ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

Objective:To investigate the effect of luteinizing hormone (LH) levels on the clinical outcome and cumulative live birth rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer in patients with normal ovarian reserve function after application of a flexible protocol of gonadotropin-releasing hormone antagonist (GnRH-A) to promote ovulation with the addition of GnRH-A. Methods:A retrospective cohort study was conducted to analyze the data of 685 patients with normal ovarian reserve function who underwent IVF/ICSI after ovulation induction with antagonist flexible regimen between January 2016 and June 2021 at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University. The quartile method was used to group patients after the addition of the antagonist by the mean value of serum LH each time they were monitored (usually twice, depending on the rate of follicular growth and patients' need) until the day of the trigger, and were divided into group A (smaller than the 25th percentile of the mean LH level of the included population, LH<1.25 U/L, n=166), group B (in the 25th to 50th percentile of the mean LH level of the included population, 1.25 U/L≤LH<1.91 U/L, n=174), group C (in the 50th to 75th percentile of the mean LH level of the included population, 1.91 U/L≤LH<2.85 U/L, n=171), and group D (greater than the 75th percentile of the mean LH level of the included population, 2.85 U/L≤LH≤7.55 U/L, n=174). The general condition, clinical data, embryo laboratory indices, clinical outcome indices of fresh embryo transfer cycle and cumulative live birth rate were compared among the 4 groups. Results:After correcting for confounding factors by multifactorial linear regression, the number of high-quality embryos and the rate of blastocyst formation of patients in group C were significantly higher than those in group A, and the differences were statistically significant ( B=0.600, 95% CI: 0.086-1.114, P=0.022; B=0.134, 95% CI: 0.052-0.216, P=0.001). The number of high-quality embryos, the number of available embryos, and the rate of blastocyst formation of patients in group D were significantly higher than those in group A, and the differences were statistically significant ( B=0.771, 95% CI: 0.259-1.284, P=0.003; B=0.730, 95% CI: 0.205-1.255, P=0.007; B=0.085, 95% CI: 0.003-0.167, P=0.042).After multifactorial logistic regression, there was no statistically significant difference in live birth rate between group A and groups B, C and D ( P>0.05). The cumulative live birth rate of patients in group D was significantly higher than that in group A, and the difference was statistically significant ( aOR=2.439, 95% CI: 1.169-4.974, P=0.014). Conclusion:In patients with normal ovarian reserve function, a flexible protocol of antagonists was applied to promote ovulation, and the addition of antagonists had no significant effect on the clinical outcome of the fresh embryo transfer cycle in terms of mean LH levels, but the quality of the embryos was significantly reduced when the mean LH level was <1.25 U/L, and this may consequently reduce the developmental potential of the embryos and the cumulative live birth rate.

Objective:To investigate the effect of luteinizing hormone (LH) levels on the clinical outcome and cumulative live birth rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer in patients with normal ovarian reserve function after application of a flexible protocol of gonadotropin-releasing hormone antagonist (GnRH-A) to promote ovulation with the addition of GnRH-A. Methods:A retrospective cohort study was conducted to analyze the data of 685 patients with normal ovarian reserve function who underwent IVF/ICSI after ovulation induction with antagonist flexible regimen between January 2016 and June 2021 at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University. The quartile method was used to group patients after the addition of the antagonist by the mean value of serum LH each time they were monitored (usually twice, depending on the rate of follicular growth and patients' need) until the day of the trigger, and were divided into group A (smaller than the 25th percentile of the mean LH level of the included population, LH<1.25 U/L, n=166), group B (in the 25th to 50th percentile of the mean LH level of the included population, 1.25 U/L≤LH<1.91 U/L, n=174), group C (in the 50th to 75th percentile of the mean LH level of the included population, 1.91 U/L≤LH<2.85 U/L, n=171), and group D (greater than the 75th percentile of the mean LH level of the included population, 2.85 U/L≤LH≤7.55 U/L, n=174). The general condition, clinical data, embryo laboratory indices, clinical outcome indices of fresh embryo transfer cycle and cumulative live birth rate were compared among the 4 groups. Results:After correcting for confounding factors by multifactorial linear regression, the number of high-quality embryos and the rate of blastocyst formation of patients in group C were significantly higher than those in group A, and the differences were statistically significant ( B=0.600, 95% CI: 0.086-1.114, P=0.022; B=0.134, 95% CI: 0.052-0.216, P=0.001). The number of high-quality embryos, the number of available embryos, and the rate of blastocyst formation of patients in group D were significantly higher than those in group A, and the differences were statistically significant ( B=0.771, 95% CI: 0.259-1.284, P=0.003; B=0.730, 95% CI: 0.205-1.255, P=0.007; B=0.085, 95% CI: 0.003-0.167, P=0.042).After multifactorial logistic regression, there was no statistically significant difference in live birth rate between group A and groups B, C and D ( P>0.05). The cumulative live birth rate of patients in group D was significantly higher than that in group A, and the difference was statistically significant ( aOR=2.439, 95% CI: 1.169-4.974, P=0.014). Conclusion:In patients with normal ovarian reserve function, a flexible protocol of antagonists was applied to promote ovulation, and the addition of antagonists had no significant effect on the clinical outcome of the fresh embryo transfer cycle in terms of mean LH levels, but the quality of the embryos was significantly reduced when the mean LH level was <1.25 U/L, and this may consequently reduce the developmental potential of the embryos and the cumulative live birth rate.

