Polymeric micelles as effective drug carriers have been paid wide attention. They have many considerable advantages in cancer therapy, such as high efficiency, long acting and high drug loading etc. The paper reviewed the type, preparation materials and drug lording methods of polymeric micelles, especially discussed the targeting strategy of tumor-targeting drug delivery systems and the ap-plication examples of polymeric micelles in targeting drug delivery systems.

OBJECTIVE:To establish a method for the simultaneous determination of chlorogenic acid,vitexin glucoside,vi-texin rhamnoside,vitexin,rutin and hyperoside in Crataegus pinnatifida. METHODS:With reference peak of vitexin glucoside, HPLC was conducted to calculate the relative correction factor(RCF)of chlorogenic acid,vitexin glucoside,vitexin rhamnoside, vitexin,rutin and hyperoside,then the contents of above-mentioned 5 components in C. pinnatifida were calculated. The column was Agilent ZORBAX SB C18 with mobile phase of 0.1% formic acid-acetonitrile-tetrahydrofuran (gradient elution) at a flow rate of 1.0 ml/min,the detection wavelength was 350 nm,column temperature was 30 ℃,and the injection volume was 10 μl. RE-SULTS:The linear range was 12.50-400.0 μg for chlorogenic acid(r=0.999 8),25.00-800.0 μg for vitexin glucoside(r=0.999 9), 31.25-1 000.0 μg for vitexin rhamnoside(r=0.999 9),6.470-260.0 μg for vitexin(r=0.999 9),2.50-80.0 μg for rutin(r=0.999 8) and 9.375-300.0 μg for hyperoside(r=0.999 9);RSDs of precision,stability and reproducibility tests were lower than 2.0%;re-coveries were 99.2%-103.9%(RSD=1.6%,n=6),97.9%-100.8%(RSD=1.2%,n=6),99.2%-100.8%(RSD=0.5%,n=6), 97.3%-101.3%(RSD=1.5%,n=6),98.0%-103.0%(RSD=1.9%,n=6)and 95.5%-101.5%(RSD=2.2%,n=6). RCFs of vitex-in glucoside with chlorogenic acid,vitexin rhamnoside,vitexin,rutin and hyperoside were 1.119,1.009,0.706,1.063 and 0.830, respectively. CONCLUSIONS:The method is simple with good precision,stability and reproducibility,and it can be sued for the simultaneous determination of 6 components in C. pinnatifida.

Objective To investigate the dynamic changes ofprocalcitonin (PCT) within 72 h of acute stroke without infection and explore the value of PCT in diagnosis of bacterial infection in the early stage of acute stroke.Methods Forty-one patients with acute stroke within 24 hours of symptom onset,admitted to our hospital from July 2012 to January 2013,were enrolled in our study.The concentrations of PCT and C-reactive protein (CRP) in the serum were measured,respectively,at 24,48 and 72 h after symptom onset.At each time point,the PCT and CRP values were compared with the upper value of normal ranges of PCT and CRP,respectively.Results The median (quartiles) PCT concentrations at 24,48 and 72 h after stroke onset were,respectively,(0.050 [0.040,0.080]) ng/mL,(0.060 [0.036,0.095]) ng/mL and [0.051 (0.040,0.079)] ng/mL,which were significantly different as compared with that of the upper value of normal range (0.05 ng/mL,P＜0.05).The median (quartiles) CRP concentrations at 24 and 48 h after stroke onset were,respectively,[3.200 (1.100,5.000)] mg/L and [4.300(1.700,9.900)] mg/L,showing no significant difference with the upper value of normal range (5.0 mg/L,P＞0.05); however,the mean CRP concentration at 72 after stroke onset was [5.300 (2.500,15.550) mg/L],enjoying significant difference as compared with the upper value of normal range (P＜0.05).Most of the patients (22 patients,53.67％) had a peak level of PCT at 24 h,while most of them (26,63.41％) had a peak level of CRP at 72 h.The concentration of PCT increased within 24 h after symptom onset,but declined in the following 72 h; in contrast,the concentration of CRP continuously increased in the first 72 h of symptom onset.Conclusions PCT concentrations may increase in the first 72 h after acute stroke,therefore,when using PCT in diagnosis of bacterial infection in the early stage of acute stroke,the influence of elevating PCT concentrations by stroke itself should be considered.But PCT usually reaches its peak level earlier than CRP and returns to normal range faster than CRP,which may be more valuable than CRP in diagnosis of bacterial infection in the early stage of acute stroke.

