Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

Objective:To compare the dosimetric parameters under different incremental modes between intensity-modulated radiation therapy(IMRT)and volume rotation intensity-modulated therapy(VMAT)for the target area of large volume brain metastases(BMs),and to explore the better way of treating BMs based on hypofractionated stereotactic radiotherapy(HSRT)of linear accelerator.Methods:A total of 30 BMs patients who underwent IMRT at The 971th Hospital of Navy of the CPLA from 2020 to 2023 were selected.In the treatment planning system(TPS),three types of IMRT plans and VMAT plans were designed,which included uniformity plan(Planuniformity)of target area dose,uniform increased plan(Planuniform increased-dose)and incremental plan(Planincremental)within target area.In the inside of the target area,the target area of high dose(GTVh)was set,and Planuniform increased-dose and Planincremental were designed to aim at GTVh.The differences of the doses of three types of treatment plans included Planuniformity,Planuniform increased-dose and Planincremental,which were respectively designed by using IMRT and VMAT,were analyzed.The mean dose(Dmean)of the target area,the 50%and 2%exposed doses(D50%and D2%)of the target area were observed and compared.The conformity index(CI),homogeneity index(HI),gradient index(GI),and the volume percentage(V10 Gy-V40 Gy)that normal brain tissue received 10 Gy-40 Gy also were observed and compared.Results:Compared with Planuniformity of IMRT,the Dmean of GTV of Planuniform increased-dose and Planincremental of IMRT increased by 10.13%and 17.9%,with statistically significant differences(t=13.680,12.771,P＜0.05).D50%increased by 8.9%and 10.8%,with statistically significant differences(t=15.190,9.929,P＜0.05).D2%increased by 15.2%and 46.4%,with statistically significant differences(t=52.320,8.746,P＜0.05).There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of IMRT(P＞0.05).Compared with Planuniformity of VMAT,the Dmean of GTV of Planuniform increased-dose and Planincremental of VMAT increased by 10.53%and 21.23%,with statistically significant differences(t=18.641,15.461,P＜0.05),and D50%increased by 9.1%and 13.4%,with statistically significant differences(t=11.382,10.952,P＜0.05),and D2%increased by 16.4%and 48.8%,with statistically significant differences(t=56.471,8.685,P＜0.05),respectively.There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of VMAT(P＞0.05).The normal brain tissue V20 Gy,V30 Gy and V40 Gy of Planuniform increased-dose and Planincremental of IMRT were respectively less than those of VMAT,and the differences of them between IMRT and VMAT were significant(tPlan uniform increased-dose=2.112,2.215,2.444,tPlan incremental=2.323,2.939,3.145,P＜0.05).There were no statistically significant difference in D2%,Dmean,and D50%between IMRT and VMAT(P＞0.05).Conclusion:On the premise of ensuring the safety of normal brain tissue at the edge of the target area,the synchronously increasing of the central dose of the target area will not significantly increase the dose for normal brain tissue.Both IMRT and VMAT can meet the requirements of increment in the inside of the target area,and VMAT has slightly better increment and higher efficiency within target area.The incremental of VMAT target area is slightly better,which also has better efficiency,while the enhancement effect of the dose of target area of Planincremental is better than that of the Planuniform increased-dose.The Plan incremental of VMAT is more suitable for HSRT treatment for BMs.

Objective To analyze the psychological status and related factors in elderly patients of different genders after percutaneous coronary intervention(PCI)for coronary heart disease(CHD).Methods A total of 303 eligible patients treated in our department from January 2021 to December 2024 were enrolled,and then divided into a male group(154 cases)and a female group(149 cases).Based on the 7-item Generalized Anxiety Disorder Scale,they were assigned into a female anxiety group(97 cases),a female non-anxiety group(52 cases),a male anxiety group(82 cases)and a male non-anxiety group(72 cases).According to the 9-item Patient Health Questionnaire,they were alsocategorized into a female depression group(92 cases),a female non-depression group(57 cases),a male depression group(75 cases)and a male non-depression group(79 cases).The basic clinical data and results of psychological assessment were recorded in each group.Statistical analysis was performed on the indicators,including total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C).Results The female patients had significantly higher scores of physical symptoms,anxiety and depression,and larger proportions of anxiety and depression than the male group(P＜0.05,P＜0.01).In the female patients,advance age,higher TC,TG and LDL-C levels and somatic symptom score were observed in those with anxiety than those without,and in those with depression group than those without(P＜0.05,P＜0.01).The male anxiety group exhibited older age,more lesion vessels,larger ratio of ≥2 stents,and higher physical symptom score when compared with the male non-anxiety group,and so were in the male depression group than the male non-depression group(P＜0.05,P＜0.01).Binary logistic regression analysis showed that age,TC,LDL-C,and somatic symptom score were risk factors for anxiety,and age,TC,HDL-C,LDL-C,and somatic symptom score were risk factors for depression in elderly female CHD patients(P＜0.05,P＜0.01).For the elderly male CHD patients,age,stents ≥2,and somatic symptom score were risk factors for anxiety(OR=1.068,95％CI:1.002-1.138,P＜0.05;OR=6.458,95％CI:2.807-14.858,P＜0.01;OR=1.148,95％CI:1.045-1.262,P＜0.01),and age,stents ≥2,and more lesion vessels were risk factors for depression(P＜0.01).Conclusion The female CHD patients undergoing PCI have higher anxiety and depression scores than the male patients.There are certain differences in the influencing factors for anxiety and depression between genders.Effective control of these risk factors may help improve the prognosis of CHD patients after PCI.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

