Effect of red osier dogwood extract on in vitro gas production, dry matter digestibility, and fermentation characteristics of forage-based diet or grain-based diet.

This in vitro batch culture study investigated the effects of red osier dogwood (ROD) extract supplementation on gas production (GP), dry matter disappearance (DMD), and fermentation characteristics in high forage (HF) and high grain (HG) diets with varying media pH level. The experiment was a factorial arrangement of treatments in a completely randomized design with 2 media pH (5.8 and 6.5) × 4 dose rates of ROD extract (0, 1, 3, and 5% of DM substrate). An additional treatment of monensin was added as a positive control for each pH level. The HF substrate consisted of 400 and 600 g/kg DM barley-based concentrate and barley silage, respectively, while the HG substrate contained 100 and 900 g/kg DM barley silage and barley-based concentrate, respectively. Treatments were incubated for 24 h with GP, DMD and fermentation parameters determined. No interaction was detected between the media pH level and ROD extract dose rate on GP, DMD and most of the fermentation parameters. The GP, DMD, and total volatile fatty acid (VFA) concentration were greater (P = 0.01) with media pH of 6.5 in both HF and HG diets. The GP were not affected by increasing ROD dose rate, except that GP linearly decreased in the HF (P = 0.04) and HG (P = 0.01) diets at 24 h; the DMD tended to linearly decrease at pH 6.5 (P = 0.06) for both HF and HG diets and at pH 5.8 (P = 0.02) for the HG diet. Adding ROD extract to the HF and HG diets linearly (P = 0.01) increased the acetate molar proportion at high or low media pH and consequently, the acetate to propionate (A:P) ratio linearly (P ≤ 0.04) increased. Supplementation of ROD extract to the HF diet linearly (P = 0.04) decreased the molar proportion of propionate at pH 6.5 (interaction between pH and ROD extract; P = 0.05), but had no effect on propionate proportion when added to the HG diet. Moreover, the proportion of branched-chain fatty acids linearly (P = 0.03) decreased with ROD extract supplementation at low pH (interaction, P < 0.05) for HF diet and linearly decreased (P = 0.05) at pH 6.5 for HG diet (interaction, P < 0.05). The NH3-N concentration was not affected by ROD supplementation in the HF diet but it linearly (P = 0.01) decreased with increasing dose rate in the HG diet. Methane concentration tended to linearly (P = 0.06) increase with ROD extract supplementation at high pH for HF diet and linearly increased at pH 5.8 (P = 0.06) and pH 6.5 (P = 0.02) for HG diet. These results indicate that the decreased DMD and increased A:P ratio observed with addition of ROD extract may be beneficial to HG-fed cattle to reduce the risk of rumen acidosis without negatively impacting fiber digestion.

[Establishing and verifying the threshold value of HLA mixed antigen reagent screening test results].

Objective: To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results. Methods: The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-Ⅰ reagent and 1 116 samples were also tested by single antigen HLA Class-Ⅱ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-Ⅰ beads and 5 HLA Class-Ⅱ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-Ⅰ antibodies and 35 anti-HLA class-Ⅱ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test. Results: The threshold values of MFI and NBG ratio of HLA mixed antigen reagent's 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-Ⅰ antibodies by HLA mixed antigen reagent and single antigen HLA Class-Ⅰ reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-Ⅱ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-Ⅰ、Ⅱ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-Ⅰ reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-Ⅱ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively. Conclusions: In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.

[Comparative analysis of population distribution, severity, emotional, and cognitive characteristics among different side idiopathic tinnitus patients].

