ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

Objective:To analyze application effect of trend analysis for safe risk in management and control for infection of medical devices,so as to optimize the management path for medical devices.Methods:Focusing on the main factors affecting the safety risks of medical devices,the least squares method of linear regression was applied for trend analysis to optimize the device management path and strengthen management.A total of 70 clinically used medical devices in the First Affiliated Hospital of Xi'an Jiaotong University from January to December 2024 were selected.These devices were managed using two models:the conventional management model and the trend analysis management model,with 35 devices under each model.The infection risk rate of medical equipment and the equipment management quality score were compared between the two management models.Additionally,160 patients managed under the two models(80 patients per model)were included to compare the patient infection rate.Results:In the 450 diagnostic and treated records of sampling inspection and consultation for medical devices from treatment equipment,diagnosis equipment,auxiliary imaging equipment and surgical equipment,the rate of infectious risk of using management mode with trend analysis were respectively 1.78%(8/450),2.22%(10/450),2.22%(10/450)and 2.44%(11/450),all of which were significantly lower than these of using conventional management mode,and the differences were significant(x2=9.904,8.902,10.465,10.770,P＜0.05).The scores of cleaning quality,the quality of disinfection and sterilization,the quality of distribution,and the retrieving quality of the management mode with trend analysis for medical devices were significantly higher than those of the conventional management mode,and the differences were statistically significant(t=15.889,13.172,15.872,17.399,P＜0.05).The infection rate of patients in the trend analysis management mode was 6.25%(5/80),which was significantly lower than that in the conventional management mode[22.50(18/80)],and the difference was statistically significant(x2=11.006,P＜0.05).Conclusion:The trend analysis for safe risk can analyze the risk factors in use and operation for medical devices from multiple perspectives,and mining main factors and conduct intervention for the devices,and reduce the incidence of safe risks of medical devices and the patients'infection rate,and improve the quality of clinical services.

Objective:To explore the application effects of traditional Chinese medicine five-tone therapy combined with personalized emotional counseling in patients with post-stroke insomnia, aiming to provide a reference for improving patients′ sleep quality in clinical practice.Methods:A quasi-experimental study was conducted. A total of 70 inpatients with post-stroke insomnia from the Department of Neurology and the Department of Rehabilitation at Lianyungang Hospital of Traditional Chinese Medicine between January 2023 and February 2024 were selected using convenience sampling method. Of these, 35 patients admitted between January and July 2023 were assigned to the control group, while 35 patients admitted between August 2023 and February 2024 were assigned to the experimental group. The control group received routine treatment and care, while the experimental group was additionally provided with traditional Chinese medicine five-tone therapy combined with personalized emotional counseling. The intervention period was four weeks for both groups. Evaluations were conducted using polysomnography, the Pittsburgh Sleep Quality Index, the Insomnia Severity Index (ISI), and the patients′ use of hypnotic medications.Results:The control group consisted of 18 males and 17 females, with an average age of (58.02 ± 5.22) years; the experimental group consisted of 22 males and 13 females, with an average age of (56.41 ± 5.49) years. After the intervention, the total sleep time, the Pittsburgh Sleep Quality Index score, and the Insomnia Severity Index score in experimental group were (376.22 ± 52.39) min, (9.36 ± 3.22) points, and (13.89 ± 2.16) points, respectively, compared to (343.78 ± 74.51) min, (12.02 ± 3.76) points, and (16.66 ± 3.04) points in the control group, with statistically significant ( t=2.11, 3.18, 4.39, all P<0.05). The experimental group′s hypnotic medication usage rate and nursing satisfaction score were 11.43% (4/35) and (81.05 ± 3.68) points, respectively, compared to 34.29% (12/35) and (76.21 ± 5.22) points in the control group, with statistically significant differences ( χ2=5.51, t=4.48; both P<0.05). Conclusions:Traditional Chinese medicine five-tone therapy combined with personalized emotional counseling can effectively improve sleep quality in post-stroke insomnia patients, reduce the use of hypnotic medications, and enhance patient satisfaction.

