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 study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

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.

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 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 retrospectively analyze the prevention and control effect and epidemic characteristics of elderly tuberculosis in Hubei Province from 2016 to 2020, and to provide a scientific basis for the prevention and treatment of elderly tuberculosis in Hubei Province． Methods The data on tuberculosis patients aged 60 and above who registered their current address in Hubei Province from 2016 to 2020 were collected and analyzed. The registration rates and composition ratios were analyzed using χ² test and χ² test for trend. Results A total of 135 976 tuberculosis patients were reported in Hubei from 2016 to 2020. The annual average registration rate of elderly tuberculosis among the elderly registered residence population (referring to the registration rate of elderly registered residence population aged 60 and above as the denominator, and tuberculosis patients aged 60 and above as the numerator) was 263.51/100 000. The highest rate was 300.02/100,000 in 2017, and the lowest was 188.19/100,000 in 2020 (χ²=70,227.603, P<0.001). In terms of composition, the average annual proportion of tuberculosis patients in the 60-70 years old group was 59.60%, which decreased year by year (χ²_trend=40.448，P<0.001 ). The average annual proportion of males was 73.35%, which was significantly higher than that of females (26.65%). The average annual proportion of farmers was 62.03%. From the perspective of case management, the annual average proportion of major epidemic online reports was 85.17%. The classification of cases was mainly based on clinical diagnosis, accounting for 48.33% annually and showing a decreasing trend year by year (χ²_trend=740.911, P<0.001). The proportion of confirmed cases was 25.08%, which showed an increasing trend (χ²_trend=380.557, P<0.001). From 2016 to 2019, the delay rate of diagnosis and treatment of elder tuberculosis patients was 49.42% (67 876/135 967), and the delay rate decreased year by year (χ²_trend=323.764, P<0.001). Conclusion The elderly population with pulmonary tuberculosis in Hubei Province shows a downward trend. It is necessary to focus on the efforts of designated hospitals to proactively identify cases, increase the proportion of confirmed cases, maintain a high tracking in place, reduce medical delays, and ensure the effectiveness of tuberculosis prevention and treatment for the elderly.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.