Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To establish a method for preserving viral nucleic acids in plasma using a blood collection card based on the dry spot method,to predict the duration of nucleic acid preservation by establishing the Arrhenius equation,and to demonstrate the feasibility of this preservation method for the re-testing of nucleic acids in blood samples retained by blood banks.Methods:Plasma samples positive for HBV,HCV,and HIV nucleic acids were prepared into preservation cards in the form of dry plasma spots for storage.The prepared preservation cards were placed under accelerated storage conditions at 37,45,50,and 55 ℃.The preservation cards were periodically retrieved from each temperature condition for nucleic acid extraction,and the nucleic acid samples were purified for subsequent PCR testing,with the recorded CT values.An Arrhenius equation model was established between the expiration time and the storage temperature,thereby predicting the validity period of nucleic acid preservation in blood collection cards under specified storage temperature conditions.Results:For the plasma samples positive for HBV,HCV,and HIV nucleic acids preserved using the dry spot method,the regression equations for the duration with temperature were as follows:y=-11546x+31.74 for HBV,y=-12949x+36.88 for HCV,and y=-12204x+34.48 for HIV,with the correlation coefficient r greater than 0.98 for all.It was predicted that at a storage temperature of 4 ℃,the preservation periods for HBV,HCV,and HIV viral nucleic acids using the dry spot method would be 20792 days,19289 days,and 14285 days,respectively.At a storage temperature of 20 ℃,the preservation periods would be 2135 days 1502 days,and 1289 days,respectively.Conclusion:The nucleic acids of the three common viral pathogens in blood samples,when preserved using the dry spot method,conform to a first-order reaction pattern in the accelerated degradation experiment.The relationship between the rate of nucleic acid degradation and the absolute temperature of storage is consistent with the Arrhenius equation.Based on the calculations using this equation,the stability and validity period of plasma nucleic acid samples preserved using the dry spot method can reach a minimum of 3 .5 years under storage conditions not exceeding 20 ℃,which essentially meets the requirements for the preservation period of blood samples retained by blood banks.

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.
Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Colorectal Neoplasms/pathology* ; Indoles/therapeutic use* ; Irinotecan/therapeutic use* ; Prospective Studies

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Esophageal Neoplasms/pathology* ; Prospective Studies ; Programmed Cell Death 1 Receptor/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Liver Diseases/etiology*

Child ; Humans ; Toxoplasmosis, Cerebral ; Hematopoietic Stem Cell Transplantation ; Thalassemia

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI ^ 1. With the increase of the proportion of serum, the inhibitory rate of 10% ~ 90% drug-containing serum to pseudomonas aeruginosa (standard/resistant) increased gradually.compared with the control group, the inhibitory effect of the Qiguiyin group on bacteria was significantly enhanced. The MIC

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

Objective:To assess the value of 4-dimensional CT angiography (4D CTA) to predict hemorrhagic transformation (HT) with a new nomogram model in acute ischemic stroke (AIS) patients after endovascular treatment (EVT).Methods:Imaging and clinical data of 101 AIS patients with internal carotid artery and/or middle cerebral artery occlusion who underwent "one-stop" CTA-CT perfusion and EVT in green channel of Beijing Hospital from March 2016 to November 2020 were analyzed retrospectively. The patients were divided into HT group (45 patients) and non-HT group (56 patients). Multivariate logistic regression analysis was used to select relevant clinical and imaging variables, such as age, initial National Institute of Health stroke scale (NIHSS) score, 4D CTA collateral circulation score, Alberta stroke program early CT score (ASPECTS), clot burden score, and a predictive nomogram model were developed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the efficacy of predictive nomogram model for diagnosing HT.Results:Univariate analysis showed that there were significant difference of age[79.00(68.00, 85.00) years, 73.00(62.75, 80.00) years, Z=-2.20, P=0.028], NIHSS score [16.00(12.00, 21.00), 9.50(6.00, 14.00), Z=-4.44, P<0.001], ASPECTS score [5.00(3.00, 8.00), 8.00(7.00, 9.00), Z=-4.23, P<0.001], 4D CTA collateral circulation score [2.00(0, 3.00), 3.00(3.00, 4.00), Z=-5.39, P<0.001], clot burden score [4.00(1.00, 7.00), 7.50(6.00, 9.00), Z=-3.42, P=0.001], location of the occlusion(internal carotid artery/middle cerebral artery occlusion was 23/22, 11/45 cases, χ2=9.70, P=0.002), and atrial fibrillation (27 and 19 cases respectively, χ2=5.83, P=0.016) between HT group and non-HT group. Multivariate logistic regression analysis showed that ASPECTS score (OR=0.64, 95%CI 0.47-0.87), NIHSS score (OR=1.13, 95%CI 1.01-1.26), 4D CTA collateral circulation score (OR=0.40,95%CI 0.22-0.76) were independent predictors of HT in AIS patients ( P<0.05). The AUC of the nomogram based on the ASPECTS score, NIHSS score and 4D CTA collateral circulation score to predict HT of AIS patients was 0.876 (95%CI 0.807-0.945), with a sensitivity of 77.8% and specificity of 87.5%. Conclusions:Patients with low ASPECTS score, high NIHSS score and low 4D CTA collateral circulation score have a higher risk of HT after EVT. The nomogram model may predict the probability of HT of AIS patients and provide effective assistance for clinical decision-making.

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.
Male ; Humans ; Anthracyclines/therapeutic use* ; Ventricular Function, Left ; Retrospective Studies ; Heart Ventricles ; Antibiotics, Antineoplastic/adverse effects* ; Polyketides/pharmacology* ; Lymphoma/drug therapy*