Thyroid nodules are a common endocrine disorder, and their early detection and accurate diagnosis are crucial for the prevention of thyroid cancer. However, the highly heterogeneous morphology and boundaries of thyroid nodules pose significant challenges to their precise identification and classification. Traditional diagnostic approaches rely heavily on physicians' experience, which increases the risk of misdiagnosis and missed diagnoses. With the rapid advancement of computer-aided diagnosis (CAD) technologies, applying deep learning algorithms to the analysis of thyroid nodule ultrasound images has shown great potential. This paper reviews the latest research progress on deep learning-based CAD methods for thyroid nodules, with a focus on their applications in image preprocessing, segmentation and classification. The advantages and limitations of current techniques are analyzed, and potential future directions are discussed. This review aims to highlight the potential of deep learning in thyroid nodule diagnosis and to provide a foundation for selecting feasible pathways for future clinical applications.
Humans ; Thyroid Nodule/diagnostic imaging* ; Deep Learning ; Ultrasonography/methods* ; Diagnosis, Computer-Assisted/methods* ; Algorithms ; Thyroid Neoplasms/diagnostic imaging* ; Image Processing, Computer-Assisted/methods*

Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology* ; Humans ; Cerebral Hemorrhage/pathology* ; Lipid Peroxidation ; Fatty Acids, Unsaturated/metabolism* ; Reactive Oxygen Species/metabolism* ; Iron/metabolism* ; Animals ; Mitochondria/metabolism*

Objective : To investigate the possible mechanism of metformin (Met) -induced cardiomyocyte autoph- agy in protecting myocardial injury in septic mice． Methods : The model of myocardial injury in septic mice was es- tablished by cecal ligation and puncture ( CLP) ．Sixty Kunming mice were randomly divided into sham operation group (Sham group) ，model group ( CLP group) ，model + dimethyl sulfoxide ( DMSO) group ( CLP + DMSO group) ，model + metformin (Met) group (Met group) ，model + Met + 3-methyladenine (3-MA) group (Met + 3- MA group) ，model + Met + compound C ( CC) group (Met + CC group) ，with 10 mice in each group．The Met， Met + 3-MA and Met + CC groups were intraperitoneally injected with Met (200 mg / kg) once a day for 2 weeks be- fore modeling．The Met + 3-MA group was intraperitoneally injected with 3-MA ( 10 mg / kg) 1 h before surgery. The Met + CC group was intraperitoneally injected with CC (20 mg / kg) 30 min before surgery．The model was es- tablished 24 h after the last injection of Met．The heart and blood of all mice were collected 24 h after surgery．The Western blot technique was employed to assess the relative expression levels of microtubule-associated protein 1 light chain 3 (LC3) isoforms，namely LC3 I and LC3 II，autophagy effector protein 1 (Beclin-1) ，ubiquitin-bind- ing protein 62 (p62) ，B-cell lymphoma / leukemia-2 (Bcl-2) ，Bcl-2-associated X protein (Bax) ，adenosine mono- phosphate (AMP) kinase (AMPK) and phosphorylated AMPK (p-AMPK) ．Myocardial pathological changes were observed by hematoxylin-eosin (HE) staining．The changes of myocardial mitochondria and autophagosomes were observed by electron microscopy．Hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardium． Electron microscopy was used to observe the changes of myocardial mitochondria and autophago- somes. Results : Compared with Sham group，the relative protein expression of Beclin-1，p62，p-AMPK / AMPK and LC3 II / LC3 I in CLP and CLP + DMSO groups had no statistical significance，but Bax increased and Bcl-2 de- creased in CLP group (P＜0. 01) ．Compared with CLP group，the relative expression of Beclin-1 protein and LC3 II / LC3 I in Met group increased and p62 decreased (P＜0. 01) ，Bax decreased and Bcl-2 increased (P＜0. 01) . Compared with Met group，the relative protein expression of Beclin-1 and LC3 II / LC3 I in Met + 3-MA group de- creased and p62 increased (P＜0. 05) ，Bax increased and Bcl-2 decreased (P＜0. 05) ．Besides，the relative pro- tein expression of p-AMPK / AMPK in Met + CC group decreased (P＜0. 05) ．HE staining showed that there was no disorder in myocardial fibers in Sham group，and a large number of inflammatory cells infiltrated the myocardial fibers of CLP group in a clear disorder．The Met group showed vacuolar changes in the myocardium，while the Met + 3-MA group showed disordered arrangement of myocardial fibers and a small amount of inflammatory cell infiltra- tion．Under electron microscopy，the morphology of myocardial mitochondria in the Sham group was normal，while in the CLP group，the arrangement of mitochondrial cristae was disordered with vacuolar changes，and occasional autophagosomes were observed．Mitochondria in Met group showed slight swelling and a large number of autophago- somes．The mitochondria in the Met + 3-MA group showed significant swelling with a small amount of autophago- somes． Conclusion The protective effect of metformin on myocardial injury in septic mice can reduce cardiomyo- cyte apoptosis and improve mitochondrial damage by activating AMPK signaling pathway to induce autophagy.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective To explore the effects of TRAF6 inhibition on autophagy,myocardial inflammation and cardiac function in septic mice.Methods Twenty-four male Kunming mice were randomly divided into 4 groups:sham,sham + C25-140(sham+C),cecal ligation and puncture(CLP),and cecal ligation and puncture+C25-140(CLP+C)group.Sham+C group and CLP+C group were intraperitoneally injected with C25-140 after operation.LVEF and LVFS were evaluated by ultrasound 24 hours after operation.Serum TNF-α and IL1-β were measured by ELISA.HE staining was used to evaluate myocardial inflammatory response.Autophagosomes and mitochondrial microstructure of cardiomyocytes were observed by transmission electron microscopy.TRAF6 mRNA in myocardial tissue was detected by qPCR.The expression of TRAF6,P62,Beclin-1 and LC3B protein was detected by W-B.The effect of C25-140 on myocardial injury in the septic mice was observed by inhibiting autophagy with 3-MA.Results Compared with the sham group,the levels of TRAF6 mRNA and TRAF6 in the myocardial tissue in the CLP group were significantly increased(P<0.05)and the serum TNF-α and IL1-β concentrations were signifi-cantly increased(P<0.05).Meanwhile,the myocardial tissue HE staining showed inflammatory cell infiltration and the LVEF and LVFS levels were significantly decreased in the CLP group(P<0.05).Compared with CLP group,the CLP+C group showed that the expression of TRAF6 mRNA and TRAF6 protein decreased(P<0.05),serum TNF-α and IL1-β decreased(P<0.05),myocardial histopathological myocardial inflammatory cell infiltration decreased,the LVEF and LVFS levels increased(P<0.05).Electron microscopy showed that the mitochondrial swelling decreased,autophagosomes increased,expression of Beclin-1 and LC3Ⅱ/Ⅰ increased,and P62 expression decreased(P<0.05).As compared with CLP+C group,the CLP+C+3-MA group showed that obvious inflamma-tory cell infiltration in the myocardial pathology and the LVEF and LVFS levels decreased after 3-MA inhibited autophagy(P<0.05).Conclusion Inhibition of TRAF6 can not only ameliorate myocardial inflammatory injury and cardiac dysfunction in septic mice,but promote the involvment of cardiomyocyte autophagy in provention from sepsis-induced myocardial injury.

