ABSTRACT
Objective: To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings. Methods: The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated. Results: In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot (P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion: Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.
Subject(s)
Disinfection , Ultraviolet Rays , Disinfection/methods , Cross Infection/prevention & controlABSTRACT
Objective: To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB. Methods: Three full-length Mycobacterium (M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M. tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results: Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance (P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group (P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group (P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group (P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group (P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups (P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant (P>0.05). Conclusion: Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Animals , Mice , BCG Vaccine , Granulocyte-Macrophage Colony-Stimulating Factor , Interleukin-10 , Interleukin-4 , Interleukin-6 , Tuberculosis/prevention & control , Antigens, Bacterial , Interleukin-12 , Recombinant Proteins , Epitopes , Bacterial ProteinsABSTRACT
Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: â The G6PC3(C295T) mutant cell model was successfully created. â¡In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ⢠ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ⣠With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.
Subject(s)
CRISPR-Cas Systems , Gene Editing , Humans , Adenine , HEK293 Cells , Mutation , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolismABSTRACT
Objective: To evaluate the effect of Wendler Glottoplasty to elevate vocal pitch in transgender women. Methods: The voice parameters of pre-and 3-month post-surgery of 29 transgender women who underwent Wendler Glottoplasty in department of otorhinolaryngology head and neck surgery of Beijing Friendship Hospital from January, 2017 to October, 2020 were retrospectively analyzed. The 29 transgender women ranged in age from 19-47 (27.0±6.3) years old. Subjective evaluation was performed using Transsexual Voice Questionnaire for Male to Female (TVQMtF). Objective parameters included fundamental frequency (F0), highest pitch, lowest pitch, habitual volume, Jitter, Shimmer, maximal phonation time (MPT), noise to harmonic ratio (NHR) and formants frequencies(F1, F2, F3, F4). SPSS 25.0 software was used for statistically analysis. Results: Three months after surgery, the score of TVQMtF was significantly decreased [(89.9±14.7) vs. (50.4±13.6), t=11.49, P<0.001]. The F0 was significantly elevated [(152.7±23.3) Hz vs. (207.7±45.9) Hz, t=-6.03, P<0.001]. Frequencies of F1, F2 and F3 were significantly elevated. No statistical difference was observed in the frequencies of F4. The highest pitch was not significantly altered while the lowest pitch was significantly elevated [(96.8±17.7) Hz vs. (120.0±28.9) Hz, t=-3.71, P=0.001]. Habitual speech volume was significantly increased [(60.0±5.2) dB vs. (63.6±9.6) dB, t=-2.12, P=0.043]. Jitter, Shimmer, NHR and MPT were not obviously altered (P>0.05). Conclusions: Wendler Glottoplasty could notably elevate the vocal pitch, formants frequencies and degree of vocal femininity in transgender women without affecting phonation ability and voice quality. It can be an effective treatment modality for voice feminization.
Subject(s)
Transgender Persons , Humans , Male , Female , Young Adult , Adult , Middle Aged , Retrospective Studies , Speech Acoustics , Voice Quality , PhonationABSTRACT
Objective: To investigate the daily variation of LPR and the significance of 48-hour oropharyngeal pH monitoring in the diagnosis of LPRD. Methods: 72 subjects with suspected LPRD who were treated in our department from June 2018 to June 2021 were included. All patients were hospitalized to complete continuous 48-hour oropharyngeal Dx-pH monitoring. The consistency of Ryan index and W index and the correlation of various reflux parameters between the first and second 24-hour were compared. SPSS 24.0 was used for statistical analysis. Results: All 72 subjects successfully completed 48-hour oropharyngeal Dx-pH monitoring. Ryan index was positive in 11 cases (15.2%) in the first 24-hour, in 17 cases (23.6%) in the second 24-hour, in 5 cases (6.9%) both first and second, and in 23 cases (31.9%) in either 24-hour, Kappa=0.211 (P=0.064), 18 cases (25%) had inconsistent results of the first 24-hour and the second 24-hour, and there was no significant difference in the positive rate between the first and second (P=0.234). The number of positive cases in 48-hour monitoring increased by 109.1% compared with 24-hour monitoring.For W index, 49 cases (68.1%) were positive in the first 24-hourf 53 cases (73.6%) were positive in the second 24-hour, 42 cases (58.3%) were positive both first and second, and 58 cases (80.6%) were positive in either 24-hour, Kappa=0.477 (P<0.001), 16 cases (22.2%) had inconsistent results of the first and second, and there was no significant difference in the positive rate between the first and second (P=0.804). The number of positive cases in 48-hour monitoring increased by 18.4% compared with 24-hour monitoring. There was no significant difference in all the reflux parameters of first and second (P>0.05). The correlation comparison showed that the correlation of various reflux parameters in the upright position was lower than that in the supine position. Conclusion: Laryngeal reflux has daily variability. Extending the monitoring time of Dx-pH to 48-hour can help reduce the missed diagnosis caused by daily variability; the use of W index can reduce the influence of daily variability on the diagnostic results of LPRD.
