Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

PURPOSE: Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. METHOD: From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. RESULTS: A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295 min, p = 0.009), blood loss (100 vs. 300 ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13 days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR 1.02, p = 0.002), poor tumor differentiation (HR 3.05, p = 0.004), and (y)pT4b stage (HR 2.35, p = 0.035) were independent risk factors for disease-free survival. CONCLUSION: LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.

The CnB1 p.D102A variant is linked to dilated cardiomyopathy via impaired Calcineurin activity.

BACKGROUND: The role of calcineurin (protein phosphatase 2B (PP2B)) in the pathogenesis of human dilated cardiomyopathy (DCM) has not been fully elucidated. We determined the potential involvement of calcineurin in the pathogenesis of DCM caused by mutations in CnB1, a subunit of calcineurin. METHODS: By whole-exome sequencing, we identified a new CnB1 variant in a Han Chinese proband with cardiomyopathy from a 3-generation family with 2 normal individuals and 3 individuals with familial dilated cardiomyopathy. The potential pathogenic variant was validated by Sanger sequencing. We performed functional and mechanistic experiments in a CnB1-knockin (KI) mouse model and at the cellular level. RESULTS: We detected a rare heterozygous CnB1 variant (p.D102A) in a proband with dilated cardiomyopathy. This variant was localized to the EF hand 3 region of CnB1, where no variants have been previously reported. KI mice harboring the p.D102A variant exhibited decreased cardiac function and cardiac dilatation. Immunoblotting, RT-PCR and immunofluorescence results showed decreased cardiomyocyte size and heart failure-related protein expression. A calcineurin activity assay demonstrated decreased calcineurin activity in the KI mice, accompanied by the decreased ability of CnB1 to bind CnA. CONCLUSIONS: CnB1 p.D102A is a disease-associated variant that confers susceptibility to cardiac dilatation. This variant is associated with impaired calcineurin activity and a subsequent decrease in the ability of CnB1 to bind CnA.

G protein regulated inducer of neurite outgrowth 1 is a potential marker for lung cancer prognosis.

Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and Western blot assays were conducted to detect GPRIN1 expression in lung cancer cells and normal control cells. To detect the functional effects of knockdown/overexpression of GPRIN1 on lung cancer cells, we performed CCK-8, colony formation and Transwell assays. Through the Kaplan-Meier method, we found that GPRIN1 expression correlated with overall survival and adverse prognosis, and Cox regression indicated that GPRIN1 is as an independent predictive factor for lung adenocarcinoma. Furthermore, the mRNA and protein expression levels of GPRIN1 in lung cancer cells were markedly higher than those in normal cells. Downregulation of GPRIN1significantly decreased cell viability, colony formation, the number of invasive and migrating cells, and levels of epithelial-mesenchymal transition-related proteins in A549 cells. Overexpression of GPRIN1showed the opposite effect in Calu-1 cells. Together, these results indicated that GPRIN1 facilitates lung cancer proliferation and migration, possibly by affecting the epithelial-mesenchymal transition of lung cancer cells, suggesting that GPRIN1may be used as an effective target for the treatment of lung cancer.

HIV incidence is rapidly increasing with age among young men who have sex with men in China: a multicentre cross-sectional survey.

OBJECTIVES: The HIV epidemic is worsening among men who have sex with men (MSM) in China, especially among those who are younger than 25 years old [younger MSM (YMSM)]. The aim of the study was to compare the prevalences of HIV incidence and recent HIV infection as well as factors associated with recent HIV infection in YMSM and older MSM (OMSM). METHODS: A multicentre cross-sectional survey was conducted among 4496 MSM recruited from seven Chinese cities. YMSM were defined as those aged < 25 years. Data on demographics and sexual behaviours were collected using structural questionnaires. Blood samples were tested for recent HIV infection and other sexually transmitted infections. RESULTS: Among the participants, 1313 were YMSM and 3183 were OMSM. Compared with OMSM, YMSM had a higher prevalence of recent HIV infection [5.4% (71 of 1313) for YMSM vs. 3.6% (115 of 3175) for OMSM; P = 0.006] and a higher HIV incidence [11.8 per 100 person-years (PY) (95% confidence interval (CI) 9.0-14.5) for YMSM vs. 7.6 per 100 PY (95% CI 6.3-9.0) for OMSM]. The incidence increased with age among YMSM, especially between the ages of 16 and 21 years. In contrast, the incidence declined with age among OMSM. Anal bleeding, recreational drug use, syphilis and herpes simplex virus 2 (HSV-2) infection were independent risk factors for recent HIV infection among YMSM. The prevalence of all these risk factors increased with age between the ages of 16 and 21 years. Anal bleeding (19.8%) and recreational drug use (19.5%) had the highest adjusted population attributable fractions (aPAFs) among YMSM. The highest aPAFs of anal bleeding (27.4%) and syphilis infection (25.5%) were found between the ages of 19 and 21 years. CONCLUSIONS: The HIV incidence in Chinese YMSM was significantly higher than that in OMSM. YMSM aged 16-21 years had an extremely high risk of recent HIV infection.