BACKGROUND:Sepsis complicated by myocardial injury is characterized by a high mortality.Metformin can prevent sepsis-induced myocardial dysfunction by exerting anti-inflammatory effects,improving oxidative stress,and reducing apoptosis.However,it is unclear whether metformin-induced autophagy plays an important role in the protective effect against sepsis-induced myocardial injury. OBJECTIVE:To explore the effect of metformin pretreatment on myocardial injury in septic mice. METHODS:A total of 40 male Kunming mice were randomly divided into sham operation group,model group,metformin group,and metformin+ 3-methyladenine group,with 10 mice in each group.The latter two groups were intraperitoneally injected with metformin for 14 days at a fixed time every day,and the metformin+3-methyladenine group was intraperitoneally injected with 3-methyladenine 1 hour before modeling.Twenty-four hours after the last injection of metformin,cecal ligation and perforation were used to construct a model of myocardial injury in septic mice.The sham operation group was not ligated and perforated.All mice were sacrificed 24 hours after surgery,and blood and myocardial specimens were collected.The levels of inflammatory factors and myocardial injury markers in serum were detected by ELISA.The mRNA expression of autophagy markers LC3B and p62 in myocardial tissue was detected by RT-qPCR.The protein expression of LC3B,Beclin-1,p62,p-AMPK,and AMPK in myocardial tissue was detected by western blot.The pathological changes in myocardial tissue were detected by hematoxylin-eosin staining. RESULTS AND CONCLUSION:Autophagy was inhibited in septic mice with myocardial injury.Compared with the sham operation group,the levels of serum tumor necrosis factor-α,interleukin-1β,interleukin-6,creatine kinase isoenzyme,and troponin T were increased in the model group(P<0.05),but there was no significant difference in p62,LC3Ⅱ/LC3Ⅰ,and p-AMPK/AMPK between the two groups(P>0.05).Compared with the model group,the levels of tumor necrosis factor-α,interleukin-6,creatine kinase isoenzyme,troponin T,and p62 were decreased in the metformin group(P<0.05),while LC3Ⅱ/LC3Ⅰ,p-AMPK/AMPK and Beclin-1 level were increased(P<0.05).Compared with the metformin group,the levels of tumor necrosis factor-α,interleukin-6,creatine kinase isoenzyme,troponin T,and p62 were increased in the metformin+3-methyladenine group(P<0.05),while LC3Ⅱ/LC3Ⅰ and Beclin-1 level were decreased(P<0.05).Myocardial hematoxylin-eosin staining indicated that myocardial fibers arranged normally in the sham operation group,but disorderedly in the model group,with interstitial edema and a large number of infiltrated inflammatory cells.A small amount of vacuolar changes were observed in the metformin group.The arrangement of myocardial fibers in the metformin+3-methyladenine group was slightly disordered,with more vacuolar changes.To conclude,metformin pretreatment may reduce myocardial injury in septic mice by activating the AMPK signaling pathway and inducing autophagy.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.