Comparative efficacy and safety of immunotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma: a systematic review and network Meta-analysis.

BACKGROUND: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events. RESULTS: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively. CONCLUSIONS: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC. TRIAL REGISTRATION: PROSPERO registration number: (CRD 42021261554).

Down-Regulated LncRNA-HOTAIR Suppressed Colorectal Cancer Cell Proliferation, Invasion, and Migration by Mediating p21.

BACKGROUND AND AIM: HOX transcript antisense intergenic RNA (HOTAIR) is a relatively well-understood RNA, which plays a central role in the pathogenesis of various tumors. The aim of the present study was to investigate the effect by which HOTAIR acts to influence the biological processes of colorectal cancer (CRC) through p21. METHODS: Reverse transcription quantitative polymerase chain reaction and Western blot methods were employed to provide verification regarding the changes in HOTAIR, PCNA, Ki67, p21, cyclin E, and CDK2 among the CRC tissues and cells. The correlation between the clinicopathological characteristics of patients and expression of HOTAIR and p21 was subsequently evaluated, followed by an analysis into the effects of HOTAIR on the biological processes of M5 cells. RESULTS: HOTAIR was found to be expressed at high levels, while p21 was determined to be at a low level among both the CRC tissues and the CRC cell lines. The expressions of HOTAIR and p21 were determined to be related to lymph node metastasis, tumor node metastasis, Dukes staging, distant metastases, histological types, and the degree of differentiation. Cells transfected with HOTAIR siRNA displayed inhibited rates of proliferation, invasion, and migration, as well as decreased cyclin E and CDK2, while apoptosis and p21 were increased. CONCLUSION: The principal findings demonstrated that down-regulation of HOTAIR elicits an inhibitory effect on proliferation, invasion, and migration, while promoting the apoptosis of CRC cells through the up-regulation of p21. We believe that HOTAIR could represent a novel target for the treatment of CRC.

Demethylzeylasteral exhibits dose-dependent inhibitory behaviour towards estradiol glucuronidation.

The disturbance of estradiol level might induce the occurence of some diseases, including cancer. Estradiol is mainly metabolized through the conjugation reactions, including the sulfation and glucuronidation reactions. The present study tried to evaluate the inhibition of estradiol glucuronidation by the major ingredients of Tripterygium wilfordii Hook F. demethylzeylasteral. Selective ion monitoring at negative ion mode ([M⁺ H⁻] = 447) was employed to monitor the two glucuronides of estradiol. The reaction rate was determined through comparison of peak area of these two glucuronides. Lineweaver-Burk plot and Dixon plot were utilized to determine the inhibition kinetic type, and the inhibition kinetic parameters (K i) were calculated using the second plot. Competitive inhibition of demethylzeylasteral towards the formation of two glucuronides of estradiol was demonstrated, and the K i values were calculated to be 453.3 and 110.9 µM, respectively. All these results will remind us the risk of elevated serum concentrations of estradiol due to the inhibition of estradiol glucuronidation by demethylzeylasteral.

Progression-free survival at 3 years is a reliable surrogate for 5-year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC. METHODS: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. RESULTS: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies. CONCLUSIONS: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.

Associations of maternal hyperglycemia in the second and third trimesters of pregnancy with prematurity.