Genetic analysis of floral organ size in broccoli × cabbage via a mixed inheritance model of a major gene plus polygene.

Broccoli and cabbage are important vegetable crops that produce hybrid seeds after insect pollination; the size of floral organs is crucial for this process. To investigate the genetic characteristics of floral organ sizes (corolla width, petal length and width, and lengths of stamen, anther, style, and stigma) and to improve the flower size and breeding efficiency of broccoli, we used multi-generation analysis of a major gene plus polygene model. Six populations obtained from a broccoli inbred line 93219 (small floral organs) and cabbage inbred line 195 (large floral organs) were used for the analysis. Corolla and petal width and stamen and anther length were controlled by the additive-dominance-epistasis polygene model. The heritability of these traits in BC1, BC2, and F2 generations was high (72.80-93.76%). Petal and stigma length were governed by the two major genes of additive-dominance-epistasis effects plus additive-dominance polygene model; the major gene heritability in the F2 generation were 79.17 and 65.77%, respectively. Style length was controlled by one major gene of additive-dominance effects plus additive-dominance-epistasis polygene model; the major gene heritability in BC1, BC2, and F2 were 40.60, 10.35, and 38.44%, respectively; the polygene heritability varied from 41.85 to 68.44%. Our results provide important genetic information for breeding, which could guide improvement of flower-related traits and lay the foundation for quantitative trait loci mapping of the flower-size traits in Brassica.

[Effects of transthyretin on biological behavior of retinal pigment epithelial cells and retinal microvascular epithelial cells].

Objective: To explore the effects of transthyretin (TTR) on biological behavior of retinal pigment epithelial cells (RPECs) and retinal microvascular epithelial cells (RMVECs). Methods: RPECs were cultured with exogenous TTR to explore the effect of TTR on the proliferation of RPECs. The expression of TTR of RPECs was silenced by TTR specific small interfering RNA and the expression of TTR was detected by using Western blotting to identify the efficacy of TTR silence. The level of vascular endothelial growth factor (VEGF) massage RNA was detected by using RT-PCR to identify the interaction between VEGF and TTR. The different proliferation and migration abilities of RMVECs with different expressions of TTR were measured by transwell system. Results: MTT assay showed that RPECs with 0 µmol/L TTR glowed faster than with 4 µmol/L TTR (t=18.08, P<0.0001). The expression level of TTR was decreased in the small interfering RNA group as compared with the negative control group (P<0.05). RT-PCR assay showed no differential expression of VEGF after the silencing of TTR (P>0.05). The transwell assay showed RMVECs with the silence of TTR proliferated more slowly than RMVECs without the treatment (t=4.901, P=0.0012), and also migrated more slowly (t=4.213, P=0.0029). Conclusions: TTR can inhibit the proliferation of RPECs and promote the proliferation and migration of RMVECs without the help of VEGF, the mechanism of which may be worth further study. (Chin J Ophthalmol, 2016, 52: 856-860).

Reliability and relative validity of three physical activity questionnaires in Taizhou population of China: the Taizhou Longitudinal Study.

OBJECTIVE: To examine the test-retest reliabilities and relative validities of the Chinese version of short International Physical Activity Questionnaire (IPAQ-S-C), the Global Physical Activity Questionnaire (GPAQ-C), and the Total Energy Expenditure Questionnaire (TEEQ-C) in a population-based prospective study, the Taizhou Longitudinal Study (TZLS). STUDY DESIGN: A longitudinal comparative study. METHODS: A total of 205 participants (male: 38.54%) aged 30-70 years completed three questionnaires twice (day one and day nine) and physical activity log (PA-log) over seven consecutive days. The test-retest reliabilities were evaluated using intra-class correlation coefficients (ICCs) and the relative validities were estimated by comparing the data from physical activity questionnaires (PAQs) and PA-log. RESULTS: Good reliabilities were observed between the repeated PAQs. The ICCs ranged from 0.51 to 0.80 for IPAQ-C, 0.67 to 0.85 for GPAQ-C, and 0.74 to 0.94 for TEEQ-C, respectively. Energy expenditure of most PA domains estimated by the three PAQs correlated moderately with the results recorded by PA-log except the walking domain of IPAQ-S-C. The partial correlation coefficients between the PAQs and PA-log ranged from 0.44 to 0.58 for IPAQ-S-C, 0.26 to 0.52 for GPAQ-C, and 0.41 to 0.72 for TEEQ-C, respectively. Bland-Altman plots showed acceptable agreement between the three PAQs and PA-log. CONCLUSION: The three PAQs, especially TEEQ-C, were relatively reliable and valid for assessment of physical activity and could be used in TZLS.

