BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective: The characteristics and differences of the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia were investigated to provide references and suggestions for the compilation of the Chinese Pharmacopoeia.
Methods: From the perspective of frame structure and main contents, the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia was compared.
Results: Each volume of the Chinese Pharmacopoeia had its general notice, including 34 to 48 items and 10 to 12 chapters based on different varieties collected in each volume. The Japanese Pharmacopoeia had 49 items not arranged by chapters. There are many differences on the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia, such as the definitions and expressions of names, determination of appearance, revision rules, risk assessment and quality control conception. The framework of the general notice in the Chinese Pharmacopoeia was clear, the content was specific and the operation was friendly. The term description of the general notice in the Japanese Pharmacopoeia was concise, and some terms need to be implemented under the guidance of professional knowledge.
Conclusion: In light of comparative study, every volume’s general notice of the Chinese Pharmacopoeia has its own characteristics. By integrating advanced analytical technique, combining the requirements with laws and regulations, and optimizing content and terms, all volume’s general notice could be explored to be coordinated and unified.

Objective To investigate the differences in plasma metabolites between patients with altitude-related hypertension(ARH)and healthy individuals,and analyze the potential pathogenesis of ARH.Methods Convenient sampling was conducted on a unit of male healthy officers and soldiers who resident at altitude of＜500 m and migrated to an altitude of 4 200 m in July 2020.Twenty of them diagnosed with ARH were assigned into the ARH group,and another 30 non-ARH individuals served as the control group.Their blood pressure,body mass index(BMI),blood oxygen saturation,and heart rate were measured and recorded,and fasting venous blood samples were harvested to screen and identify plasma metabolites with ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS).Metabolite fingerprinting was performed using unsupervised Principal Component Analysis(PCA)and supervised Orthogonal Partial Least Squares Discrimination Analysis(OPLS-DA)models in order to assist in biomarker screening.The quality of the OPLS-DA model was assessed and validated to guarantee the stability and reliability of the model.Differential plasma metabolites were screened using independent sample t test and fold change(FC)analysis,and volcano plots were drawn.Finally,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway analysis was used to perform functional pathway enrichment and topological analysis on the screened differential metabolites.Results Compared to the control group,the ARH group showed significantly higher systolic and diastolic blood pressure and heart rate,and lower arterial oxygen saturation(P＜0.05).PCA analysis showed that 81.96％of the variance was explained in the positive ion mode and 79.25％in the negative ion mode,indicating significant metabolic differences between the 2 groups.OPLS-DA model analysis indicated that in the positive ion mode,PC1 explained 77.36％of the variance and PC2 explained 12.25％of the variance,with R2Y=0.96 and Q2Y=0.91;in the negative ion mode,PC1 explained 84.15％of the variance and PC2 explained 17.24％of the variance,with R2Y=0.99 and Q2Y=0.86.Inter-group difference exceeded 75％,and intra-group difference was less than 20％.The 7-fold cross-validation and 200 permutation test confirmed that the model was stable and reliable.In the positive ion mode,the Y-axis intercepts of the R2 and Q2 fitted lines were 0.58 and-0.48,respectively;in the negative ion mode,the Y-axis intercepts were 0.93 and-0.41,respectively.A total of 32 significantly different metabolites were screened out,including amino acids,nucleosides,fatty acids,and organic alkaloids.KEGG analysis revealed that among the 10 metabolic pathways,4 were amino acid metabolic pathways,with the aminoacyl-tRNA biosynthesis pathway having the most enriched metabolites.Conclusion Based on UHPLC-MS/MS technology,untargeted metabolomics analysis identifies 32 significantly different metabolites,which may serve as characteristic biomarkers for ARH,and the aminoacyl-tRNA biosynthesis pathway may be associated with the pathogenesis of ARH.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:The antimicrobial resistance of Staphylococcus aureus(S.aureus)has become a challenge in the treatment of infectious diseases.It is of great clinical value to discovery effective antimicrobial agents against multi-drug resistant S.aureus and its biofilms.This study aims to explore the antibacterial activity of the antiparasitic drug closantel against methicillin-resistant S.aureus and its biofilms through drug repurposing. Methods:The sensitivity of S.aureus to closantel was assessed using microbroth dilution and disk diffusion methods.The bacteriostatic and bactericidal activities of closantel were determined by time-kill curves and colony count.Scanning electron microscopy combined with SYTOX Green and DiSC3(5)fluorescence probes were used to study the bactericidal mechanism of closantel.The influence of resistance was assessed by continuous exposure to sub-inhibitory concentrations of closantel.The anti-biofilm activity was evaluated using 96-well plates and crystal violet staining,and cytotoxicity was measured using the CCK-8 assay. Results:The minimal inhibitory concentration(MIC)of closantel for both methicillin-sensitive and methicillin-resistant S.aureus ranged from 0.125 to 1.000 μg/mL.Disk diffusion tests showed that 80 pg of closantel created an inhibition zone,which increased in diameter with higher drug amounts.Sub-inhibitory concentrations(0.031 μg/mL)of closantel significantly inhibited S.aureus proliferation,reducing bacterial turbidity from 0.26±0.00 to 0.11±0.01(t=16.06,P＜0.001),with stronger inhibition at higher concentrations.Closantel at 0.25×MIC inhibited S.aureus proliferation for 12 hours,while lxMIC inhibited it for over 24 hours,with the number of viable bacteria decreasing as the drug concentration increased.Mechanistic studies indicated that closantel effectively disrupted the integrity of S.aureus cell membranes,significantly increasing SYTOX Green and DiSC3(5)fluorescence intensity.Even after 25 days of continuous exposure to sub-inhibitory concentrations of closantel,no resistance developed.Closantel at 0.0625 μg/mL significantly inhibited biofilm formation,reducing it from 1.29±0.16 to 0.62±0.04(t=11.62,P＜0.001),showing a clear dose-dependent effect.Closantel at 2 μg/mL also significantly eradicated established biofilms,reducing biofilm mass from 1.62±0.34 to 0.51±0.39(t=4.84,P＜0.01).Additionally,closantel exhibited extremely low cytotoxicity,with half-maximal lethal concentrations for HepG2 liver cancer cells and normal LO2 liver cells both exceeding 64 μg/mL. Conclusion:Closantel exhibits strong antibacterial activity against S.aureus and its biofilm with low cytotoxicity against human cells,making it a promising candidate for new therapeutic strategies against S.aureus-related infections.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Narrative medicine, an interdisciplinary subject merging medicine and the humanities, serves as a vital instrument in capturing, comprehending, and integrating the diverse perspectives of all stakeholders involved in the realm of illness. In the context of pediatric palliative care, the implementation of narrative medicine fosters effective doctor-patient communication and enhances the doctor-patient relationship. This article delves into the importance and practicality of narrative medicine in pediatric palliative care, shedding light on the hurdles faced during its implementation. The study highlights the pressing need for further extensive and in-depth research of narrative medicine in pediatric palliative care, aiming to provide evidence-based insights that can inform clinical interventions and decision-making processes.