Objective:To analyze the duration of the second stage of labor without epidural anesthesia and its association with pregnancy outcome.Methods:This retrospective study involved 12 789 women who delivered without epidural anesthesia in the First Affiliated Hospital of Kunming Medical University from January 1, 2014 to December 31, 2017. These subjects were divided into primipara group (9 517 cases) and multipara group (3 272 cases). Demographic characteristics, maternal and neonatal outcomes and the duration of the second stage of labor were compared between the two groups using two independent samples t-test, Mann-Whitney U test and Chi-square test (Fisher's exact test). Differences in the maternal and neonatal outcomes were also analyzed among different subgroups in primiparae [length of second stage: <1 h group ( n=6 265), ≥1-2 h group ( n=2 305), ≥2-3 h group ( n=831) and ≥3 h group ( n=116)] and multiparae [length of second stage <1 h group ( n=3 144), ≥1-2 h group ( n=102) and ≥2 h group ( n=26)]. The association between second stage length and pregnancy outcomes was analyzed with Cramer's V. After adjusted for maternal age, gestational weeks at delivery, body mass index before pregnancy, complications during pregnancy and neonatal birth weight, the relationship between the duration of the second stage and adverse outcomes was analyzed by binary logistic regression analysis. Results:The 95 th percentile of the second-stage labor duration was 143 min for primiparae and 52 min for multiparae. The rates of vaginal delivery, forceps delivery, cesarean section in the second stage, episiotomy, third- or fourth-degree perineal laceration, postpartum hemorrhage, grade Ⅱ postpartum hemorrhage, transfusion, umbilical arterial blood gas pH<7.15 and transferring to neonatal intensive care unit (NICU) were all correlated with the duration of second stage in primiparae (Cramer's V values: 0.22, 0.23, 0.03, 0.22, 0.05, 0.10, 0.03, 0.03, 0.03 and 0.07, respectively, all P<0.05), and so did those of vaginal delivery, forceps delivery, episiotomy, postpartum hemorrhage, grade Ⅱ postpartum hemorrhage, transfusion and transferring to NICU in multiparae (Cramer's V values: 0.18, 0.19, 0.28, 0.14, 0.09, 0.13 and 0.06, respectively, all P<0.05). Logistic analysis showed that in primiparae, the duration of second stage >1 h was an independent risk factor for episiotomy, third- or fourth-degree perineum laceration, forceps delivery, postpartum hemorrhage, admission to NICU and umbilical arterial blood gas pH<7.15 [adjusted OR (95% CI): 2.080 (1.907-2.268), 1.773 (1.080-2.911), 1.625 (1.420-1.859), 1.365 (1.231- 1.514), 1.305 (1.165-1.462) and 1.246 (1.081-1.436), respectively], while second stage length >2 h was the independent risk factor for episiotomy, forceps delivery, third- or fourth-degree perineum laceration, postpartum hemorrhage, grade Ⅱ postpartum hemorrhage, blood transfusion, admission to NICU and umbilical arterial blood gas pH<7.15 [adjusted OR (95% CI): 4.844 (4.132-5.678), 4.223 (3.571-4.993), 3.289 (1.806-5.989), 1.952 (1.675-2.274), 1.781 (1.057-3.001), 1.654 (1.025-2.668), 1.682 (1.421-1.991) and 1.298 (1.039-1.620), respectively]. In multiparae, the length of second stage >1 h was an independent risk factor for episiotomy, blood transfusion, forceps delivery, postpartum hemorrhage and admission to NICU [adjusted OR (95% CI): 8.796 (5.717-13.534), 7.469 (2.874-19.411), 6.135 (3.217-11.699), 2.697 (1.624-4.477) and 1.814 (1.063-3.097), respectively], while the duration of second stage >2 h was the independent risk factor for episiotomy, third- or fourth-degree perineum laceration, blood transfusion, grade Ⅱ postpartum hemorrhage, forceps delivery and postpartum hemorrhage [adjusted OR (95% CI): 38.868 (14.948-101.063), 28.046 (2.780-282.490), 20.076 (5.384-74.866), 16.327 (3.406-78.274), 14.337 (5.351-38.411) and 9.036 (3.880-21.011), respectively]. Conclusions:The duration of the second stage of labor without epidural anesthesia is between that reported by Friedman and by Zhang. A prolonged second stage of labor may increase the risk of adverse pregnancy outcomes.