Cytomegalovirus Infection and Alzheimer's Disease: A Meta-Analysis.

BACKGROUND: Evidence on the association of cytomegalovirus (CMV) infection with Alzheimer's disease (AD) is scarce and the results are inconsistent. OBJECTIVE: To investigate the association of CMV infection with the risk of AD. METHODS: Observational studies on the relationship between CMV infection and AD were identified from PubMed, Embase, Web of Science, and the Cochrane Library until September 30, 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effect meta-analysis was performed using a generic inverse-variance method, followed by sensitivity analyses and subgroup analyses based on study designs, regions, adjustments, and population types. RESULTS: Our search yielded 870 articles, of which 200 were duplicates and 663 did not meet the inclusion criteria, and finally yielded seven studies with 6,772 participants. No strong evidence was observed in the summary analysis for the association of CMV infection and risk of AD (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 0.88, 2.03, I2 =69.9%). However, subgroup analysis showed that an increased risk of AD was detected in East Asians (OR = 2.39; 95% CI: 1.63, 3.50, I2 = 0.00%), cohort studies (OR = 1.99; 95% CI: 1.35, 2.94, I2 = 28.20%), and studies with confounder adjustment (OR = 2.05; 95% CI: 1.52, 2.77, I2 = 0.00%). CONCLUSIONS: This meta-analysis provides evidence to support the heterogeneity of the associations between CMV infection and AD. Future studies with larger sample sizes and multi-ethnic populations are necessary.

High MCM6 expression promotes proliferation and correlates with poor prognosis in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis. Minichromosome maintenance genes (MCM2-7) crucial for DNA replication are significant biomarkers for various tumor types; however, their roles in TNBC remain underexplored. MATERIALS AND METHODS: We utilized four TNBC-related GEO databases to examine MCM2-7 gene expression and predict its prognosis in TNBC, performing single-cell analysis and GSEA to discover MCM6's potential function. The Cancer Dependency Map gene effect scores and CCK8 assay were used to assess MCM6's impact on TNBC cell proliferation. The correlations between MCM6 expression, immune infiltrates, and immune cells were also analyzed. WGCNA and LASSO Cox regression built a risk score model predicting TNBC patient survival based on MCM6-related gene expression. RESULTS: MCM2-7 gene expression was higher in TNBC tissues compared to adjacent normal tissues. High MCM6 expression correlated with shorter TNBC patient survival time. GSEA and single-cell analysis revealed a relationship between elevated MCM6 expression and the cell cycle pathway. MCM6 knockdown inhibited TNBC cell proliferation. A risk model featuring MCM6, CDC23, and CCNB1 effectively predicts TNBC patient survival. CONCLUSIONS: MCM6 overexpression in TNBC links to a worse prognosis and reduced cell proliferation upon MCM6 knockdown. We developed a risk score model based on MCM6-related genes predicting TNBC patient prognosis, potentially assisting future treatment strategies.

[Clinical effects of plantar split-thickness skin grafts in repairing the deep burn wounds in the back and buttocks].

