Objective:To investigate the prognostic value of tumor mutation burden(TMB)in pancreatic neuroendocrine tumours(PanNETs).Methods:Data of 96 PanNETs patients was in-cluded in the study and cut-off value of TMB was determined according to the time dependent re-ceiver operator characteristic(ROC)curve and area under the curve(AUC).Logistic regression analysis was used to determine the clinical and pathological features associated with TMB.Cox re-gression analysis was used to detect the correlation between TMB and the overall survival time(OS)of patients.Kaplan-Meier method was used to construct the survival curve.Results:Ac-cording to the time dependent ROC curve and AUC,the optimal truncation value of TMB was deter-mined to be 0.6 mut/Mb.Logistic regression analysis indicated that high TMB was independently correlated with age[OR=1.126(1.057-11.199),P＜0.001]and extrapancreatic spread[OR=15.931(2.228-113.892),P=0.006].Kaplan-Meier curve showed that patients with high TMB had a poor OS[HR=5.042(1.41917.917),P=0.012].Multivariate Cox regression analysis indicated that TMB was an independent prognostic factor of PanNETs[HR=7.578(1.409-40.744),P=0.018].Conclusion:TMB is independently correlated with age and extrapancreatic spread,and is an independent prog-nostic factor for PanNETs patients and PanNETs patients with high TMB have a poorer prognosis.

Objective To investigate the value of optical coherence tomography(OCT)in predicting the risk of major adverse cardiovascular events(MACE)in patients of acute coronary syndrome(ACS).Methods Four hundred and forth-eight ACS patients admitted to the First Affiliated Hospital of Xinjiang Medical University who underwent percutaneous coronary intervention(PCI)and OCT from February 2015 to February 2022 were selected as the study subjects.We found 749 non-culprit coronary lesions.And follow up the patients,median follow-up was 5 years[interquartile interval(IQR):3-7 years].Kaplan-meier was used to estimate the cumulative incidence of MACE,multivariate Cox regression was used to analyze the risk of MACE with OCT parameters non-culprit coronary lesions,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of OCT parameters for MACE in non-culprit coronary lesions.Results A total of 749 non-culprit coronary lesions were detected,and 41 MACE cases were caused by non-culprit coronary lesions imaged by OCT.Compared with plaques without thin-cap fibroatheroma(TCFA)and minimal lumen area(MLA)＜3.5 mm2,the incidence of MACE was significantly associated with vulnerable plaques with TCFA and MLA＜3.5 mm2(33％vs.3％,HR 13.62,95％CI 6.71-27.65,P＜0.001).Multivariate Cox regression analysis showed that larger maximum lipid arc(HR 1.02,95％CI 1.01-1.03,P＜0.001),smaller maximum lipid cap thickness(HR 0.97,95％CI 0.96-0.99,P＜0.001)and MLA(HR 0.31,95％CI 0.18-0.55,P＜0.001)were independent risk factors for MACE.The area under ROC curve(AUC)of the thinnest fiber cap thickness for predicting MACE occurrence was 0.858(95％CI 0.802-0.913),and the optimal cutoff value was 66.5 μm.The AUC of maximum lipid arc for predicting MACE occurrence was 0.853(95％CI 0.786-0.920),and the optimal cut-off value was 180.35°.The AUC of MLA for predicting MACE was 0.821(95％CI 0.766-0.876),and the optimal cutoff was 3.575 mm2.Conclusions The non-culprit coronary lesions with TCFA and MLA＜3.5 mm2 were significantly associated with an increased risk of subsequent MACE development at the lesion level,and OCT imaging helps early identification of the risk of MACE development in non-culprit coronary lesions in patients of ACS.

ObjectiveTo further study the pathogenic role of different types of Chlamydia trachomatis （CT） proteins in tubal factor infertility， evaluate the clinical detection value of Chlamydia trachomatis protein antibody in predicting tubal factor infertility. MethodsA total of 58 cases of tubal factor infertility （TFI）， 41 cases of fertile controls （FC） and 18 cases of infertile controls （IFC） were included. For serum detection， first， CT-IgG ELISA kit was used to detect the expression of CT-IgG in serum of three groups of people； then， 6 kinds of Chlamydia trachomatis proteins were expressed and purified in the early stage to establish the antibody test for these proteins， and ELISA detection method was used to detect the expression of their antibodies in the serum of TFI group， FC group and IFC group， respectively； and finally， the antibody OD value of the 6 kinds of Chlamydia trachomatis proteins in the three groups of subjects were statistically described， and CT-IgG was used as the reference standard to draw the receiver operating characteristic curve （ROC curve） of each CT antibody. The Youden Index determines the cutoff value for each antibody. Taking TFI as the reference class， two disordered multiple classification logistic regression models were established with the FC and IFC groups， respectively； and the reference class was used to explore the value of various antibodies and age in predicting TFI， FC and IFC of Chlamydia trachomatis. The back-off method was used to screen the variables. ResultsThe OD value of CT376 antibody in the TFI group was higher than that in the FC group （0.86 vs. 0.60， P=0.026）. The CT376 antibody OD value in the TFI group was higher than that in the IFC group （0.86 vs. 0.64， P=0.026）. The CT443 antibody OD value in the IFC group was higher than that in the TFI group （0.59 vs. 0.34， P=0.036） and higher than that in the FC group （0.59 vs. 0.30， P=0.02）. The multiple classification logistic regression analysis established between TFI and FC showed that CT-IgG ［P<0.001， OR=0.084， 95%CI （0.025， 0.284）］， CT376 antibody ［P=0.068， OR=0.359， 95%CI （0.120， 1.078）］. CT-IgG is an independent risk factor for tubal infertility， and CT376 antibody cannot be an independent risk factor for tubal infertility. The multiple classification logistic regression analysis established between TFI and IFC showed that among infertile patients， CT-IgG ［P<0.05， OR=0.194， 95%CI （0.046， 0.817）］， CT376 antibody ［P<0.05， OR=0.176， 95%CI （0.038， 0.818）］ and CT381 antibody ［P<0.05， OR=0.112， 95%CI （ 0.016， 0.796）］ were independent risk factors for tubal infertility. ConclusionThe expression of CT376 antibody in tubal infertility patients is higher than that in fertile and infertile controls， suggesting that CT-induced tubal factor infertility may be related to CT376. CT-IgG， and CT376 antibodies are meaningful in predicting CT-induced tubal factor infertility.

