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 association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

Aim To determine the antiviral and anti-inflammatory effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency(4-1)against in vitro infection of SARS-CoV-2 and common coronaviruses.Methods The main chemical substances of 4-1 were analyzed by LC-MS.The toxicity and antiviral effects of of 4-1 were detected by MTT and by CPE assay, respectively.The viral loads in cell supernatant and the expression of inflammatory factors induced by viral infection were determined by qRT-PCR.Results The recommended prescription 4-1 contained 94 chemical compounds, including flavonoids, steroids, sesquiterpenoids, and so on.The range of selection indexes for SARS-CoV-2 and common coronaviruses was 8.44±0.4952.26±2.3.This prescription could inhibit the proliferation of SARS-CoV-2, the expression of ACE2 and S mRNA, and down regulate IL-1α and CCL-5/RANTES at 10, 5, and 2.5 g•L-1 doses.Further, at doses of 20, 10 and 5 g•L-1, it could inhibit the proliferation of three common coronaviruses and suppress the overexpression of IL-6, CXCL-8/IL-8, CXCL-10/IP-10, TNF-α, IFN-α, CCL-2/MCP-1, MIG and CCL-5/RANTES induced by OC43/229E infection.The inhibitory effects were dose-dependent.Conclusions The prescription 4-1 has antiviral and anti-inflammation effects against multiple coronaviruses.This study provides the research basis for the treatment of common respiratory viral infections and emerging infectious diseases such as COVID-19 by using traditional Chinese medicine.

The present study aimed to explore the regulatory targets and anti-inflammatory mechanism of Jingfang Mixture based on network pharmacology and animal tests. The active ingredients of Jingfang Mixture and the corresponding targets were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Inflammation-related targets were searched from GeneCards and DisGeNET, and the targets of active ingredients of Jingfang Mixture against inflammation were obtained. The protein-protein interaction(PPI) network was analyzed by STRING and plotted. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out based on DAVID. The results of network pharmacology showed 159 active ingredients and 276 targets of Jingfang Mixture and 664 inflammation-related targets were screened out, and 90 targets of active ingredients of Jingfang Mixture against inflammation were obtained. As revealed by the PPI network, protein kinase B1(AKT1), caspase-3(CASP3), interleukin-1β(IL1 B), prostaglandin-endoperoxide synthase 2(PTGS2), and tumor necrosis factor(TNF) might be the key proteins for the anti-inflammatory effect of Jingfang Mixture. KEGG enrichment analysis demonstrated the pathways involved TNF, nuclear factor-kappa B(NF-κB), and mitogen-activated protein kinase(MAPK). The anti-inflammatory effect of Jingfang Mixture was explored through the mouse model of urticaria. The results indicated that Jingfang Mixture could down-regulate the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases(ERK1/2), and NF-κB. The present study revealed the anti-inflammatory effect of Jingfang Mixture with multi-component and multi-target characteristics, which is expected to provide a scientific basis and important support for further research, development, and application.
Animals ; Mice ; Anti-Inflammatory Agents/therapeutic use* ; Cyclooxygenase 2 ; Drugs, Chinese Herbal/therapeutic use* ; Inflammation/drug therapy* ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; NF-kappa B/genetics*

