OBJECTIVE:To study the factors affecting the compatible stability of amphotericin B(AmB)and 5%glucose injec-tion from different manufacturers,and to provide reliable evidence for the selection of solvent carrier of AmB. METHODS:After the combination of AmB and 5%glucose injection from different manufacturers(manafactarer A,B,C,D,E),it was shielded from light with room temperature(25℃)for 0,1,2,4,6 and 8 h. HPLC was conducted to determine the content changes of AmB in samples and observe the character,clarity and pH values. RESULTS:With the prolonging of time,insoluble impurities were detected in AmB and 5%glucose injection with the pH value less than 4.2 and the content of main drugs was decreased. Only 5%glucose injection from manufacturer A was in line with the requirements of AmB compatibility. CONCLUSIONS:The compatible stability of AmB and 5%glucose injection is closely related to pH values. It is suggested that manufacturers of infusions make clear descriptions of the pH value to select suitable infusions and safe drugs.

Objective:To analyze deceleration capacity of heart rate (DC) in patients with ventricular arrhythmia , and explore its predictive value for ventricular arrhythmia .Methods :Dynamic electrocardiogram (DCG) data of outpatients and inpatients ,who were treated in our hospital from Jan 2012 to Jul 2015 ,were retrospectively ana‐lyzed .A total of 41 rehabilitation patients with ventricular tachycardia (VT) directly detected by DCG were treated as VT group ,another 37 cases with similar general data and non‐tachycardia were enrolled as non‐tachycardia group in the same period .DCG was used to measure and calculate DC in all subjects , DC indexes were compared between two groups .Results:DC<4.5 ms was regarded as abnormal and DC<2.5 ms was regarded as significantly abnor‐mal .Compared with non-tachycardia group ,DC significantly reduced [ (8.72 ± 1.78) ms vs .(4.01 ± 1.90) ms] , P<0.01 ;there were significant rise in abnormal DC rate (5.41% vs .51.22% ) and significant abnormal DC rate (0 vs .29.27% ) in VT group , P<0.01 both .Conclusion:Detection rate of abnormal DC is high in VT patients .DC measurement is helpful for predicting ventricular arrhythmia and sudden cardiac death .

[Objective] To observe NGF on cultured human retinal vascular endothelial cells (HRCEC) proliferation. [Methods] The MTT assay was used to analyze the impact of culture HRCEC on different factors (NGF concentration groups, NGF + K252a concentration groups, bFGF group, bFGF + K252a groups, the normal culture medium groups) in normal and hypoxic condition. [Results] With the increase of NGF concentration (20,50,100 ng/mL), HRCEC significantly increased (normal condition: 0.254±0.033,0.696±0.029, 1.136±0.051; hypoxic condition: 0.422±0.036, 0.798±0.044, 1.376±0.052, P< 0.05). Compared NGF + K252a group with the same concentration of NGF (100 ng/ml) group, HRCEC reduced (P<0.05), with increasing the concentration of K252a (50,100,200 nmol/L), the trend of HRCEC decreasing is become more significant (normal condition:0.864±0.067, 0.496±0.025, 0.202±0.078; hypoxic condition:K252a 1.042±0.047,0.700±0.065, 0.401±0.078, P<0.05). [Conclusion] NGF can promote the proliferation of HRCEC, the effect could be specifically blocked by TrkA inhibitor K252a.

Objective:To observe the feature of Lorenz plots of dual parasystole ,and explore its differential diagnosis significance .Methods :Lorenz plot data of seven patients diagnosed as dual parasystole was retrospectively analyzed . They were compared with those of single source premature beat ,dual premature beat and single source parasystole . Results :All case data were divided into six groups (seven cases in each group) ,its features were :group 1 [ (single source atrial premature beat (APB)] ,plots were characterized with three distribution and sinus rhythm located on 45° line ;group 2 (dual source APB) were five distribution with the same sinus rhythm location ,the points set before and after premature were located on its two sides ,the plot was symmetry ,slopes of line B were within 0~1 in group 1 and 2 and its slopes were no significant difference (P>0.05);group 3 was single source ventricular premature beat (VPB) ,show four distribution pattern ,sinus rhythm was located on 45° line ,the points set before and after prema-ture were almost parallel to X and Y axis ;group 4 ( dual source VPB) were in six distribution with the same sinus rhythm location ,its difference with single source VPB was the points set before and after premature were symme-try;slopes of line B all trends to 0 in group 3 and 4 ,their slope also no significant difference (P>0.05);Group 5 (single source parasystole ) was characterized as four distribution vertical to 45° line ,premature point set was vertical to 45° line ,point set before and after premature were vertical to axis X and Y respectively ;group 6 (dual parasysto-le) were seven distribution vertical to 45° line ,were similar to that of single source parasystole ,the difference was figure of group 6 was dual distribution ;slopes of line B were close to ∞ in group 5 and 6 ,and its difference were no significant (P>0.05) .The line B slopes in group 5 and 6 were significantly higher than those of group 1&2 [ (∞ ) vs .(4.78 ± 0.19)] ,and those of group 1&2 were significantly higher than those of group 3&4 (0.36 ± 0.06) ,P<0.01 all .Conclusion:There are significant difference in Lorenz plot features among single (dual) source atrial/ven-tricular premature beats ,single source parasystole and dual parasystole .Lorenz plot is helpful to differential diagno-sis of parasystole .

Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95％ CI:12.2-17.4) in group A and 13.2 months (95％ CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3％ and 61.2％,respectively.The ORR were 78.0％ vs.57.1％ (x2 =5.16,P =0.028),and the DCR were 95.1％ vs.92.9％ (P＞0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.

Objective To investigate the efficacy and safety of whole brain radiotherapy combined with ectatinib hydrochloride in the treatment of non-small cell lung cancer (NSCLC) brain metastases. Methods A total of 44 patients with brain metastases from NSCLC from June 2013 to June 2017 were randomly divided into combination therapy group and radiotherapy group. The efficacy and safety between the two groups were compared. Results The median follow-up was 18.5 months. The mPFS of the combination therapy group and the radiotherapy group were 9.3 months and 6.6 months, respectively (log-rank P=0.006). The mPFS of the EGFR mutant and wild type in the combination group were12.2 months and 6.5 months (log-rank P=0.002). The mPFS of EGFR mutants and wild-type patients in the radiotherapy group were 6.4 months and 6.8 months, respectively (log-rank P=0.933). The mOS in the combination therapy group and the radiotherapy group were 14.2 months and 12.6 months, respectively (log-rank P=0.035). The mOS of the EGFR mutant and wild type in the combination group were 19.1 months and 12.7 months, respectively (log-rank P=0.006). The mOS of EGFR mutants and wild-type patients in the radiotherapy group were 12.6 months and 10.4 months, respectively (log-rank P=0.449).The ORR of the two groups was 78.3％ and 47.6％, respectively (log-rank P=0.035), and the DCR was 91.3％ and 85.7％, respectively (χ2=0.341, P=0.560).In terms of adverse reactions, the incidence of rash in the combined group was 56.5％, of which 3 cases were grade 3-4. The adverse reactions such as fatigue, nausea and vomiting, diarrhea, liver and kidney damage, and leukopenia were all grade 1-2, and there was no statistically significant difference between the two groups. Conclusion Ectinib hydrochloride combined with whole brain radiotherapy can improve the objective response rate of patients with non-small cell lung cancer with brain metastases, prolong the median local progression-free survival and median overall survival, and the patient's adverse reaction tolerance is good.

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 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.

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 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.