ObjectiveTo analyze the criminal behavior characteristics of alcohol-related crime offenders and explore the relationship between criminal behavior characteristics and criminal responsibility capacity. MethodsBasic information， alcohol use information， psychiatric symptoms before and after the crime， criminological behavioral characteristics and conclusion of judicial evaluation were collected. ResultsThe drinking history of the chronic alcoholism group 25.0 （13.3~30.0） years was significantly longer than that of the acute alcoholism group 1.2 （0~14.3） years. In the chronic alcoholism group， 85.0% drank alcohol at least once a day， 52.5% had morning or bedtime drinking habits， and 92.5% drank mainly alone. Violent crimes accounted for 57.6%. Delirium existed in 52.5% of the chronic alcoholics' mental state at the time of the crime， and 84.6% of the acute alcoholics' mental state was hazy. In the chronic alcoholism group， 42.5% committed the crime with pathological motive， and in the acute alcoholism group， 69.2% committed the crime with realistic motive. Acute alcoholism group 96.2% were assessed as complete criminal responsibility capacity， and chronic alcoholism group 50.0% were assessed as complete criminal responsibility capacity. ConclusionCompared with acute alcoholism offenders， chronic alcoholics had a longer drinking duration， more frequency drinking， and obvious morning drinking or bedtime drinking habits. The nature of alcoholism crime cases was mostly violent. Compared with the chronic alcoholism group， the acute alcoholism group had highly selective motives for committing crimes and were mostly rated as complete criminally responsibility.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

In the practice of forensic pathology, fat embolism is one of the common causes of death, which can be divided into two categories: traumatic and non-traumatic. Non-traumatic fat embolism refers to the blockage of small blood vessels by fat droplets in the circulatory blood flow caused by non-traumatic factors such as underlying diseases, stress, poisoning and lipid metabolism disorders. At present, it is believed that the production of non-traumatic fat embolism is related to the disturbance of lipid metabolism, C-reactive protein-related cascade reaction, the agglutination of chylomicron and very low-density lipoprotein. The forensic identification of the cause of death of non-traumatic fat embolism is mainly based on the case, systematic autopsy, HE staining and fat staining, but it is often missed or misdiagnosed by forensic examiners because of its unknown risk factors, hidden onset, the difficulty of HE staining observation and irregular implementation of fat staining. In view of the lack of attention to non-traumatic fat embolism in forensic identification, this paper reviews the concepts, pathophysiological mechanism, research progress, existing problems and countermeasures of non-traumatic fat embolism, providing reference for forensic scholars.
Autopsy ; Embolism, Fat/pathology* ; Forensic Medicine ; Forensic Pathology ; Humans ; Pulmonary Embolism/pathology*

Objective: To evaluate the application effect of smart classroom teaching mode in undergraduate teaching of endodontics. Methods: Through micro-lecture and massive open online course which were closely integrated with clinical practice and frontier advances, we build a new smart classroom teaching mode of endodontics relying on information technology such as the medical education cloud APP platform. The mode was applied to the undergraduate teaching of grade 2017 (110 students) and grade 2018 (107 students) in 2020 and 2021 respectively (experimental group). The theoretical examination was conducted for the grade 2016 (control group, 111 students applied traditional teaching methods) in 2019, and for two experimental grades in 2020 and 2021 respectively. A questionnaire survey was conducted for the 2018 undergraduates to investigate the experience of the smart classroom teaching mode, and the application effect of the smart classroom teaching mode was evaluated by comparing the offline theoretical test scores of grades 2016, 2017 and 2018. Results: The results of the questionnaire showed that students in grade 2018 recognized the overall form of smart classroom teaching mode, and 75.2% (79/105) of the students satisfied with the teaching process, considering that it could enhance learning interest and enthusiasm, improve self-learning ability, facilitate the understanding and memory of knowledge points, as well as increase the extension and expansion of professional knowledge. Thirty-seven point one percent (39/105) of the students thought that smart classroom teaching mode was not conducive to the interaction between teachers and students and couldn't improve learning efficiency. Comparing the final theoretical examination scores of students in three years, it was found that the average scores of 2021 (78.79±9.88) and 2020 (76.45±8.33) were significantly higher than that of 2019 (67.67±10.58) (t=6.77, P<0.001; t=8.51, P<0.001). The average score in 2021 was higher than that in 2020, although the difference was not significant (t=1.79, P=0.223). Conclusions: The application of smart classroom mode improved the teaching effect of endodontics, which is worthy of further promotion to provide a positive reference in improving the educating effects of oral medicine.
Humans ; Learning ; Endodontics ; Students ; Dental Care ; Surveys and Questionnaires