Objective:To investigate the effects of gambogenic acid(GNA)on the proliferation and apoptosis of CAL27 cell xenograft tumor in nude mice.Methods:18 SPF nude mice were randomly divided into 3 groups(n=6).All nude mice were inoculated with CAL27 cells at logarithmic growth stage to establish subcutaneous transplanted tumor models.The mice in low and high dose GNA groups were treated with GNA of 8.0 mg/kg iv.and 16.0 mg/kg iv.every other day,respectively,and those in the control group was given the same amount of normal saline.The tumor growth curve was plotted during drug administration.2 weeks later,the nude mice were sacrificed,the tumor tissue was removed and the tumor inhibition rate was evaluated by the tumor size measurements.TUNEL as-say was used to detect the apoptosis of transplanted tumor cells in the groups.The expression levels of AKT,Bcl-2 and PI3K proteins in tumor tissue were detected by immunohistochemistry(IHC).The toxicity and side effects of GNA on normal tissues were detected by HE staining.Results:The transplanted tumors in low and high dose GNA groups grew slowly,and the tumor weight and volume were significantly lower than those in the control group(P＜0.05),the tumor inhibition ratio of low and high dose groups was 57.58％and 83.68％respectively.TUNEL results showed that the apoptosis index of GNA low and high dose groups was higher that of control group(P＜0.05).IHC results showed that the expression of AKT,Bcl-2 and PI3K in the tumor tissues of nude mice in low and high dose GNA groups was lower than that in the control group(P＜0.05).HE results showed that GNA had not effect on normal tissues and or-gans(P＜0.05);Conclusion:GNA may induce CAL27 cell apoptosis by regulating the expression of AKT,Bcl-2 and PI3K,and in-hibites the development of human tongue squamous cell carcinoma with little effect on normal tissues and organs.

OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

OBJECTIVE To evaluate the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia using a rapid health technology assessment （HTA） method， and provide an evidence-based basis for clinical decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang database and foreign HTA official websites were systematically searched， and the search time frame of the databases was from the establishment of the database to May 25th 2022. After data extraction and quality evaluation of the literature according to the inclusion and exclusion criteria， a descriptive analysis of the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia was performed. RESULTS & CONCLUSIONS A total of 1 HTA report， 3 systematic reviews/meta-analysis and 5 economic studies were included. In terms of effectiveness， compared with ferric carboxymaltose， the hemoglobin level of patients using iron isomaltoside increased more， but there was no significant difference in the proportion of responding patients； compared with iron sucrose， it had non- inferiority in increasing and maintaining hemoglobin level， and there was no difference in the quality of life. In terms of safety， the incidence of adverse events of ferric carboxymaltose， iron sucrose and iron isomaltoside were 12.0%， 15.3% and 17.0%， respectively. Iron isomaltoside had a lower incidence of hypophosphatemia， compared with ferric carboxymaltose. There was no statistical difference in the incidence of hypophosphatemia among iron isomaltoside， iron sucrose， iron-dextrin and nanocrystalline iron oxide. The conclusion of the incidence of treatment-emergent adverse event， the incidence of serious adverse events and the withdrawal rate of patients due to adverse events was not clear. In terms of economy， the economy of iron isomaltoside is better than that of iron sucrose， and the economy of iron isomaltoside versus that of ferric carboxymaltose had not been finalized.

The prevalence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year and it has become one of the most common chronic liver diseases in the world. Studies have shown that circular RNA (circRNA) is closely associated with NAFLD and is considered a potential diagnostic biomarker and therapeutic target for NAFLD. This article summarizes the regulatory role of circRNA in the pathogenesis of NAFLD and its value in diagnosis and treatment and points out that circRNA plays an important role in the development and progression of NAFLD and may have important clinical significance in the diagnosis and treatment of NAFLD.

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.