Objective:To evaluate whether the mechanism by which mesenchymal stem cell-derived exosomes (MSC-exo) mitigated endotoxin-induced lung injury was related to the heme oxygenase-1 (HO-1)/mitochondrial signaling pathway in alveolar macrophages of mice.Methods:In vivo experiment Eighteen C57BL/6 wild-type (WT) mice were divided into 3 groups ( n=6 each) using a random number table method: control group (C group), lipopolysaccharide (LPS) group (L group) and LPS + MSC-exo group (LM group). Six HO-1 conditional knockout mice (HO-1 -/-) were selected and served as HO-1 -/- + MSC-exo + LPS group (HML group). The model of endotoxin-induced lung injury was prepared by injection of LPS 15 mg/kg. MSC-exo (2×10 11 particles) was intravenously injected at 1 h before injection of LPS in LM group. MSC-exo (2×10 11 particles) was intravenously injected and 1 h later LPS was injected in HML group. The expression of HO-1 in macrophages was detected using immunofluorescence, lung injury was assessed following hematoxylin-eosin staining, the wet/dry weight ratio (W/D ratio) was determined, and the mitochondrial morphology was observed with a transmission electron microscope. Cell experiment Alveolar macrophages (MH-S) were divided into 4 groups ( n=20 each) using a random number table method: control group (C group), LPS+ phosphate buffer solution group (LP group), LPS+ MSC-exo group (LM group), and LPS+ MSC-exo+ HO-1 small-interfering RNA group (LMS group). Cells were incubated for 12 h with LPS 10 μg/ml in LP, LM and LMS groups. In addition, LM group was incubated with MSC-exo 100 μg/ml, LP group was incubated with the equal volume of phosphate buffer solution, and the alveolar macrophages were transfected with HO-1 small interfering RNA and incubated with MSC-exo 100 μg/ml in LMS group at the same time. The concentrations of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in supernatant were measured by enzyme-linked immunosorbent assay, HO-1 expression was detected by Western blot, the mitochondrial membrane potential was measured using JC-1 staining, and the expression of reactive oxygen species (ROS) was detected by fluorescence. Results:In vivo experiment Compared to C group, the lung injury score and W/D ratio were significantly increased ( P<0.05), the fluorescence signal of HO-1 in macrophages was enhanced, and the damage to mitochondria was aggravated in L group. Compared to L group, the lung injury score and W/D ratio were significantly decreased ( P<0.05), the fluorescence signal of HO-1 in macrophages was enhanced, and the damage to mitochondria was reduced in LM group. Compared to LM group, the lung injury score and W/D ratio were significantly increased ( P<0.05), macrophages had no HO-1 fluorescence signal, and the damage to mitochondria was aggravated in HML group. Cell experiment Compared to C group, the concentrations of IL-1β and TNF-α in supernatant were significantly increased, the expression of HO-1 was up-regulated ( P<0.05), and the mitochondria predominantly exhibited green JC-1 fluorescence, accompanied by an enhanced ROS fluorescence signal in LP group. Compared to LP group, the concentrations of IL-1β and TNF-α in supernatant were significantly decreased, the expression of HO-1 was up-regulated ( P<0.05), and the mitochondria predominantly exhibited red JC-1 fluorescence, accompanied by a weakened ROS fluorescence signal in LM group. Compared to LM group, the concentrations of IL-1β and TNF-α in supernatant were significantly increased, the expression of HO-1 was down-regulated ( P<0.05), and the mitochondria predominantly exhibited green JC-1 fluorescence, accompanied by an enhanced ROS fluorescence signal in LMS group. Conclusions:The mechanism by which MSC-exo attenuates endotoxin-induced lung injury may be related to up-regulation of HO-1 expression in alveolar macrophages and reduction of mitochondrial damage in mice.

Objective:To explore the treatment methods and prognosis of pregnancy-related uterine arteriovenous malformation (UAVM).Methods:A retrospective analysis was conducted on clinical data from 81 patients with UAVM treated at Peking Union Medical College Hospital between March 2019 and March 2024. Clinical manifestations, diagnostic approaches, treatment strategies and prognosis were evaluated.Results:(1) General Information: the age of patients with UAVM was (32.7±4.6) years, with median gravidity and parity of 1 (quartile range: 1, 2) and 0 (0, 1), respectively. Pregnancy termination methods included surgical abortion or curettage in 46 cases (57%, 46/81), medical induction in 17 cases (21%, 17/81), spontaneous abortion in 16 cases (20%, 16/81), vaginal delivery in 1 case (1%, 1/81), and laparoscopic pregnancy tissue removal in 1 case (1%, 1/81). (2) Clinical manifestations: clinical presentations comprised vaginal bleeding in 59 cases [73%, 59/81; median blood loss: 740 ml (440, 1 360 ml)], massive hemorrhage in 9 cases (11%, 9/81, and bleeding combined with lower abdominal pain in 8 cases (10%, 8/81). Ultrasonography revealed intrauterine masses in 65 cases [80%, 65/81; median size: 2.5 cm (1.8, 4.2 cm)]. Elevated serum human chorionic gonadotrophin-β subunit (β-hCG) levels were observed in in 55 cases [85%, 55/65; median: 62.6 U/L (14.9, 300.1 U/L)]. The median time to UAVM diagnosis via ultrasound was 30.0 days (16.0, 52.0 days) after pregnancy termination, with median peak systolic velocity (PSV) and resistance index of 59.8 cm/s (45.0, 79.6 cm/s) and 0.39 (0.36, 0.43), respectively. (3) Treatment and prognosis: treatment modalities included expectant management in 49 cases (36%, 29/81), medication in 13 cases (16%, 13/81), lesion resection in 31 cases (38%, 31/81), and uterine artery angiography in 8 cases (10%, 8/81; 5 confirmed as arteriovenous fistula). The median time of PSV returning to normal after treatment was 53.8 days (36.0, 93.4 days). The average time for β-hCG returning to normal was (60.4±20.4) days. The median return time of menses was 59.0 days (43.0, 75.4 days).Conclusions:Pregnancy-related UAVM carries a high risk of life-threatening hemorrhage, necessitating management in centers equipped for emergency uterine artery embolization. Informed consent must emphasize disease progression risks and prognosis. Treatment stratification should integrate clinical parameters and imaging features.

Objective To investigate the value of ultrasound for differentiating pancreatoblastoma(PB)and solid pseudopapillary tumor of pancreas(SPT)in children.Methods Data of 7 children with PB(PB group)and 22 with SPT(SPT group)were retrospectively analyzed.The clinical data and lesion's ultrasonic manifestations were compared between groups.Receiver operating characteristic(ROC)curves of clinical and ultrasound related parameters being significantly different between groups showed by univariate analysis were draw,and the area under the curve(AUC)were calculated to evaluate their efficacy for differentiating PB and SPT.Ultrasound parameters with P＜0.05 in univariate analysis were incorporated into binary logistic analysis,and a ultrasound regression model was constructed to distinguish PB and SPT,and its diagnostic efficacy was evaluated.Results Significant differences of children'age,gender,serum alpha fetoprotein level,and the shape,maximum diameter,texture,calcification and local invasion of lesions were found between groups(all P＜0.05).AUC of single serum alpha fetoprotein level,the shape,maximum diameter,texture,calcification and local invasion of lesion for differentiating PB and SPT was 1.000,0.766,0.854,0.776,0.789 and 0.714,respectively(all P＜0.05).The shape(OR=8.704,P=0.075)and maximum diameter of lesions(OR=1.695,P=0.042)showed with ultrasound were both important differentiating factors for PB and SPT,and AUC of the ultrasound regression model constructed based on them was 0.886.Conclusion Ultrasound could effectively differentiate PB and SPT in children.

Objective To quantitatively evaluate structural changes in the TMD disc using magnetic resonance T2 mapping technology at open and closed mouth positions,and assess its significance.Methods 127 newly diagnosed patients with TMD and 51 controls in the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Yunnan University from June 2023 to January 2024 were prospectively collected.All subjects underwent routine TMJ sequence and T2 mapping sequence scans.After scanning,the pseudo-color images were processed,and T2 values of the joint disc(anterior and posterior bands)were measured at open and closed mouth positions to analyze their correlation with TMD disc displacement.Results The T2 values of the posterior zone of the joint disc in both open and closed positions were higher than those in the anterior zone of the joint disc in the case group(P<0.05);for different anterior displacement degrees of the joint disc,T2 values showed a progressive increase from the normal position group to the mild and moderate anterior displacement groups,while the severely displaced group demonstrated a decreasing trend(P<0.01);joint clicking and occlusal abnormalities were independent risk factors for non-reducible anterior joint disc displacement in TMD patients.Conclusion Scans during both mouth-opening and closing positions can be used to assess joint disc injury in TMD;T2 mapping technology can quantitatively and sensitively reflect changes in the biochemical composition of joint disc microstructure.

