5p and its downstream gene ITGB1 was explored through luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results showed that microRNA-424-5p level was significantly lower in NSCLC tissues than that of adjacent normal tissues. Compared with patients with high expression of microRNA-424-5p, the pathological stage of those with low expression of microRNA-424-5p was significantly higher. In vitro experiments showed that microRNA-424-5p overexpression remarkably decreased cell proliferation and increased cell apoptosis, which were further validated in microRNA-424-5p inhibitor group. Subsequently, ITGB1 expression was found significantly up-regulated in NSCLC cell lines and tissues. Meanwhile, ITGB1 expression was negatively correlated with microRNA-424-5p level. In addition, a recovery experiment indicated that overexpression of ITGB1 could counteract the effect of microRNA-424-5p mimics on the proliferation and apoptosis of NSCLC cells. All these findings revealed that microRNA-424-5p and ITGB1 affected the malignant progression of NSCLC. CONCLUSIONS: MicroRNA-424-5p was closely correlated with the pathological stage and poor prognosis of NSCLC, thereby inhibiting the occurrence and development of NSCLC.

Effects of MiR-21 on the proliferation and migration of vascular smooth muscle cells in rats with atherosclerosis via the Akt/ERK signaling pathway.

OBJECTIVE: To explore the effects and mechanism of action of micro ribonucleic acid (miR)-21 on the proliferation and migration of vascular smooth muscle (VSM) in atherosclerosis (AS). MATERIALS AND METHODS: The rats were fed with a high-fat diet, and the oil red staining was adopted to compare AS between Sprague Dawley (SD) rats and miR-21 knockdown rats. At the in-vitro level, primary rat VSM cells (VSMCs) were selected and divided into miR-NC blank control group [miR-normal control (NC) group] and miR-21 overexpression group (miR-21 group) for relevant experimental detection. Wound healing assay and transwell assay were used to detect the effects of miR-21 on the proliferation and migration of VSMCs. Westernn blotting was applied to examine the changes in the levels of Cyclin D, a cell cycle-related protein, and the key factors of the Akt/ERK signaling pathway, such as phosphorylated-Akt (p-AKT), AKT, p-ERK1/2, and ERK1/2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell activity assay kit was applied to determine the effects of miR-21 on the proliferation of VSMCs through regulating the Akt/ERK signaling pathway after the ERK signaling pathway inhibitor PD98059 and AKT inhibitor MK-2206 were given. RESULTS: Compared with that in miR-NC group, the level of AS in miR-21 knockdown rats were decreased significantly (p < 0.05). In the cell-level experiment, the overexpression of miR-21 promoted abnormal proliferation of VSMCs and activated the Akt/ERK signaling pathway (p < 0.05). MTT assay results revealed that inhibiting the Akt/ERK pathway could reverse the effects of miR-21 promoting proliferation and migration. CONCLUSIONS: MiR-21 promotes the proliferation and migration of VSMCs by activating the Akt/ERK pathway and aggravates AS. Knocking down miR-21 or inhibiting the Akt/ERK pathway can suppress the activation of VSMCs.

[Analysis on trend of leukemia mortality from 1999 to 2015 in Tianjin, China].

From 1999 to 2015, there were 6 186 cases of leukemia deaths in tianjin residents, the males accounted for 58.28% (3 605) and 52.31% (3 236) deaths lived in urban areas; the crude mortality rate of Leukemia increased from 3.47/100 000 to 4.28/100 000 [t=7.09, P<0.001, annual percent change (APC)=1.30%] and the standardized mortality rate decreased from 3.15/100 000 to 3.01/100 000 (t=-2.95, P=0.006, APC=-0.65%). Special attention should be focused on children, the elderly, males and rural residents.

miRNA211 induces apoptosis of cervical cancer SiHa cells via down-regulation of inhibitor of apoptosis proteins.