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

BACKGROUND: Existing clinical prediction models for in vitro fertilization are based on the fresh oocyte cycle, and there is no prediction model to evaluate the probability of successful thawing of cryopreserved mature oocytes. This research aims to identify and study the characteristics of pre-oocyte-retrieval patients that can affect the pregnancy outcomes of emergency oocyte freeze-thaw cycles. METHODS: Data were collected from the Reproductive Center, Peking University Third Hospital of China. Multivariable logistic regression model was used to derive the nomogram. Nomogram model performance was assessed by examining the discrimination and calibration in the development and validation cohorts. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration plots. RESULTS: The predictors in the model of "no transferable embryo cycles" are female age (odds ratio [OR] = 1.099, 95% confidence interval [CI] = 1.003-1.205, P = 0.0440), duration of infertility (OR = 1.140, 95% CI = 1.018-1.276, P = 0.0240), basal follicle-stimulating hormone (FSH) level (OR = 1.205, 95% CI = 1.051-1.382, P = 0.0084), basal estradiol (E2) level (OR = 1.006, 95% CI = 1.001-1.010, P = 0.0120), and sperm from microdissection testicular sperm extraction (MESA) (OR = 7.741, 95% CI = 2.905-20.632, P < 0.0010). Upon assessing predictive ability, the AUC for the "no transferable embryo cycles" model was 0.799 (95% CI: 0.722-0.875, P < 0.0010). The Hosmer-Lemeshow test (P = 0.7210) and calibration curve showed good calibration for the prediction of no transferable embryo cycles. The predictors in the cumulative live birth were the number of follicles on the day of human chorionic gonadotropin (hCG) administration (OR = 1.088, 95% CI = 1.030-1.149, P = 0.0020) and endometriosis (OR = 0.172, 95% CI = 0.035-0.853, P = 0.0310). The AUC for the "cumulative live birth" model was 0.724 (95% CI: 0.647-0.801, P < 0.0010). The Hosmer-Lemeshow test (P = 0.5620) and calibration curve showed good calibration for the prediction of cumulative live birth. CONCLUSIONS The predictors in the final multivariate logistic regression models found to be significantly associated with poor pregnancy outcomes were increasing female age, duration of infertility, high basal FSH and E2 level, endometriosis, sperm from MESA, and low number of follicles with a diameter >10 mm on the day of hCG administration.
Embryo Transfer ; Female ; Fertilization in Vitro ; Humans ; Nomograms ; Oocytes ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies

Objective:To explore the effect of modified Xiongxiesan on the proliferation of airway smooth muscle tissues and the expressions of matrix metalloproteinase-9（MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1） in cough variant asthma （CVA） model rats. Method:A total 48 male SD rats were randomly divided into the normal control group （8 rats） and model group （40 rats）. CVA model of rats were established through the intraperitoneal administration with 2 mg ovalbumin （OVA） and 100 mg Al（OH）₃， and then aerosol inhalation of 1％ OVA 15 days later. The same volume of sterile saline was given to the normal group through the intraperitoneal injection. Then 40 rats in the modeling group were randomly divided into model group， modified Xiongxiesan group （TCM group， 6 g·kg^-1·d^-1）， montelukast group （0.4 mg·kg^-1·d^-1）， chemokine receptor1/2 （CXCR1/2） inhibitor group （G31P group injected subcutaneously via the neck with a dose of 0.5 mg·kg^-1 every other day）， and CXCR1/2 inhibitor and modified Xiongxiesan group （G31P+TCM group）， with 8 rats in each group. The control group and the model group were orally given distilled water 10 mL·kg^-1·d^-1. Then the rats were sacrificed， and lung samples were collected. Histological changes were examined by hematoxylin-eosin（HE）. Basement membrane perimeter （PBM），wall area of bronchial tube （WAt），wall area of bronchial smooth muscle （WAm） and the number of smooth muscle cells （N） were measured using image pro-plus software and standardized based on PBM. The expressions of PCNA， MMP9 and TIMP1 were detected by immunohistochemistry. Result:Compared with the control group， there were a large number of inflammatory cells infiltration and moderate hyperplasia of smooth muscle area in the model group， which however were alleviated in other groups. The expressions of PCNA and MMP-9，TIMP1 were higher in the model group，which were reduced in other groups significantly. Conclusion:Modified Xiongxiesan can reduce the thickness of airway smooth muscle tissue in the CVA model rats， which may be correlated with the inhibition of the CXCR1/2 pathway， thereby reducing the proliferative activity of smooth muscle tissue and inhibiting the expression of related matrix metalloproteinases.