Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

Current census of oncology critical care medicine in China.

OBJECTIVE: The purposes of this survey were to show the current situation of oncology critical care medicine in China by questionnaire, to understand the resource distribution of oncology critical care medicine and to analyze and evaluate the existing resources and reserve capacity of oncology critical care medicine in China. METHODS: We conducted the survey mainly in the form of an online questionnaire. The Committee of Cancer Critical Care Medicine of the Chinese Anticancer Association (CACA) initiated the survey on 1 November 2017, and 36 member hospitals nationwide participated in the survey. The questionnaire included 10 items: investigator information, hospital information, general information of oncology critical care department, staffing of oncology critical care department, management in oncology critical care department, technical skills in oncology critical care department, patient source in oncology critical care department, equipment configuration in oncology critical care department, special skills in oncology critical care department and summary of the information. RESULTS: The survey results included information from 28 member units, all of which were tertiary hospitals, distributed in 20 provinces and 4 direct-controlled municipalities. The results are as follows. (i) The total ratio of beds in the oncology critical care department to hospital beds was 1.06%, and the average number of beds in the oncology critical care department was 16.36. (ii) The ratio of physicians in the oncology critical care department to beds was ∼0.62:1, and the ratio of nurses to beds was ∼1.98:1. (iii) According to the census of the population and gross domestic product (GDP) of different regions conducted by the State Statistics Bureau in 2017, the ratio of beds in the oncology critical care department for tumor patients to the population was 4.55 beds per 10 million people, and the ratio of beds in the oncology critical care department to GDP was 8.00 beds per RMB 100 billion, on average. (iv) According to the requirements of the guidelines for the development and management of critical care medicine in China, the facilities in departments of oncology critical care medicine meet the requirements, and the technical skills of medical staff are competent. CONCLUSION: The development of oncology critical care in China is becoming better, but there is still a certain gap compared with the intensive care unit standards in China and the average level of the nationwide. The development of oncology critical care medicine is urgent.

Effect of Polyphenols on Cognitive Function: Evidence from Population-Based Studies and Clinical Trials.

Due to progressive population aging, a new dementia case occurs at every 3 seconds, placing a heavy burden of disease. Identifying potential risk or preventive factors is emphasized owing to a lack of effective treatment for dementia. There has been emerging evidence on the link of certain dietary components, particularly polyphenols, to brain wellness and cognitive outcomes. Findings from animal and in vitro studies appear more consistent and conclusive. However, such an association has not been investigated in depth in human beings. In this review, we examined studies on the effect of dietary polyphenols (including flavonoids, curcumin, and resveratrol) on cognitive function. Intervention in early stages of dementia/Alzheimer's disease might be a target to slow down age-related cognitive decline before disease onset. We summarized 28 epidemiological studies (8 cross-sectional and 20 cohort studies) and 55 trials in this review. Preliminary evidence from epidemiological data provides the necessity for intervention trials, even though the measures of polyphenol intake tend to be less precise. Clinical trials are in favor of the role of some polyphenols in benefiting specific domains of cognition. This review also describes the divergence of results and current limitations of research in this field.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib.

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.

[Association between resting heart rate trajectory pattern and risk of cardiovascular and cerebrovascular diseases].