Proteolysis-targeting chimeras(PROTACs)represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can,potentially revolu-tionizing drug discovery and treatment strategies.However,the links between in vitro and in vivo data are poorly understood,hindering a comprehensive understanding of the absorption,distribution,metabolism,and excretion(ADME)of PROTACs.In this work,14C-labeled vepdegestrant(ARV-471),which is currently in phase Ⅲ clinical trials for breast cancer,was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics(PK)by estab-lishing a physiologically based pharmacokinetics(PBPK)model.For in vitro-in vivo extrapolation(IVIVE),hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did.PBPK models,which were initially developed and validated in rats,accurately simulate ARV-471's PK across fed and fasted states,with parameters within 1.75-fold of the observed values.Human models,informed by in vitro ADME data,closely mirrored postoral dose plasma profiles at 30 mg.Furthermore,no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans.This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

Objective To investigate the effect of hypertensive disorders of pregnancy(HDP)on the adverse growth and development outcomes of premature infants with gestational age<32 weeks.Methods Premature infants with gestational age<32 weeks admitted to the neonatal intensive care unit of Yinchuan Maternal and Child Health Hospital General Hospital and Yuehai Branch from 2017 to 2024 were selected as the study sub-jects,and general information of premature infants and mothers was collected to analyze the relationship be-tween HDP and adverse growth and development outcomes in these infants.Results A total of 173 premature infants were included,including 88 males(50.9%)and 85 females(49.1%).There were 41 cases(23.7%)of small for gestational age infants(SGA)and 132 cases(76.3%)of non SGA infants.A total of 65 cases(37.6%)had HDP mothers and 108 cases(62.4%)had non HDP mothers.Among SGA premature infants,75.6%(31/41)had a mother with HDP,while among non SGA premature infants,25.8%(34/132)had a mother with HDP.Regardless of whether premature infants were born with SGA or not,compared with the non HDP group,the HDP group had a higher incidence of extrauterine growth retardation(EUGR),congeni-tal hypothyroidism(CH),and parenteral nutrition associated cholestasis(PNAC)(P<0.05).In non SGA premature infants,compared with the non HDP group,the HDP group had a higher incidence of metabolic bone disease(MBD),and the difference was statistically significant(P<0.05).Multivariate logistic regres-sion analysis showed that HDP was an independent factor affecting the occurrence of EUGR in SGA preterm infants(P<0.05).HDP was an independent risk factor for CH,EUGR,and PNAC in non SGA preterm in-fants(P<0.05).Conclusion Maternal HDP can increase the risk of EUGR,CH,and PNAC in premature in-fants with gestational age<32 weeks,and is associated with poor postnatal growth and development out-comes in offspring.

