Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Gallbladder cancer with delayed diagnoses, as a malignant tumor diagnosed intraoperatively or postoperatively incidentally in benign gallbladder diseases, radical surgical treatment is its core treatment, and the necessity of re-operation, timing of surgery, choice of surgical procedure, definition of resection extent, and preoperative neoadjuvant therapy still remain controversial. Re-operation for gallbladder cancer with delayed diagnoses needs to balance tumor radicalization, postoperative risk, and survival benefit, and combining neoadjuvant therapy to facilitate radical treatment, and develop individualized protocols. The multidisciplinary team should integrate innovative technologies and multi-center prospective studies to promote the development of precise treatment strategies for gallbladder cancer with delayed diagnoses and optimize the survival of patients.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective: To investigate oral health related quality of life and associated factors of adolescents between 12 and 15 years old, and to provide countermeasures and suggestions for oral health promotion of adolescents. Methods: This cross-sectional study recruited 3 840 adolescents aged 12-15 through multi-stage stratified cluster sampling method. The oral clinical examination and oral health questionnaire were conducted. Descriptive analysis, non-parametric testing and logistic regression analysis were used to analyze the oral health-related quality of life and associated factors. Results: Oral problems showed moderate to severe impact on quality of life,especially on eating (27.1%). Ordinal Logistic regression analysis showed that low sugar intake frequency, few teeth with gingival bleeding, no history of dental pain in the past 12 months,no history of tooth injuries, and administrative region of residence (Nanhai, Shunde) were associated with higher oral health-related quality of life,(OR=0.6-0.8，P<0.05). Conclusion The oral health-related quality of life of adolescents in Foshan was slightly better than the average national level. It is recommended to accurately formulate and ensure the full implementation of oral public health measures based on the comprehensive analysis of the local area, and combine various efforts to strengthen education on reducing excessive intake of sugar, prevent gingival bleeding, relieve and treat toothache in time, pay attention to adolescents with histories of dental trauma, and update the concepts of receiving oral health examination for the adolescents themselves, parents and teachers, and help adolescents develop the habit of regular oral examinations.

Objective To investigate the clinicopathological features of undifferentiated pancreatic carcinoma with osteoclast-like giant cells (UOC).Methods Clinical and pathological data of 6 patients with UOC admitted in Navy Medical University affiliated Changhai Hospital from April 2011 to December 2017 were retrospectively analyzed.The expressions of Cam5.2,EMA,CD68,vimentin,lysozyme,E-cad,C-erbB-2,p53,MUC1,MLH1,MSH2,MSH6,Osteoponin and Ki-67 were detected by immunohistochemistry,and Kras gene mutations was measured by fluorescence quantitative PCR method.Results There were two main types of UOC cells.One type was oval or spindle mononuclear tumor cells,and the other was osteoclast-like giant cells scattered among mononuclear cells.Immunohistochemical staining results showed that the epithelial markers like CAM5.2,EMA,E-cad,MLH1,MSH2,MSH6 and Ki-67 of the components of ductal adenocarcinoma in 6 UOC patients were all positively expressed,and the mesenchymal markers like vimentin,CD68,lysozyme and tumor-related markers like Her-2,p53 and MUC1 were all negatively expressed.Vimentin,CD68,lysozyme and Osteoponin were positively expressed in osteoclast-like giant cells,but epithelial markers like Cam5.2,EMA,E-cad,MLH1,MSH2 and MSH6 were negatively expressed.6 UOC patients all had K-ras codon 12 mutation,and the mutant type was GGT ＞ TGT,GGT ＞ GTT,GGT ＞ GCT,and no codon 13 mutation was observed.Conclusions Osteoclast-like giant cells may be reactive multinucleated giant cells rather than neoplastic components.

Objective To investigate the effect of perioperative secondary thoracotomy on the risk of thrombosis in patients with thoracic trauma.Methods A retrospective case control study was conducted on the clinical data of 175 patients with thoracic trauma who underwent thoracotomy from January 2000 to December 2016.According to whether the patients underwent secondary thoracotomy,they were divided into secondary thoracotomy group (36 cases) and the control group (139 cases).In the secondary thoracotomy group,there were 25 males and 11 females,with age of (65.4 ± 5.5) years and thoracic abbreviated injury score (AIS) of (3.8 ±0.6) points.In the control group,there were 98 males and 41 females,with the age of (64.6 ±5.3)years and thoracic AIS of (3.7 ±0.8)points.The ICU stay,thoracic drainage,bed rest time,and the incidence of thrombosis in two groups were compared,and the levels of endothelin (ET-1),D-dimer aggregation and platelet were measured.Logistic regression analysis was used to analyze the impact of secondary thoracotomy on the risk of thrombosis.Results Compared with the control group,patients in the secondary thoracotomy group had longer ICU stay [(4.2 ± 1.4) d ∶(1.8± 1.0)d](P＜0.01),more thoracic drainage [(1 550 ±250)ml ∶ (635 ± 184)ml] (P＜0.01),and longer bed rest time [(5.4 ± 1.6) days ∶ (1.5 ± 0.9) days] (P ＜ 0.01).There were significant differences in levels of ET-1 and D-dimer aggregation between two groups (P＜0.01).There was significant difference in platelet count after 5 days (P ＜ 0.01).Twelve cases of deep venous thrombosis (33％) occurred in the secondary thoracotomy group,of which six cases died of thrombus related complications.Eight cases (5.7％) of deep venous thrombosis occurred in the control group,all of which recovered (P ＜ 0.05).In multivariate analysis,ET-1 (OR =7.46,95％ CI 4.53-11.06,P ＜ 0.05),D-dimer aggregation (OR =4.28,95％ CI 2.65-8.37,P ＜ 0.05),and platelet count (OR =1.13,95 ％ CI 0.56-1.98,P ＜ 0.05) were independent risk factors for thrombosis events.Conclusions Perioperative secondary thoracotomy increases the risk of thrombotic events.ICU hospitalization,thoracic drainage,and bed time are associated with thrombosis events.ET-1,D-dimer aggregation,and platelet count are independent risk factors for thrombosis events.

