ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis （DOP） in mice by regulating the advanced glycation end products （AGEs）/receptor activator of nuclear factor-κB ligand （RANKL）/nuclear factor-κB （NF-κB） signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific， dominant negative insulin-like growth factor-1 receptor （MKR） mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group， low- and high-dose Jingui Shenqiwan group （1.3， 2.6 g·kg^-1）， and an alendronate sodium group （0.01 g·kg^-1）， with 10 mice in each group. Additionally， 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period， fasting blood glucose （FBG） measurement and oral glucose tolerance test （OGTT） were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs， phosphorylated NF-κB （p-NF-κB）， and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway， osteoprotegerin （OPG）， and Runt-related transcription factor 2 （RUNX2） proteins in femoral bone tissues. ResultCompared with the normal group， mice in the model group exhibited significantly increased FBG （P<0.01）， trabecular bone degeneration， abnormal bone morphological parameters， significantly increased area under the curve （AUC） of OGTT （P<0.01）， enlarged kidney volume， significantly increased kidney function indicators and kidney index （P<0.01）， disrupted renal glomeruli and renal tubule structures， significantly increased expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues （P<0.05）， and significantly decreased expression of OPG and RUNX2 in femoral bone tissues （P<0.01）. Compared with the model group， mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC （P<0.01）. Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore， the expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues was significantly reduced （P<0.05， P<0.01）， and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased （P<0.05， P<0.01）. ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions， thereby alleviating the symptoms of DOP in mice， demonstrating a therapeutic effect on DOP from the perspective of the kidney.

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 analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.

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.

Objective To explore the appropriate target ranges of blood glucose in intensive insulin therapy (ⅡT) for acute hyperglycemia following traumatic brain injury (TBI).Methods A randomized,open-label and controlled clinical trial was performed on 208 patients,admitted to our hospitals from Junuary 2014 to Sepember 2016.They were divided into ⅡT group (n=156),who were subdivided into slight (10.1-13.0 mmol/L),moderate (7.1-10.0 mmol/L),and strict (4.4-7.0 mmol/L) control blood glucose groups (n=52),and non-ⅡT group (n=52).Survival analysis 6 months after treatment was performed by Kaplan-Meier method.Modified Rankin scale (mRS) scores and Barthel index (BI),Glasgow Outcome scale (GOS) scores,concentrations of lactic acid in cerebrospinal fluid (CSF) and glycosylated hemoglobin,Glasgow coma scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ) scores,Length of staying in intensive care unit (ICU) and incidence of adverse events were compared between the patients from different groups at different treatment times.Results Blood glucose level within 7 d of admission in patients ofⅡT group was in target ranges.The survival rate of patients from slight and moderate control blood glucose groups was significantly higher than that in the non-ⅡT group and strict control blood glucose group 6 months after treatment (x2=4.237,P=0.040;x2=5.621,P=0.018).As compared with those in the non-ⅡT group and strict control blood glucose group,the mRS scores 3 months after treatment were significantly decreased,and GOS scores and BI one,3 and 6 months after treatment were significantly increased in patients from slight and moderate control blood glucose groups (P＜0.05).As compared with that in the non-ⅡT group,and slight and moderate control blood glucose groups,the glycosylated hemoglobin level 7 d after treatment was significantly decreased in strict control blood glucose group (P＜0.05).As compared with those in the non-ⅡT group and strict control blood glucose group,the concentration of lactic acid in CSF 7 d after treatment,APACHE Ⅱ scores 7 and 14 d after treatment,length of staying in ICU and incidence of adverse events were significantly decreased in patients from slight and moderate control blood glucose groups (P＜0.05).The mean value of blood glucose in slight and moderate control blood glucose groups was (8.40±0.39) mmol/L.Conclusion Proper ⅡT improves the outcomes of TBI patients and (8.40±0.39) mmol/L are established as the target ranges in ⅡT for TBI.

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 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 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 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.