Background Per- and polyfluoroalkyl substances (PFASs) are a class of persistent organic pollutants that pose potential health risks to humans. Infants and young children have higher requirements for food safety due to the underdeveloped detoxification and immune systems. Therefore, developing a comprehensive method for determination of PFASs and their novel alternatives in infant complementary food is of great significance. Objective To develop an analytical method using liquid chromatography high-resolution mass spectrometry technology for determination of 55 PFASs in plant- and animal-derived infant complementary fruit purees. Methods Oasis WAX (200 mg, 6 CC) solid-phase extraction columns were used for sample enrichment and purification. The pH of the acetonitrile extract was adjusted using 0%, 1%, 1.5%, and 2% formic acid aqueous solutions to evaluate its impact on the recovery rate of target compounds. Additionally, the impact of a 2 mL methanol wash during the purification process on the recovery of target compounds was assessed to determine the optimal pretreatment conditions. Three types of chromatographic columns—Agilent Poroshell 120 EC-C₁₈, Thermo InfinityLab Poroshell 120 Aq-C₁₈, Acquity Waters BEH-C₁₈, and changes in mobile phase, were compared for their effects on retention time, peak shape, and response of target compounds. The method was validated in terms of selectivity, linear range, detection limit, and precision. The established method was applied to 49 commercial samples of infant complementary fruit purees. Results Adjusting the sample pH using 1.5% formic acid water and incorporating a 2 mL methanol wash during purification achieved satisfactory recovery rates. The target compounds were chromatographically separated using an Agilent Poroshell 120 EC-C₁₈ column with a gradient elution system. The mobile phase consisted of methanol-water (methanol/water: 2/98, v/v) containing 5 mmol·L⁻¹ ammonium formate as mobile phase A, and methanol as mobile phase B. Good separation was achieved within 15 min, resulting in optimal chromatographic peak shapes. The 55 target compounds exhibited good linearity across the standard curve range, with correlation coefficients (R²) greater than 0.99. The method detection limits ranged from 0.02 to 0.05 µg·L⁻¹. In the plant- and animal-based fruit puree samples, the spiked recovery rates ranged from 60% to 112% and 57% to 119%, respectively, with relative standard deviations (RSD) ≤ 30%. A total of 9 traditional PFASs and 5 novel PFASs were positive in 49 samples of infant complementary fruit purees. Conclusion This method enables comprehensive detection of 55 traditional and emerging PFASs, offering wide coverage, high accuracy, and excellent sensitivity. It provides technical support for characterizing contamination by traditional and emerging PFASs in food matrices.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Objective:This study aims to analyze the gamma band effective connectivity characteristics of the prefrontal-striatal circuitry in bipolar disorder patients with and without a history of manic episodes, as well as in major depressive disorder patients, during the recognition of positive emotional faces, this study aims to identify unique neurophysiological features that may aid in the early detection of bipolar disorder.Methods:This retrospective study collected clinical data and magnetoencephalography (MEG) imaging data from patients performing a positive emotional face recognition task at the Affiliated Brain Hospital of Nanjing Medical University from May 2009 to December 2019. The study included 75 patients with major depressive disorder and 29 patients with bipolar disorder in a depressive episode (rBD group). Concurrently, 39 age-and gender-matched healthy controls (HC group) were recruited. After a follow-up period of at least 5 years, 23 out of the 75 patients with major depressive disorder converted to bipolar disorder (ctBD group), while the remaining 52 who did not convert maintained a diagnosis of major depressive disorder.Results:There were statistically significant differences in gamma-band effective connectivity in the prefrontal-striatal circuit when recognizing positive emotional faces among the converted to bipolar disorder (ctBD), raw bipolar disorder, major depressive disorder, and HC groups ( H=9.04, 10.30, 8.30, 13.43, 14.38, 12.62, 9.82, 8.94, 24.62, 7.89, 18.53, 9.97, 9.58, 12.79, P<0.05). The ctBD group, rBD group, and major depressive group all showed reduction in effective connectivity from the right orbital inferior frontal gyrus (ORBinf.R) to the left orbital inferior frontal gyrus (ORBinf.L) [ Z=-1.98, -3.38, -2.88], from the right orbital inferior frontal gyrus to the right ventral striatum (VS.R) ( Z=-2.05, -2.76, -2.11; P<0.05) and from the left ventral striatum (VS.L) to the left orbital middle frontal gyrus (ORBmid.L) ( Z=-2.76, -1.98, -2.43; P<0.05). Among the disease groups, the ctBD group showed significantly enhanced effective connectivity strength compared to the major depressive group from the right amygdala (AMYG.R) to the left orbital inferior frontal gyrus(0.04(0.03, 0.08)), from the right amygdala to the left ventral striatum(0.05(0.03, 0.09)), and from the right ventral striatum to the right anterior cingulate and paracingulate gyri (ACG.R) (0.04(0.02, 0.08)) ( Z=4.17, 3.70, 3.35; P<0.001).The ctBD group also exhibited enhanced effective connectivity compared to the rBD group from ORBinf.R to the ACG.R, fron the AMYG.R to the ORBinf.L, from the AMYG.R to the VS.L, and from the VS.R to the ACG.R ( Z=2.05, 4.61, 3.60, 3.04; P<0.05).The rBD group demonstrated reduced effective connectivity compared to the major depressive disorder group from the right orbital middle frontal gyrus(ORBmid.R) to the left anterior cingulate and paracingulate gyri (ACG.L), ORBinf.R to the ACG.R and from the ORBinf.R to the AMYG.R ( Z=-2.12, -2.40, -2.22; P<0.05). Conclusion:There are significant differences in the gamma-band effective connectivity characteristics of the prefrontal-striatal pathway when recognizing positive emotional faces between patients with bipolar disorder in depressive episodes and those with depression, as well as differences between bipolar depressed patients with and without a history of manic episodes.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Clinical pharmacist teacher training is an important mean to improve the quality of clinical pharmacy talent cultivation and ensure the service ability and level of the clinical pharmacist team.The Pharmacy Administration and Pharmacy Practice in Healthcare Institutions-Part 4-8-2:Pharmacy Administration-Pharmacy Training Management-Clinical Pharmacist Teacher Training was based on the newly revised management document for clinical pharmacist teacher training of the Chinese Hospital Association.After sorting out relevant materials,such as standards,policies and regulations,technical specifications,liter-ature,documents of the Chinese Hospital Association,expert opinions,and the current situation of clinical pharmacist teacher training in China,the standard was formulated.In the standard,12 key elements,which can be divided into 3 parts of base manage-ment,training process and assessment,quality management and evaluation improvement,were standardized.This article aimed to introduce the construction method and content of the standard,to facilitate the understanding of the standard content for medical institutions which joined or willing to join the clinical pharmacist teacher training base,and to provide a reference for other medi-cal institutions to carry out related work.

With the rapid development of personalized medicine, recommending the optimal treatment regimes among multiple options for individual patients has become a key topic in the study of individualized treatment rules. Existing methods often face challenges such as limited accuracy and robustness when handling multi-category treatment problems. This study proposes a weighted random forest method that formulates the treatment decision problem as a weighted classification task. By incorporating the expected loss differences among treatment outcomes, the method enhances its learning process and improves recommendation performance with the non-parametric nature and flexibility of random forests. The weighted random forest method is further applied to real-world hypertension intervention data to generate personalized antihypertensive treatment recommendations based on the patient's baseline characteristics, demonstrating its potential value in clinical practice. This research aims to provide a new approach for individualized treatment rules in multi-treatment settings and to support the development of data-driven clinical decision-making systems.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.