Subject(s)
Laryngopharyngeal Reflux , Larynx , Humans , Laryngopharyngeal Reflux/diagnosis , Hydrogen-Ion Concentration , HypopharynxABSTRACT
Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Subject(s)
Stomach Neoplasms , Chemotherapy, Adjuvant , Female , Gastrectomy , Humans , Male , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
OBJECTIVE: To observe the postoperative bleeding after percutaneous renal biopsy (PRB) in Tibet, To analyze and summarize the risk factors associated with bleeding in high altitude patients to improve the safety of surgery. METHODS: A retrospective analysis of 150 cases of PRB in the Department of Nephrology, People's Hospital of Tibet Autonomous Region from May 2016 to May 2018 were carried out, and the correlations between the potential risk factors (gender, age, blood pressure, hemoglobin, platelet, serum creatinine) and postoperative bleeding events were analyzed. RESULTS: During the study period, the 150 patients receiving procedure of PRB were enrolled in our hospital, with an average age of (41.2±15.6) years, of whom 58.7% (88/150) were male, 41.3% (62/150) were female, and major bleeding complications occurred in 12 biopsies (8.0%, 12/150). Six cases for men and women, respectively. The mean age in the bleeding group seemed to be higher than that in the non-bleeding group [(48.3±20.0) years vs. (40.6±15.1) years, P=0.099]. There was no significant difference in the incidence of hypertension, hemoglobinemia, urea nitrogen and prothrombin time between the two groups. The level of serum creatinine in the hemorrhage group seemed to be higher than that in the non-bleeding group (P=0.090), and the time of the hemorrhagic group was longer than that in the non-bleeding group (P=0.069). The platelet count in the bleeding group was significantly lower than that in the non-bleeding group (P < 0.05). Multivariate Logistic regression analysis showed that the prolonged activation of partial prothrombin time and lower platelet count had a relatively high risk of bleeding, which was statistically significant (P=0.079, P=0.082). CONCLUSION: PRB is safe and reliable on the whole in plateau areas; Old age, low platelet count, decreased renal function and prolonged activated partial coagulation time are related to postoperative bleeding of PRB, and hyperhemoglobin is not a risk factor for bleeding. High hemoglobin is not a risk factor for postoperative bleeding of PRB at high altitude.
