[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.

No causal effects between rosiglitazone and cardiovascular disease or risk factors: a Mendelian randomization study.

OBJECTIVE: Although many observational studies have shown an association between rosiglitazone and cardiovascular disease (CVD) or risk factors, controversy remains. We conducted a Mendelian randomized (MR) study to explore whether rosiglitazone is causally related to CVDs and risk factors. PATIENTS AND METHODS: Single-nucleotide polymorphisms associated with rosiglitazone at genome-wide significance were identified from a genome-wide association study of 337,159 European-ancestry individuals. Four treatments with rosiglitazone-associated single-nucleotide polymorphisms associated with a higher risk of CVDs were used as an instrumental variable (IV). Summary-level data for 7 CVDs and 7 risk factors were obtained from UK Biobank and consortia. RESULTS: We found no causal effects of rosiglitazone, either on CVDs or risk factors. The results were consistent in sensitivity analyses using Cochran's Q test, MR-PRESSO method, leave-one-out analysis and Mendelian randomization-Egger method (MR-Egger), and no directional pleiotropy was observed. Sensitivity analyses confirmed that rosiglitazone was not significantly associated with CVDs and risk factors. CONCLUSIONS: The findings from this MR study indicate no causal relationship between rosiglitazone and CVDs or risk factors. Hence, previous observational studies may have been biased.

[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.

Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice.

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and '9 + 2' flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.

The relationship between HSP60 gene polymorphisms and susceptibility to atherosclerosis.

OBJECTIVE: To explore the potential correlation between heat shock protein 60 (HSP60) gene polymorphisms and susceptibility to atherosclerosis. PATIENTS AND METHODS: A total of 160 atherosclerosis patients treated in our hospital from February 2017 to February 2019 were randomly enrolled as case group, and 200 healthy adults receiving physical examination were selected as control group at the same period. Venous blood was drawn from all subjects to extract deoxyribonucleic acid (DNA). TaqMan probe technology was employed to genotype two loci rs2340690 and rs788016 of HSP60 gene in all 260 subjects. The correlations between HSP60 gene polymorphisms and the incidence rate and pathological grade of atherosclerosis were analyzed. RESULTS: There were three genotypes (AA, AG, and GG) in HSP60 rs2340690 and three (GG, AG, and AA) in HSP60 rs788016. No significant differences in the frequency of each genotype were found between the two groups (p>0.05). HSP60 rs2340690 and HSP60 rs788016 had no significant associations with the incidence rate of atherosclerosis in the dominant, recessive, and additive genetic models. In the case of pathological grade IV, the proportion of atherosclerosis patients carrying GG genotype of HSP60 rs2340690 was higher than those carrying AA genotype and AG genotype of HSP60 rs2340690 (p<0.05). The probability in atherosclerosis patients carrying rs788016 A was higher than those carrying rs2340690 G (p<0.05). When atherosclerosis patients carried both genotype G of HSP60 rs2340690 and genotype A of HSP60 rs788016, the odds ratio (OR) was 1.721 (p=0.049). CONCLUSIONS: The HSP60 gene polymorphisms are certainly correlated with the pathological grade and incidence rate of atherosclerosis.

[Epidemiological characteristics of pre-hospital mortality due to acute myocardial infarction from 1999 to 2016 in Tianjin city].

To explore the epidemiological characteristics, trends and relevant factors of pre-hospital mortality due to acute myocardial infarction (AMI) from 1999 to 2016 in Tianjin city, based on mortality surveillance information and household registration population information. Standardized mortality rates were calculated using the year 2000 world standard population. From 1999 to 2016, the research result showed that the pre-hospital crude mortality rates of AMI were 39.47/100 000 to 90.64/100 000 and the standardized mortality rates were 30.92/100 000 to 53.90/100 000. The proportion of pre-hospital AMI deaths was 73.96%-81.92% (t=1.09, P>0.05) within the same period. Aged, female, rural residents, unmarried, divorced, widowed, low education level, and outdoor workers have a relative higher proportion of pre-hospital AMI mortality.

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.

[The trend of chronic lower respiratory disease mortality of the residents in Tianjin, China, 2000-2016].