Objective To observe the therapeutic effect of central venous catheter drainage and intrapleural injection of urokinase on tuberculous pleurisy patients.Methods 60 hospitalized patients with tuberculous pleurisy were selected,and they were divided into two groupsby simple random grouping method.Both two groups received 3HRZE/6HR anti-tuberculosis treatment.30 patients in the observation group were treated with central venous catheter drainage and intrapleural injection of urokinase.30 patients in the control group were treated with conventional pleurocentesis.The duration of pleural effussion drainage,incidence of pleural thickening,hospitalization time and expense,and the adverse reaction rate were observed during treatment.Results In the observation group,the curative effect at 1 week was 46.7％,the duration of pleural effussion drainage was (20.5 ± 6.7)days,the incidence rate of pleural thickening was 26.7％,the hospitalization time was (9.4 ± 2.7) days,the hospitalization expense was (6 675.4 ± 1 818.4) RMB,the incidence rate of adverse reaction was 3.3％.In the control group,the curative effect at 1 week was 20.0％,the duration of pleural effussion drainage was (25.1 ± 7.7) days,the incidence rate of pleural thickening was 46.7％,the hospitalization time was (10.3 ± 2.8)days,the hospitalization expense was (7 508.9 ± 1 692.1) RMB,the incidence rate of adverse reaction was 20..0％.There were statistically significant differences between the two groups in the curative effect at 1 week (x2 =4.800,P =0.028),duration of pleural effussion drainage (t =2.484,P =0.016),incidence of pleural thickening (t =4.444,P =0.035) and incidence rate of adverse reaction (x2 =4.043,P =0.044).No statistically significant differences were observed between the two groups in hospitalization time(t =1.270,P =0.209) and expense (t =1.838,P =0.071).Conclusion In comparison to conventional pleurocentesis,the treatment of central venous catheter drainage and intrapleural injection of urokinase for tuberculous pleurisy is markedly efective,it is safe and Worthy of popularizing in clinical application.

To explore the relationship between telomere length changes and age, and to provide data and reference for further study of geriatric medical problems.
 Methods: The healthy people over 20 years old were chosen as subject from several hospitals by random sampling method, and their peripheral blood samples were collected. The relative length of telomere was detected by quantitative real-time PCR, and the relationship between age and telomere length was analyzed by statistical software.
 Results: A total of 1 022 samples were obtained. There were significant differences in the relative telomere length among different age groups (F=21.492, P<0.001). Telomere length and age showed negative correlation (r=-0.325, P<0.001), the regression equation was y=-0.008x+1.772 (x for age, y for the average telomere length, P<0.001).
 Conclusion: The telomere length for peripheral blood leukocytes in healthy people varies between different age groups, suggesting that telomere length gradually decreases with age.
Adult ; Age Factors ; Humans ; Leukocytes, Mononuclear ; Regression Analysis ; Telomere ; genetics ; Young Adult

Objective To study the correlation between serum lipids and thyroid function after withdrawn of thyroid hormone in the patients with differentiated thyroid cancer .Methods One hundred and thirty cases of differentiated thyroid carcinoma treated by operative therapy in our hospital form August 2014 to August 2015 were selected .Serum FT4 ,TSH ,FT3 ,triglyceride ,total cho-lesterol ,LDL-C ,HDL-C indexes were detected before discontinuation of levothyroxine sodium (L-T4) ,before operation and 3 weeks after drug withdrawn .Thus the correlation between blood lipid levels and thyroid function was analyzed .Results The HDL-C and the TSH level was positively related before operation (P<0 .05) ,other indexes had no obvious correlation with thyroid function (P>0 .05);the blood lipid levels after medication withdrawn had no obvious correlation with thyroid function (P>0 .05);the total cholesterol levels after medication discontinuation had negative correlation with FT 3 and FT4 levels(P<0 .05);HDL-C was nega-tively correlated with FT3 and FT4 levels(P<0 .05) ,and positively correlated with TSH level (P<0 .05);LDL-C was negatively correlated with FT4 (P<0 .05) .Conclusion When the application treatment of thyroid hormone is suspended ,with the TSH level increase ,the HDL-C level has somewhat elevation ;total cholesterol ,HDL-C and LDL-C levels are negatively correlated with FT 3 and FT4 ,after discontinuation of medication withdrawn ,the blood lipids metabolism abnormality is closely related with thyroid function decline .