ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective: To explore the interaction between school bullying and insomnia in relation to depression-anxiety-stress emotions among primary and secondary school students,so as to provide a basis for preventing negative emotional states in adolescents. Methods: In October 2024, a stratified cluster sampling method was used to select 3 058 students in grade 5-6 of primary, junior and senior high school in Sheyang County of Jiangsu Province. The Delaware Bullying Victimization Scale, Insomnia Severity Index, Depression-Anxiety-Stress Scale-21, and Study Condition Questionnaire were employed to investigate school bullying, insomnia, depression-anxiety-stress emotions, and academic performance. The χ 2 test and Logistic regression were used to analyze the association between school bullying and insomnia interactions and depression-anxiety-stress emotions among primary and secondary school students, multiplicative interaction analysis was conducted, and additive interaction analysis was performed using R software. Results: The detection rates of depression-anxiety-stress emotions among primary and secondary school students were 21.6%, 28.4% and 10.8%, respectively. The detection rates of physical bullying, relationship bullying, verbal bullying and cyberbullying in school bullying were 10.6%, 14.0%, 22.3%, and 6.2%, respectively. The detection rate for insomnia was 23.1%. Results from Logistic regression analysis showed that, after adjusting for relevant factors, physical, relational, verbal, and cyberbullying and insomnia were positively correlated with the detection rates of depression ( OR = 5.72- 10.93), anxiety ( OR =6.35-12.17), and stress emotions ( OR =5.97-14.52) among primary and secondary school students (all P <0.01). The multiplicative interaction between physical, relational, verbal, and cyberbullying and insomnia was positively correlated with the detection rates of depression ( OR =8.00-18.01), anxiety ( OR =11.35-17.76), and stress emotions ( OR =7.64-9.12) in primary and secondary school students (all P <0.01). Additive interactions were observed between physical, relational, verbal, and cyberbullying and insomnia in relation to the detection rates of depression, anxiety, and stress emotions among primary and secondary school students (both RERI and AP >0 and the credible interval excluded 0, SI >1 and the credible interval excluded 1). Conclusion School bullying and insomnia are associated with depression, anxiety, and stress emotions among primary and secondary school students, and they exhibit both multiplicative and additive interactions.

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

Objective To explore the developmental trajectories of oral hygiene compliance and its influencing factors in children after dental caries surgery.Methods A prospective cohort study design was adopted.A total of 268 children who underwent dental caries surgery were selected as the research subjects.General and clinical data of the children were collected.The oral hygiene compli-ance changes after surgery were evaluated using the Oral Hygiene Compliance Scale.The develop-mental trajectories of oral hygiene compliance after surgery were described using the group-based traj-ectory model.Multivariate Logistic regression analysis was used to explore the influencing factors of the compliance developmental trajectories.Results The oral hygiene compliance of children after dental caries surgery could be divided into three types of developmental trajectories:the high-compliance slow-decline group[49(18.28％)],the medium-compliance slow-decline group[56(20.90％)],and the low-compliance stable-change group[163(60.82％)].Multivariate Logistic regression analysis showed that the child's gender,mother's educational level,fathers smoking history,annual per capi-ta household income,Social Support Scale score,Oral Health Self-Efficacy Scale score,and Expec-ted Social Impact Scale score were all independent influencing factors for the oral hygiene compliance to present different types of developmental trajectories(P＜0.05).Conclusion The oral hygiene compliance of children after dental caries surgery presents different types of developmental trajectories,and there are individual differences in their initial compliance levels and rates of change.Clinically,oral hygiene care intervention measures should be implemented according to the specific conditions of children to maintain their oral health.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

Objective: To investigate the association between plant-based diet and different types of obesity, so as to provide references for obesity prevention. Methods: Residents aged 35-75 years from 33 counties (cities, districts) in Zhejiang Province were selected as study subjects using a multistage stratified random sampling method between April and December 2024. Demographic information and living behaviors were collected using questionnaire surveys. Height, weight and waist circumference were measured, and body mass index (BMI) was calculated. BMI ≥28.0 kg/m2 was defined as obesity, waist circumference ≥90 cm in males or ≥85 cm in females was defined as central obesity, and individual with obesity who also had central obesity was defined as having compound obesity. Food intake over a 3-day period was collected using the consecutive 3-day 24-hour dietary recall method. The plant diet index (PDI), healthful plant diet index (HPDI), and unhealthful plant diet index (UPDI) were calculated, and categorized into quintiles (Q1-Q5) based on their distribution. Association between the PDI, PDI, UPDI and different types of obesity were analyzed using multivariable logistic regression models. Results: A total of 4 882 individuals were surveyed, including 2 233 males (45.74%) and 2 649 females (54.26%). The average age was (55.42±12.14) years. There were 537 individuals of obesity, 1 718 individuals of central obesity, and 500 individuals of compound obesity, with detection rates of 11.00%, 35.19%, and 10.24%, respectively. Multivariable logistic regression analysis showed that, after adjusting for demographic information and living behaviors, compared with Q1 group, HPDI Q5 group showed a 29.6% lower risk of obesity (OR=0.704, 95%CI: 0.525-0.943) and a 32.1% lower risk of compound obesity (OR=0.679, 95%CI: 0.502-0.918). Conversely, the UPDI Q5 group exhibited a 39.5% higher risk of obesity (OR=1.395, 95%CI: 1.032-1.886) and a 39.8% higher risk of compound obesity (OR=1.398, 95%CI: 1.025-1.907). No statistically significant association was found between PDI and obesity, central obesity, and compound obesity (all P>0.05). As HPDI increased, the risks of obesity and compound obesity showed decreasing trends; as UPDI increased, the risks of obesity and compound obesity showed increasing trends (all Ptrend<0.05). Conclusion A healthful plant-based diet is associated with reduced risks of obesity and compound obesity, while an unhealthful plant-based diet is associated with increased risks of obesity and compound obesity.