To provide basis for prevention and treatment by analyzing the clinical features, emotional and cognitive states and their correlations of idiopathic tinnitus. Cross-sectional study was used. Thirty-six right, 44 left, and 46 bilateral idiopathic tinnitus patients diagnosed in Beijing Tongren Hospital were prospectively enrolled from October, 2020 to February, 2022. The clinical data was recorded and the THI, DBI, STAI, and MoCA were evaluated. The clinical features and the incidence of severe tinnitus, hearing lose, anxiety, and cognitive impairment were compared by one-way ANOVA, Kruskal-Wallis H, and chi-square test. The correlation between tinnitus or hearing and emotional and cognitive states were evaluated by multivariable correlation analysis. There was no significant difference in age, BMI, years of education, tinnitus duration, and the incidence of hearing loss among groups (F=0.730,P=0.484;F=1.535,P=0.219;F=1.506,P=0.226;χ²=4.242,P=0.120;χ²=6.672,P=0.083). In right, left, and bilateral tinnitus patients, the number of severe tinnitus was 12, 7, and 20 cases and the incidence was 33.3%, 15.9%, and 43.5%; the number of depression was 13, 14, and 26 cases and incidence was 36.1%, 31.8%, and 53.5%; the number of trait anxiety was 3, 2, and 10 cases and the incidence was 8.3%, 4.5%, and 21.7%. Compared with left tinnitus patients, the incidence of severe tinnitus, depression, and trait anxiety was higher in bilateral tinnitus patients (χ²=8.139,P=0.004;χ²=5.558,P=0.018;χ²=5.753,P=0.007). The incidence of state anxiety and cognitive impairment were no significant difference among groups (χ²=0.142,P=0.931;χ²=1.338,P=0.512). The overall incidence of state anxiety and cognitive impairment were 16.7%(21/126) and 37.3%(47/126) respectively. There was positive correlation between THI score and BDI, S-AI, and T-AI scores (r=0.529,P=0.001; r=0.649,P<0.001; r=0.483,P=0.003) and negative correlation between THI and MoCA scores (r=-0.364,P=0.029) in right tinnitus group. The positive correlation was found between THI score and BDI, S-AI, and T-AI scores in left tinnitus group (r=0.508,P<0.001; r=0.506,P<0.001; r=0.357,P=0.017). The positive correlation between THI score and BDI, S-AI, and T-AI scores (r=0.753,P<0.001; r=0.527,P<0.001; r=0.536,P<0.001) and the positive correlation between tinnitus duration and MoCA score(r=0.334,P=0.023) were also found in bilateral tinnitus group.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Development and application of a reverse-transcription recombinase-aided amplification assay for subgroup J Avian leukosis virus.

Subgroup J Avian leukosis virus (ALV-J) is an important pathogen of poultry tumor diseases. Since its discovery, it has caused significant economic losses to the poultry industry. Thus, the rapid detection of molecular level with strong specificity is particularly important whether poultry are infected with ALV-J. In this study, we designed primers and probe for real-time fluorescent reverse-transcription recombinase-aided amplification assay (RT-RAA) based on the ALV-J gp85 sequence. We had established a real-time fluorescent RT-RAA method and confirmed this system by verifying the specificity and sensitivity of the primers and probe. In addition, repeatability tests and clinical sample regression tests were used for preliminary evaluation of this detection method. The sensitivity of established method was about 101 copies/µL, and the repeatability of the CV of the CT value is 4%, indicating repeatability is good. Moreover, there was no cross-reactivity with NDV, IBV, IBDV, H9N2, MDV, and REV, and other avian leukosis virus subgroups, such as subgroups A, B, C, D, K and E. Importantly, the real-time fluorescent RT-RAA completed the test within 30 min at a constant temperature of 41°C. Forty-two clinical samples with known background were tested, and the test results were coincided with 100%. Overall, these results suggested that the real-time fluorescent RT-RAA developed in this study had strong specificity, high sensitivity, and good feasibility. The method is simple, easy, and portable, that is suitable for clinical and laboratory diagnosis, and provides technical support for the prevention and control of ALV-J.

[Clinicopathological features of NTRK3 gene rearrangement papillary thyroid carcinoma].

Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.

Clinical characteristics and microbiology of nosocomial enterococcal bloodstream infections in a tertiary-level hospital: a retrospective study, 2007-2019.