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

Objective To systematically evaluate the risk factors for new-onset atrial fibrillation (NOAF) after off-pump coronary bypass grafting (OPCABG). Methods PubMed, EMbase, Web of Science, The Cochrane Library, Wanfang data, CBM, VIP, and CNKI databases were systematically searched by computer to collect studies related to the risk factors for NOAF after OPCABG from the establishment of the database to July 2023. Literature screening and quality evaluation were conducted independently by two researchers. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature. RevMan 5.3 and Stata15.0 were used for meta-analysis. Results Finally, 19 case-control studies related to the risk factors for NOAF after OPCABG were included, all of which were high-quality literature with NOS score≥6 points, with a total of 7019 subjects. The results of meta-analysis showed that the following factors were associated with NOAF after OPCABG: (1) the patient’s own factors: age (MD=3.51, 95%CI 2.39 to 4.63, P<0.01); (2) preoperative factors: history of hypertension (OR=1.17, 95%CI 1.04 to 1.32, P=0.01), history of myocardial infarction (OR=1.21, 95%CI 1.06 to 1.38, P<0.01), history of percutaneous coronary intervention (OR=2.22, 95%CI 1.03 to 4.77, P=0.04), EuroSCOREⅡ score (MD=0.59, 95%CI 0.25 to 0.94, P<0.01), low-density lipoprotein (MD=0.11, 95%CI 0.02 to 0.20, P=0.02), left atrial diameter (MD=1.64, 95%CI 0.24 to 3.04, P=0.02); (3) postoperative and treatment factors: left ventricular end-diastolic diameter (MD=1.16, 95%CI 0.33 to 1.99, P<0.01), left ventricular ejection fraction (MD=0.90, 95%CI 0.07 to 1.73, P=0.03), mechanical ventilation time (MD=2.78, 95%CI 1.65 to 3.90, P<0.01), B-type natriuretic peptide (MD=219.67, 95%CI 27.46 to 411.88, P=0.03), ICU retention time (MD=7.07, 95%CI 5.64 to 8.50, P<0.01). Conclusion The existing evidence shows that age, history of hypertension, history of myocardial infarction, history of percutaneous coronary intervention, preoperative EuroSCOREⅡscore, preoperative low-density lipoprotein, preoperative left atrial diameter, postoperative left ventricular end-diastolic diameter, postoperative left ventricular ejection fraction, postoperative mechanical ventilation time, postoperative B-type natriuretic peptide, and postoperative ICU retention time are risk factors for NOAF after OPCABG. Clinical attention should be paid to the above factors to achieve early identification, thereby reducing the incidence of NOAF after OPCABG and improving the clinical prognosis of patients.

Proteolysis-targeting chimeras (PROTACs) represent a promising class of drugs that can target disease-causing proteins more effectively than traditional small molecule inhibitors can, potentially revolutionizing drug discovery and treatment strategies. However, the links between in vitro and in vivo data are poorly understood, hindering a comprehensive understanding of the absorption, distribution, metabolism, and excretion (ADME) of PROTACs. In this work, ¹⁴C-labeled vepdegestrant (ARV-471), which is currently in phase III clinical trials for breast cancer, was synthesized as a model PROTAC to characterize its preclinical ADME properties and simulate its clinical pharmacokinetics (PK) by establishing a physiologically based pharmacokinetics (PBPK) model. For in vitro-in vivo extrapolation (IVIVE), hepatocyte clearance correlated more closely with in vivo rat PK data than liver microsomal clearance did. PBPK models, which were initially developed and validated in rats, accurately simulate ARV-471's PK across fed and fasted states, with parameters within 1.75-fold of the observed values. Human models, informed by in vitro ADME data, closely mirrored postoral dose plasma profiles at 30 mg. Furthermore, no human-specific metabolites were identified in vitro and the metabolic profile of rats could overlap that of humans. This work presents a roadmap for developing future PROTAC medications by elucidating the correlation between in vitro and in vivo characteristics.

[Purpose]To analyze the trends of incidence and age at onset of leukemia in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of leukemia from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province.All datasets were checked and evaluated based on data quality control criteria and were included in the analysis.Crude incidence rate(CIR),age-standardized incidence rate by Chinese standard population(ASIRC),the average annual percentage change(AAPC),the standardized average age at onset,the changes in the age structure of incidence and the changes in the birth cohort by year were calculated.[Results]The incidence rate of leukemia significantly increased from 5.22/105 in 2009 to 7.88/105 in 2019,with a significant upward trend(for CIR,AAPC=4.95％,95％CI:3.82％～6.09％;for ASIRC,AAPC=2.97％,95％CI:1.52％～4.43％).The incidence rates were in-creased in all age groups and increased with the birth cohort by years.There was a tendency of backward shift for the age composition of the population,with the increasing of composition for those over 60 years old.The mean age at onset increased from 48.62 years old in 2009 to 57.96 years old in 2019,with a backward shift in the mean age(β=0.773,P＜0.001),and the mean age at onset increased with the year only in rural areas after standardization(β=0.428,P=0.017).[Conclusion]Leukemia incidence rate in Jiangsu Province increased from 2009 to 2019,and the age at onset has shifted backwards.It's important to strengthen the early prevention and control of leukemia.