Objective: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of cardiovascular and cerebrovascular diseases (CVDs). Methods: This prospective cohort study included 63 040 participants who took part in the health examination in 2006 and one of the health examinations on 2008 or 2010 and were free of myocardial infarction, stroke, arrhythmia, cancer and not treated with ß-recepter blocker. The outcomes were the first occurrence of myocardial infarction and stroke during the follow up ended on December 31, 2015. RHRs were measured in 2006, 2008, and 2010. We used latent mixture modeling SAS Proc procedure to identify RHR trajectories. We identified 4 distinct RHR trajectory patterns based on the data derived from 2006 and on the pattern change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing). Collected the general clinical data of the patients. Cox regression model was used to determine the association between RHR trajectory patterns and the risk of CVDs during follow up. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: There were statistical significance among the 4 distinct RHR trajectory patterns on the following variables: age, gender, smoking status, drinking status, physical activity, education status, history of use antihypertensive drugs, history of hypertension,history of diabetes, body mass index, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and the level of high-sensitivity C-reactive protein (all P<0.01). The moderate-increasing pattern experienced the highest risk of developing stroke and CVDs among all 4 patterns. The cumulative incidence of cerebral infarction, cerebral hemorrhage and CVDs in the order of low-stable trajectory, moderate-stable trajectory and moderate-increasing trajectory. The cumulative incidences of cerebral infarction, cerebral hemorrhage and CVDs in elevated-decreasing trajectory group were significantly lower than those in moderate-increasing trajectory group, but higher than those in moderate-stable trajectory group. Compared to the low-stable pattern, adjusted HR was 1.3 (95%CI 1.0-1.6) for the moderate-increasing pattern after adjustment for potential confounders. Conclusion: Our study finds that individuals with moderate-increasing RHR trajectory pattern are associated with higher risk of cardiovascular and CVDs.

[Mechanism of androgen in improving erectile dysfunction in castrated rats by regulating androgen receptor/vascular endothelial growth factor].

Objective: To explore the mechanism of androgen in improving erectile dysfunction in castrated rats. Methods: Forty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups:normal control group (Group A); castration group (Group B, in which rats were castrated); intervention groups (group C and D), in which rats were treated with different concentrations of testosterone undecanoate orally every day at 10 mg/kg (low dose) and 20 mg/kg (high dose), respectively after being castrated. Animals in group A and B were given 0.9% NS instead. After 8-week treatment, the level of serum testosterone, intra cavernous pressure (ICP) and mean arterial pressure (MAP) were detected, and the expression of androgen receptor (AR)and vascular endothelial growth factor (VEGF) were detected in the penis by Immunohistochemistry and Western blot. Results: The level of serum testosterone was significantly lower in group B [(1.3±0.6) nmol/L] than in group A [(17.1±1.5) nmol/L] (P<0.05).After testosterone supplementation, serum testosterone levels in group C [(8.7±1.2) nmol/L] and group D [(15.5±1.6) nmol/L] were higher than that in group B (all P<0.05). Max ICP/MAP of group C and D were higher than that in group B (all P<0.05). Immunohistochemistry and Western blot showed that the expression levels of AR and VEGF in group B were significantly lower than those in group A, C and D, and group D > group C (all P<0.05). Conclusion: Androgen replacement therapy with testosterone undecanoate can improve the erectile function of castrated rats by protecting the integrity of endothelial cells through AR/VEGF pathway.

MiR-483 suppresses cell proliferation and promotes cell apoptosis by targeting SOX3 in breast cancer.

OBJECTIVE: To explore the mechanism underlying the effect of microRNA-483 (miR-483) in the progression of breast cancer (BC). PATIENTS AND METHODS: MiR-483 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in both BC cells and tissue samples. The associations between miR-483 expression level and patients' overall survival rate were explored. Furthermore, cell proliferation assay and cell apoptosis assay were conducted, respectively. In addition, Western blot analysis and Luciferase assay were performed to explore the underlying mechanism. RESULTS: The expression level of miR-483 was significantly decreased in tumor samples compared to that in adjacent tissues, which was also associated with patients' overall survival time. Moreover, cell growth was promoted, and cell apoptosis was inhibited after miR-483 was knocked down in vitro. Furthermore, SOX3 acted as a direct target of miR-483, and the expression of SOX3 was negatively correlated with the expression of miR-483 in tumor tissues. CONCLUSIONS: These results suggested that miR-483 could suppress BC cell proliferation and promote BC cell apoptosis via targeting SOX3, which might be a potential therapeutic target in BC.

[Problems and suggestions for the application of diagnosis-related groups system in burn surgery].

The diagnostic codes of diagnosis-related groups system used in our country are different from the clinical diagnostic criteria of burns. The author suggests that the diagnostic codes should be improved according to clinical criteria in terms of the total area and depth of burns and inhalation injury, and the diagnosis of burns with related special causes and sites should be added to the clinical criteria.

Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats.

OBJECTIVE: Vascular dementia (VD) is a type of memory, cognition, and behavior disorder caused by ischemic stroke or hemorrhagic stroke. It is a common pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation plays a key role in VD. Interleukin-1ß (IL-1ß) is a kind of pro-inflammatory cytokine, while its mechanism in VD occurrence and development is still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided into three groups, including sham group, VD model group (established by bilateral common carotid artery ligation), and IL-1ß group (treated by IL-1ß monoclonal antibody intracerebroventricular injection on based on model group). Rat learning ability was evaluated by Morris water maze assay. IL-1ß expression in brain tissue and peripheral blood was examined by using Real Time-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Hippocampus apoptosis was detected by caspase 3 activity detection kit. B-cell lymphoma-2 (Bcl-2) and p38 mitogen-activated protein kinase (MAPK) protein levels were assessed by Western blot assay. RESULTS: IL-1ß expression was increased, caspase 3 activity was enhanced, Bcl-2 level was declined, and p-P38 phosphorylation was elevated in brain tissue and peripheral blood from VD model group compared to sham group (p<0.05). IL-1ß monoclonal antibody significantly reduced IL-1ß expression, improved learning ability, attenuated caspase 3 activity, increased Bcl-2 level, and declined p-P38 expression in VD rats compared to model group (p<0.05). CONCLUSIONS: IL-1ß can delay VD occurrence and development through the P38-MAPK signaling pathway to regulate cell apoptosis and improve learning ability.

[The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection].

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats.

Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves age-related erectile dysfunction (ED). Autophagy has been implicated in age-related diseases, including ED. However, the molecular mechanisms underlying hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18 months of age and divided into three groups: young WTR (yWTR) as the control group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that hKLK1 improved the impaired erectile function of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the aWTR group. hKLK1 may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR pathway. These observations indicate that hKLK1 is a potential gene therapy candidate for age-related ED.

Continuous blood purification treatment for endotoxin-induced acute respiratory distress syndrome.

This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy. During the treatment process, the variations in dynamic lung compliance, oxygenation index, hemodynamics, and urine volume per hour at different times (Baseline, 0, 2, 4, and 6 h) were recorded. The levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were measured using the enzyme-linked immunosorbent assay. The histomorphological changes of the lung, heart, and kidney were visualized using a light microscope. The nuclear factor κB p65 protein content of the heart, lung, and kidney tissues was also detected using western blot. The experimental group outperformed the control group in both respiratory and hemodynamic events. CBP treatment cleared TNF-α, IL-6, and IL-10 partially from serum and BALF. The pathological examination of the heart, lung, and kidney tissues revealed that the injury was less severe in the experimental group. CBP treatment can improve the organ functions of pigs affected with endotoxin-induced ARDS and protect these organs to some extent.

Continuous blood purification treatment for endotoxin-induced acute respiratory distress syndrome

This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy. During the treatment process, the variations in dynamic lung compliance, oxygenation index, hemodynamics, and urine volume per hour at different times (Baseline, 0, 2, 4, and 6 h) were recorded. The levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were measured using the enzyme-linked immunosorbent assay. The histomorphological changes of the lung, heart, and kidney were visualized using a light microscope. The nuclear factor κB p65 protein content of the heart, lung, and kidney tissues was also detected using western blot. The experimental group outperformed the control group in both respiratory and hemodynamic events. CBP treatment cleared TNF-α, IL-6, and IL-10 partially from serum and BALF. The pathological examination of the heart, lung, and kidney tissues revealed that the injury was less severe in the experimental group. CBP treatment can improve the organ functions of pigs affected with endotoxin-induced ARDS and protect these organs to some extent.

Exogenous Estradiol Benzoate Induces Spermatogenesis Disorder through Influencing Apoptosis and Oestrogen Receptor Signalling Pathway.