OBJECTIVE To investigate the current status and characteristics of occupational exposure in a stomato-logical hospital and explore the influencing factors for occupational exposure among dentists so as to propose pre-ventive and control measures for occupational exposure in the stomatological hospital.METHODS A retrospective study was carried out to analyze 180 incidents of occupational exposures in Qingdao Stomatological Hospital Affili-ated to Qingdao University from 2020 to 2024,involving the departments,names,genders,age,average annual workload,average annual outpatient days,exposure links,instruments leading to exposures,exposure sources,occupational type and professional titles.The incidence of occupational exposure was compared among the subjects with different occupations,professional titles and department affiliations.Logistic regression analysis was per-formed for the influencing factors for the occupational exposures among the dentists.RESULTS The incidence of occupational exposures was 7.52％(180/2395)within the 5 years,and the sharp instrument injury(99.40％)was the predominant exposure approach.The department of oral and maxillofacial surgery,department of restorative dentisty and department of prosthodontics were the departments at high risk of occupational exposures.There was significant difference in the incidence of occupational exposures among the staff and the doctors with different pro-fessional titles(P＜0.05).The subjects for whom the exposure source was positive or failed to be tracked accoun-ted for 56.11％.The professional title(OR=0.328)was a protective factor for the occupational exposure among the doctors,and the high-risk department(OR=4.912)was a risk factor for the occupational exposure(P＜0.05).CONCLUSIONS The occupational exposures to the stomatology department staff are characterized by high prevalence,monotonous type,concentrated distribution of populations and uncontrollable occupational exposures.It is necessary to complete the preoperative screening of infectious diseases,strengthen the awareness of prevention,standardize the technical procedures and boost the innovation of auxiliary instruments so as to re-duce the incidence of occupational exposures.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To investigate the application value of dermoscopy and reflectance confocal microscopy (RCM) in identifying field cancerization in actinic keratosis (AK) in the elderly.Methods:A retrospective analysis was conducted on clinical, dermoscopic, and RCM features of elderly (> 60 years old) patients, who were confirmedly diagnosed with AK and had complete medical records at Shanghai Skin Disease Hospital from January 2022 to December 2023.Results:A total of 132 elderly patients with AK were included. Dermoscopy showed brownish-gray pseudonetwork pigment patterns, follicular horn plugs, irregular branched vessels, and rosette signs in AK lesions. Histopathological examination in 51 patients revealed that 47 (92.16%) were confirmedly diagnosed with AK. Field cancerization was observed in 106 patients (80.3%), among whom 66 (62.26%) had irregular branched vessels, 88 (83.02%) predominantly exhibited brownish-gray pseudonetwork pigment patterns, and 83 (78.30%) showed scattered brown pigment networks/fingerprint-like patterns. Post-treatment follow-up of 63 patients showed varying degrees of changes in vascular and pigment structures by dermoscopy, with significant reductions in follicular horn plugs and superficial yellow-white scales or keratin masses. RCM examinations in 41 AK patients all showed disordered arrangements of keratinocytes presenting as atypical honeycomb patterns, with atypical cells in the AK lesions; in the field cancerization areas of 20 patients, RCM revealed keratinocytes disorderedly arranged in an irregular honeycomb pattern, with some keratinocytes exhibiting mild atypia. Thirty-four AK patients underwent dynamic RCM monitoring before and after 1, 3 and 6 months of ALA-PDT treatment, which showed gradual regularization of arrangements of keratinocytes and reduction of atypical cells, as well as reappearance of atypical keratinocytes upon recurrence.Conclusions:The incidence of field cancerization was relatively high in elderly AK patients. Dermoscopy and RCM are helpful for the early identification of AK and field cancerization, especially in patients with multiple lesions and with difficulties in multi-site biopsy.