OBJECTIVE: Cervical cancer severely threatens patients' lives. MicroRNAs contribute to regulatory function in the growth and apoptosis of cells. The present study investigated the effect of miRNA211 on growth and apoptosis of cervical cancer SiHa cells. MATERIALS AND METHODS: miRNA211 and control miRNA were synthesized and transfected into cervical cancer SiHa cells. MTT assay and flow cytometry were used to study the effect of miRNA211 on growth and apoptosis of SiHa cells. RT-PCR and Western blot were used to detect the expression of inhibitor of apoptosis proteins (IAPs) at both mRNA and protein levels. Groups of miRNA (NC), miRNA211, miRNA+siRNA IAP, miRNA211+siRNA IAP were established and levels of IAP and caspase 3 from each group were measured after transfection. RESULTS: After transfection with miRNA211, the growth of SiHa cells was significantly inhibited and apoptosis of SiHa cells was induced, with the reduction of IAPs at both mRNA and protein levels (p<0.05). Knockdown of IAPs enhanced the apoptosis of SiHa cells that were induced by miRNA211, while the overexpression of limited the pro-apoptotic effect of miRNA211 on SiHa cells. CONCLUSIONS: MiRNA211 inhibits the growth of SiHa cells via down-regulation of IAPs.

Unmanipulated haploidentical transplantation conditioning with busulfan, cyclophosphamide and anti-thymoglobulin for adult severe aplastic anaemia.

We conducted a retrospective analysis to evaluate outcomes of haploidentical transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults received haploidentical transplantation between May 2011 and December 2016. Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti-thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and peripheral blood transplantation. The patients' median age was 25 years. Forty-nine patients survived for more than 28 days and all achieved donor myeloid engraftment. The median time for myeloid engraftment and platelet recovery was 13 days (range, 10-21) and 17.5 (range, 7-101) days. The cumulative incidence (CI) of grade II-IV and III-IV acute GvHD) was 20.00±0.33% and 6.00±0.12%, respectively. The incidence of chronic GvHD was 14.00±0.36% and 25.90±0.71%, and that of moderate-severe chronic GvHD was 2.51±0.06% and 6.92±0.25% at 1 and 3 years, respectively. The 3-year estimated overall survival and failure-free survival were both 83.5±5.4% with a median follow-up of 21.1 months. Multivariate analysis showed hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of ⩾3 was significantly associated with worse outcome. Haploidentical transplantation conditioning including Bu/Cy/ATG was a safe and effective strategy for adult SAA patients, and HCT-CI might be an outcome predictor in these patients.

[Study on smoking attributed death and effects of smoking cessation in residents aged 35-79 years in Tianjin, 2016].

Objective: To analyze the influence of smoking on deaths in residents aged 35-79 years and the effects of smoking cessation in Tianjin. Methods: The data of 39 499 death cases aged 35-79 years in 2016 in Tianjin were collected, the risks for deaths caused by smoking related diseases and excess deaths as well as effects of smoking cessation were analyzed after adjusting 5 year old age group, education level and marital status. Results: Among the 39 499 deaths cases, 1 589 (13.56%) were caused by smoking, the percentage of the excess mortality of lung cancer caused by smoking was highest (47.60%); the risk of death due to lung cancer in smokers was 2.75 times higher than that in non-smokers (95%CI: 2.47-3.06). Among the female deaths, 183 (7.29%) were caused by smoking, the percentage of the excess mortality of lung cancer was highest (28.90%); and the risk of death of lung cancer in smokers was 4.04 times higher than that in non-smokers (95%CI: 3.49-4.68). The OR for disease in ex-smokers was 0.80 compared with 1.00 in smokers (95%CI: 0.72-0.90). The OR in males who had quitted smoking for ≥10 years was lower (0.74, 95%CI: 0.63-0.86) than that in those who had quitted smoking for 1-9 years (0.85, 95%CI: 0.74-0.98), but the difference was not significant. Conclusion: Smoking is one of the most important risk factors for deaths in residents in Tianjin. Smoking cessation can benefit people's health.

Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma (CN0): a study of 273 resections.

OBJECTIVE: The role of routine central lymph node dissection (CLND) for clinically central lymph node negative (CN0) papillary thyroid microcarcinoma (PTMC) remains uncertain. We aim to determine the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma. PATIENTS AND METHODS: A total of 273 patients diagnosed with clinically central lymph node negative PTMC from 2014 to 2016 were included. The predictive risk factors for CLNM were analyzed with respect to age, sex, tumor size, tumor multifocal, lymphadenectasis of lateral neck, capsular invasion, extra capsular spread (ECS), coexistence of chronic lymphocytic thyroiditis (Hashimoto thyroiditis, HT) and nodular goiter (NG), BRAFV600E mutation and subtype of papillary thyroid carcinoma (PTC). Univariate and multivariate analyses were performed to identify the risk factors for CLNM. RESULTS: Among the 273 patients, the CLNM occurred in 80 patients (29.3%). By univariate and multivariate analyses, tumor size (OR 2.07; p<0.001), multifocal (OR 2.67; p<0.004), lymphadenectasis of lateral neck (OR 9.28; p<0.001), tumor extent (OR 42.01; p<0.001) were independently correlated with CLNM. In further study, dorsal part of solitary lesion (OR: 16.312, 95%CI: 3.349-79.455, p=0.001), capsular invasion (OR: 42.012, 95% CI: 5.209-338.861, p<0.001), 6 6 mm, dorsal part of solitary lesion, multifocal, lymphadenectasis of lateral neck and capsular invasion.

