Abstract： Objective　To establish a screening-diagnosis-evaluation system of neonatal congenital heart disease (CHD) suitable for Hainan Province based on the application of percutaneous blood oxygen saturation measurement and cardiac auscultation screening, and to provide a basis for further promotion of the evaluation effect. Methods　Screening agencies (all midwifery institutions) used the "double index method" to screen newborns for congenital heart disease. Those who were screened positive for any index were transferred to diagnostic institutions (the people's hospitals of all cities and counties and some tertiary hospitals) for echocardiography examination within 1 week. Those with abnormal results were transferred to the treatment institution (two tertiary hospitals) for reconfirmation and evaluation. All data were managed online. Results　In this study, 96 913 newborns born in midwifery institutions in 19 cities and counties were screened, with a response rate of 99.44%. The ratio of male infants (50 836) to female infants (46 077) was 1.10∶1. A total of 2 284 positive patients were screened by dual index method, and ultrasound diagnosis was performed, with the rate of cardiac ultrasonography of 98.07% (2 240/2 284) and a high response rate. A total of 238 cases of congenital heart disease were diagnosed (incidence rate of 0.25%), with the top three main types were ventricular septal defect, atrial septal defect, and patent ductus arteriosus. The sensitivity (88.24%) and Youden index (0.86) of dual-indicator screening for CHD detection were significantly higher than the other separate indicators. Through Kappa consistency test analysis, the consistency of dual-indicator screening with simple heart murmur screening results was excellent, with a Kappa coefficient value of 0.835 (>0.75); the consistency of dual-indicator screening and simple POX screening results was good, with a Kappa coefficient value of 0.429 (between 0.40-0.75), and the differences were statistically significant (P<0.001). By the end of the study, 136 children had undergone open-chest/occlusion surgery, with good postoperative recovery, and the rest were followed up. Conclusions　The neonatal CHD screening-diagnosis-assessment technology system established in this study, with close connections between various blocks, high screening response rate and echocardiography examination rate, is beneficial for the early diagnosis and treatment of CHD children, and has certain application value in institutions at all levels in Hainan Province, and is worth further promotion.

Objective To observe the changes of cell cycle on cancer cells after dihydroartemisinin and X-ray irradiation. Methods Human HeLa cells of cervical cancer with p53 mutation was used and human SiHa cells of cervical cancer with wild p53 was used as control. Flow cytometry was used to detect the effect of dihydroartemisinin (20 and 100 μmol/L) and irradiation (6 Gy)on cell cycle. Western blot was used to measure the levels of cell cycle protein. Results G2 arrest was observed in irradiated HeLa cells, which the proportion of cells in G2 phase was increased from 14.45% to 73. 58% after 6 Gy X-ray irradiation, but it was abrogated by dihydroartemisinin from 73. 58% to 48.31%in HeLa cells, and it had no change on the SiHa cells. The elevated Weel protein and the lowered Cyclin B1 protein were observed with the G2 arrest severity. The expression of radiation-induced Weel protein was suppressed and the Cyclin B1 protein was increased after dihydroartemisinin treatment, which was in accordance with the abrogation of radiation-induced G2 delay. Conclusions The main effect of irradiation on cell cycle of p53 mutated HeLa cells is G2 arrest. Dihydroartemisinin could abrogate it, which is associated with the changes of Weel protein and Cyclin B1 protein. In Siha cells, the main effect of irradiation on cell cycle is G1 arrest, and dihydroartemisinin has no effect on it.

