Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Objective To explore the changes in serum epidermal growth factor receptor(EGFR)and cancer anti-gen 125(CA125)levels in pregnant women with adenomyosis(AM)and their relationship with pregnancy outcomes.Methods A total of 108 pregnant women with AM(AM pregnant women group)admitted to Baoding Maternal And Child Health Hospital from June 2021 to August 2023 were collected and divided into a good preg-nancy group(n=43)and a poor pregnancy group(n=65)based on pregnancy outcomes.Meanwhile,AM patients were selected as AM group and 108 pregnant women with normal pregnancy test were selected as control group.ELISA was applied to detect the serum level of EGFR and CA125.Pearson correlation was applied to analyze the correlation between serum EGFR and CA125 in AM pregnant women.Multivariate logistic regression was applied to analyze the factors that affected the outcome of AM pregnancy.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum EGFR and CA125 levels for AM pregnancy outcomes.Results Compared with the control group,serum level of EGFR and CA125 in AM group and AM pregnant women group were significantly increased and serum level of EGFR and CA125 in AM pregnant women group was higher than that in AM group(P＜0.05).As the depth grading of endometrial invasion increased,serum level of EGFR and CA125 increased sequentially;The serum level of EGFR and CA125 was obviously elevated in diffuse type and proliferate phase(P＜0.05).The expression level of EGFR and CA125 in the serum of AM pregnant women with premature rupture of membranes,premature birth,placenta previa,and miscarriage was significantly increased(P＜0.05).According to Pearson correlation analysis,there was a positive correlation between serum EGFR and CA125 in AM pregnant women(r=0.487,P＜0.05).The serum level of EGFR and CA125 in good pregnancy group was lower than that in poor pregnancy group(P＜0.05).The area under the curve(AUC)of serum EGFR,CA125,and their combined prediction for AM pregnancy outcome was 0.880,0.835,and 0.955,re-spectively and the combined prediction of AUC for AM pregnancy outcome was significantly higher than that of se-rum EGFR and CA125 alone prediction(Zcombination-EGFR=2.279,Zcombination-CA125=3.304,both P＜0.05).Conclusions Serum level of EGFR and CA125 in AM pregnant women is elevated,which is closely related to pregnancy outcomes and is potential risk factor for poor pregnancy in AM.The combination of the two is more ef-fective in predicting pregnancy outcomes in AM.

Objective:To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. Methods:A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c. 548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.

Objective To evaluate the efficacy,safety,and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia(IDA)by rapid health technology assessment,and to provide evidence for clinical decision-making.Methods PubMed,Embase,the Cochrane Library,CNKI,WanFang,SinoMed,and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports,systematic reviews/Meta-analysis,and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose(IS),iron dextran(ID),ferric carboxymaltose(FCM),and iron isomaltoside(IIM)from the inception to August 15,2024.Two researchers independently screened the studies,extracted data and assessed the quality of included studies.The results were then qualitatively described and analyzed.Results A total of 32 studies were included,including one health technology assessment report,16 systematic reviews/Meta-analysis,and 15 pharmacoeconomic evaluations.In terms of effectiveness,FCM had a higher response rate than that of IS(P＜0.05),FCM and IIM had no statistical difference(P＞0.05).Regarding hemoglobin level change,patients treated with FCM had higher hemoglobin levels than those treated with IS(P＜0.05);the improvement in hemoglobin levels between IIM and FCM was inconclusive.In terms of ferritin level change,FCM might be superior to the other three intravenous iron formulations.In terms of safety,the adverse event rates for FCM,IS,ID and IIM were 12.0％,15.3％,12.0％and 17.0％,respectively;IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS(P＜0.05);FCM had the highest rate of hypophosphatemia among the four formulations(P＜0.05),and there was no significant difference among IIM,IS and ID(P＞0.05);IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS.In terms of economy,FCM and IIM had an economic advantage compared to IS.The economic efficiency ranking among IS,ID,and FCM was in the order of FCM,ID,and IS,the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.Conclusion FCM and IIM have good efficacy,safety and economy in the treatment of IDA,but most of the included economy studies based on foreign populations,and domestic economic studies need to be further demonstrated.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.

Breast cancer has overtaken lung cancer as the most common malignancy in women. Although the early diagnostic rate has continuously improved, recurrence and metastasis remain a problem to be solved. Therefore, scientists should search for effective prognostic markers for breast cancer patients and adopt individualized programs for different patients. Studies have shown that cancer prognosis, to a certain extent, is related to the nutrition inflammation index. Preoperative prognostic nutritional index (PNI) and controlled nutritional status (CONUT) are indicators that comprehensively reflect the nutritional level and inflammatory state of patients, respectively. Different from other cancers, the incidence of breast cancer is related to nutritional status, and an extremely high or low score is not conducive to the prognosis of breast cancer patients. This paper reviews the research progress of PNI and CONUT in breast cancer.

Objective:To investigate the application value of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosome aneuploidy.Methods:A total of 5 730 pregnant women who were screened for fetal chromosomal diseases in the Quzhou Maternal and Child Health Hospital from January 2017 to March 2019 were included in this study. All of them underwent noninvasive prenatal DNA screening and nuchal translucency thickness measurement. The results of amniocentesis were used as the gold standard to evaluate the diagnostic efficacy of noninvasive prenatal DNA screening, nuchal translucency thickness measurement and their combination.Results:Noninvasive prenatal DNA screening revealed that 64 (1.12%) women out of 5 730 pregnant women had high risk of developing chromosomal abnormalities. Ultrasound examination results showed that nuchal translucency was thickened in 140 (2.44%) women. The outcome of adverse pregnancy increased with the increase of nuchal translucency thickness. Among the 68 pregnant women who underwent amniocentesis, 51 women developed chromosomal abnormalities, with trisomy 21 syndrome being the majority (23/51,45.10%). The diagnostic efficacy of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosomal aneuploidy reached the ideal level.Conclusion:Noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement has a high clinical application value. The combined method can be used as the main prenatal DNA screening method for pregnant women and it can effectively avoid the birth of children with chromosomal abnormalities.

Metoprolol and propafenone are commonly used drugs in cardiovascular diseases. Both drugs are metabolized by liver cytochrome P450 (CYP) 2D6. However, propafenone is not only a CYP2D6 substrate, but also a CYP2D6 inhibitor, which may interact with metoprolol and cause adverse reactions. This interaction also depends on CYP2D6 genotype. For patients with CYP2D6 phenotypes of poor metabolizer (PM) and intermediate metabolizer (IM), the combination with propafenone can increase plasma concentration of metoprolol due to the inhibition of propafenone on CYP2D6. Therefore, the combination of metoprolol and propafenone should be avoided as far as possible. For the patients who need the combined treatment with the 2 drugs, attention should be paid to the monitoring of blood pressure, heart rate, and electrocardiogram changes during medication. If possible, CYP2D6 genotype should be detected and the drug dose should be adjusted according to the test results.