BACKGROUND: Enterococci are important pathogens causing nosocomial bloodstream infections (BSIs) and cannot be treated with appropriate timely empirical antibiotics due to their natural resistance to many kinds of antibiotics. AIM: To analyse the clinical characteristics and microbiological features of nosocomial bloodstream infections caused by enterococci. METHODS: The clinical characteristics and microbiological features of nosocomial enterococcal BSI patients in Xiamen University Zhongshan Hospital were examined in a case-controlled retrospective study. All patient information was collected through an electronic surveillance system. FINDINGS: A total of 199 cases were identified as nosocomial enterococcal BSIs over a period of 13 years. The incidence of BSIs fluctuated from 0.21% to 0.81%. In the distribution of wards, enterococcal BSIs in hepatobiliary surgery ranked first. Intra-abdominal diseases (odds ratio: 3.36; 95% confidence interval: 2.15-5.27; P < 0.001), chemotherapy history (4.37; 2.06-9.25; P < 0.001), and urinary catheterization (2.34; 1.52-3.61; P < 0.001) were risk factors for nosocomial enterococcal BSI acquisition. Vancomycin-resistant enterococci and linezolid-insensitive enterococci strains were not found. CONCLUSION: Patients with a history of intra-abdominal disease, chemotherapy and urinary catheterization are at higher risk of nosocomial enterococcal bloodstream infections. The enterococcus strains were still sensitive to commonly used antibiotics.

[Development and outlook on human challenge trial of vaccine].

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

[Historical changes of a missionary hospital - Shanghai General Hospital (1864-1953)].

The Christian missionaries preached through medicine by combining religious preaching with secularisation and social adaptiveness of medicine in the 19th century. They attempted to avoid the negative influence of culture differences between the West and China. Desjacques Marin, one of the missionaries in China, was entrusted by Benoit Edan, a French consul in Shanghai to establish a hospital in 1864, named the "General Hospital". This hospital was moved to the north bank of Suzhou Creek in 1877 and renamed as the Gongji Hospital. The hospital was designated by the Japanese Army in 1940 as a hospital for sick foreign prisoners in the war. It was taken over as an enemy property by the government of the Republic of China in 1945 and became a public hospital opened formally to Chinese patients. It was renamed as "Shanghai First People's Hospital" in 1953. Review of the historical changes of the missionary hospital is of significance for the study on Chinese medical history and medical communication between China and the West.

Large ultrafast-modulated Voigt effect in noncollinear antiferromagnet Mn3Sn.

The time-resolved magneto-optical (MO) Voigt effect can be utilized to study the Néel order dynamics in antiferromagnetic (AFM) materials, but it has been limited for collinear AFM spin configuration. Here, we have demonstrated that in Mn3Sn with an inverse triangular spin structure, the quench of AFM order by ultrafast laser pulses can result in a large Voigt effect modulation. The modulated Voigt angle is significantly larger than the polarization rotation due to the crystal-structure related linear dichroism effect and the modulated MO Kerr angle arising from the ferroic ordering of cluster magnetic octupole. The AFM order quench time shows negligible change with increasing temperature approaching the Néel temperature (TN), in markedly contrast with the pronounced slowing-down demagnetization typically observed in conventional magnetic materials. This atypical behavior can be explained by the influence of weakened Dzyaloshinskii-Moriya interaction rather than the smaller exchange splitting on the diminished AFM order near TN. The temperature-insensitive ultrafast spin manipulation can pave the way for high-speed spintronic devices either working at a wide range of temperature or demanding spin switching near TN.

[Complexities and challenges in the management of portal vein thrombosis in cirrhosis].

Portal vein thrombosis is a common complication of liver cirrhosis. Based on the recent "Expert Consensus on the Management of Portal Vein Thrombosis in Liver Cirrhosis (2020, Shanghai)", we analyzed a series of differences in the field of portal vein thrombosis in liver cirrhosis and point out the complexities and challenges faced by clinical anticoagulation treatment, so as to provide a reference for further clinical exploration of the standardized management of portal vein thrombosis in liver cirrhosis.

Alcohol intake and the risk of chronic kidney disease: results from a systematic review and dose-response meta-analysis.

