OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate （TRV130） in improving postoperative cognitive dysfunction （POCD） in elderly rats based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway. METHODS Rats were randomly divided into the control group （normal saline）， the model group （normal saline）， the TRV130 group （2.8 mg/kg）， the TLR4/NF-κB pathway inhibitor （TAK-242） group （3 mg/kg）， the β -arrestin inhibitor （Barbadin） group （3 mg/kg）， and the traditional opioid drug （morphine） group （2.8 mg/kg）， with 15 rats in each group. Except for the control group， POCD models were established in all other groups. From the first day after surgery， drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration， the pathological damage of hippocampal tissue was observed； the cognitive function， serum inflammatory factor levels， hippocampal neurons apoptosis rate， and the expression of ionized calcium-binding adapter molecule 1 （Iba-1）， glial fibrillary acidic protein （GFAP）， and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group， the neurons in the CA1 region of the hippocampus were disordered and sparse， with decreased number， pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group， the escape latency， serum levels of tumor necrosis factor α （TNF-α）， interleukin-6 （IL-6）， and IL-1β， hippocampal neurons apoptosis rate， average fluorescence intensities of Iba-1 and GFAP， mRNA expression levels of TLR4 and NF-κB p65， and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group （ P ＜0.05）； the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased （ P ＜0.05）. Compared with the model group， the cognitive function， pathological， inflammatory， and apoptosis-related indicators were significantly improved in the TRV130 group， TAK-242 group， and Barbadin group （ P ＜0.05）； the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group （ P ＜0.05）. CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

Objective:To evaluate the improvement in the outcome of intracapsular condylar fractures(ICFs)treatment with pre-cise soft tissue reduction in combination with open reduction and internal fixation(PSTR-ORIF)by comparson with traditional open reduction and internal fixation(T-ORIF).Methods:40 patients with ICFs were treated by T-ORIF and PSTR-ORIF(n=20)re-spectively.Preoperative and 6-month postoperative whole-mouth panoramic tomography,CT and MRI imaging data were analyzed,the repositioning of the soft and hard tissues of temporomandibular joints(TMJs),the Helkimo index,clinical symptoms and subjec-tive symptoms were compared between the 2 groups.Results:In PSTR-ORIF(26 sides)and T-ORIF(27 sides)groups,the rate of complete anatomical restoration of fractured segments at 6 months after surgery was 96.15％and 81.48％,and the overall effective rate of ICF articular disc restoration was 96.15％and 74.07％respectively,the height of the ascending mandibular branch was bet-ter restored in patients with B-type fracture after surgery(P＜0.05).At 6 months postoperatively,patients in the PSTR-ORIF group showed significant improvement in mouth opening,mandibular anterior extension distance,and lateral movement compared with the T-ORIF group(P＜0.05).The Helkimo index showed that the PSTR-ORIF group got a significant improvement in the complaint symptom index score and the clinical symptom index score compared with the T-ORIF group(P＜0.05).Conclusion:PSTR-ORIF is more effective than T-ORIF in the treatment of ICFs for the healing of condylar fractures,restore postoperative TMJ mobility and reduce the postoperative joint discomfort through good repositioning of soft tissues.

Objective:To establish a qualitative analysis of Rhodiola crenulata for determing six components inclu-ding gallic acid,salidroside,tyrosol,1,2,3,4,6-O-gallic glucose,rhodiosin,oxorlin-7-O-rhamnoside by HPLC,and to find out the feasibility of the method of linear calibration using two reference substances in qualitative analysis of chromatographic peaks.Methods:The real retention time of 6 components in Rhodiola crenulata on 19 chromatographic columns were determined.Gallic acid and rhodiosin were selected as the reference substances,and the method of linear calibration using these 2 substances was used to predict the retention time.Tyrosol was also chosen as the reference to predict the retention time with the relative retention time method(RRT method).Comparing the accuracy of these two methods.Results:Compared to the RRT method,the method of linear calibration with two reference substances was more accurate for predicting the retention time and more adapatable for many kinds of chromatographic columns.Conclusion:As a new alternative reference substance method,the method of linear calibration using two reference substances can assist chromatographic peak determination better and has broad application prospects.

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

BackgroundMajor depressive disorder （MDD）， a prevalent mental disorder， is characterized by persistent depressed mood， impaired concentration， loss of interest in daily activities， decreased appetite， and sleep disturbances. Randomized controlled trials （RCTs） indicate potential benefits of Bifidobacterium supplementation for MDD， but the evidence base remains insufficient to draw definitive conclusions. ObjectiveTo explore the causal association between Bifidobacterium and MDD through a Mendelian randomization （MR） approach， with the hope of providing genetic evidence to elucidate the etiological mechanisms and risk factors underlying MDD. MethodsSummary-level data from genome-wide association studies （GWAS） was conducted， specifying Bifidobacterium as the exposure variable and MDD as the outcome variable， to rigorously investigate the causal association between Bifidobacterium and MDD. Multiple complementary analytical approaches were employed， including inverse-variance weighted， weighted median estimator， MR-Egger regression， weighted mode and simple mode， to derive robust causal estimates. Furthermore， to ensure the robustness and validity of the findings， a series of comprehensive sensitivity analysis were systematically performed， encompassing MR-Egger regression test， MR-PRESSO test and leave-one-out analysis. ResultsInverse-variance weighted revealed a causal link from Bifidobacterium to MDD （OR=1.018， 95% CI： 1.001–1.035， P=0.035）， whereas no evidence of reverse causality was observed （OR=0.603， 95% CI： 0.116–3.130， P=0.547）. ConclusionBifidobacterium is a risk factor for MDD， and its presence may increase the risk of MDD onset.

Guidelines for Digital Ancient Books of TCM Indexing(T/CIATCM 119-2024)is based on the theoretical knowledge,disciplinary methods,and practical applications of TCM classical cataloging.Taking digital ancient books of TCM as the object,it systematically reveals the content of TCM knowledge,which is an essential indexing processing standard for building an intelligent retrieval system for TCM ancient books,and can provide support for the deep development and innovative utilization of TCM knowledge.It can not only promote the co-construction and sharing of ancient book resources in the TCM industry,but also promote the standardization construction and application of TCM information.This standard specifies the principles,methods,and examples of free indexing of digital ancient books of TCM based on their original content.It is applicable to the indexing and processing of digital ancient books of TCM for TCM professional libraries and related institutions,and to the data processing and construction of various types of TCM ancient book databases.