OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective:To investigate the predictive value of 18F-FDG PET related metabolic parameters on microsatellite instability-high (MSI-H) and human epidermal growth factor receptor-2(HER2) expression in colorectal cancer (CRC). Methods:The 18F-FDG PET imaging, clinical and pathological data of 101 CRC patients (58 males, 43 females; age 68.0(58.0, 75.0) years) admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to March 2024 were retrospectively collected, including 17 cases in MSI-H group, 84 cases in microsatellite stability/microsatellite instability-low (MSS/MSI-L) group, 23 cases in HER2 expression group, 34 cases in non-HER2 expression group, and 44 patients without HER2 detection. Univariate analyses (independent-sample t test, Mann-Whitney U test, χ2 test) and multivariate logistic regression analysis were used to screen out independent risk factors, and ROC curve was used to evaluate the predictive efficacy. Bootstrap method was used to verify the model internally. Results:There were significant differences in metabolic tumor volume (MTV) 80% between MSI-H group and MSS/MSI-L group (2.1(1.6, 4.0) vs 1.4(1.0, 2.7) cm 3;Z=-2.10, P=0.036), and total lesion glycolysis (TLG) 80% and carcinoembryonic antigen (CEA) were significantly different between those 2 groups ( Z=-2.27, χ2=6.40, both P<0.05). There were significant differences in TLG 80% (29.0(16.1, 41.0) vs 14.3(9.4, 22.9) g; Z=-2.80, P=0.005) between HER2 expression group and non-HER2 expression group, and significant differences were also found in MTV 80%, heterogeneity index (HI) and CV ( Z=-2.24, t values: -2.26, 2.54, all P<0.05). The independent risk factors for MSI-H were MTV 80% (odds ratio ( OR)=1.326, 95% CI: 1.015-1.733, P=0.038) and CEA ( OR=0.200, 95% CI: 0.056-0.706, P=0.012), with the AUC for the combined model of 0.730 (95% CI: 0.605-0.856), and the concordance index (C-index) of 0.716. The independent risk factors for HER2 expression were TLG 80% ( OR=1.037, 95% CI: 1.001-1.073, P=0.041) and CV ( OR=1.467, 95% CI: 1.073-2.005, P=0.016), with the AUC for the combined model of 0.775 (95% CI: 0.645-0.875), and the C-index of 0.757. Conclusions:18F-FDG PET can be used as a noninvasive tool to evaluate CRC microsatellite status and HER2 gene amplification. MTV 80% and CEA are independent risk factors for MSI-H; TLG 80% and CV are independent risk factors for HER2 expression.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Accurate identification of the glomerular ultrastructure is critical for the diagnosis of chronic kidney diseases,but the high cost of acquiring high-quality annotated data limits the application of fully-supervised learning.Therefore,a multi-class semi-supervised semantic segmentation framework based on segment anything model(MC4S-SAM)is proposed.After improving the mask decoder of segment anything model to enable multi-class semantic segmentation without requiring prompt information,the improved model is used to generate and refine pseudo-labels through a self-training strategy,and multi-level consistency regularization constraints are incorporated to enhance the model's performance.Experimental results show that,in the task of segmenting the glomerular mesangial ultrastructure,MC4S-SAM outperformes the fully-supervised model by 11.72%in mean intersection over union(mIoU)and 11.45%in mean Dice similarity coefficient(mDSC)when the labeled data accountes for 1/16 of the total.When the labeled data proportion is 1/4,the mIoU and mDSC reach 68.91%and 78.73%,respectively,demonstrating its significant potential for aiding the diagnosis of chronic kidney diseases.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To explore the changes in plasma lipoprotein associated phospholipase A2(Lp-PLA2)and silencing information regulatory protein 1(SIRT1)in patients with sepsis complicated with acute kidney injury(AKI)and their relationship with short-term prognosis.Methods:243 sepsis patients who received treatment in our hospital from May 2022 to May 2024 were prospective selected,including 80 sepsis patients with AKI(AKI group)and 163 sepsis patients without AKI(non AKI group),the plasma Lp-PLA2 and SIRT1 levels between the two groups were compared.They were divided into good prognosis group and poor prognosis group according to 28 d prognosis after admission in AKI group.The influencing factors of short-term prognosis in sepsis patients complicated with AKI were analyzed by multiple logistic regression model.The short-term prognostic value of plasma Lp-PLA2 and SIRT1 alone and in combination for sepsis complicated with AKI patients was analyzed using receiver operating characteristic(ROC)curve.Results:Compared with non AKI group,AKI group had higher Lp-PLA2 and lower SIRT1(P＜0.05).39 deaths within 28 d after admission in AKI group(poor prognosis group),41 cases survived(good prognosis group),with poor prognosis rate of 48.75％(39/80).Sequential organ failure assessment(SOFA)score,acutephysiology and chronic health evaluationⅡ(APACHEⅡ)score,creatinine(Scr),lactate dehydrogenase albumin ratio(LAR)in poor prognosis group were higher than those in good prognosis group,while procalcitonin(PCT)was lower than that in good prognosis group(P＜0.05).Compared with the good prognosis group,poor prognosis group had higher Lp-PLA2 and lower SIRT1 at admission(P＜0.05).Elevated SOFA score,elevated Scr,elevated APACHEⅡ score,and elevated plasma Lp-PLA2 were risk factors for poor prognosis in sepsis patients complicated with AKI(P＜0.05),while elevated plasma SIRT1 was a protective factor(P＜0.05).ROC curve analysis results showed that,the combined detection of plasma Lp-PLA2 and SIRT1 predicted a poor prognosis for sepsis patients with AKI with an area under the curve(AUC)of 0.935,which was better than the prediction of 0.813 and 0.858 for plasma Lp-PLA2 and SIRT1 alone.Conclusion:Sepsis complicated with AKI patients have elevated plasma Lp-PLA2 and decreased SIRT1,combined detection of the two can assist in predicting the risk of poor prognosis.

OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9％.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P＜0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

We reported the clinical,imaging,and treatment process of a patient with severe cranial penetrating injury caused by a nail from a nail gun that accidentally shot into the eye and penetrated into the skull while working.The patient was admitted to the Qingpu Branch of Zhongshan Hospital,Fudan University after being injured by the nail gun.The patient was admitted to the hospital 1 hour after injury with coma.After admission,the foreign body was completely removed and part of the hematoma was cleared through emergency surgery.After surgery,there were high-risk complications such as cerebral edema peak,intracranial hypertension,intracranial infection,cerebrospinal fluid leakage,and intracranial pseudoaneurysm.The patient eventually regained consciousness and was transferred to rehabilitation treatment.