Objective:To summarize the effect of Chinese Children′s Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol.Methods:This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis.Results:Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ 2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ 2=44.329, P<0.01) and failure to achieve CR at the end of the treatment (χ 2=49.459, P<0.01) were independent factor for predicting survival. Conclusion:Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

OBJECTIVE：To explore the metabolic charact eristics of Miao medicine Laportea bulbifera extract in isolated human intestinal flora. METHODS ：L. bulbifera was extracted with 70％ ethanol reflux extraction. After concentration，extraction with n-butanol and drying ，L. bulbifera extract was obtained. Taking 0.05 g/mL L. bulbifera extract 1 mL mixed with isolated human intestinal flora fluid 10 mL and cultured for 36 h in anaerobic environment （setting up blank control without drugs or human intestinal bacterial solution ），so as to simulate the metabolic process of the extract in human intestine. The metabolites were detected by UPLC-Q-TOF/MS. The determination was performed on Agilent Eclipse Plus C 18 RRHD column with mobile phase consisted of 0.01％ formic acid water solution- 0.01％ formic acid acetonitrile solution （gradient eluetion ）at the flow rate of 0.25 mL/min. The column temperature was set at 40 ℃，and the sample size was 1 µL. ESI detection was adopted and scanned by negative ion mode （ESI－）；the capillary voltage was 4.5 kV，the ion source temperature was 120 ℃，the collision energy was 15-32 V，and the scanning range was m/z 50-1 000. The “Strip”module of MassLynx V 4.1 software was used to analyze the differential chromatograms between the reaction solution and the blank control of L. bulbifera extract. Mass spectrum data and UNIFI so ftware were used to predict relative molecular weight and formula ；based on the information of substance control and related literature reports ， the structure and biotransformation pathway of L. bulbifera metabolites in isolated human intestinal flora were predicted and analyzed. RESULTS & CONCLUSIONS ： A total of 3 prototype ： products（rutin，quercetin，kaempferol-3-O-rutinoside）and 22metabolites （mainly the metabolites of quercetin ，mono- caffeoylquinic acid ，isoquercitrin，etc.） were detected after metabolized in isolated human intestinal flora. Itsbiotransformation pathway is phase Ⅰ reaction，which mainly consisted of reduction ，oxidation and hydrolysis.