Subject(s)
Hemorrhage , Adult , Aged , Biopsy , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Male , Middle Aged , Partial Thromboplastin Time , Retrospective Studies , Risk Factors , TibetABSTRACT
Purpose To investigate the possibility of using the methylation level of PAX1/ZNF582 gene as molecular marker to differentiate the progression of cervical cancer. Methods From January 2016 to March 2018, 150 patients, who were admitted to Cervical Disease Diagnosis and Treatment Center of Xuzhu Maternity and Child Care Hospital, were enrolled in this study. Patients were classified into chronic cervicitis (for 19 cases), low-grade squamous intraepithelial lesion (LSIL) (18 cases), high-grade squamous intraepithelial lesion (HSIL) (37 cases) and squamous cell carcinoma (SCC) (31 cases). All patients underwent several tests including Thin-prep cytology test (TCT), HPV DNA detection and detection of methylation level of PAX1/ZNF582 genes. Results For diagnosis of HSIL, the area under curve (AUC) was 0.878 (95% CI 0.806 ~ 0.950); the threshold for PAX1 was 12.285, the sensitivity and specificity were 91.9% and 72.8%, respectively. The AUC of ZNF582 gene detection was 0.900 (95% CI 0.842 ~ 0.959), the threshold was 11.56, while the sensitivity and specificity were 97.3% and 76.7%, respectively. Among various tests we conducted, PAX gene detection methods showed the highest specificity (97.30%). PAX1/ZNF582 gene detection method demonstrated the highest accuracy. Conclusions For patients with high-grade cervical lesion and cervical cancer, the methylation level of PAX1/ZNF582 gene could be applied as a noteworthy biomarker for diagnosis and for cervical cancer classification (AU)
Subject(s)
Humans , Female , Young Adult , Adult , Middle Aged , Aged , Carcinoma, Squamous Cell/genetics , Transcription Factors/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Chronic Disease , DNA Methylation , DNA, Viral , Disease Progression , Genetic Markers , Sensitivity and Specificity , Uterine Cervical Neoplasms/virologyABSTRACT
BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
Subject(s)
Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Adult , Antineoplastic Combined Chemotherapy Protocols , China , Double-Blind Method , Female , Humans , Indazoles , Maintenance Chemotherapy , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Piperidines , Poly(ADP-ribose) Polymerase Inhibitors/adverse effectsABSTRACT
PURPOSE: To investigate the possibility of using the methylation level of PAX1/ZNF582 gene as molecular marker to differentiate the progression of cervical cancer. METHODS: From January 2016 to March 2018, 150 patients, who were admitted to Cervical Disease Diagnosis and Treatment Center of Xuzhu Maternity and Child Care Hospital, were enrolled in this study. Patients were classified into chronic cervicitis (for 19 cases), low-grade squamous intraepithelial lesion (LSIL) (18 cases), high-grade squamous intraepithelial lesion (HSIL) (37 cases) and squamous cell carcinoma (SCC) (31 cases). All patients underwent several tests including Thin-prep cytology test (TCT), HPV DNA detection and detection of methylation level of PAX1/ZNF582 genes. RESULTS: For diagnosis of HSIL, the area under curve (AUC) was 0.878 (95% CI 0.806 ~ 0.950); the threshold for PAX1 was 12.285, the sensitivity and specificity were 91.9% and 72.8%, respectively. The AUC of ZNF582 gene detection was 0.900 (95% CI 0.842 ~ 0.959), the threshold was 11.56, while the sensitivity and specificity were 97.3% and 76.7%, respectively. Among various tests we conducted, PAX gene detection methods showed the highest specificity (97.30%). PAX1/ZNF582 gene detection method demonstrated the highest accuracy. CONCLUSIONS: For patients with high-grade cervical lesion and cervical cancer, the methylation level of PAX1/ZNF582 gene could be applied as a noteworthy biomarker for diagnosis and for cervical cancer classification.
Subject(s)
Carcinoma, Squamous Cell/genetics , Kruppel-Like Transcription Factors/genetics , Paired Box Transcription Factors/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Alphapapillomavirus/genetics , Area Under Curve , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Chronic Disease , DNA Methylation , DNA, Viral/analysis , Disease Progression , Female , Genetic Markers , Humans , Middle Aged , Neoplasm Grading , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Uterine Cervicitis , Young Adult , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virologyABSTRACT
Objective: To analyze the resistance mutational profiles of multi-drug resistant Mycobacterium tuberculosis in China and the correlation between major mutation types and genotypes based on the whole-genome sequencing data. Methods: Search and download of the genome-wide sequencing data of M. tuberculosis published in China by August 2019 on NCBI database were conducted. Mutation frequency of drug resistance-related gene loci based on whole-genome sequencing was used to predict the molecular susceptibility of strains, and the correlation between mutation types and genotypes was analyzed. Results: According to the results of molecular resistance and susceptibility profiles, 1 024 MDR strains were identified from 2 019 M. tuberculosis strains. The major mutation types of resistance-related genes to common drugs were katG S315T (73.2%, isoniazid), rpoB S450L (63.1%, rifampicin), rpsL K43R (70.0%, streptomycin), embB M306V (37.4%, ethambutol), pncA_promoter T (-11)C (7.9%, pyrazinamide), gyrA A90V (32.3%, fluoroquinolones), rrs A1401G (67.7%, second-line injection drugs), fabG1_promoter C (-15) T (87.0%, Ethionamide), folC I43T (30.4%, P-aminosalicylic acid). Among them, the frequencies of katG S315T, embB M306V, rpsL K43R, gyrA A90V in lineage 2 were significantly higher than those in lineage 4, and folC I43T was only found in lineage 2. The proportion of katG S315T was significantly higher in the ancient Beijing genotype compared to the modern genotype, in contrast, the proportion of rpsL K43R was significantly higher in modern Beijing genotype, the differences were significant (all P<0.05). Conclusions: The results showed the main mutation types of resistance-related genes of MDR strains to many commonly used anti-tuberculosis drugs in China based on whole-genome sequencing, providing a basis for the development of sensitive and specific rapid molecular detection methods. At the same time, it was also found that the major mutation types of MDR-related genes were related to the genotype of the strains.