ARID1A gene knockdown promotes neuroblastoma migration and invasion.

Neuroblastoma is the most common extracranial solid tumor in childhood which often acquires drug resistance and becomes aggressive phenotypes. The high-risk patients suffer from high mortality due to the limitation of the treatment strategies. ARID1A (AT-rich interactive domain-containing protein 1A), a subunit of SWI/SNF complexes, is considered as a tumor suppressor in many cancers. The aim of the present study was to investigate the effect of ARID1A on migration and invasion in neuroblastoma cells. The shRNA targeting ARID1A was designed and delivered into SK-N-SH cells to knock down ARID1A expression. Knockdown of ARID1A by shRNA significantly increased the viability and invasion ability, and caused G1 arrest inhibition and DNA synthesis increase in SK-N-SH cells. Moreover, Knockdown of ARID1A increased the activity and expression of matrix metalloproteinase (MMP)-2 and -9 in SK-N-SH cells. Furthermore, ARID1A knockdown caused diminished expression of E-cadherin, enhanced expression of N-cadherin and ß-catenin nuclear translocation in SK-N-SH cells. These results suggest that loss of ARID1A may associate with the promotion of invasion and metastasis of neuroblastoma. Our findings indicate ARID1A is a tumor suppressor in neuroblastoma.

JAK2 tyrosine kinase inhibitor AG490 suppresses cell growth and invasion of gallbladder cancer cells via inhibition of JAK2/STAT3 signaling.

The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry. As a consequence, we found that JAK2 inhibitor AG490 inhibited cell growth and invasion, and induced cell apoptosis and cycle arrest in GBC-SD and SGC-996 cells. Furthermore, the expression levels of p-JAK2, p-STAT3, VEGFC-/-D and cyclinD1 were downregulated, while p53 expression was upregulated in AG490-treated GBC cells indicated by Western blot assay. Therefore, our findings demonstrate that JAK inhibitor AG490 inhibits growth and invasion of GBC cells via blockade of JAK2/STAT3 signaling and provides the potential therapeutic strategy for the treatment of GBC patients.

[Analysis on cancer deaths and cause-eliminated-life-expectancy among residents of Tianjin, 2015].

Objective: To explore the causes of cancer deaths and cause-eliminated-life-expectancy among residents of Tianjin. Methods: Data from the death registry system of Tianjin residents in 2015 were collected and cancers were grouped according to the classification of Global Burden of Disease. Specific cancer crude death rate and cause eliminated life expectancy (CELE) were calculated. Results: In 2015, 17 641 Tianjin residents died of cancer, with the crude death rate as 171.79 per 100 thousand and the standardized rate according to the Chinese population in 2000 as 86.32 per 100 thousand. The cancer deaths among men was 10 165, with crude death rate of 197.39 per 100 thousand and standardized rate was 95.41 per 100 thousand. While among females the cancer deaths was 7 476, with crude death rate as 146.04 per 100 thousand and standardized rate as 76.65 per 100 thousand. The top five leading deaths on cancers among men were lung, liver, stomach, "colon, rectum and anal" , pancreas, while lung, breast, liver, "colon, rectum and anal" , stomach were in women. The life expectancy increased 3.53 and 2.88 years among men and women respectively after the exclusion of cancer deaths. When lung cancer death was excluded, the life expectancy increased 1.25 and 0.97 years respectively among men and women. Lung cancer was the main reason of life expectancy lost than cancer of other locations. Conclusion: Cancers, with lung cancer in particular, were the major diseases causing death and life expectancy lost in the Tianjin residents which called for urgent effective intervention programs to develop.