Objective: To explore the clinical effects of plantar split-thickness skin grafts in repairing the deep burn wounds in the back and buttocks. Methods: A retrospective observational study was conducted. From January 2011 to February 2022, 98 patients with deep burn who met the inclusion criteria were admitted to the 910th Hospital of Joint Service Support Unit of PLA, including 64 males and 34 females, aged 17 to 78 years, with total burn areas of 35%-95% total body surface area (TBSA). The area of full-thickness burns in the back and buttocks ranged from 5% to 17% TBSA and the wounds were repaired only using stamp-shaped split-thickness skin grafts from plantar areas of both feet or combined with Meek microskin grafts or stamp-shaped skin grafts from other sites. According to the times of skin graft harvesting from both soles, these patients were divided into one-harvesting group (29 cases), two-harvesting group (38 cases), three-harvesting group (21 cases), and four-harvesting group (10 cases). The area of skin grafts harvested each time from both soles, the healing time of donor sites after each skin graft harvesting, and the survival rate of plantar skin graft in recipient site at 7 days after each skin graft harvesting in 98 patients, the interval between two adjacent skin graft harvesting in 69 patients with skin grafts harvested twice or more, as well as the healing time of donor site and survival rate of skin graft in recipient site after the last skin graft harvesting from both soles of patients in the 4 groups were recorded. The patients were followed up to observe the appearance, texture, and scar in recipient site of plantar skin grafts as well as the scar and function in plantar donor sites. Data were statistically analyzed with one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Results: In the 98 patients, the area of skin graft was 2.0%-4.5% ((3.4±0.6)%) TBSA harvested each time from both soles, the healing time of donor site after each skin graft harvesting was 7-10 (7.8±1.1) d, and the survival rate of plantar skin graft in recipient site at 7 days after each skin graft harvesting was 93% (92%, 95%). The interval between two adjacent skin graft harvesting in the 69 patients was 7-38 (11.2±0.5) d. The healing time of donor site and survival rate of skin graft in recipient site after the last skin graft harvesting from both soles of patients in the 4 groups showed no statistically significant differences (P>0.05). A total of 88 patients were followed up for 3 months to 5 years, the appearance in recipient site of plantar skin graft was smooth, the texture was firm, the scar hyperplasia was mild, and the area was compressive- and wear-resistant. Among them, the plantar donor site recovered well in 85 patients, without obvious scar hyperplasia and only 3 patients had small area of scar hyperplasia in the non-weight-bearing areas which did not affect walking or wearing shoes or socks. Ten patients were lost in the follow up after discharge. Conclusions: Stamp-shaped split-thickness skin grafts can be repeatedly harvested from both soles of patient to repair the deep burn wounds in the back and buttocks, with high survival rate of skin grafts, thus can reduce the burden of other donor sites. Moreover, the skin grafts have good wear-resistance and pressure-resistance, without affecting postoperative normal walk.

CYP7A1 polymorphism influences the LDL cholesterol-lowering response to atorvastatin.

WHAT IS KNOWN AND OBJECTIVE: Response to the lipid-lowering effect of the statins is known to show significant inter-individual variability. Our aim was to investigate whether genetic variants of the CYP3A5 gene, CYP7A1 gene and ABCG8 gene influence the lipid-lowering response to atorvastatin. METHODS: One hundred and seven unrelated Chinese Han hypercholesterolemia patients were recruited from among the inpatients and outpatients of Tangshan Gongren Hospital of Hebei, China. Three polymorphisms of the CYP3A5 gene, seven polymorphisms of the CYP7A1 gene and seven polymorphisms of the ABCG8 gene were selected using a tagging single-nucleotide polymorphism (tSNP) strategy and genotyped using Snapshot platform. RESULTS: SNP rs8192870, located in the first intron of the CYP7A1 gene, was associated with the LDL level lowering response to atorvastatin. The LDL levels were reduced by 27.89% for the GG/GA genotype carriers and 35.26% for the AA genotype carriers, respectively, after atorvastatin treatment (P = 0.021). The significance remained after adjusting for covariates. In addition, we observed that rs4148222 in the 11th intron of the ABCG8 gene significantly associated with the baseline levels of HDL (P = 0.046). WHAT IS NEW AND CONCLUSION: CYP7A1 gene polymorphism influences the LDL-lowering effects of atorvastatin in Chinese Hans. If replicated by others, identification of the tagged functional variant would be needed.

[A prospective randomized controlled study on the curative effects of enteral immunonutrition support therapy in adult burn patients at nutritional risk].