Subject(s)
Tuberculosis, Multidrug-Resistant , Antitubercular Agents , China , Drug Resistance , Genome-Wide Association Study , Humans , Microbial Sensitivity Tests , MutationABSTRACT
Lung cancer is the main cause of cancer incidence and mortality around the world. Prucalopride is an agonist for the 5-hydroxytryptamine 4 receptor, but it was unknown whether prucalopride could be used to treat lung cancer. To investigate the biological effects of prucalopride on proliferation, apoptosis, invasion, and migration of lung cancer cells, and its underlying molecular mechanism in the progression of lung cancer, we performed this study. The Cell Counting Kit 8 assay was used to measure the proliferation of A549/A427 lung cancer cells treated with prucalopride. Transwell assay was applied to evaluate cell invasion and migration. Cell apoptosis was detected by flow cytometry and Western blot analyses. The expression levels of related proteins in the PI3K/AKT/mTor signaling pathway were analyzed by Western blotting. Prucalopride inhibited the proliferation, invasion, and migration of A549/A427 human lung cancer cells. It also induced autophagy and apoptosis and decreased the expression of the phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) in these cells. This study implied an inhibitory role for prucalopride in the progression of human lung cancer.
Subject(s)
Benzofurans/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Proto-Oncogene Proteins c-akt/therapeutic use , Signal Transduction/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic , HumansABSTRACT
Adolescents have been largely neglected from tuberculosis control efforts. In low- to medium burden settings much of the tuberculosis burden in this age group occurs from school outbreaks. We report on a large tuberculosis outbreak in adolescents from a boarding high school in Jiangsu Province, China. From March to June 2018, a tuberculosis outbreak occurred in a boarding high school. We conducted an outbreak investigation involving clinical diagnostic tests and molecular analysis to determine the outbreak origin. Cases were detected through symptom screening, tuberculin skin testing (TST), chest radiography, sputum smear, solid sputum culture and GeneXpert MTB/RIF. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping and spoligotyping methods were performed on Mycobacterium tuberculosis (M. tuberculosis) isolates to identify the outbreak origin. A total of 845 students and 131 teachers/staff attended a TST screening for tuberculosis infection. The prevalence of elevated tuberculin reactions at ≥5, ≥10 and ≥15 mm was 12.19% (119/976), 6.35% (62/976) and 3.28% (32/976), respectively. Radiographic abnormalities were present in 5.73% (56 of 976) individuals, 40 students and 16 teachers/staff. Of these, 12 students were diagnosed with confirmed tuberculosis. In total, 14 students (two index cases and 12 confirmed cases) were diagnosed and reported in the tuberculosis outbreak, an attack rate of 1.7% (14/847) among students (two index cases and 845 screened students). Results from MIRU-VNTR typing and spoligotyping analyses demonstrated that three M. tuberculosis strains belong to the Beijing family with corresponding MIRU-VNTR alleles. This school-based tuberculosis outbreak among adolescents demonstrates that transmission among individuals in this age group is common and must be prioritised. It suggests that identifying and timely diagnosis of smear-positive cases, especially in the early phase of outbreaks, is the key to preventing further spread among close contacts.
