Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Objective To investigate the predictive value of preoperative frailty for pulmonary com-plications(PPCs)after cardiac surgery in elderly patients.Methods A total of 162 elderly patients,109 males and 53 females,aged 65-83 years,BMI 18-36 kg/m2,ASA physical status Ⅱ-Ⅳ,underwent elec-tive open heart surgery from July 2022 to January 2023 were collected.The patients were divided into two groups according to the occurrence of PPCs:the PPCs group(n=57)and the non-PPCs group(n=105).General information,smoking history,alcohol consumption history,EuroSCORE Ⅱ,frailty,chronic comorbidities(hypertension,diabetes mellitus,myocardial infarction,pulmonary hypertension,chronic ob-structive pulmonary disease,sleep apnea syndrome,etc.),Hb,creatinine,albumin,pulmonary function indices,left ventricular ejection fraction,type of surgery,duration of surgery,aortic clamping time,and cardiopulmonary bypass time were collected.Factors with P＜0.2 and clinically significant in the univariate regression analysis were included in the multivariate logistic regression analysis,and the predictive efficacy of the Fried frailty scale and EuroSCORE Ⅱ for PPCs were compared by the area under the ROC curve(AUC).Results PPCs occurred in 57 patients(35.2％).Multifactorial Logistic regression analysis showed that frailty(OR=3.14,95％CI 1.05-9.37,P＜0.05)and EuroSCORE Ⅱ(OR=2.16,95％CI 1.01-4.60,P＜0.05)were risk factors for the development of PPCs.The predictive power of Fried frailty scale(AUC=0.76,95％CI 0.68-0.82)was significantly higher than that of EuroSCORE Ⅱ(AUC=0.65,95％CI 0.57-0.72)(P＜0.05).Conclusion Preoperative frailty is the independent risk factors for pulmonary complications after cardiac surgery in elderly patients,and the Fried frailty scale has a better predictive efficacy compared to EuroSCORE Ⅱ,a traditional risk predictor.

Objective:To compare the difference and consistency of anterior corneal surface and total corneal refractive power and astigmatism measured by CASIA2, IOLMaster 700 and Pentacam in patients with age-related cataract.Methods:A diagnostic test was conducted.Two-hundred patients (200 eyes) with age-related cataract were enrolled in Tianjin Medical University Eye Hospital from March to April 2021.The steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Km), degree and axis of astigmatism of the anterior and the total corneal surface of patients were measured by CASIA2, IOLMaster 700 and Pentacam, respectively.The astigmatism was transformed into J0 and J45 by Fourier transform formula.The differences and correlation of the measurements obtained with the three instruments were analyzed by one-way repeated measures analysis of variance and Pearson correlation analysis.The consistency was evaluated by Bland-Altman test.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2021KY-07).Results:There were statistically significant differences in anterior corneal surface Kf and J0 measured by the three instruments ( F=18.563, 16.172; both at P=0.001). The Kf measured by CASIA2 was significantly higher than that measured by IOLMaster 700, and the J0 measured by IOLMaster 700 was significantly higher than that measured by Pentacam (both at P<0.05). There were statistically significant differences in total corneal Ks, Kf, Km and J0 measured by the three instruments, which from IOLMaster 700 were the largest, followed by CASIA2, then Pentacam ( F=1 300.447, 1 274.117, 1 609.713, 10.372; all at P=0.001). Pearson correlation analysis showed that the corneal refractive power measured by the three instruments was highly correlated (all at r>0.935, P<0.01), and the correlation of astigmatism values was weaker than the corneal refractive power ( r=0.623-0.908, all at P<0.01). Bland-Altman analysis showed that the three instruments had good consistency in measuring the anterior corneal surface refractive power, anterior corneal surface astigmatism and total corneal astigmatism, which were clinically acceptable, while the consistency of total corneal refractive power measurement was poor.The difference in measuring total corneal refractive power was large between IOLMaster 700 and Pentacam, and relatively small between CASIA2 and Pentacam. Conclusions:The consistency of CASIA2, IOLMaster 700 and Pentacam is good in measuring the anterior corneal surface refractive power of patients with age-related cataract, which can be substitutable, but poor in measuring the total corneal refractive power.The total corneal refractive power measurement from IOLMaster700 is the largest, the smallest from Pentacam, which is not recommended to be clinically exchangeable.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

We report the diagnosis and treatment of a neonate with primary pulmonary hypertension. The full-term baby was delivered vaginally in good condition at birth and admitted eight days after birth due to intermittent cyanosis. The chest X-ray showed a scattered sheet-like shadow in both lungs, and the cardiac color doppler studies suggested patent ductus arteriosus. Following admission, the neonate was given three days of anti-infection and headbox oxygen treatment. Despite subsequent high-frequency ventilator assisted ventilation combined with nitric oxide inhalation and continuous intravenous milrinone and oral sildenafil, the baby's condition worsened, and she died fifteen minutes after withdrawing resuscitation. Genetic studies revealed a chr13:37446983 mutation in SMAD9.