[Trend of premature mortality from chronic and non-communicable diseases in Tianjin, 1999-2015].

Objective: To explore the trends and distribution of premature mortality caused by four main non-communicable diseases (NCDs) including cardiovascular and cerebrovascular diseases, cancer, chronic respiratory disease and diabetes in different sex and residential areas in Tianjin so as to provide basis for setting up prevention and control programs on premature mortality. Methods: Population data on premature mortality in 1999-2015 were from the 'Tianjin population based mortality surveillance system' maintained by Tianjin Centers for Disease Control and Prevention (CDC). Data related to permanent residents was from the Tianjin Municipal Public Security Bureau. Standardized premature mortality rates were calculated and adjusted for age and gender according to the '2000 world standard population'. Premature mortality probabilities were analyzed according to the methods recommended by WHO. Joinpoint regression and Cochran-Armitage trend methods were used to determine the significance of differences on the trends of mortality. Results: From 1999 to 2015, the premature mortality appeared consistent (P<0.001) declining in the above-said four diseases with the APC of probabilities as-2.92%, -1.13%, -9.51% and -3.39%, respectively. The probabilities of premature mortality were all declining consistently in both men and women and in both urban and rural areas in Tianjin. From 1999 to 2015, the probabilities of the four main NCDs were between 19.67% and 12.85% (APC=-2.49%, P<0.001), higher in women (from 17.02% to 9.17%, APC=-3.84%, P<0.001) than that in men (from 22.27% to 16.47%, APC=-1.59%, P<0.001), in urban (from 21.04% to 12.34%, APC=-3.26%, P<0.001) than that in rural areas (from 17.80% to 13.54%, APC=-1.54%, P<0.001). Conclusion: Our findings suggested that premature mortality in Tianjin was decreasing during 1999-2015 but attention should still be called for on males and people living in the rural areas to further reducing the premature mortality.

Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor-Bearing Mice.

Tumstatin (Tum) is a powerful angiostatin that inhibits proliferation and induces apoptosis of tumorous vascular endothelial cells. A nonpathogenic and anaerobic bacterium, Bifidobacterium longum (BL), selectively localizes to and proliferates in the hypoxia location within solid tumor. The aims of this study were to develop a novel delivery system for Tum using engineered Bifidobacterium and to investigate the inhibitory effect of Tum on tumor in mice. A vector that enabled the expression of Tum under the control of the pBBADs promoter of BL was constructed and transformed into BL NCC2705 by electroporation. The mouse colon carcinoma cells CT26 (1 × 10(7)/mL) were subcutaneously inserted in the left armpit of BALB/c mice. The tumor-bearing mice were treated with Tum-transformed BL, and green fluorescent protein (GFP)-transformed BL was used as a negative control. The microvessel density (MVD) in the transplanted tumor was determined, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling was used to detect apoptosis of vascular endothelial cells in transplanted tumor. The in vitro expression of Tum was examined in BL after l-arabinose induction. Bifidobacterium longum with pBBAD-Tum (BL-Tum) showed significant antitumor effect in tumor-bearing mice. The weight, volume, growth, and MVD, as well as the percentage of apoptotic vascular endothelial cells of transplanted tumors in the tumor-bearing mice treated with Tum-transformed BL were all significantly lower than those in the GFP negative control group. Intragastric administration, injection in tumor and vena caudalis injection of Tum-transformed BL exerted marked antitumor effects in tumor-bearing mice. This is the first demonstration of the utilization of Tum-transformed BL as a specific gene delivery system for treating tumor.

Tobacco serine/threonine protein kinase gene NrSTK enhances black shank resistance.

A serine/threonine protein kinase gene (NrSTK) was cloned from Nicotiana repanda based on the sequence of a previously isolated resistance gene analog (RGA). Expression of RGA was induced by challenge with the pathogen black shank. The NrSTK gene was predicted to encode a protein kinase that contained an ATP binding site at residues 41-69 and a serine/threonine protein kinase activation sequence spanning the region 161-173. Overexpression of NrSTK in the susceptible tobacco variety Honghuadajinyuan significantly enhanced resistance to black shank, indicating that NrSTK plays a role in incompatibility reactions between tobacco and the pathogen. Characterization of NrSTK will help elucidate the molecular mechanisms involved in black shank resistance in N. repanda.

Association between the -607 C > A polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis.

The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta-analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions.