Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

AIM:This study aims to investigate whether triiodothyronine(T3)can enhance skin wound heal-ing by activating the the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of inter-feron genes(STING)signaling pathway to modulate the inflammatory phase.METHODS:Mice were randomly assigned to five groups:normal,control,T3,RU.521+T3,and RU.521(a cGAS inhibitor).With the exception of the normal group,a full-thickness skin defect model was established in the other groups.Wound healing was observed daily.Mice were euthanized on post-injury days 1,2,4,7,and 10,with five mice per group.Pathological changes and collagen fiber formation were assessed using hematoxylin-eosin(HE)and Masson staining,respectively.Immunohistochemical staining was performed to evaluate the expression of cGAS,STING,mouse EGF-like module-containing mucin-like hormone recep-tor-like 1(EMR1 or F4/80),C-X-C motif chemokine ligand 8(CXCL-8),and CXCL-10.Western blotting was conducted to measure protein levels of cGAS,STING,C-C motif chemokine ligand-2(CCL-2),and nuclear factor-κB(NF-κB).En-zyme linked immunosorbent assay(ELISA)was utilized to quantify the levels of interferon-β(IFN-β),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α).RESULTS:From days 1 to 4 post-injury,the wound healing rate and collagen fiber formation in the T3 group were significantly greater than those in the control,RU.521+T3,and RU.521 groups(P＜0.05).Additionally,the T3 group displayed more favorable pathological changes compared to the other groups.No ex-pression of cGAS and STING was observed in the normal group,while low levels were found in the RU.521+T3 and RU.521 groups.The T3 and control groups exhibited higher expression levels,with the T3 group showing significantly ele-vated expression on days 1 to 4 post-injury(P＜0.05)but lower expression on day 7 compared to the control group(P＜0.05).The expression of the macrophage marker F4/80 was higher in the T3 group compared to the control,RU.521+T3,and RU.521 groups on days 1 to 7 post-injury(P＜0.05).Furthermore,chemokines CXCL-8,CXCL-10,and CCL-2 showed increased levels in the T3 group on days 1 to 2 or 1 to 4 post-injury(P＜0.05)but were lower at other time points(P＜0.05)compared with the control,RU.521+T3,and RU.521 groups.Additionally,the levels of pro-inflammatory fac-tors IFN-β,IL-6,TNF-α,and NF-κB in the T3 group were significantly higher on day 1 post-injury(P＜0.05),while lev-els on days 2 to 7 were lower compared to the control,RU.521+T3,and RU.521 groups(P＜0.05).CONCLUSION:T3 accelerates the healing of impaired skin wounds,potentially through the enhanced activation of the cGAS-STING signal-ing pathway.This process increases the expression of chemokines and pro-inflammatory factors and promotes macrophage recruitment during the early post-injury phase,ultimately regulating the inflammatory response.

Objective:To explore the clinical application value of artificial intelligence（AI）-assisted training in enhancing the accuracy of nuchal translucency（NT）identification，standardization of measurement，and diagnostic efficacy for abnormalities among ultrasound residents.Methods:A retrospective collection of 300 standard fetal NT ultrasound images was conducted at the Center for Medical Ultrasound，Suzhou Hospital Affiliated of Nanjing Medical University from January 2018 to June 2024. The AI model performed NT measurements and diagnoses once. Four sonographers of different seniority levels（including two resident physicians）independently conducted NT measurements and diagnoses twice. Prior to the experiment，the middle-age and resident sonographers had uniformly completed traditional theory training. Following the first independent measurements，the two resident sonographers received additional AI-assisted training，after which all 4 sonographers performed the second independent measurements. A fetal medicine expert evaluated blindly all the results and compared the differences in NT recognition accuracy，measurement standard rate and diagnosis accuracy between the middle-age sonographer（traditional training only）and two resident sonographers（traditional + AI-assisted training）.Results:For the middle-aged sonographer who only received traditional lecture-based training，the accuracy of NT recognition，standardization rate of measurement，or diagnostic accuracy were not significantly improved befroe and after the training，and the diffrence was not statistically significant（ χ2=0.189，1.887，0.326；all P>0.05）. In contrast，the second-year resident（Resident 2）and first-year resident（Resident 1），who received both traditional lecture-based training and AI training，demonstrated some improvements in the accuracy of NT measurement site recognition，though the differences were not statistically significant（ χ2=1.301，2.418；all P>0.05）. However，both residents did significant improvements in the standardization rate of NT measurement（ χ2=25.768，17.035；all P<0.05）. In terms of diagnostic accuracy，Resident 1 did significant improvement（ χ2=10.180， P<0.05），while Resident 2 also did some improvement，though the difference was not statistically significant（ χ2=2.573， P>0.05）. Conclusions:The AI-assisted training system enhances the ability of ultrasound resident sonographers to recognize，measure，and diagnose NT，providing a novel and efficient training model for standardized residency training in ultrasound specialties.

Objective:To investigate the diagnostic value of fetal cardiac ultrasound view visualization in the first trimester for congenital heart disease（CHD）.Methods:A retrospective analysis was performed on 13 323 singleton fetuses who underwent first-trimester（11-13 +6 weeks）ultrasound screening at the Ultrasound Medicine Center，the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to June 2024. Cardiac views including the four-chamber view（4CV），left ventricular outflow tract view（LVOT），and Results:The study group showed significantly higher rates of "poorly visualized" 4CV，LVOT，and 3VT than the control group（2.70% vs. 0.14%， P=0.005；36.49% vs. 4.76%， P<0.001；36.49% vs.2.46%， P<0.001）. The efficacies of combination 1（any view abnormal）and combination 2（any view "poorly visualized" or "abnormal"）were comparable，with AUCs of 0.86 and 0.85（ P=0.424）. The AUCs of combination 3（3VT "poorly visualized" or any view "abnormal"）and combination 4（4CV "poorly visualized" or any view "abnormal"）were 0.88 and 0.86（ P=0.424），all significantly higher than combination 5（LVOT "poorly visualized" or any view "abnormal"，AUC=0.84，all P<0.05）. Conclusions:"Poorly visualized" cardiac views in the first trimester demonstrate good diagnostic efficacy for CHD，particularly when 3VT or 4CV are affected，warranting heightened clinical vigilance for fetal cardiac anomalies.

Objective To identify potential ergonomic risk factors of works and quickly assess their risks of developing work-related musculoskeletal disorders (WMSDs) in the medical staff. Methods A total of 188 medical staff were selected as the research objects using a two-stage random sampling method. The method for the identification of musculoskeletal stress factors (PLIBEL) was used to analyze the adverse ergonomic factors in the work process, and the rapid entire body assessment (REBA) was used to quickly assess the whole-body posture load. Results The PLIBEL assessment results showed that various adverse ergonomic factors affected different parts of the body during the work process of medical staff. Specifically, 18 adverse ergonomic factors were identified in the neck, shoulders, and upper back, while 10 adverse ergonomic factors were identified in the elbow, forearm, hand, and lower back. Rehabilitation therapists and nurses engaged in patient handling in general wards and medication preparation and blood collection were exposed to ≥35 adverse ergonomic factors. The REBA assessment showed that the REBA score was 3-12 points for medical staff during their work process. Rehabilitation therapists were classified as having an extremely high ergonomic risk. High-risk occupations included ward housekeeping nurses, surgery assistant nurses, operating-room instrument nurses, and surgeons. Medium-risk occupations included general ward nurses (medication preparation and blood collection, venipuncture/infusion, and patient handling), intensive care unit (ICU) nurses, internal medicine residents, and dentists. Low-risk occupations included administrative front-desk nurses, outpatient internal medicine physicians, and technicians/physicians in ultrasonography, laboratory medicine, physical examination, and occupational health departments. Conclusion Adverse ergonomic factors of medical staff predominantly affect the neck, shoulders, upper back, elbows, forearms, hands, and the lower back during the work process. Rehabilitation therapists, ward housekeeping nurses, ICU nurses, operating-room instrument nurses, and surgeons are high-risk groups for WMSDs. Attention should be paid to the management and control of adverse ergonomic factors for medical staff to prevent the occurrence of WMSDs.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.