Subject(s)
Disease Outbreaks , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , China/epidemiology , Female , Humans , Male , Middle Aged , Schools , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/prevention & controlABSTRACT
Objective: To investigate the inhibitory effect of programmed cell death factor 4 (PDCD4) on arsenic trioxide (As(2)O(3))-induced cell growth and nuclear factor kappa B (NF-κB) signaling pathway in neuroblastoma. Methods: The PDCD4 overexpression vector was transfected into neuroblastoma cells and detected by fluorescence quantitative PCR and Western blot. As(2)O(3) was used to treat PDCD4 overexpressing neuroblastoma cells. MTT assay was used to measure the proliferation. Colony formation assay was used to determine the cell clone forming ability. Apoptosis was measured by flow cytometry. Western blot was used to detect the expression of NF-κB p65 and cleaved caspase-3 protein in cells. Results: The transfection of PDCD4 overexpression vector significantly increased the expression level of PDCD4 in neuroblastoma cells. The cell survival rates of the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 100%, (72.14±5.20)%, (62.58±3.14)% and (40.87±2.47)%, respectively. The colony formation rates in these four groups were (91.25±8.36)%, (65.32±7.14)%, (57.23±5.28)% and (37.14±3.64)%, respectively. In addition, the cell apoptotic rates of these four groups were (3.57±0.24)%, (28.64±3.20)%, (36.41±4.58)% and (49.65±5.27)%, respectively. Therefore, overexpression of PDCD4 in the absence or presence of As(2)O(3) inhibited cell proliferation and clone formation ability, while promoted apoptosis. Furthermore, the expression levels of cleaved caspase-3 in the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 0.21±0.03, 0.30±0.02, 0.43±0.05 and 0.57±0.06, respectively. And the expression levels of NF-κB p65 protein were 0.68±0.04, 0.52±0.03, 0.43±0.04, and 0.32±0.02, respectively. Compared with the control group, the expression levels of NF-κB p65 protein in PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were significantly decreased (P<0.05), whereas the expression level of cleaved Caspase-3 protein was significantly increased (P<0.05). The changes in As(2)O(3)+ PDCD4 group were more significant than those in PDCD4 group and As(2)O(3) groups (both P<0.05). Conclusion: PDCD4 enhances the inhibitory effect of As(2)O(3) on the growth and NF-κB signaling pathway in neuroblastoma cells.
Subject(s)
Apoptosis Regulatory Proteins/genetics , Apoptosis/drug effects , Arsenic Trioxide/pharmacology , NF-kappa B/physiology , Neuroblastoma/drug therapy , RNA-Binding Proteins/genetics , Signal Transduction/drug effects , Antineoplastic Agents , Apoptosis Regulatory Proteins/metabolism , Cell Differentiation/drug effects , Cell Survival/drug effects , Humans , RNA-Binding Proteins/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Objective: To investigate the effects and mechanisms of miR-144 on proliferation, apoptosis and cisplatin (DDP) resistance of neuroblastoma cells. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expressions of miR-144 and MYCN in neuroblastoma cell lines, including SH-SY5Y and SK-N-SH, and human umbilical vein endothelial cells HUVEC. The miR-negative control, miR-144 mimics, si-negative control, si-MYCN, miR-144 mimics and pcDNA, miR-144 mimics and pcDNA-MYCN co-transfected SH-SY5Y cells were described as miR-NC, miR-144, si-NC, si-MYCN, miR-144+ pcDNA and miR-144+ pcDNA-MYCN group, respectively. The half maximal inhibitory concentration (IC(50)) and cell proliferation were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The protein expressions of MYCN, p21, cyclin D1, Bax, Bcl-2 were analyzed by western blot. Cell apoptosis was detected by flow cytometry. The cell fluorescence activity was detected by double luciferase reporter gene assay. Results: Compared with HUVEC cells, the expressions of miR-144 in neuroblastoma cells SH-SY5Y and SK-N-SH significantly decreased, while the mRNA and protein expression of MYCN significantly increased. The IC(50) of DDP was 9.16 µg/ml in SH-SY5Y cells. The absorbance value in 490nm (A(490) value) of miR-144 group was 0.30±0.03, significantly lower than 0.46±0.03 of miR-NC group. The cell apoptotic rate of miR-144 group was 26.94%±2.01%, significantly