Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.

Objective:To explore the clinical value of prostatic exosomal protein(PSEP)and PSA in the diagnosis of PCa with PSA in the gray zone(4-10 μg/L)and Prostate Imaging Reporting and Data System category3(PI-RADS-3)lesions.Meth-ods:From 2019 to 2022,211 patients with the PSA gray zone and PI-RADS-3 lesions underwent prostate multi-parameter MRI,pros-tate needle biopsy or transurethral resection/enucleation of the prostate.We collected the baseline urine samples from the patients,ex-amined the content of PSEP in the urine by ELISA and evaluated the performance of PSEP and PSA in the diagnosis of PCa.Re-sults:Among the total number of patients,57 were confirmed with PCa(the positive group)and the other 154 with benign prostate conditions(the negative group)by biopsy pathology.The free PSA level(fPSA),free to total PSA ratio(f/tPSA)and PSEP content were dramatically lower in the positive than in the negative group(all P<0.01).Uni-and multivariate analyses showed f/tPSA and PSEP to be independent factors for predicting PCa with the PSA gray zone and PI-RADS-3 lesions,with the AUC values of 0.70 and 0.78,best cutoff values of 0.18 and 1.45 μg/L,sensitivity of 84.21%and 70.18%,and specificity of 58.44%and 77.27%,re-spectively(P<0.01).The multivariate model with combined use of f/tPSA and PSEP(AUC:0.82,best cutoff value:0.31,sensi-tivity:82.46%,specificity:75.32%)outperformed either f/tPSA or PSEP alone in the diagnosis of PCa with the PSA gray zone and PI-RADS-3 lesions(P<0.01,P=0.04).Conclusion:For patients with the PSA gray zone and PI-RADS-3 lesions,f/tPSA and PSEP are significant predictors of PCa.The multivariate model of PSEP combined with f/tPSA can replace f/tPSA in the detection of PCa to improve diagnostic performance and avoid unnecessary prostate biopsy.

Objective To investigate the causal relationship between obstructive sleep apnea(OSA)and hypertension using bidirectional Mendelian randomization(MR).Methods Genetic data for OSA were obtained from the Genome-wide association study(GWAS)of FinnGen Biobank,including 16 761 cases and 201 194 controls,from which 5 single-nucleotide polymorphisms(SNPs)were screened as instrumental variables(IVs)for OSA.Genetic data for hypertension were obtained from GWAS of UK Biobank,including 124 227 cases and 337 653 controls from which 214 SNPs were selected as IVs for hypertension.Multiple MR methods,mainly Inverse variance weighted(IVW),were used for analysis.Sensitivity analysis of MR results was performed using MR-Egger regression et al,and IVs were evaluated using F values.Results OSA was associated with an increased risk of hypertension(OR=1.053,95%CI 1.019-1.089,P<0.01),and hypertension was significantly associated with the risk of developing OSA(OR=1.812,95%CI 1.354-2.425,P<0.001).Heterogeneity was observed in both two-way outcomes(OSA→ hypertension,P<0.001;hypertension→ OSA,P<0.001),but no evidence of horizontal pleiotropy was detected(OSA→ hypertension,P=0.666;hypertension→ OSA,P=0.556).The IVs selected in this study were strong instrumental variables for both OSA and hypertension(OSA-IVs F=14.695;hypertension-IVs F=39.624).Conclusions Our findings indicate a bidirectional causal relationship between OSA and hypertension,with a particularly significant effect of hypertension on the development of OSA.

Purpose To investigate the clinical,imaging,pathological features,differential diagnosis and prognosis of em-bryonic dysplastic neuroepithelial tumor(DNT).Methods The clinical data of 33 DNT patients were collected.Immunohis-tochemical results of Olig2,NeuN,Syn,GFAP,IDH1,CD34,BRAF V600E,H3K27M and Ki67 were examined by EnVision method.Histopathological morphology and immunohistochemical features were retrospectively analyzed and relevant literature was reviewed synchronously.Results A total of 28 cases were fol-lowed up,including 10 females and 18 males.The age of onset was 4～57 years,with average 24.97 years.Refractory epilepsy was a common symptom.The lesions were mainly located in the supratentorial cortex,and most of them were well-defined,lobu-lated,cystic or cystic and solid.Microscopically,DNT was mainly composed of oligodendrocytes,neurons floating in the mucous matrix,and proliferative astrocytes.Calcification was rare,and no necrosis or microvascular hyperplasia was ob-served.Immunohistochemistry showed that neurons expressed NeuN and Syn,oligodendrocytes expressed Olig2,and prolifera-tive astrocytes expressed GFAP;p53 was mostly wild-type,and the proliferation index of Ki67 was low(mostly less than 4％).Conclusion DNT is a benign tumor with mixed glial and neu-ronal structures.Precise pathological diagnosis needs to be care-fully considered with imaging characteristics,microscopic mor-phology,immunohistochemistry and molecular test results if nec-essary.Prognosis after complete surgical resection is good.

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:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective Naturally,Aedes albopictus carries both the A and B supergroups of Wolbachia strains,which are symbiotic bacteria that can influence the transmission of mosquito-borne diseases by inhibiting the ability of their host to transmit viruses or by reducing the population density of their host,and the strength of this effect is closely related to its density in host cells.In this study,an accurate qPCR-based method for detecting Wolbachia genotype and density in mosquitoes was established.Methods The wsp gene of Wolbachia carried by Ae.albopictus was cloned and sequenced,and specific primers for the non-conserved regions of the w AlbA and w AlbB wsp genes were designed.Results The application of this method showed great sensitivity and specificity.The primers did not cross-react between the two Wolbachia supergroups.Further,with this method,it was possible to detect decreases in Wolbachia density in host cells following treatment with tetracycline at different concentrations,and the optimal tetracycline treatment concentration was determined to be 0.1 mg/mL.Conclusion This method can provide technical supports for studies of the effects of Wolbachia on physiological reproduction and innate immunity in mosquitoes.

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/chemistry* ; Rehmannia/chemistry* ; Flavonoids/analysis*