Hyperglycemia in pregnancy (HIP) is related to adverse pregnancy outcomes. However, women with hyperglycemia in the second and third trimester of pregnancy (HISTTP) were not been observed. We aim to reveal associations between HISTTP and prematurity. To confirm which risk factor is better in predicting preterm delivery.This retrospective study included 660 patients, of which 132 have HISTTP and 528 have euglycemia. Univariate analysis was used to extract risk factors and multivariates logistic regression analysis to obtain odds ratio (OR) for prematurity. Mean decrease gini (MDG) in random forest algorithm was used to rank the risk factors.HISTTP women have higher prepregnancy BMI and a higher percentage of family history of hypertension, maternal adiposity, maternal anemia, gestational diabetes mellitus (GDM), prematurity, neonatal asphyxia in 1-minute (P < .05). Univariate analysis of prematurity showed that preterm women had higher rate of HISTTP (P < .01), second births, elderly pregnancy, hypertention, family history of hypertention and multiple perinatal infant (P < .05). Multivariate logistic regression analysis indicates that HISTTP (OR = 2.984, P = .0017), maternal hypertension (OR = 5.208, P = .001) and multiple perinatal infants (OR = 59.815, P < .0001) are independent risk factors for prematurity. After ranked the MDG, the top 3 risk factors were multiple perinatal infants, maternal hypertension, HISTTP. MDG of HISTTP is higher than that of GDM.Women with HISTTP deserve to be concerned, whose prematurity rate are increased. HISTTP is an independent risk factor and a better predictor of prematurity.

Cu2O@Fe-Ni3S2 nanoflower in situ grown on copper foam at room temperature as an excellent oxygen evolution electrocatalyst.

Herein, we have synthesized successfully a three-dimensional/two dimensional (3D/2D) core-shell Cu2O@Fe-Ni3S2 nanoflower on copper foam at room temperature. Remarkably, by virtue of rich active sites and vacancies, large surface area, high conductivity and close contact with the electrolyte, the Cu2O@Fe-Ni3S2 catalyst exhibits superior stability and oxygen evolution reaction performance.

[Meningoencephalitis caused by Angiostrongylus cantonensis: report of 1 case].

One rare case of meningoencephalitis caused by Angiostrongylus cantonensis is reported. The development of the disease, clinical features, accessory examinations, and the subsequent treatment were described and analyzed briefly.

[Clinical evaluation of DLF, CLF and DFM regimens based on platinum compound plus 5-fluorouracil for treatment of advanced esophageal carcinoma].

BACKGROUND & OBJECTIVE: Combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin is regarded as the standard regimen for advanced esophageal carcinoma. This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens, based on platinum compound plus 5-fluorouracil in the treatment of advanced esophageal carcinoma, and to further explore prognostic factors of advanced esophageal carcinoma. METHODS: From October 1999 to December 2004, 98 patients with advanced esophageal carcinoma were enrolled in the study. They were non-randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m(2), followed by a 5-FU bolus 400 mg/m(2) and 48-hour infusion of 5-FU 3,000 mg/m(2) every 3 weeks, combined with cisplatin 80 mg/m(2) (DLF, n=48) or with carboplatin AUC=5 on day 1 (CLF, n=32), or with cisplatin 80 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1-5 plus pingyangmycin 5 mg/m(2) on day 1, 3, 5 (DFM, n=18). Survival analysis and prognostic factors were evaluated by Kaplan-Meier method and Cox regression analysis. RESULTS: All 98 patients were assessable for response and toxicity. There were 13 complete response, 36 partial response, 45 no changes and 4 progressive disease with a total response rate of 46.86%. The response rates of DLF, CLF and DFM regimens were 60.42%,46.86% and 27.78%, respectively (DLF vs DFM, P=0.027). The major side effects were nausea-vomiting, alopecia, bone marrow suppression and mucositis, and the others were uncommon. All side effects were tolerable and mild except for nausea-vomiting. Nausea-vomiting was mildest in CLF among the three regimens. After a median follow-up of 9 months, the overall median survival was 9 months (95% CI, 6.67 to 11.33 months), the median survival of the patients treated with DLF, CLF or DFM regimen was 10, 9 and 7 months, respectively (P=0.7402). Better prognosis was correlated with good conditions of patients before chemotherapy (KPS> or =80, P=0.000) and metastasis to lymph node, parenchyma or bone in stead of visceral organs (P=0.026). There was no correlation between the prognosis and age, sex, types of pathology and the regimen of therapy. CONCLUSIONS: The DLF regimen is tolerable and more effective, thus could be recommended as a front-line standard treatment for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble and older patients since it has the mildest side effects. The prognostic factors of advanced esophageal carcinoma include conditions before chemotherapy and the location of metastasis.