higher than 9.68%±0.52% of miR-NC group. The IC(50) value of DDP in miR-144 group was 2.95±0.26, significantly lower than 9.23±0.61 of miR-NC group. The expressions of p21, cyclin D1, Bax, Bcl-2 in miR-NC and miR-144 group were 2.67±0.19, 0.41±0.04, 2.12±0.21, 0.18±0.01 and 1.01±0.07, 1.00±0.06, 1.00±0.05, 1.00±0.06, respectively, with statistical significance (all P<0.05). Knockdown of MYCN showed the similar effects with those of miR-144 overexpression in SH-SYSY cells. MiR-144 significantly inhibited the fluorescence activity of ectopic MYCN expressing cells and negatively regulated the expression of MYCN. Overexpression of MYCN can reverse the effects of miR-144 on proliferation inhibition, apoptosis promotion and sensitization of SH-SY5Y cells to DDP. Conclusion: MiR-144 inhibits proliferation, promotes apoptosis and enhances the sensitivity of neuroblastoma cells to DDP through targeting MYCN, which provides a potential treatment for neuroblastoma.
Subject(s)
Apoptosis/genetics , Cell Proliferation/genetics , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , MicroRNAs/genetics , N-Myc Proto-Oncogene Protein/therapeutic use , Neuroblastoma/drug therapy , Neuroblastoma/genetics , Antineoplastic Agents/pharmacology , Apoptosis/physiology , Cell Line, Tumor , Cell Proliferation/physiology , Child , Gene Expression Regulation, Neoplastic , Humans , N-Myc Proto-Oncogene Protein/genetics , Neuroblastoma/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Tibial dyschondroplasia (TD) is a type of bone deformity found in fast-growing chickens, which induce inflammatory responses. Prostaglandins (PGs) implicate in bone formation and bone resorption, associated with inflammation in an autocrine/paracrine manner. This study used qRT-PCR and immunohistochemistry analysis to identify the expression patterns of PG-related genes in the erythrocytes of broiler chickens and explore the effects of thiram-induced TD and the recombinant glutathione-S-transferase A3 (rGSTA3) protein on the expression of PG-related genes: GSTA3, cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E synthase (PTGES), prostaglandin E2 receptor (PTGER) 3, PTGER4 and prostaglandin reductase 1 (PTGR1). Interestingly, the results showed that these seven PG-related genes expression was identified in the erythrocytes of broiler chicken, and thiram-induced TD suppressed the expression of these PG-related genes in the initial stage of TD and promoted their expression in TD recovery. These findings demonstrated that the immunoregulatory function of erythrocytes can be inhibited in the early stage of TD and promoted in the recovery stage by modulating the expression of PG-related genes. Further, the rGSTA3 protein can modulate the expression of PG-related genes in erythrocytes and participate in the recovery of TD.
Subject(s)
Chickens , Glutathione Transferase/pharmacology , Osteochondrodysplasias/veterinary , Poultry Diseases/genetics , Prostaglandins/genetics , Tibia/pathology , Animals , Avian Proteins/pharmacology , Erythrocytes/metabolism , Mutagens/pharmacology , Osteochondrodysplasias/chemically induced , Osteochondrodysplasias/genetics , Poultry Diseases/chemically induced , Prostaglandins/metabolism , Recombinant Proteins/pharmacology , Thiram/pharmacologyABSTRACT
Tea plant (Camellia sinensis [L.] O. Kuntze) is a woody crop of high economic importance worldwide; however, information on the molecular mechanisms underlying the regulation of flower development in this species is limited. In the present study, two GLOBOSA (GLO) -like MADS-box genes, CsGLO1 and CsGLO2, were isolated from C. sinensis 'Ziyangzhong' and were characterized to elucidate their roles in flower development. We found that CsGLOl and CsGLO2 are nuclear-localized transcription factors without transactivation ability but with a robust interaction. They have similar patterns of expression, both mainly restricted to petals and stamens. Moreover, ectopic expression of either CsGLO1 or CsGLO2 in Arabidopsis thaliana resulted in a partial conversion of sepals to petals, suggesting full GLOBOSA functional activity. Our results indicate that CsGLO1 and CsGLO2 paralogs might redundantly contribute to petal and stamen, providing the first insight into their role in tea plant flower development.