Abstract: Objective To explore the trend of maternal mortality in Hainan Province during the period of 2003-2022, both in the province and in urban and rural areas, and to forecast the maternal mortality rate for the period 2023-2025. Methods The 2003-2022 data collected from Hainan Province's three-tier network for maternal mortality surveillance was examined using the Chi-square test for trend (CMH) to analyze the province-wide and urban-rural maternal mortality trends. The time series model forecasting using exponential smoothing was used to predict the maternal mortality rate in Hainan Province from 2023 to 2025. Results　From 2003 to 2022, a total of 201 011 616 live births and 463 maternal deaths were reported in Hainan Province, with a maternal mortality rate of 23.03 per 100 000. Over 20 years, the maternal mortality rate in Hainan Province showed a downward trend, with an annual rate of decline of -4.13%. The rate decreased significantly during this period.. From 2003 to 2022, the maternal mortality rate in rural areas of Hainan Province was 25.74/100 000 (373/1 448 943), and it was significantly higher than that in urban areas, 16.04/100 000 (90/561 173). In the first 10 years, the gap between urban and rural areas progressively reduced, but it widened significantly in the last decade, especially after 2017. The maternal mortality rate was significantly lower in urban than rural areas, and the differences had statistical significance. The annual rates of decline in maternal mortality in Hainan Province and in urban and rural areas from 2003 to 2022 were -5.0% and -3.71%, respectively, showing a negative growth with the decrease rate in rural areas lower than urban areas. The maternal mortality rate in Hainan Province showed a fluctuating downward trend, different from the stable trend of national decrease. The mortality rates for direct obstetric causes of death (233 cases) and indirect obstetric causes of death (230 cases) were 11.59/100 000 and 11.44/100 000, respectively. The results of the maternal mortality review showed a predominance of avoidable deaths (315 cases, 68.03%). Brown's cubic exponential smoothing predicted the maternal mortality rate in Hainan Province for 2023-2025 as 9.45/100 000, 8.17/100 000, and 6.89/100 000. Conclusions　The maternal mortality rate in Hainan Province is largely influenced by maternal deaths in rural areas, and maternal health care in rural areas should be emphasized. Measures such as intervening to address the main factors influencing avoidable maternal deaths, strengthening high-risk maternal management, improving the level of critical maternal care, and providing subsidies for critical maternal care can sustainably reduce the maternal mortality rate in Hainan.

Objective To study the radiosensitizing effect of caffic acid phenethyl ester(CAPE)on human cervical cancer HeLa cells.Methods MTT assay was used to measure the relation between the inhibition effect and CAPE concentrations by CAPE with different concentrations on HeLa cells for 24 hours.HeLa cells were divided into the control and experimental groups,both of which were given 0,2,4,6 and 8 Gy of 60Co γ-irradiation,respectively.The cell clones were counted.Meanwhile HeLa cells were divided into the control,CAPE,irradiation and combination groups.Flow cytometric analysis was adopted to detect the changes of cell cycle distribution induced by CAPE.Results The inhibition rate of CAPE acting on Hela cells increased with concentrations(F=126.49～3654.88,P＜0.01).HeLa cells cloning survival decreased with the increase of radiation dose(F=174.42～9422.81,P＜0.01).At the game radiation dose,HeLa cells cloning survival was less in experimental group than conlrol group(F=120.14～251.91,P＜0.01).The mean lethal dose(D0)(1.45 and 1.82 Gy)and the quasi-threshold dose(Dq)(1.89 and 3.21 Gy)of HeLa cells in experimental group decreased comparing with control group,SER was 1.26.Compared with the sole irradiation group,cells in G2/M phase of the CAPE group and the sole irradiation group increased(P＜0.01)while the combination group decreased(P＜0.01).Conclusions CAPE could increase the radiation sensitivity of HeLa cells by G2/M arrest and may be related to the inhibition of the sub-lethal damage repair.