Objective: To explore the trends and distribution of chronic obstructive pulmonary disease (COPD) mortality of the residents with different characteristics from 2000 to 2016 in Tianjin. Methods: COPD mortality data in 2000-2016 were from Tianjin population based mortality surveillance system. The mortality rate of COPD, difference in the rate by gender, age, and geographic distribution, and the trend over years were analyzed. Age-sex-standardized mortality rates of COPD were calculated using the year 2000 world standard population. Joinpoint regression and Cochran-Armitage trend analysis were used to examine the trend of mortality. Results: The crude COPD mortality rate in Tianjin decreased from 57.57/100 000 in 2000 to 28.23/100 000 in 2016 (annual percent change (APC)=-5.01%, Z=-64.76, P<0.001), and the standardized mortality rate decreased from 56.53/100 000 in 2000 to13.88/100 000 in 2016 (APC=-9.17%, Z=-100.83, P<0.001). The crude COPD mortality rate of males decreased from 54.57/100 000 to 27.77/100 000 (APC=-4.89%, Z=-43.63, P<0.001) and the standardized mortality rate decreased from 57.52/100 000 to 14.63/100 000 (APC=-9.07%, Z=-71.48, P<0.001). The crude COPD mortality rate of females decreased from 60.63/100 000 to 28.68/100 000 (APC=-5.12%, Z=-47.92, P<0.001) and the standardized mortality rate decreased from 55.53/100 000 to 13 13/100 000 (APC=-9.27%, Z=-71.13, P<0.001). The crude mortality rate of COPD in urban areas decreased from 45.07/100 000 to 19.54/100 000 (APC=-5.35%, Z=-42.38, P<0.001) and the standardized mortality rate decreased from 39.24/100 000 to 7.45/100 000 (Z=-63.97, P<0.001, APC=-10.22%). The crude mortality rate of COPD in rural areas decreased from 70.20/100 000 to 37.24/100 000 (APC=-4.77%, Z=-48.77, P<0.001) and the standardized mortality rate decreased from 78.88/100 000 to 25.70/100 000 (APC=-7.59%, Z=-72.43, P<0.001). The COPD mortality rate in rural areas was higher than that in urban areas (P<0.001). The COPD mortality rate in 35 years old and over decreased from 2000 to 2016 (P<0.001). Conclusion: The COPD mortality in Tianjin decreased from 2000 to 2016. More efforts are need to reduce COPD mortality in Tianjin, in particular people in rural areas.

[A study of clinical and genetic characteristics of a Leber hereditary optic neuropathy family with the heteroplasmic m.14484T>C mutation].

Objective: To study clinical and genetic characteristics of a Leber hereditary optic neuropathy (LHON) family with the heteroplasmic m.14484T>C mutation. Methods: A cross-sectional study. The objects of the study included a 31-year-old male LHON patient with the heteroplasmic m.14484T>C mutation (the proband) who visited Department of Ophthalmology in the Affiliated Central Hospital of Qingdao University in March 2015 and other 36 matrilineal relatives in a four-generation family (12 males and 24 females aged 2-81 years, median 27 years). The visual acuity, intraocular pressure, fundus, color vision, visual field, visual evoked potential and optical coherence tomography were evaluated in maternal members. The mitochondrial DNA (mtDNA) sequence of fragments including m.14484 loci was detected by Sanger sequencing in 33 members. The sequencing peaks were analyzed by QSVanalyzer software to get the heteroplasmy levels of m.14484T>C mutation. The mtDNA of the proband was amplified by PCR and sequenced. Assembled sequence of mtDNA was compared with the updated consensus Cambridge sequence. The differences in visual evoked potential, optical coherence tomography and heteroplasmy levels were compared between two groups by the t-test, and among multiple groups by the single factor variance analysis. Results: Among the 33 maternal members of the family, 4 patients, 28 carriers and 1 person without a mutation were confirmed. The penetrance was 12.5% (4/32) . In addition to 4 patients with obvious abnormality on the ophthalmic examination, 5 carriers also appeared anomaly on the electrophysiological and visual function examinations. Compared to carriers, the amplitude of P100 was obviously decreased in the LHON patients[ (5.6±2.6) µV vs. (15.6±9.6) µV, t=2.880, P=0.006]. Significantly reduced values were seen in the average retinal nerve fiber layer thickness[ (71±17) µm vs. (99±11) µm, t=5.969, P< 0.001], in each side of the sub-area macular thickness, and in the nasal side of the lateral sub-area macular thickness [ (260±16) µm vs. (291±12) µm, t=5.593, P<0.001] between the LHON patients and carriers. The heteroplasmic levels were 80%±3% in the LHON patients, and 27%±18% in the unaffected members;the difference was significant (t=-8.395, P<0.001). The average degree of heteroplasmy had no difference between male and female members (48%±34% vs. 35%±28%, t=-1.147, P=0.258). The average mutation load was 29%±14% in the second generation members, 36%±29% in the third generation members, and 51%±36% in the fourth generation members;the differences were not statistically significant (F=1.152, P=0.330). The difference in the heteroplasmic levels was not statistically significant between mothers and their offspring (31%±25% vs. 42%±32%, t=1.165, P=0.251). Compared to Cambridge consensus sequence, 41 mutations was found in mtDNA of the proband, of which, 10 were missense mutations, including mutations m.4216T>C and m.3394T>C. According to the phylogenetic tree, the haplotype of the proband was M9a (M9a1a1c1a). Conclusions: In the family with the heteroplasmic m.14484T>C mutation, clinical manifestations of LHON appear in the individuals whose heteroplasmic level is more than 75%, and all of patients show typical chronic optic atrophy on the ophthalmic examination. The carriers with the m.14484T>C mutation also appear anomaly on the electrophysiological and visual function examinations. The heteroplasmic level of m.14484T>C mutation has a tendency to increase during the transmission in the family. The primary mutation m.14484T>C coordinate mutations m.4216T>C and m.3394T>C to increase the penetrance and incidence of abnormal visual function in carriers. (Chin J Ophthalmol, 2018, 54: 526-534).