Objective: To explore the effects of enteral immunonutrition support therapy on nutritional metabolism, immune function, and inflammatory response in adult burn patients at nutritional risk as assessed by the modified 2nd nutrition risk screening (NRS) 2002. Methods: A prospective randomized controlled study was conducted. From December 2019 to January 2022, 500 adult patients who were admitted to the Affiliated Huaihai Hospital of Xuzhou Medical University and had nutritional risk assessed by the modified 2nd NRS 2002 were recruited into the study. According to burn severity, the patients were divided into common burn patients (n=450) and severe burn patients (n=50). According to the random number table, the patients with common burn were divided into common burn diet nutrition group and common burn diet enteral immunonutrition group, with 225 patients in each group, and the patients with severe burn were divided into severe burn diet enteral non-immunonutrition group and severe burn diet enteral immunonutrition group, with 25 patients in each group. The patients in each group were given the corresponding nutritional support therapies on the basis of routine burn treatment. On post injury day (PID) 1, 3, 7, 14, and 21, the total energy intake and total protein intake of the patients in 4 groups were recorded, the plasma prealbumin, albumin, transferrin, serum immunoglobulin A (IgA), IgG, IgM, peripheral blood CD3 positive T cell percentage, CD4 positive T cell count, CD8 positive T cell count, the ratio of CD4 positive T cells to CD8 positive T cells, natural killer cell percentage, plasma interleukin-6 (IL-6), free mitochondrial DNA (mtDNA) copy number, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) of the patients in 4 groups were detected, and the nitrogen balance of the patients in 4 groups on the day was calculated. On PID 7, 14, and 21, the modified 2nd NRS 2002 scores of the patients in 4 groups were reassessed. The sepsis incidence during treatment and the length of hospital stay of the patients in 4 groups and the length of intensive care unit (ICU) stay of the patients in the 2 severe burn groups were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, Mann-Whitney U test, independent sample t test, analysis of variance for repeated measurement, and Bonferroni correction. Results: A total of 476 patients completed the trial, with 213 patients in common burn diet nutrition group (112 males and 101 females, aged (37±19) years), 218 patients in common burn diet enteral immunonutrition group (115 males and 103 females, aged (42±16) years), 22 patients in severe burn diet enteral non-immunonutrition group (11 males and 11 females, aged (35±8) years), and 23 patients in severe burn diet enteral immunonutrition group (12 males and 11 females, aged (35±8) years). Compared with those in common burn diet nutrition group, the patients in common burn diet enteral immunonutrition group had significantly higher total energy intake on PID 1 (t=6.06, P<0.01), significantly lower total energy intake on PID 7 and significantly lower total protein intake on PID 1 (with t values of 6.17 and 4.59, respectively,P<0.01). On PID 21, the total energy intake of patients in severe burn diet enteral immunonutrition group was significantly lower than that in severe burn diet enteral non-immunonutrition group (t=2.70, P<0.01). The total protein intake of patients in severe burn diet enteral immunonutrition group and severe burn diet enteral non-immunonutrition group were similar at each time point post injury (P>0.05). Compared with those in common burn diet nutrition group, the patients in common burn diet enteral immunonutrition group had significantly higher level of prealbumin on PID 3, 7, 14, and 21 (with t values of 2.05, 2.33, 2.45, and 2.11, respectively, P<0.05), significantly higher level of albumin on PID 7, 14, and 21 (with t values of 2.30, 2.56, and 2.15, respectively, P<0.05), significantly higher level of transferrin on PID 7 and 14 (with t values of 1.99 and 2.27, respectively, P<0.05), significantly higher nitrogen balance on PID 14 and 21 (with t values of 2.51 and 2.07, respectively, P<0.05), and significantly lower modified 2nd NRS 2002 score on PID 21 (t=1.99, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, the patients in severe burn diet enteral immunonutrition group had significantly higher level of prealbumin on PID 3, 7, 14, and 21 (with t values of 2.50, 2.64, 2.18, and 2.39, respectively, P<0.05), significantly higher level of albumin​on PID 7, 14, and 21 (with t values of 2.27, 2.39, and 2.69, respectively, P<0.05), significantly higher level of transferrin and nitrogen balance but significantly lower modified 2nd NRS 2002 score on PID 14 and 21 (with t values of 2.30, 2.35, 2.41, 2.16, 2.31, and 2.73, respectively, P<0.05). Compared with those in common burn diet nutrition group, patients in common burn diet enteral immunonutrition group had significantly higher level of IgA and IgG on PID 7, 14, and 21 (with t values of 2.19, 2.36, 2.17, 2.49, 1.97, and 2.24, respectively, P<0.05), significantly higher level of IgM on PID 21 (t=2.06, P<0.05), significantly higher percentage of CD3 positive T cells and ratio of CD4 positive T cells to CD8 positive T cells on PID 3, 7, 14, and 21 (with t values of 2.49, 2.25, 2.33, 2.41, 2.39, 2.24, 2.46, and 2.18, respectively, P<0.05), significantly higher CD4 positive T cell count (with t values of 2.15 and 2.27, respectively, P<0.05) but significantly lower CD8 positive T cell count on PID 14 and 21 (with t values of 2.58 and 2.35, P<0.05), and significantly higher percentage of natural killer cells on PID 7, 14, and 21 (with t values of 2.53, 2.21, and 2.36, respectively, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, patients in severe burn diet immunonutrition group had significantly higher level of IgA on PID 7 and 14 (with t values of 2.15 and 2.03, respectively, P<0.05), significantly higher level of IgG on PID 7, 14, and 21 (with t values of 2.09, 2.56, and 2.15, respectively, P<0.05), significantly higher level of IgM on PID 21 (t=2.08, P<0.05), significantly higher percentage of CD3 positive T cells, CD4 positive T cell count, and percentage of natural killer cells on PID 14 and 21 (with t values of 2.52, 2.14, 2.14, 2.39, 2.56, and 2.19, respectively, P<0.05), significantly lower CD8 positive T cell count but significantly higher ratio of CD4 positive T cells to CD8 positive T cells on PID 7, 14, and 21 (with t values of 2.27, 2.81, 2.01, 2.11, 2.69, and 2.05, respectively, P<0.05). Compared with those in common burn diet nutrition group, patients in common burn diet enteral immunonutrition group had significantly lower level of IL-6 (with t values of 2.34 and 2.32, respectively, P<0.05) and significantly lower free mtDNA copy number on PID 14 and 21 (with Z values of -2.28 and -2.34,respectively, P<0.05), significantly lower level of sTREM-1 on PID 7, 14, and 21 (with t values of 2.02, 2.94, and 3.72, respectively, P<0.05). Compared with those in severe burn diet enteral non-immunonutrition group, patients in severe burn diet enteral immunonutrition group had significantly lower level of IL-6 and sTREM-1 on PID 7, 14, and 21 (with t values of 2.15, 2.29, 2.47, 2.43, 2.07, and 2.32, respectively, P<0.05), and significantly lower free mtDNA copy number on PID 14 and 21 (with Z values of -2.49 and -2.21, respectively, P<0.05). During treatment, the sepsis incidences of patients in 2 common burn groups were similar (P>0.05), the sepsis incidences of patients in 2 severe burn groups were similar (P>0.05). The length of ICU stay of patients in severe burn diet enteral immunonutrition group was (11±3) d, which was significantly shorter than (14±3) d in severe burn diet enteral non-immunonutrition group (t=3.12, P<0.01). The length of hospital stay of patients in common burn diet enteral immunonutrition group was significantly shorter than that in common burn diet nutrition group (t=3.11, P<0.01). The length of hospital stay of patients in severe burn diet enteral non-immunonutrition group was similar to that in severe burn diet enteral immunonutrition group (P>0.05). Conclusions: Enteral immunonutrition support therapy for adult burn patients at nutritional risk assessed by the modified 2nd NRS 2002 can better improve the nutritional status and the immune function of patients, reduce inflammatory response of the body, and shorten the length of hospital stay in common burn patients and the length of ICU stay in severe burn patients.