Objective:To explore the clinical application value of frozen-thawed single blastocyst derived from nonpronuclear (0PN) zygotes, monopronuclear (1PN) zygotes and two-pronuclei (2PN) discarded embryos.Methods:A retrospective cohort analysis of the data of patients who underwent frozen-thawed single blastocyst transfer at the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from March 2014 to November 2020. According to the different sources of transplanted blastocysts, they were divided into 4 groups including group A derived from 2PN available embryos (2PN embryos with morphological rating Ⅰ-Ⅲ), group B derived from 0PN embryos, group C derived from 1PN embryos, group D derived from 2PN discarded embryos (2PN embryos with morphological rating Ⅳ). The basic data of the four groups were analyzed,and group A was used as the reference group to compare the clinical pregnancy outcomes of groups B, C and D, respectively. The neonatal situation was compared at the cycle of singleton live birth. Logistic regression was used to correct for confounding factors and calculate the adjusted odds ratio (a OR) and 95% confidence interval ( CI). Results:After correcting for confounding factors by logistic regression, the live birth rate in group B was significantly lower than that in group A (a OR=0.701, 95% CI: 0.534-0.920, P=0.011). The clinical pregnancy rate and the live birth rate in group D were significantly lower than those in group A (a OR=0.595, 95% CI: 0.456-0.777, P<0.001; a OR=0.600, 95% CI: 0.449-0.800, P=0.001). The differences in miscarriage rate, pregnancy complications and multiple pregnancy rate were not statistically significant compared with group A (all P>0.05). The differences in all the above indicators in group C were not statistically significant compared with group A ( P>0.05). The risk of occurrence of macrosomia (group B: a OR=2.367, 95% CI: 1.299-4.315, P=0.005; group D: a OR=2.711, 95% CI: 1.463-5.026, P=0.002), large for gestational age (group B: a OR=1.930, 95% CI: 1.158-3.217, P=0.012; group D: a OR=2.039, 95% CI: 1.174-3.543, P=0.011) were significantly higher in groups B and D than in group A. The differences in the risk of occurrence of low birth weight, small for gestational age and preterm birth were not statistically significant in groups B and D compared with group A ( P>0.05), and the difference in the risk of occurrence of the above indicators was not statistically significant in group C compared with group A ( P>0.05). Conclusion:When 2PN embryos are not available, abandoned 0PN, 1PN, and 2PN embryos can be transferred after blastocyst culture, but attention should be paid to the increased risk of macrosomia and large for gestational age in offspring.

Objective:To investigate the timing of the first frozen-thawed embryo transfer (FET) on clinical and perinatal outcomes in whole embryo freezing patients, who used the medroxyprogesterone acetate (MPA) in progestin primed ovarian stimulation (PPOS).Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with the first FET after ovulation induction by PPOS protocol in Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to November 2021. According to the time interval between the day of oocytes retrieved and the day of the first FET in the ovulation induction cycle, they were divided into two groups. Group A: transplantation was performed during the first menstrual cycle after oocyte retrieval (time interval ≥24 d and <45 d, n=80), group B: transplantation was performed at least one month apart after oocytes retrieved (time interval ≥45 d, n=1 040). After propensity score matching (PSM), the general data, clinical excretion promotion, embryo laboratory indicators, indicators related to the first FET cycle, clinical and perinatal outcomes were compared between the two groups. Results:Before PSM, the age of group A was significantly higher than that of group B [38 (35, 41) years vs. 37 (32, 40) years, P=0.020]. After PSM, there were no significant differences in general data, ovulation induction cycle data, embryo laboratory indicators, clinical pregnancy rate, live birth rate and perinatal outcomes between the two groups (all P>0.05). Conclusion:Compared with FET at least one month after oocytes retrieval, FET during the first menstrual cycle after PPOS does not affect clinical or perinatal outcomes. FET can be performed as early as possible after oocytes retrieval according to the condition of patients to shorten the time to reach their first live birth.