Many prospective cohort studies have investigated the association between the consumption of alcohol and CKD risk and have revealed inconsistent results. In the present study, we aimed to perform a meta-analysis of these studies to assess this association.We searched the PubMed and Embase databases up to 2020 and reviewed the reference lists of relevant articles to identify appropriate studies. We calculated the pooled relative risks with 95% CIs using random effects models, and then performed subgroup and meta-regression analyses. Dose-response meta-analyses were performed by sex separately. We identified 25 eligible prospective cohort studies, including 514,148 participants and 35,585 incident CKD cases. Compared with the category of minimal alcohol intake, light (RR = 0.90, I2 = 49%), moderate (RR = 0.86, I2 = 40%), and heavy (RR = 0.85, I2 = 51%) alcohol intake were associated with a lower risk of CKD. Subgroup meta-analysis by sex indicated that light (RR = 0.92, I2 = 0%), moderate (RR = 0.83, I2 = 39%) and heavy (RR = 0.76, I2 = 40%), alcohol consumption were inversely associated with CKD risk in male. Dose-response meta-analyses detected a nonlinear inverse association between alcohol consumption and the risk of CKD in all participants and linear inverse association in female participants. This meta-analysis shows that light (<12 g/day), moderate (12-24 g/day), and heavy (>24 g/day) alcohol consumption are protective against chronic kidney disease in adult participants especially in males.

[Application of pulse contour cardiac output monitoring technology in fluid resuscitation of severe burn patients in shock period].

Objective: To investigate the application of pulse contour cardiac output (PiCCO) monitoring technology in fluid resuscitation of severe burn patients in shock period. Methods: From January 2015 to December 2019, 33 patients with severe burns who were hospitalized in Guangzhou Red Cross Hospital, meeting the inclusion criteria, were recruited into a retrospective cohort study with their clinical information collected. The patients were divided into PiCCO monitoring group with 15 cases (13 males and 2 females, aged (43±13) years) and routine monitoring group with 18 cases (14 males and 4 females, aged (39±9) years) according to the monitoring method used. After admission, all the patients were rehydrated following the rehydration formula of the Third Military Medical University for shock period. In routine monitoring group, the fluid resuscitation of patients was performed by monitoring indicators such as urine volume and blood pressure, while PiCCO monitoring was performed among patients in PiCCO monitoring group, and their fluid resuscitation was guided by the patient's condition and the hemodynamic parameters (without pursuing normal levels of the parameters) of PiCCO monitoring on the basis of normal monitoring indicators in routine monitoring group. The colloids coefficients, the electrolyte coefficients (compared with the corresponding rehydration formula value of 0.75 mL·kg(-1)·% total body surface area (TBSA)(-1) of the Third Military Medical University for shock period during the first 24 h post injury), the total rehydration coefficients, and the urine volumes during the first and second 24 h post injury, the lactic acid level, the base excess level, and the oxygenation index at admission and 24, 48 h after admission, and the mechanical ventilation time, the wound healing time, and the death ratio of patients in the two groups were recorded. The cardiac index, the global end-diastolic volume index (GEDVI), the intrathoracic blood volume index (ITBVI), the extravascular lung water index (EVLWI), and the systemic vascular resistance index (SVRI) of patients in PiCCO monitoring group at post injury hour 24, 48, and 72 and the abnormal cases were recorded. Data were statistically analyzed with Fisher's exact probability test, independent-sample or one-sample t test, analysis of variance for repeated measurement, and Bonferroni correction. Results: During the first 24 h post injury, the colloids coefficients of patients in PiCCO monitoring group was (0.69±0.15) mL·kg(-1)·%TBSA(-1), which was significantly less than (0.85±0.16) mL·kg(-1)·%TBSA(-1) in routine monitoring group (t=-2.612, P<0.05). Compared with the rehydration formula value of the Third Military Medical University for shock period, only the colloids coefficient of patients in routine monitoring group during the first 24 h post injury was significantly increased (t=2.847, P<0.05). There were no statistically significant differences between the two groups in the colloids coefficients of patients during the second 24 h post injury, or the electrolyte coefficients, the total rehydration coefficients, the urine volumes of patients during the first and the second 24 h post injury (t=0.579, -0.011, 0.417, -1.321, -0.137, 0.031, 1.348, P>0.05). The lactic acid level, the base excess level, the oxygenation index of patients at admission and 48 h after admission, and the oxygenation index of patients at 24 h after admission between the two groups were similar (t=-1.837, 0.620, 0.292, -1.792, 1.912, -0.167, 1.695, P>0.05). The levels of lactic acid and base excess of patients in PiCCO monitoring group were (4.8±1.4) and (1.2±5.5)mmol/L, respectively, which were significantly better than (7.0±1.5) and (-2.8±3.0) mmol/L in routine monitoring group at 24 h after admission (t=-3.904, 2.562, P<0.05 or P<0.01). There were no statistically significant differences between the two groups in the mechanical ventilation time or the wound healing time of patients (t=-0.699, -0.697, P>0.05), or the death ratio of patients (P>0.05). In PiCCO monitoring group, the GEDVI, and the ITBVI of patients were lower than the normal low values at post injury hour 24 and 48, which were in the normal range at post injury hour 72; the cardiac index of patients increased gradually and recovered to normal at post injury hour 48; the SVRI of patients increased significantly at post injury hour 24 and then gradually decreased to normal; the EVLWI average of patients at all time points post injury were less than 10 mL/kg. At post injury hour 24, most of the hemodynamic parameters of more than or equal to 8/15 patients in PiCCO monitoring group were abnormal, and the abnormal proportion decreased later. Conclusions: On the basis of traditional monitoring indicators, the use of PiCCO monitoring technology combined with the patient's condition (without pursuing normal levels of the parameters) in guiding the fluid resuscitation in severe burn patients can reduce the usage of colloid and better improve tissue perfusion, with the resuscitation effect being better than conventional monitoring.