[A prospectively randomized controlled study of the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients].

Objective: To observe the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients. Methods: Thirty-two severe burn patients who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from June 2017 to January 2019 were recruited into a prospectively randomized controlled study. According to the random number table, the patients were divided into conventional insulin therapy alone group, conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group, with 8 patients in each group, with genders of 5 males and 3 females, 4 males and 4 females, 3 males and 5 females, 4 males and 4 females, and ages of (35±7), (36±9), (33±11), and (38±7) years, respectively. Patients in conventional insulin therapy alone group were treated with conventional insulin therapy on the basis of routine treatment to control the blood glucose. Patients in conventional insulin therapy+glutamine group were supplemented with alanyl-glutamine for more than 14 days in addition to the treatment in conventional insulin therapy alone group. Patients in intensive insulin therapy alone group were treated with intensive insulin therapy on the basis of routine treatment to control the blood glucose. Patients in intensive insulin therapy+glutamine group were supplemented with alanyl-glutamine in addition to the treatment in intensive insulin therapy alone group. On treatment day (TD) 1, 3, 7, and 14, the blood glucose, albumin, prealbumin, white blood cell count, procalcitonin (PCT), and C-reactive protein (CRP) of patients in the 4 groups were detected. The cardiac index (CI), stroke volume index (SVI), global end-diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) of patients in the 4 groups on TD 1, 3, and 7 were measured. Data were statistically analyzed with Fisher's exact probability test, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method. Results: All patients in the 4 groups successfully completed the study, and there were no withdrawal cases. On TD 3, 7, and 14, the blood glucose of patients in intensive insulin therapy alone group ((5.9±1.3), (5.8±0.6), (5.5±0.5) mmol/L) and intensive insulin therapy+glutamine group ((5.9±1.1), (5.6±1.1), (5.2±0.8) mmol/L) were significantly lower than those in conventional insulin therapy alone group ((9.1±0.5), (8.4±0.9), (7.4±1.1) mmol/L, P<0.05). Compared with those in conventional insulin therapy alone group, the levels of albumin of patients in conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group were significantly increased on TD 7 and 14 (P<0.05). Compared with the level of albumin of patients in intensive insulin therapy+glutamine group, the levels of albumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly decreased on TD 14 (P<0.05). Compared with those in conventional insulin therapy alone group, the levels of prealbumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly increased on TD 7 and 14 (P<0.05). Compared with those in intensive insulin therapy+glutamine group, the levels of prealbumin of patients in intensive insulin therapy alone group and conventional insulin therapy+glutamine group were significantly decreased on TD 1, 7, and 14 (P<0.05). There were no statistically significant differences in the white blood cell count, PCT, and CRP of patients in the 4 groups in pairwise comparison between groups on TD 1, 3, 7, and 14 (P>0.05). On TD 3 and 7, the levels of cardiac index, SVI, GEDVI, and SVRI of patients in intensive insulin therapy+glutamine group were significantly higher than those in conventional insulin therapy alone group (P<0.05), while the levels of EVLWI and PVPI were significantly lower than those in conventional insulin therapy alone group (P<0.05). Conclusions: Glutamine combined with intensive insulin therapy can improve the hypermetabolism in patients after severe burns, reduce the decomposition and consumption of endogenous nutrient substrates, and at the same time help the recovery of cardiac function and maintenance of hemodynamic stability.