[The trend of intracerebral hemorrhage mortality of the residents with different characteristics in Tianjin, China, 1999-2015].

Objective: To explore the trends and distribution of intracerebral hemorrhage (ICH) mortality of the residents with different characteristics from 1999 to 2015 in Tianjin. Methods: ICH mortality data in 1999-2015 were from Tianjin population based mortality surveillance system. The mortality rate of ICH, difference in the rate by gender, age, and geographic distribution, and trends over the years were analyzed. Standardized mortality rates of ICH were calculated using the year 2000 world standard population. Joinpoint regression and Cochran-Armitage trend were used to examine the trends in mortality. Results: A total of 102 279 ICH death cases were observed in Tianjin from year 1999 to 2015. The crude ICH mortality rate in Tianjin decreased from 76.35/100 000 in 1999 to 51.46/100 000 in 2015 (annual percent change (APC)=-1.96%, Z=-31.08, P<0.001) , and the standardized mortality rate decreased from 72.41/100 000 to 29.00/100 000 (APC=-5.20%, Z=-70.91, P<0.001). The crude mortality rate of ICH mortality in males decreased from 87.26/100 000 to 59.89/100 000 (APC=-1.79%, Z=-21.71, P<0.001) and the standardized mortality rate decreased from 85.65/100 000 to 35.75/100 000 (APC=-4.93%, Z=-52.32, P<0.001). The crude mortality rate of ICH mortality in females decreased from 65.21/100 000 to 42.98/100 000 (APC=-2.18%, Z=-22.28, P<0.001) and the standardized mortality rate decreased from 59.17/100 000 to 22.26/100 000 (APC=-5.63%, Z=-48.15, P<0.001). The ICH mortality rate under 35 years old increased from 0.78/100 000 to 0.92/100 000 (APC=4.41%, Z=5.07, P<0.001), especially in males increasing from 0.90/100 000 to 1.54/100 000 (APC=6.59%, Z=6.52, P<0.001). The crude mortality rate of ICH in urban areas decreased from 69.74/100 000 to 41.79/100 000 (APC=-3.18%, Z=-31.43, P<0.001) and the standardized mortality rate decreased from 57.56/100 000 to 20.42/100 000 (APC=-6.59%, Z=-53.43, P<0.001). The crude mortality rate of ICH in rural areas decreased from 82.99/100 000 to 61.49/100 000 (APC=-1.10%, Z=-14.06, P<0.001) and the standardized mortality rate decreased from 91.55/100 000 to 43.14/100 000 (APC=-3.78%, Z=-43.21, P<0.001). The ICH mortality rate in rural areas was higher than that in urban areas (P<0.05). Conclusion: ICH mortality rate in Tianjin decreased from 1999 to 2015. Further efforts to reduce ICH mortality in Tianjin is needed, in particular males, under 35 years old, and people in rural areas.

[Analysis on trend of cerebral infarction mortality from 1999 to 2015 in Tianjin of China].