Subject(s)
Camellia sinensis/genetics , MADS Domain Proteins/genetics , Plant Proteins/genetics , Gene Expression Regulation, Plant , Genes, PlantABSTRACT
OBJECTIVE: To investigate the regulating roles of miR-199b in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The expression of miR-199b of 45 human HCC tissues and the corresponding para-cancerous tissue samples were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Western blot was employed to investigate the level of JAG1. Transwell assay was used to monitor the ability of cell migration and invasion. Cell proliferation was tested by CCK-8 assay and luciferase reporter assay was done to clarify whether JAG1 was a target of mir-199b. RESULTS: miR-199b expression level was decreased in 45 paired tumor tissues in contrast with the corresponding para-carcinoma tissues. The expression level of miR-199b was closely associated with TNM stage, tumor size, and 5-year overall survival. Transwell assay result showed that miR-199b inhibited HCC cell migration and invasion. Cell counting kit-8 (CCK-8) results demonstrated that miR-199b could suppress HCC cell proliferation. Luciferase reporter assay suggested that Jagged1 (JAG1) was a direct target of miR-199b in HCC cells. miR-199b could negatively regulate JAG1 expression by targeting JAG1. CONCLUSIONS: miR-199b exerted tumor suppressive functions in HCC by targeting JAG1, and it may be a potential target treatment for hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/genetics , Jagged-1 Protein/metabolism , Liver Neoplasms/genetics , MicroRNAs/genetics , Carcinoma, Hepatocellular/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Signal Transduction/geneticsABSTRACT
Background: Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient's metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography-quantified body composition and short-term outcomes after gastrectomy for gastric cancer. Methods: Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed "sarcopenia," "myosteatosis," and "visceral obesity." The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed. Results: The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (p = 0.013), myosteatosis (p = 0.017), and low serum retinol-binding protein (p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein (p = 0.026). Conclusions: Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer.
Subject(s)
Adenocarcinoma , Body Composition , Gastrectomy , Stomach Neoplasms , Tomography, X-Ray Computed , Adenocarcinoma/blood , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Aged , Female , Humans , Male , Middle Aged , Muscle, Skeletal/pathology , Obesity, Abdominal/blood , Obesity, Abdominal/diagnostic imaging , Obesity, Abdominal/surgery , Postoperative Complications , Retinol-Binding Proteins/analysis , Sarcopenia/blood , Sarcopenia/diagnostic imaging , Sarcopenia/surgery , Stomach Neoplasms/blood , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
Thiram, a carbamate pesticide, is known to induce tibial dyschondroplasia (TD) in broiler chickens. This study used a thiram-induced TD model to explore whether apoptosis-related genes were expressed in erythrocytes of broiler chickens and the impacts of thiram-induced TD and the recombinant GSTA3 protein in regulating these genes expression. In this study, mRNA and protein expression of six types of apoptosis-related genes (Bcl-2, Bax, Murine double minute MDM2, Bcl-2-associated athanogene BAG-1, BAG-3, STAT3) were identified in erythrocytes of broiler chickens by real-time PCR and immunohistochemistry, and we also found that thiram-induced TD induced the decreased expression of these antiapoptotic genes in the initial stage of TD and promoted their expression in TD recovery, which suggested that the expression of these apoptosis-related genes in erythrocytes is highly related to the development of TD. Further, the recombinant GSTA3 protein promoted the expression of all apoptosis-related genes in the initial stage of TD and recovered the normal expression of these genes in the recovery stage of TD, which indicated that the recombinant GSTA3 protein may participate in the recovery of TD. Further studies are needed to elucidate the mechanism of the response of erythrocytes to thiram-induced TD and the recombinant protein GSTA3 in broiler chickens.