Objective To investigate the radiosensitizing effects of dihydroartemisinin(DHA)on human HeLa cells of cervical cancer irradiated by X rays.Methods Cell growth kinetics was determined using MTF assay.Cell survival was analyzed by elonogenic assay.The change of cell cycle and apeptosis was measured by flow cytometry.Results Dihydroartemisinin inhibited the growth of HeLa cells of human cervical cancer and showed a dose-dependent and time-dependent manner.Dihydroartemisinin(20 μmol/L)showed the radiosensitizing effects on HeLa cells,and the sensitizing enhancement ratio(SER)was 1.47.Dihydroartemisinin abrogated radiation-induced G2 arrest of the tested HeLa cells,the G2 ratio of medicine + radiation group dechned from 73.58% to 48.31%.Dihydroartemisinin enhanced the apoptosis of HeLa cells by X-irradiation,the apoptosis rates of medicine + radiation group significantly increased from 29.46%,48.04%,70.21% to 45.79%,66.36% and 79.58%,respectively for 2,4 and 6 Gy.Conclusions Dihydroartemisinin could increase the radiesensitivity of HeLa cells of human cervical cancer.Abrogation of radiation-induced C2 arrest could be part of the mechanism.

Abstract: Objective　To evaluate the free thalassaemia screening programme for preconception and pregnancy in Hainan Province, and to provide a theoretical basis for optimizing the screening process for thalassaemia. Methods From November 2020 to July 2021, a survey was conducted on 10 396 adults with Hainan household registration who participated in the Epidemiological Survey of Thalassemia in Hainan Residents in 19 cities and counties of Hainan Province. All of them underwent routine blood tests, haemoglobin electrophoresis tests and genetic tests for thalassaemia. The optimal diagnostic cut-off values for mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and haemoglobin adult type 2 (HbA2) were determined using screening test indexes such as receiver operating characteristic curve and sensitivity. The diagnostic effectiveness of different primary screening programs for thalassemia gene carriers was evaluated. Results Using the existing MCV single-indicator thalassemia primary screening protocol in Hainan Province, where individuals with MCV<82 fL undergo thalassemia gene testing, resulted in a high missed diagnosis rate (34.06%) and low sensitivity (65.94%). The optimal cut-off values for MCV screening for alpha-and beta-thalassaemia were 84.45 fL and 79.05 fL, respectively; the optimal cut-off values for MCH screening for alpha-and beta-thalassaemia were 27.95 pg and 25.15 pg, respectively. The optimal cut-off value for HbA2 screening for alpha-thalassaemia was less than 2.55% and greater than 3.35% for beta-thalassaemia. The "combined HbA2 or MCH or MCV screening protocol" with the cut-off values recommended in this study had a better performance in primary screening for thalassemia, with the highest sensitivity (92.96%) and negative predictive value (92.67%) and the lowest underdiagnosis rate (7.04%), statistically significant differences compared with the existing protocol (P<0.05). Conclusions The current process of screening for thalassemia in Hainan Province may lead to missed diagnoses. The combined use of MCV, MCH and HbA2 for thalassemia screening, adopting locally suitable cutoff values for primary screening indicators, can improve the incidence of missed reporting of thalassemia and enhance diagnostic effectiveness.

Objective To investigate the radiosensitizing effects of artesunate on human HeLa cells of cervical cancer in vitro.Methods Hela cells were irradiated with 60Co γ-rays.The dose rate was 0.635 Gy/min and the radiation dose was 0,1,2,4,6 Gy,respectively.The anti-proliferation activities of artesunate on HeLa cells were evaluated with MTT assay,to determine the most appropriate drug concentration.The effect of radiosensitivity was observed by using clonogenic assay.The single-hit multitarget model was used to plot the HeLa cell's dose-survival curve,to calculate mean lethal dose,quasithreshold dose and sensitization enhancement rate,and to evaluate its radiosensitization effect.The apoptosis was analyzed with flow cytometry (FCM) to further test the radiation senseitization of artesunate on HeLa cells.Results The inhibition of artesunate on HeLa cells increased with concentration.In radiation group,the cell cloning efficiency were 91.67% ,82.02% ,58.60% ,25.01%,respectively,and in artesunate (2.0 μ mol/L) + radiation group,the cell cloning efficiency were 74.93% ,60.53% ,22.38% ,5.05%.In radiation group and artesunate (2.0 μmol/L) + radiation group,the mean lethal dose(D0) was 2.95 and 2.07 Gy,respectively,while the qusai-threshold dose (Dq) were 2.01 and 1.24 Gy,respectively,and SER was 1.43.Compared with 2 and 6 Gy radiation group,the apoptosis rate of drug + radiation group increased from 12.26% ,40.08% to 22.71% ,59.92%.Conclusions The inhibiting effect of artesunate on HeLa cells is concentration-dependent.Artesunate has radiosensitizing effect on HeLa cells in vitro.