MiR-20a suppresses proliferation and facilitates apoptosis of breast cancer cells via the MTOR signaling pathway.

OBJECTIVE: The paper aimed to explore the role of micro ribonucleic acid (miR)-20a in regulating the proliferation and apoptosis of breast cancer cells. MATERIALS AND METHODS: The expression of miR-20a in breast cancer cells was analyzed via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry were employed to analyze the proliferation and apoptosis of cells. Thereafter, the target proteins of miR-20a were predicted using TargetScan, a website for miRNA target gene prediction, and the interaction between miR-20a and the target genes was detected through the Luciferase reporter gene assay, qRT-PCR assay, and Western blotting. Finally, the miR-20a inhibitor and target gene expression plasmids were co-transfected for rescue experiment to study whether the target genes participate in the inhibitory effect of miR-20a on the proliferation of breast cancer cells. RESULTS: It was found that the expression of miR-20a was upregulated in breast cancer cell lines. Silencing miR-20a expression inhibited the proliferation and promoted the apoptosis of breast cancer cell. Besides, it was demonstrated that late endosomal/lysosomal adaptor, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) activator 3 (LAMTOR3) were a direct target of miR-20a. The knockdown of LAMTOR3 expression repressed the influence of miR-20a on the proliferation of breast cancer cells. CONCLUSIONS: MiR-20a targets LAMTOR3 gene to regulate the mTOR signaling pathway, thereby suppressing the proliferation and facilitating the apoptosis of breast cancer cells. It suggests that miR-20a exerts a carcinogenic effect in breast cancer, which may be a potential target for the treatment of breast cancer.

[Efficacy of nilotinib in the first-line treatment of chronic myeloid leukemia and the analysis of factors affecting molecular responses].

Objectives: This study aimed to investigate the efficacy and safety of nilotinib as the first-line treatment for patients with chronic myelogenous leukemia (CML) and analyze the factors affecting the realization of the major molecular response. Methods: A retrospective study was conducted on 86 newly diagnosed CML patients from the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to June 2017, who were using nilotinib 300 mg, twice a day, as the first-line treatment. There were 49 males and 37 females. Results: At 12 months, the MMR, MR4, and MR4.5 rates were 59.3%, 22.1%, and 15.1%, respectively. At 24 months, the MMR, MR4, and MR4.5 rates were 76.2%, 44.0%, and 27.4%, respectively.The median follow-up time was 42 months (range, 21-66 months) . The median progression-free survival time (PFS) was 42 months (range, 9-66 months) at a PFS rate of 93%. The time required for BCR-ABL transcript to decrease by half compared with the diagnosis was defined as the halving time (HT) . HT was the influencing factor of the 12-month MMR (OR=0.896, P<0.001) and MR4.5 (OR=0.377, P=0.003) . The most common non-hematologic adverse reactions were rash (37.2%) and headache (32.6%) , and most were grade 1/2. The most common hematologic adverse reactions were mainly neutropenia (27.9%) and thrombocytopenia (32.4%) . Conclusion: Nilotinib was an effective and safe first-line treatment for CML patients. HT ≤ 13.68 days is protective factor for long-term progression-free survival.