Objective To investigate the correlation of serum levels of soluble programmed death ligand 1(sPD-L1),tumor necrosis factor-associated apoptosis-inducing ligand(TRAIL)and fibroblast growth factor 23(FGF-23)with risk stratification and death in patients with acute pulmonary embolism(APE).Methods A total of 113 pa-tients with APE admitted to the hospital from January 2022 to January 2024 were selected as APE group,and 50 healthy subjects were selected as control group.The 113 patients with APE were divided into high risk group(39 cases),medium risk group(45 cases)and low risk group(29 cases)by risk stratification.Accord-ing to the death of APE patients,they were divided into survival group(83 cases)and death group(30 cases).The levels of serum sPD-L1,TRAIL and FGF-23 were measured by enzyme-linked immunosorbent assay(ELISA).Multiple Logistic regression was used to analyze the risk factors affecting death of APE patients.Receiver operating characteristic(ROC)curve was drawn to analyze the value of serum sPD-L1,TRAIL and FGF-23 levels in evaluating mortality in APE patients.Pearson correlation analysis was used to investigate the correlation between serum sPD-L1,TRAIL and FGF-23 levels and cardiac function indicators in APE patients.Results The levels of serum sPD-L1,TRAILand FGF-23 in the APE group were significantly higher than those in the control group(P＜0.001).The serum sPD-L1,TRAIL and FGF-23 levels in the death group were significantly higher than those in the survival group(P＜0.001).The levels of serum sPD-L1,TRAIL and FGF-23 in the high-risk group were higher than those in the medium and low-risk groups,and the medium risk group was higher than the low-risk group,and the differences were statistically significant(P＜0.001).Multiple Logistic regression analysis showed that elevated levels of cardiac troponin Ⅰ(cTnⅠ),B type brain na-triuretic peptide(BNP),sPD-L1,TRAIL and FGF-23 were risk factors for mortality in APE patients(P＜0.05).ROC curve analysis showed that the combination of sPD-L1,TRAIL and FGF-23 had the largest area under curve for predicting death in APE patients,which was 0.924(95％CI:0.861-0.986),with a sensitivity of 96.8％and a specificity of 81.2％.Correlation analysis showed that the levels of serum sPD-L1,TRAIL and FGF-23 were positively correlated with cTnⅠ and BNP in APE patients(P＜0.001).Conclusion The lev-els of serum sPD-L1,TRAIL and FGF-23 are significantly elevated in APE patients,and their high expression is associated with high-risk stratification and mortality.The combination of these three indexes has good eval-uation value for APE patient mortality.

OBJECTIVE: To elucidate the role and underlying mechanism of ubiquitin-specific protease 35 (USP35) in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS), thereby enhancing our comprehension of the pathogenesis of RA and identifying potential therapeutic targets for its treatment. METHODS: (1) RA-FLS were cultured in vitro and transduced with lentiviral vectors to establish stable cell lines: A USP35-knockdown line (short hairpin ribonucleic acid of USP35, shUSP35) and its control (negtive control of short hairpin ribonucleic acid, shNC), as well as a overexpression of USP35 line (USP35 OE) and its control (Vector). To investigate the role of USP35 in ferroptosis regulation, a ferroptosis model was induced in RA-FLS by treatment with 1 μmol/L Erastin. The cells were divided into six groups: shNC, shNC + Erastin, shUSP35 + Erastin, Vector, Vector + Erastin, and USP35 OE + Erastin. (2) Cell viability was detected using the cell counting kit-8 (CCK-8). (3) Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione/glutathione disulfide (GSH/GSSG) ratios, and Ferrous ion (Fe²⁺) levels were measured using specific assay kits to evaluate oxidative stress, lipid peroxidation, and glutathione redox status in the cells. (4) Protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected using Western blotting to investigate their potential involvement in USP35-mediated ferroptosis regulation. RESULTS: (1) Compared with the shNC +Erastin group, the cell viability of the shUSP35+Erastin group was significantly decreased (P < 0.001), while it was notably increased in the USP35 OE+Erastin group compared with the Vector+Erastin group (P < 0.001). These findings indicated that USP35 could alleviate the inhibitory effect of Erastin on RA-FLS cell viability. (2) In comparison to the shNC+Erastin group, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.001) were significantly elevated, and the GSH/GSSG ratio was increased (P < 0.05) in the shUSP35+Erastin group. Conversely, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe²⁺ (P < 0.05) were significantly decreased, and the GSH/GSSG ratio was decreased (P < 0.05) in the USP35 OE+Erastin group compared with the Vector+Erastin group. These results suggested that USP35 could inhibit Erastin-induced oxidative stress and lipid peroxidation in RA-FLS. (3) In Erastin-induced RA-FLS, the expression of USP35 was positively correlated with the protein levels of SLC7A11 and GPX4, indicating a potential mechanism by which USP35 regulated ferroptosis in these cells. CONCLUSION USP35 inhibits ferroptosis in RA-FLS, potentially through the increased expression of SLC7A11 and GPX4.
Ferroptosis ; Humans ; Arthritis, Rheumatoid/metabolism* ; Synoviocytes/pathology* ; Reactive Oxygen Species/metabolism* ; Ubiquitin-Specific Proteases/metabolism* ; Fibroblasts/pathology* ; Cell Survival ; Piperazines/pharmacology* ; Endopeptidases/metabolism* ; Cells, Cultured ; Cell Line ; Amino Acid Transport System y+

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

Objective To analyze the risk factors affecting the progression-free survival(PFS)of patients with intrahepatic cholangiocarcinoma(ICC)after surgical resection,and a predictive nomogram model was constructed based on blood test indicators.Methods A total of 99 ICC patients who received their first treatment at Hunan Provincial People's Hospital from January 2020 to December 2022 were selected as research subjects,they were divided into training group(n=70)and validation group(n=29).The independent risk factors for postoperative recurrence were identified using least absolute shrinkage and selection operator(LASSO)regression analysis and multivariate Cox risk regression analysis.The accuracy and clinical utility of the method were further tested by consistency index,receiver operating characteristic(ROC)curve,calibration graph,decision curve analysis,and progression-free survival curve.Results LASSO and multivariate Cox risk regression analysis showed that patient's gender,tumor-lymph node metastasis,differentiation grade,tumor diameter,aspartate aminotransferase,alpha-fetoprotein,total bile acid after surgery,and monocyte changes before and after surgery were independent factors affecting the PFS of ICC patients.The predictive model based on the risk factor showed that the consistency index of the training group was 0.884 and that of the validation group was 0.838.The area under ROC curve for training group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.965 and 0.923,respectively;for validation group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.821 and 0.923,respectively.The risk score calculated according to the nomogram divided ICC patients into high-risk group and low-risk group with high postoperative recurrence risk,and the median PFS in high-risk group was significantly shorter than that in low-risk group(P＜0.05).Conclusion The nomogram constructed by this study has good predictive effect and can be used as a supplementary evaluation for predicting PFS after ICC patients.

Objective Analysing the risk factors for the occurrence of pre-frailty or frailty of the community elderly in Chengdu and constructing a risk prediction model.Methods The general information questionnaire,MNA-SF scale,Changsha version of the MoCA scale,PSQI scale,FRAIL scale,and Traditional Chinese Medicine Constitution Scale for the elderly were used in the cross-sectional survey.A total of 400 elderly people who completed community physical examinations in Chengdu from April 2022 to April 2023 were selected as the research objects.Based on multivariate Logistic regression analysis,the independent influencing factors were determined,and RStudio software was used to construct a risk prediction model nomogram.The physical examination data of 200 elderly people collected in Deyang City from June 2023 to October 2023 were used for external verification.The area under the ROC curve,Hosmer-Lemeshow test and calibration curve,and decision curve were used to evaluate the discrimination,calibration,and clinical practicability of the model.Results Age,abdominal circumference,number of chronic diseases,PSQI score,allergy history,and balanced constitution were independent influencing factors for pre-frailty/frailty in the elderly in the community(P<0.05),and the regression equation was as follows:Logit(P)=0.063×age+0.025×abdominal circumference-1.006×allergy history+0.300×number of chronic diseases+0.082×PSQI-1.013×balanced constitution-8.269.The area under the ROC curve of the modeling group was 0.779(95%CI:0.733-0.825),the sensitivity was 67.1%,the specificity was 76.3%,and the maximum Youden index was 0.434.The area under the ROC curve of the external validation group was 0.783(95%CI:0.709-0.856),the sensitivity was 62.0%,the specificity was 95.0%,and the maximum Youden index was 0.570.The Hosmer-Lemeshow goodness of fit test results of the two groups were χ2=3.285,P=0.915 and χ2=8.376,P=0.398,and the calibration curve fit was good.DCA showed that the threshold probability of clinical benefit was 5%-99%and 21%-98%.Conclusions The pre-frailty/frailty risk prediction model established in this study has good predictive efficacy for the elderly in the community,and the use of this model for screening and early intervention of high-risk populations can be clinically beneficial.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Notch signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer,the literature on the regulation of Notch signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results 362 and 85 related literatures were published in Chinese and English respectively until January 2024.Since 2013,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;Hunan University of Chinese Medicine were the institutions with the most publications in the Chinese database,and Beijing University of Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Notch signaling pathway are focused on cerebral ischemia,myelosuppression and hepatic fibrosis.Diseases such as Asthma,colorectal cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.Conclusion Recent years have seen a rapid development of traditional Chinese medicine's disease prevention and treatment that targets Notch signaling pathway.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.