OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPLs). Chemokine-like factor-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system and may closely related to APS. This review aimed to systematically summarize the possible effects of CMTM on APS. Publications were collected from PubMed and Web of Science databases up to August 2020. CKLF, CKLFSF, CMTM, antiphospholipid syndrome, immune cells, and immune molecules were used as search criteria. Immune cells, including neutrophil, dendritic cells (DCs), T-cells, B-cells, and inflammatory cytokines, play an important role in the development of APS. Chemokine-like factor 1 (CKLF1) has a chemotactic effect on many cells and can affect the expression of inflammatory cytokines and adhesion molecules through the nuclear factor- kB (NF- kB) pathway or mitogen-activated protein kinase (MARK) pathway. CKLF1 can participate in the maturation of DCs, T lymphocyte activation, and the activation of neutrophils through the MAPK pathway. CMTM1 may act on Annexin A2 by regulating Ca 2+ signaling. CMTM2 and CMTM6 are up-regulated in neutrophils of APS patients. Some CMTM family members influence the activation and accumulation of platelets. CMTM3 and CMTM7 are binding partners of B-cell linker protein (BLNK), thereby linking B cell receptor (BCR) and activating BLNK-mediated signal transduction in B cells. Moreover, CMTM3 and CMTM7 can act on DCs and B-1a cell development, respectively. CMTM may have potential effects on the development of APS by acting on immune cells and immune molecules. Thus, CMTM may act as a novel prognostic factor or immunomodulatory treatment option of APS.

Objective:To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD).Methods:The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD.Results:One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients ( P<0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group ( P<0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients ( P<0.05), and depression score was an independent risk factor for RGERD [ OR=3.915 (95% CI1.464-10.466), P =0.007]. Conclusions:RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

OBJECTIVE: To analyze the causes of the esophagogastric junction outlet obstruction (EGJOO) patients, to discuss the differences of the clinical manifestation and esophageal motility characteristics between the anatomic EGJOO (A-EGJOO) and functional EGJOO (F-EGJOO) subgroups, and to search the diagnostic values of the specific metrics for differentiating the subgroups of EGJOO patients. METHODS: For the current retrospective study, all the patients who underwent the esophageal high resonance manometry test were retrospectively analyzed from Jan 2012 to Oct 2018 in Peking University Third Hospital. The EGJOO patients were enrolled in the following research. The clinical characteristics, such as symptoms and causes of the patients were studied. Then the patients were divided into two subgroups as A-EGJOO subgroup and F-EGJOO subgroup. The clinical symptoms and the main manometry metrics were compared between these two subgroups. The significant different metrics between the two groups were selected to draw receiver operating characteristic (ROC) curves and the diagnostic values were analyzed in differentiating the A-EGJOO and F-EGJOO subgroups. RESULTS: The most common symptom of EGJOO was chest pain or chest discomfort (30.63%), then the dysphagia (29.73%), and acid regurgitation/heartburn (27.03%). Non-erosive reflux disease (36.04%) was the most popular cause for EGJOO, then the reflux esophagitis (17.12%). Besides the intra-EGJOO and extra-EGJOO lesions, the connective tissue disease (6.31%) and central nervous diseases (2.70%) were found to be the etiology of EGJOO. The causes of the rest 19 EGJOO were unknown. A-EGJOO patients presented significantly higher intra bolus pressure (IBP) than that of F-EGJOO [6.80 (5.20, 9.20) mmHg vs. 5.10 (3.10, 7.60) mmHg, P=0.016]. The area under curve of IBP was 0.637. When IBP≥5.15 mmHg, the sensitivity was 78.60% and specificity 50.70% to differentiate A- or F-EGJOO. CONCLUSION Chest pain or chest discomfort was the most common symptom in EGJOO patients. Besides the intraluminal structural disorders, the extra-luminal causes were found in EGJOO patients. A-EGJOO presented higher IBP than that of F-EGJOO patients. The cutoff value of IBP to differentiate A-EGJOO from EGJOO was 5.15 mmHg with sensitivity 78.06% and specificity 50.70%. However for the low area under curve, the diagnostic value of IBP was limited.
Deglutition Disorders ; Esophageal Motility Disorders/diagnosis* ; Esophagogastric Junction ; Humans ; Manometry ; Retrospective Studies

BACKGROUND: Particulated juvenile cartilage allograft is simple and easy to obtain, and relevant clinical studies are underway in the USA. However, how the transplanted juvenile cartilage fragments exert biological effects through biochemical mechanisms and genetic signal transduction is still unclear. There is as yet no report on this technology in China. OBJECTIVE: To explore the feasibility of articular cartilage defects repaired with particulated juvenile cartilage allograft. METHODS: The cartilage fragments were obtained from juvenile Pitman-Moore strains (provided by the Laboratory Animal Center of the Army Medical University in China) and cultured in vitro. Brdu immunofluorescence assay was performed at 1, 3, and 7 days of culture. The particulated juvenile cartilage allograft/fibrin gel composites were subcutaneously transplanted into the SCID rats (provided by the Laboratory Animal Center of the Army Medical University). The specimens were taken for hematoxylin-eosin staining, safranin O staining and immunohistochemistry after 1 month. Cartilage defects of 8 mm in diameter were made in the knee joint of 10 adult Pitman-Moore strains (Laboratory Animal Center of the Army Medical University), and were randomized into two groups, which were then transplanted with the particulated juvenile cartilage allograft/fibrin gel composites (experimental group) or nothing (control group). The specimens were taken for hematoxylin-eosin staining, safranin O fast green staining, toluidine blue and immunohistochemistry at 3 months after transplantation. RESULTS AND CONCLUSION: Little Brdu incorporation was detected in juvenile cartilage fragments at 1 day of culture, some Brdu incorporation was defected at 3 days of culture. At 7 days of culture, a progressive increase in the Brdu signal was detected in chondrocytes within the cultured cartilage fragments, which seemed to localize along the tissue edge. At 1 month after subcutaneous transplantation, the particulated juvenile cartilage allograft still survived and were surrounded by few proliferative chondrocytes. There was no obvious tissue repair in the control group at 3 months after transplantation. In the experimental group, there was obvious tissue repair, the color of the newly formed tissues was similar to the normal cartilage tissue, which integrated well with the surrounding normal cartilage tissue, and the cells distributed evenly. These results imply that particulated juvenile cartilage allograft can achieve good results in repairing articular cartilage defects.