As the exact role for exogenous oestrogen in spermatogenesis is not fully understood, the aim of this study was to investigate the effect of estradiol benzoate (EB) exposure to male mice on their spermatogenesis and fertility. Sixty male mice aged 4 weeks were randomly divided into three groups, including a control group and two treatment groups. The mice of the control group were injected with 250 µl paraffin oil only by every other day subcutaneous injection for 4 weeks. Meantime, the mice of the treatment groups were injected with EB at the concentration of 5 or 10 mg/kg, respectively. Results showed that EB slowed down the body weight gains and generated testicular atrophy with spermatogenesis disorder compared with that of the control mice, and consequently induced their infertility. Moreover, the number of TUNEL-positive cells in the testis of EB-treated mice was significantly increased with the EB concentration rise. In comparison with controls, the mRNA expression level of pro-apoptosis factors (Fas, TNF, Cytochrome C, Apaf1, Chop, Caspase-3, Caspase-8, Caspase-9 and Caspase-12) and key genes in oestrogen receptor (ER) signalling pathway (ER α, ER ß, Erk1/2, Hsp90 and DAX-1) were upregulated in the testes of the treatment groups. Furthermore, Western blotting results proved the protein expression level of Fas, TNF, Cytochrome C, Chop, Caspase-3, cleaved Caspase-3, Caspase-9, Erk1/2 and Hsp90 were upregulated, and the phosphorylation level of Erk1/2 was also increased. These results indicate that EB may impair spermatogenesis through influencing the apoptosis and ER signalling pathway.

Endogenous hormonal equilibrium linked to bamboo culm development.

Moso bamboo (Phyllostachys heterocycla) is the most important bamboo species in China and is famous for its fast-growing culms. To investigate the possible relationship between internode development and endogenous hormones, the concentrations of indole-3-acetic acid (IAA), zeatin riboside (ZR), gibberellins (GA3), and abscisic acid (ABA) were analyzed in culm samples from plants at different developmental stages during a single growing season and, at the same time, anatomical structure was closely monitored. Cell division was the dominant process in internode development during early development, while cell elongation predominated at later stages. There was a negative correlation between the rates of cell division and cell elongation. The four endogenous hormones (IAA, ZR, GA3, and ABA) displayed fluctuations in their levels at different developmental stages but their peak activities were not synchronous. Cell division rate had a significant positive correlation with ZR concentration. Cell elongation had a significant positive correlation with the ratio of promoting hormones (IAA, GA3, and ZR) to inhibitory hormone (ABA) concentrations. We conclude that hormonal equilibrium might regulate the division and elongation of bamboo culms.

Association of the TNF-α+489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis.

The association between the TNF-α +489 G/A polymorphism and chronic obstructive pulmonary disease (COPD) remains controversial because of small group size and varied design among different studies. In the present study, a meta-analysis was conducted to assess the association between the +489 G/A polymorphism and COPD risk. A comprehensive search was conducted to identify articles that have reported an association between the TNF-α +489 G/A polymorphism and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under both dominant (AA+GA vs GG genotypes) and allele (A vs G) models. Heterogeneity was assessed, as well as publication bias. Nine articles with ten eligible studies were included in this analysis. Significant association between the +489 G/A polymorphism and COPD was identified in Asians under the allele model (OR = 1.582, 95%CI = 1.035-2.419). However, no significant difference was found in the Caucasian groups. Strong evidence for between-study heterogeneity was identified under both models, and no publication bias was detected. Our results indicated a potential role of the A allele of the TNF-α +489 G/A polymorphism in increasing COPD risk in Asians, but not in Caucasians. Additional studies will be necessary to verify this conclusion.

Generation of Foxo3-targeted Mice by Injection of mRNAs Encoding Transcription Activator-like Effector Nucleases (TALENs) into Zygotes.

