A high performance liquid chromatography (HPLC) method utilizing correction factors was established for the quantitative detection of related substances in flumazenil. Separation was achieved using an Agilent Pursuit XRs C18 column (250 mm × 4.6 mm, 5 μm) with an isocratic elution of dilute phosphoric acid, methanol, and tetrahydrofuran as the mobile phases. Correction factors calculated from a standard curve method were applied to determine the impurity content. The quantification of impurities in flumazenil was conducted using both external standard and correction factor methods, followed by validation and comparison of the two. For the identification of degradation products, a forced degradation approach was employed to prepare a flumazenil degradation solution, and the resulting impurities were confirmed by LC-MS analysis. The separation of flumazenil and its impurities was found to be efficient. The limits of quantification for impurities A, B, D, and E were established at 0.169 9, 0.314 7, 0.143 9, and 0.270 8 ng, respectively, with the limits of detection at 0.055 8, 0.096 9, 0.048 8, and 0.089 0 ng. These impurities demonstrated a strong linear relationship across the concentration ranges of 0.034 9-7.847 0, 0.038 7-8.710 7, 0.034 6-7.794 1, and 0.032 4-7.292 8 µg·mL^-1, respectively (n = 7). The method achieved average recoveries between 98.25% and 99.42%, with an RSD of less than 2.0% (n = 9), indicating high accuracy. The external standard and correction factor methods were used to determine the related substances in flumazenil, and the results of the two methods were consistent. The established HPLC method is characterized by its high accuracy, sensitivity, and repeatability, and is suitable for determining related substances in flumazenil.

Background and purpose:Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration,and the 1-,3-and 5-years observed overall survival(OS)rates and disease-free survival(DFS)rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China.Methods:A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was November 30,2023.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year OS rate and DFS rate,and survival data were described by different subgroups including age group,gender,treatment period,tumor staging,and pathological characteristics.Results:With a median follow-up time of 50.99 months,the 5-year OS rate of surgically resected gastric cancer patients was 70.37%,and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%.The 5-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 94.32%,82.56%,51.01%and 23.97%,respectively.The differences in survival among patients with different age,tumor location,gross classification,Borrmann classification and Laurence classification were significant.Conclusion:Staging is an important factor directly affecting the survival of gastric cancer patients.Screening and early diagnosis and treatment in large population,especially high-risk group,should be strengthened to further improve the patients'survival.

Objective To analyze the incidence and mortality of pancreatic cancer in 2022 globally and in China based on the Global Cancer Statistics 2022 published by the International Agency for Research on Cancer,considering characteristics such as gender,age,and human development index(HDI).Methods Pancreatic cancer data from 185 countries and regions were sourced from the GLOBOCAN 2022 database,and HDI data were compiled based on the Human Development Report 2022 published by the United Nations Development Programme.Cancer data were stratified by age,gender,and HDI to describe the prevalence of pancreatic cancer globally and in China.Pearson correlation analysis was used to evaluate the correlation of standardized incidence rate(SIR),standardized mortality rate(SMR),and mortality-to-incidence ratio(M/I)with HDI.Results In 2022,the number of pancreatic cancer incident cases worldwide was 510 992,ranking 12th among all cancer incidents,with an SIR of 4.7 per 100 000(ranking 15th).The number of pancreatic cancer deaths globally was 467 409,ranking 6th among all cancer deaths,with an SMR of 4.2 per 100 000(ranking 9th).In China,the number of pancreatic cancer incident cases was 118 672(ranking 10th among all cancer incidents),accounting for 23.22%of the global pancreatic cancer incidents,with an SIR of 4.4 per 100 000(ranking 13rd).The number of pancreatic cancer deaths in China was 106 295(ranking 6th among all cancer deaths),accounting for 22.74%of the global pancreatic cancer deaths,with an SMR of 3.9 per 100 000(ranking 8th).The incidence,mortality,SIR,and SMR in males were higher than those in females both globally and in China.SIR and SMR were positively correlated with HDI(r=0.77 and 0.77,both P＜0.001),while M/I was negatively correlated with HDI(r=-0.43,P＜0.001).The incidence,mortality,SIR and SMR of pancreatic cancer showed an increasing trend with age,and rapidly increased from 45-49 years old.Conclusion The disease burden of pancreatic cancer is serious globally and in China.The incidence and mortality of pancreatic cancer show an upward trend with age,and they are higher in males than in females.HDI is positively correlated with SIR and SMR of pancreatic cancer,while negatively correlated with M/I.

Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9％NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)％,(91.57±1.03)％,(54.72±7.34)％,(88.35±4.36)％,(63.55±12.73)％and(81.04±4.31)％;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P＜0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P＜0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P＜0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P＜0.05,P＜0.01),reduced the expression of NF-κB(P＜0.01),and reduced the phosphorylation of IKBα(P＜0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

In recent years,natural antimicrobial peptides have become an important direction in the development of novel antibiotics.Cecropin has the characteristics of wide antibacterial spectrum,good tolerance and low adverse drug reactions.As the first antimicrobial peptide discovered in the family of Cecropin,Cecropin A has many important biological activities.In this paper,the research on the antibacterial,antifungal,antiparasitic and antitumor activities of Cecropin A and its derivatives in recent years was reviewed,and its application prospect was prospected,in order to provide reference for further research and development of cecropin.

Migraine is a common primary headache,which is the second leading cause of disability worldwide,espe-cially resistant and refractory migraine.Treatments for migraine are diverse.This article summarizes the progress in the prevention and treatment of resistant and refractory migraine,aiming to promote clinicians'understanding of such types of migraine.

Headache is a common disease of the nervous system,with a high risk of disability,but currently the di-agnosis rate of headache remains at a relatively low level,mainly relying on the self-treatment by patients.In recent years,as headache diseases attract more attention,headache nurses are playing an increasingly important role in the management of headache patients,and headache nursing has become an important link in improving the prognosis of patients.This ar-ticle mainly introduces the importance and necessity of headache nursing in the management of headache patients.

Background and purpose:Effective treatment for cervical cancer patients is one of the global strategies to eliminate cervical cancer.By analyzing the metastasis characteristics and survival status of patients with distant metastasis of cervical cancer from a hospital-based cancer registry data,our study provided real-world evidence for better survival of cervical cancer and finally eliminating cervical cancer.Methods:A total of 572 cervical cancer patients who had metastasis cancer at the initial diagnosis or developed distant metastasis during follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study.Medical records review,telephone visits and death registry data linkage were applied in collecting endpoint data.The first follow-up date was the diagnose date of metastasis,and the last follow-up date was November 1,2020.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year overall survival(OS)rates for overall and site-specific patients.Results:The median follow-up time was 38.93 months,and 348 cases died during the follow-up.72.55%were single site metastasis,and 27.45%were multiple metastases.Among all metastatic sites,the proportion of lung metastasis was the highest,41.26%,15.21%to bone,and 11.54%to liver.After metastasis,the 1-year,3-year and 5-year OS rates were 62.29%(95%CI:62.25-62.33),33.13%(95%CI:33.08-33.18)and 23.42%(95%CI:23.37-23.47),respectively.In single site metastasis,1-year OS was the highest after metastasis to the lung(72.52%).Besides,there was no significant difference among different metastatic sites,both in 3-year and 5-year OS.Conclusion:The most frequent distant metastatic sites of cervical cancer are lung,bone and liver.The survival rate after metastasis is poor.Further research with systematic treatment strategy is required for better survival.

Objective This study aims to evaluate the effect of vitamin D supplementation in the earliest stages of pregnancy(12-16 weeks)on the development of preeclampsia(PE)in primiparous women.Methods Primiparous women who visited Maternal and Child Care Center of Qinhuangdao from January 1,2019 to January 31,2022 were recruited as study subjects.According to the random number table method,primiparous women were randomly divided into the control group(calcium carbonate D3 tablets)and the experimental group(calcium carbonate D3 tablets+vitamin D).The main observed outcome of the study was the incidence of preeclampsia.Preterm birth,neonatal birth weight,neonatal height at birth,mode of delivery,and neonatal Apgar scores were the secondary observed outcomes.A Logistic regression was used to explore the relationship between vitamin D supplementation and study outcomes.In addition,serum 25 hydroxyvitamin D was measured by ELISA before and after the intervention.Results A total of 586 primiparas were recruited,70 were lost,and 516 were included(264 in the control group and 252 in the experimental group).The incidences of PE,preterm birth,cesarean birth,and birth weight in the experimental group were significantly lower than those of the control group(P<0.05).After the end of the intervention,the serum level of 25 hydroxyvitamin D had increased significantly in both groups(P<0.05),while there was no significant change in calcium ions(P>0.05).Furthermore,serum 25 hydroxyvitamin D levels were significantly higher in the experimental group than in the control group(P<0.05).In addition,the birth length,1-minute Apgar,5-minute Apgar and 10-minute Apgar scores of the experimental group were all higher than the control group(P<0.05).Multivariate Logistic analysis showed that vitamin D supplementation was the independent protective factor for PE[OR=0.336,95%CI(0.120,0.939),P=0.037],cesarean section[OR=0.539,95%CI(0.364,0.798),P=0.002],misoprostol-induced delivery[OR=0.066,95%CI(0.009,0.504),P=0.009],preterm birth[OR=0.487,95%CI(0.238,0.995),P=0.048]and low birth weight[OR=0.391,95%CI(0.189,0.806,P=0.011].Conclusion Vitamin D supplementation reduces the incidence of PE and reduces the incidence of adverse pregnancy and fetal outcomes.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.