Objective: To explore the trends and distribution of cerebral infarction between sexes, ages and urban-rural areas from 1999 to 2015 in Tianjin, China, and provide data for targeted prevention and control strategies of cerebral infarction in Tianjin. Methods: Cerebral infarction mortality data from January 1, 1999 to December 31, 2015 were obtained from Tianjin population based mortality surveillance system established by the Tianjin Centers for Disease Control and Prevention, and population data of permanent residents were obtained from Tianjin Municipal Public Security Bureau. The trends change and affecting factors including gender, age, and geographic distribution on mortality following cerebral infarction were analyzed. Results: (1) Cerebral infarction mortality rate in Tianjin increased from 1999 to 2015 with the crude mortality rate of 57.06/100 000 to 105.22/100 000 (Z=59.65, P<0.01, annual percent change(APC)=3.39%) and decreased with the standardized mortality rate from 55.59/100 000 to 56.12/100 000 (Z=-5.47, P<0.01, APC=-0.35%). (2) The crude mortality rate (64.23/100 000 to 118.72/100 000) and standardized mortality rate (65.44/100 000 to 67.23/100 000) of male cerebral infarction was higher than that of female (crude: 49.73/100 000 to 91.64/1/100 000, standardized: 45.73/100 000 to 45.01/100 000) from 1999 to 2015. (3) With the increase of age, the mortality of cerebral infarction increased gradually from 1999 to 2015 (all Z>0.00,all P<0.01). (4) The mortality rate of cerebral infarction in urban areas increased with the crude mortality rate from 71.43/100 000 to 103.20/100 000 (Z=17.34, P<0.01, APC=1.30%) and decreased with the standardized mortality rate from 61.04/100 000 to 43.77/100 000 (Z=-32.49, P<0.01, APC=-3.06%) from 1999 to 2015. The mortality rate of cerebral infarction in rural areas increased with the crude mortality rate from 42.63/100 000 to 107.32/100 000 (Z=69.14, P<0.01, APC=5.95%) and with the standardized mortality rate from 48.34/100 000 to 77.09/100 000 (Z=36.88, P<0.01, APC=5.95%) from 1999 to 2015. Conclusions: Cerebral infarction crude mortality increased and standardized mortality decreased from 1999 to 2015 in Tianjin. Further efforts to reduce cerebral infarction mortality in Tianjin are needed, special attention should be focused on the elderly, male 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.

[Analysis on the trends in mortality following acute myocardial infarction from 1999 to 2015 in Tianjin of China].

Objective: To explore the trends change in mortality following acute myocardial infarction (AMI) from 1999 to 2015 in Tianjin, China. Methods: AMI mortality data from 1999 to 2015 were obtained from Tianjin population based mortality surveillance system operated by the Tianjin Centers for Disease Control and Prevention (CDC), and population data of permanent residents were obtained from Tianjin Municipal Public Security Bureau. The trends change and affecting factors including gender, age, and geographic distribution on mortality following AMI were analyzed. Results: (1)The standardized mortality rate of AMI in Tianjin from 1999 to 2015 was 52.32/100 000 to 48.62/100 000. Adjusted AMI mortality rate from 1999 to 2013 was 52.32/100 000 to 73.72/100 000, indicating an increased trend(Z=32.15, P<0.001)with an annual percent change (APC) of 2.53%. Adjusted AMI mortality rate was decreased from 2013 to 2015: 73.72/100 000 to 48.62/100 000 (Z=-22.80, P<0.001), and APC was -19.07%. Above trends change was similar for male and female residents (all P<0.001). (2)The AMI standardized mortality rate of male was significantly higher than that of female during the 17 years. The AMI standardized mortality of male was significantly higher than that of female in<35, 35-44, 45-54, 55-64 and ≥65 years old group, respectively. AMI mortality rate increased with age. (3)Except in the year of 2002 and 2003, the AMI mortality rate were significantly higher in rural residents than in urban residents during this study period (P<0.001). Adjusted AMI mortality in urban residents increased from 1999 to 2009(Z=8.05, P<0.001, APC=1.43%), and decreased in the year from 2009 to 2015 (Z=-18.71, P<0.001, APC=-6.32%). Adjusted AMI mortality in rural residents increased in the year of 1999 to 2013(Z=56.05, P<0.001, APC=5.84%), and decreased in the year of 2013 to 2015 (Z=-24.40, P<0.001, APC=-21.35%). Conclusions: Our results suggest that AMI mortality in Tianjin increased from 1999 to 2013, and decreased from 2013 to 2015, and male and rural residents have higher AMI mortality. Related prevention and intervention measures should be taken to decrease AMI mortality, especially for male and rural residents.

[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.