Objective To evaluate the clinical effects of short-term (3-6 months) and long-term (12 months) dual antiplatelet therapy (DAPT) after the implantation of coronary drug-eluting stents (DES). Methods The eligibilities of the patients included stable angina, acute coronary syndrome and silent ischemia. The lesions were in a native coronary vessel. The clinical observation endpoints were all-cause death, cardiogenic death, myocardial infarction, stroke, stent thrombosis, target lesion revascularization, severe bleeding, and true adverse clinical events. The clinical observation endpoints were all-cause death, cardiogenic death, myocardial infarction, stroke, stent thrombosis, target lesion revascularization, severe bleeding, and true adverse clinical events. By searching Pubmed, Chinese biomedical literature and other Chinese and English databases and manual search, qualified randomized controlled studies were evaluated and data were extracted for meta-analysis. Results A total of 12 randomized controlled studies were conducted. Detsky scores were all greater than 5 points. There were a total of 25949 patients in the study with a follow-up rate of 97.9%. There were no significantly different in all cause death (OR = 0.86，95%CI 0.71-1.05，P = 0.14), cardiac death (OR = 0.94，95% CI 0.70-1.25，P = 0.67), stent thrombosis (OR = 1.36，95%CI 0.94-1.98，P = 0.11), stroke (OR = 1.01，95%CI 0.71-1.42，P = 0.98), target lesion revascularization (OR = 0.121，95%CI 0.94-1.55，P = 0.14),and true adverse clinical events (OR = 0.98，95%CI 0.83-1.14，P = 0.75). The incident rate of myocardial infarction during the follow-up period was higher in the short-term group than in the long-term group (OR = 1.27, 95% CI 1.02-1.59, P = 0.04). The proportion of severe bleeding in the long-term group increased significantly (OR = 0.69, 95% CI 0.50-0.95, P = 0.02). Asian population studies showed that all-cause mortality was higher in the long-term treatment group than in the short-term group (OR = 0.72, 95% CI 0.53-0.97, P = 0.03), and there was no significant difference in severe bleeding between the two groups. Conclusion According to the defined clinical observation endpoints, the short-term dual antiplatelet effect is not inferior to the long-term group. Seven asian group studies have shown that the long-term group has high all-cause mortality. It can not rule out the deviation and/or population caused by the small sample size or individual variation. The results need to be further verified. This result can be used as a clinical warning to adjust the dual antiplatelet cycle based on the individualized risk of bleeding and coronary lesions.

Objective: To observe the treatment of inflammatory myopathy-associatied cardiomyopathy and its impact on prognosis of disease. Methods: In this single-center retrospective study, 29 cases of inflammatory myopathy-associated cardiomyopathy were collected in Peking Union Medical College Hospital from 1999 to 2016. The clinical data and adverse events during follow up were documented. Among 29 patients there were 11 cases of polymyositis, 8 cases of dermatomyositis, 8 cases of overlap syndrome and 2 cases of nonspecific myositis.All the patients started with sufficiene prednisone (1-2 mg·kg^-1·d^-1). 7 cases received intravenous immune globulin, while 12 cases were prescribed with steroid pulse therapy, 16 cases with methotrexate, 15 cases with cyclophosphamide, 6 cases with cyclosporine A, while 11 cases with combination of immune suppressors (methotrexate plus cyclophosphamide or cyclosporine A). After a median follow up of 4.8 years (2 month to 15 years), 14 cases died including 9 of cardiac death. Patients with cardiac deaths had lower usage percentages of intravenous gamma globulin (0 vs. 7/20, P=0.05) and steroid pulse therapy (1/9 vs. 11/20, P=0.043) than controls. Comparing with controls, patients in the group of adverse events were more prone to choose methotrexate alone rather than combination of immune suppressors (all-cause death: 1/14 vs. 8/15, P=0.014; cardiac death: 0 vs. 9/20, P=0.027). Kaplan-Meier survival analysis showed significant difference of survival rates between patients with combination of immune suppressors and controls (Log Rank χ²=6.001, HR=7.58, P=0.014), as well as between patients with β receptor blockers and controls (Log Rank χ²=4.589, HR=2.95, P=0.032). Conclusions We recommend a management strategy that emphasize both primary disease controlling and cardiac remodeling improvement in patients with inflammatory myopathy-associated cardiomyopathy. On the basis of sufficient glucocorticoids, intravenous gamma globulin, steroid pulse therapy, combination of methotrexate plus other immune suppressants, and β receptor blockers were worthy to be considered.