In this study, for exploring the mechanism of forkhead box O3(Foxo3) participating in regulation of the activation of primordial oocytes, Foxo3-targeted mice were generated by injection of mRNAs encoding transcription activator-like effector nucleases (TALENs) into mouse zygotes. The TALEN sites were designed with high conservative homologous region among pig, bovine, buffalo and mouse by commercial bio-companies. The TALENs mutagenic non-homologous end-joining (NHEJ) repair activity were determined to be 31.3% in human embryonic kidney 293T (HEK-293T) cells by dual luciferase reporter assay system. Then, we firstly injected TALEN-mRNAs into the cytoplasm of mouse zygotes by micromanipulation, and four of 48 mouse blastocysts were identified as mutation by sequencing. Subsequently, by the method of TALEN-mRNAs injected into the zygotes with pronucleus micromanipulation technique, we obtained seven Foxo3 mutants of 20 FVB/NJ backgrounds mice which were Foxo3-independent alleles with frameshift and deletion mutations. It was very interesting that all seven were heterozygous mutants (Foxo3(-/+) ), and the gene mutagenesis rates of the mice reached 35%. The five Foxo3 mutant females were all infertile in the following 6 months after birth. The histological examination results showed that there were rare primordial follicles and primary follicles in the ovary of Foxo3 mutant compared to that of wide-type female mice. Moreover, one of two mutant males was subfertile and another was fertile normally. Those results suggested that the mutant of Foxo3 severely affected the fertile ability of female and perhaps male in some degree; furthermore, an even more efficient TALENs-based gene mutation method has been established to be poised to revolutionize the study of mouse and other species genetics.

Aberrant TAL1 activation is mediated by an interchromosomal interaction in human T-cell acute lymphoblastic leukemia.

Long-range chromatin interactions control metazoan gene transcription. However, the involvement of intra- and interchromosomal interactions in development and oncogenesis remains unclear. TAL1/SCL is a critical transcription factor required for the development of all hematopoietic lineages; yet, aberrant TAL1 transcription often occurs in T-cell acute lymphoblastic leukemia (T-ALL). Here, we report that oncogenic TAL1 expression is regulated by different intra- and interchromosomal loops in normal hematopoietic and leukemic cells, respectively. These intra- and interchromosomal loops alter the cell-type-specific enhancers that interact with the TAL1 promoter. We show that human SET1 (hSET1)-mediated H3K4 methylations promote a long-range chromatin loop, which brings the +51 enhancer in close proximity to TAL1 promoter 1 in erythroid cells. The CCCTC-binding factor (CTCF) facilitates this long-range enhancer/promoter interaction of the TAL1 locus in erythroid cells while blocking the same enhancer/promoter interaction of the TAL1 locus in human T-cell leukemia. In human T-ALL, a T-cell-specific transcription factor c-Maf-mediated interchromosomal interaction brings the TAL1 promoter into close proximity with a T-cell-specific regulatory element located on chromosome 16, activating aberrant TAL1 oncogene expression. Thus, our study reveals a novel molecular mechanism involving changes in three-dimensional chromatin interactions that activate the TAL1 oncogene in human T-cell leukemia.

Association of -238G/A and -863C/A polymorphisms in the TNF-α gene with chronic obstructive pulmonary disease based on a meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease; increasing evidence indicates that the TNF-α polymorphism is associated with progression of this disease. Few studies have focused upon association between TNF-α -238G/A or -863C/A polymorphism and COPD risk. Reported associations have been controversial because of small sample size and varied study design among the different studies. We performed a meta-analysis to assess the correlation of these two polymorphisms in the TNF-α gene with COPD risk. A comprehensive search was conducted to identify all published articles on the association between TNF-α -238G/A or -863C/A polymorphism and COPD risk from different databases. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and the heterogeneity and publication bias were assessed. Eight articles with 10 eligible studies met our inclusion criteria; six studies were of the -238G/A polymorphism and the others involved the -863C/A polymorphism. In the case of the -863C/A polymorphism, significant association was detected only in Asians in the A allele carriers (GA+AA versus GG genotype) and allele (A versus G allele) model (OR = 0.505, 95%CI = 0.321-0.795 and OR = 0.560, 95%CI = 0.368-0.851, respectively). However, no significant association was detected for the -238G/A polymorphism. No evidence of between-study heterogeneity and publication bias was detected. We suggest a potentially protective role of the A allele in the TNF-α -863C/ A polymorphism against developing COPD in Asians. This hypothesis needs further studies for confirmation.