MicroRNA-365 inhibits the progression of lung adenocarcinoma through targeting ETS1 and inactivating AKT/mTOR pathway.

OBJECTIVE: MicroRNAs (miRNAs) act as important regulators in human cancers by regulating the gene expression. The dysregulation of miR-365 has been investigated in many cancers. However, the function of miR-365 remains unknown in lung adenocarcinoma. Therefore, the regulatory mechanism of miR-365 was explored in lung adenocarcinoma. PATIENTS AND METHODS: The expression of miR-365 was detected in cell lines and 67 lung adenocarcinoma tissues using qRT-PCR. The Kaplan-Meier analysis was used to determine the association between miR-365 expressions and the survival rate in patients with lung adenocarcinoma. Transwell assay was then performed to investigate the effect of miR-365 on invasion and migration of lung adenocarcinoma cells. RESULTS: Downregulation of miR-365 and upregulation of ETS1 were identified in lung adenocarcinoma. Furthermore, miR-365 reversely regulated ETS1 expression in lung adenocarcinoma. Functionally, the overexpression of miR-365 inhibited proliferation, migration, and invasion of lung adenocarcinoma cells. However, the upregulation of ETS1 lessened the inhibitory effect of miR-365 in lung adenocarcinoma. In addition, miR-365 inhibited EMT and inactivated AKT/mTOR pathway in lung adenocarcinoma. CONCLUSIONS: MiR-365 inhibits the progression of lung adenocarcinoma by targeting ETS1 and inactivating the AKT/mTOR pathway.

LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells.

OBJECTIVE: The aim of this study was to elucidate the biological function of long non-coding RNA (lncRNA) HOTTIP (HOXA transcript at the distal tip) in the development of acute myeloid leukemia (AML), and to investigate the potential mechanism. PATIENTS AND METHODS: Relative expression levels of HOTTIP, microRNA-608 and DDA1 in AML patients were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Meanwhile, the expressions of these genes in AML cell lines were detected as well. The regulatory effects of HOTTIP, microRNA-608 and DDA1 on the proliferative ability and cell cycle progression of AML cells were examined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Dual-luciferase reporter gene assay was performed to confirm the binding condition of microRNA-608 to HOTTIP and DDA1. Finally, the specific role of HOTTIP/microRNA-608/DDA1 axis in the development of AML was verified through a series of rescue experiments. RESULTS: HOTTIP was highly expressed in AML-M5 patients than normal controls. No significant difference in HOTTIP expression was found between patients with other subtypes of AML (M0, M1, M2, M3, M4 and M6) and normal controls. HOTTIP expression was significantly up-regulated in AML cell lines U-937 and THP-1. Up-regulation of HOTTIP remarkably promoted the proliferative potential and cell cycle progression of AML cells. Dual-luciferase reporter gene indicated that HOTTIP could bind to microRNA-608, which was lowly expressed in AML-M5 patients. Overexpression of microRNA-608 significantly inhibited the proliferative ability and cell cycle progression of U-937 and THP-1 cells. More importantly, microRNA-608 could partially reverse the regulatory effect of HOTTIP on AML cells. Meanwhile, DDA1 was verified as the target of microRNA-608. Subsequent experiments elucidated that DDA1 significantly accelerated the proliferation and cell cycle of AML cells. Furthermore, DDA1 could reverse the inhibitory effect of microRNA-608 on proliferative ability and cell cycle progression of AML cells. CONCLUSIONS: HOTTIP accelerated the proliferative ability and cell cycle of AML cells via up-regulating DDA1 expression by sponging microRNA-608.