Objective To evaluate the effect of artemether on the cell cycle and the radiosensitivity in human nasopharyngeal carcinoma cell line CNE-1.Methods Cell growth inhibition was assessed with MTT.The method of colony-forming was used to detect the radiation sensitivity.Cell cycle distribution was analyzed by using flow cytometry.The protein expressions of clyclin B1 and Weei were detected by using Western blot.Results The growth of CNE-1 cells was inhibited in a dose-dependent manner.The concentration of 20 μmol/L artemether had radiosensitive effect on CNE-1 cells at 24 h after administration,and SER was 1.481.When CNE-1 cell was irradiated,the G2/M cells increased (t =4.59,P ＜ 0.05).After exposure to combination of artemether and irradiation,the G2/M cells were decreased (t= 10.60,P ＜ 0.05).Western blot showed that artemether increased the level of cyclin B1 expression and inhibited the level of Weel expression.Conclusions The noncytotoxic concentration of artemether could enhance radiosensitization of CNE-1 cells.The radiosensitivity enhancement of artemether might depend on the exposure time.The effect is most obvious when radiation is delivered 24 h after expose to artemetherr.The radiosensitizing effect could be related to apoptosis.

Objective To investigate the radiosensitizing effects of artemisinin on CNE human nasopharyngeal carcinoma cells in vitro.Methods CNE human nasopharyngeal carcinoma cell line was used in this study.Cell growth kinetics was determined by MTT assay.Effect of the drug on radiosensitivity of CNE cells was analyzed by clonogenic assay.The change of cell cycle was measured by flow cytometry.Results The inhibition of CNE cells growth by artemisinin was increased with concentrations.Artemisinin (1 μmol/L)could enhance the radiosensitizing effects on CNE cell line,and the sensitizing enhancement ratio(SER)was 1.26.Artemisinin abrogated radiation-induced G2/M arrest of the tested CNE cells.Compared with the radiation alone group,the proportion of G2/M phase cells increased in radiation combined with drug group.Conclusions Artemisinin could reduce radiation-induced G2/M arrest and enhance the cytotoxicity of γ-irradiation on the CNE ceils.

Objective To understand the prevalence of autism spectrum disorders (ASD) in children aged 0-6 years old and influencing factors in Hainan province.Methods A total of 37 862 children aged 0-6 years were selected from 18 counties in Hainan province for a screening by using questionnaire of "warning signs in child development",then field diagnosis was made,and general descriptive statistic analysis was conducted.The prevalence of ASD and related factors were analyzed with x2 test and unconditional logistic regression model.Results Among 37 862 children aged 0-6 years,235 were diagnosed with ASD,the prevalence of ASD was 0.62％ (0.99％ in boys,0.17％ in girls),the differences was significant (x2=101.91,P=0.000).The prevalence of ASD increased with age (x2=288.62,P=0.000).The prevalence of ASD was significantly higher in urban area than in other areas (x2=114.77,P=0.000).Factors such as full term pregnancy or not,neonatal asphyxia,father' s characteristics,father' s habit of chewing areca or smoking,mother' s general mood,and mother' s induced abortion history were the influencing factors for ASD.Conclusion The prevalence of ASD in children aged 0-6 years was high in Hainan and was influenced by genetic factors,pregnancy and delivery process,parents unhealthy habit before and during pregnancy and other factors.