Objective:To explore the clinical application value of frozen-thawed single blastocyst derived from nonpronuclear (0PN) zygotes, monopronuclear (1PN) zygotes and two-pronuclei (2PN) discarded embryos.Methods:A retrospective cohort analysis of the data of patients who underwent frozen-thawed single blastocyst transfer at the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from March 2014 to November 2020. According to the different sources of transplanted blastocysts, they were divided into 4 groups including group A derived from 2PN available embryos (2PN embryos with morphological rating Ⅰ-Ⅲ), group B derived from 0PN embryos, group C derived from 1PN embryos, group D derived from 2PN discarded embryos (2PN embryos with morphological rating Ⅳ). The basic data of the four groups were analyzed,and group A was used as the reference group to compare the clinical pregnancy outcomes of groups B, C and D, respectively. The neonatal situation was compared at the cycle of singleton live birth. Logistic regression was used to correct for confounding factors and calculate the adjusted odds ratio (a OR) and 95% confidence interval ( CI). Results:After correcting for confounding factors by logistic regression, the live birth rate in group B was significantly lower than that in group A (a OR=0.701, 95% CI: 0.534-0.920, P=0.011). The clinical pregnancy rate and the live birth rate in group D were significantly lower than those in group A (a OR=0.595, 95% CI: 0.456-0.777, P<0.001; a OR=0.600, 95% CI: 0.449-0.800, P=0.001). The differences in miscarriage rate, pregnancy complications and multiple pregnancy rate were not statistically significant compared with group A (all P>0.05). The differences in all the above indicators in group C were not statistically significant compared with group A ( P>0.05). The risk of occurrence of macrosomia (group B: a OR=2.367, 95% CI: 1.299-4.315, P=0.005; group D: a OR=2.711, 95% CI: 1.463-5.026, P=0.002), large for gestational age (group B: a OR=1.930, 95% CI: 1.158-3.217, P=0.012; group D: a OR=2.039, 95% CI: 1.174-3.543, P=0.011) were significantly higher in groups B and D than in group A. The differences in the risk of occurrence of low birth weight, small for gestational age and preterm birth were not statistically significant in groups B and D compared with group A ( P>0.05), and the difference in the risk of occurrence of the above indicators was not statistically significant in group C compared with group A ( P>0.05). Conclusion:When 2PN embryos are not available, abandoned 0PN, 1PN, and 2PN embryos can be transferred after blastocyst culture, but attention should be paid to the increased risk of macrosomia and large for gestational age in offspring.

Objective:To investigate the timing of the first frozen-thawed embryo transfer (FET) on clinical and perinatal outcomes in whole embryo freezing patients, who used the medroxyprogesterone acetate (MPA) in progestin primed ovarian stimulation (PPOS).Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with the first FET after ovulation induction by PPOS protocol in Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to November 2021. According to the time interval between the day of oocytes retrieved and the day of the first FET in the ovulation induction cycle, they were divided into two groups. Group A: transplantation was performed during the first menstrual cycle after oocyte retrieval (time interval ≥24 d and <45 d, n=80), group B: transplantation was performed at least one month apart after oocytes retrieved (time interval ≥45 d, n=1 040). After propensity score matching (PSM), the general data, clinical excretion promotion, embryo laboratory indicators, indicators related to the first FET cycle, clinical and perinatal outcomes were compared between the two groups. Results:Before PSM, the age of group A was significantly higher than that of group B [38 (35, 41) years vs. 37 (32, 40) years, P=0.020]. After PSM, there were no significant differences in general data, ovulation induction cycle data, embryo laboratory indicators, clinical pregnancy rate, live birth rate and perinatal outcomes between the two groups (all P>0.05). Conclusion:Compared with FET at least one month after oocytes retrieval, FET during the first menstrual cycle after PPOS does not affect clinical or perinatal outcomes. FET can be performed as early as possible after oocytes retrieval according to the condition of patients to shorten the time to reach their first live birth.