MCM-41 supported Cu-Mn catalysts for catalytic oxidation of toluene at low temperatures.

Complete catalytic oxidation of toluene was investigated on Cu-Mn doped mesoporous and microporous catalysts, i.e., Cu-Mn/MCM-41, Cu-Mn/beta-zeolite, Cu-Mn/ZSM-5 (where SiO2/Al2O3 is either 25 or 38), and Cu-Mn/porous silica, in the presence of excess oxygen. The result shows that mesoporous catalysts have exhibited the highest catalytic activity among these catalysts above. The less amount of coke formation due to the unique mesoporous structures could play a key role in the high activity on the mesoporous catalyst. In addition, the bimetallic Cu-Mn-MCM-41 supported catalyst shows higher oxidation activity than either single metal catalyst, i.e., Cu-MCM-41 and Mn-MCM-41. The highly dispersed Cu-Mn mixed oxides on mesoporous structures probably provide active sites for the complete oxidation of toluene on these mesoporous catalysts.

The Arabidopsis Information Resource (TAIR): a comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant.

Arabidopsis thaliana, a small annual plant belonging to the mustard family, is the subject of study by an estimated 7000 researchers around the world. In addition to the large body of genetic, physiological and biochemical data gathered for this plant, it will be the first higher plant genome to be completely sequenced, with completion expected at the end of the year 2000. The sequencing effort has been coordinated by an international collaboration, the Arabidopsis Genome Initiative (AGI). The rationale for intensive investigation of Arabidopsis is that it is an excellent model for higher plants. In order to maximize use of the knowledge gained about this plant, there is a need for a comprehensive database and information retrieval and analysis system that will provide user-friendly access to Arabidopsis information. This paper describes the initial steps we have taken toward realizing these goals in a project called The Arabidopsis Information Resource (TAIR) (www.arabidopsis.org).

Oligomerization triggers binding of a Bacillus thuringiensis Cry1Ab pore-forming toxin to aminopeptidase N receptor leading to insertion into membrane microdomains.

Bacillus thuringiensis Cry1A toxins, in contrast to other pore-forming toxins, bind two putative receptor molecules, aminopeptidase N (APN) and cadherin-like proteins. Here we show that Cry1Ab toxin binding to these two receptors depends on the toxins' oligomeric structure. Toxin monomeric structure binds to Bt-R1, a cadherin-like protein, that induces proteolytic processing and oligomerization of the toxin (Gomez, I., Sanchez, J., Miranda, R., Bravo A., Soberon, M., FEBS Lett. (2002) 513, 242-246), while the oligomeric structure binds APN, which drives the toxin into the detergent-resistant membrane (DRM) microdomains causing pore formation. Cleavage of APN by phospholipase C prevented the location of Cry1Ab oligomer and Bt-R1 in the DRM microdomains and also attenuates toxin insertion into membranes despite the presence of Bt-R1. Immunoprecipitation experiments demonstrated that initial Cry1Ab toxin binding to Bt-R1 is followed by binding to APN. Also, immunoprecipitation of Cry1Ab toxin-binding proteins using pure oligomeric or monomeric structures showed that APN was more efficiently detected in samples immunoprecipitated with the oligomeric structure, while Bt-R1 was preferentially detected in samples immunoprecipitated with the monomeric Cry1Ab. These data agrees with the 200-fold higher apparent affinity of the oligomer than that of the monomer to an APN enriched protein extract. Our data suggest that the two receptors interact sequentially with different structural species of the toxin leading to its efficient membrane insertion.

Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea.

We investigated whether IL-10 produced endogenously would influence the development of HSV-1-induced acute corneal disease. Murine corneal epithelial cells and fibroblasts cultured in vitro expressed IL-10 mRNA and protein constitutively and also IL-10 receptors. Inclusion of IL-10 neutralizing antibody in the culture medium significantly (p<0.05) enhanced TNF-alpha-induced IL-6 and MIP-2 production by both corneal cell types. Endogenous IL-10 synthesis, which also occurred in vivo, was not modulated by Herpes virus infection or by depletion of neutrophils or natural killer cells. Antibody to IL-10 given locally at the time of HSV-1 intracorneal infection was associated with significantly (p<0.05) enhanced production of IL-6, MIP-2, and MIP-1alpha, increased neutrophil infiltration, and more extensive corneal disease. Similarly, mice with a disrupted IL-10 gene developed more severe corneal disease than wild-type controls. Collectively, these observations suggest that locally produced IL-10 can act in an autocrine/paracrine fashion to down-regulate the production of proinflammatory mediators and thus limit corneal inflammation.