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Objectives The hospital environment has been implicated in the enrichment and exchange of pathogens and antibiotic resistance, but its potential in shaping the symbiotic microbial community of hospital staff is unclear. This study was designed to evaluate the alteration of the gut microbiome in medical workers compared to non-medical controls. Methods A prospective cross-sectional cohort study was conducted in the intensive care unit (ICU) and other departments of a centre in north-eastern China. Faecal samples of 175 healthy medical workers—short-term (1–3 months) workers (n = 80) and long-term (>1 year) workers (n = 95)—and 80 healthy non-medical controls were analysed using 16S rRNA amplicon sequencing. The hospital environmental samples (n = 9) were also analysed. Results The gut microbiomes of medical workers exhibited marked deviations in diversity and alteration in microbial composition and function. Short-term workers showed significantly higher abundances of taxa such as Lactobacillus, Butyrivibrio, Clostridiaceae, Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter, and Desulfovibrio and lower abundances of Bacteroides and Blautia than the controls. Long-term workers showed higher abundances of taxa such as Dialister, Veillonella, Clostridiaceae, Clostridium, Bilophila, Desulfovibrio, Pseudomonas, and Akkermansia and lower abundances of Bacteroides and Coprococcus than the controls. The medical workers' department (ICU versus non-ICU) and position (resident doctor versus nursing staff) also impacted their gut microbiome. Compared with the non-ICU workers, workers in the ICU showed a significant increase in the abundances of Dialister, Enterobacteriaceae, Phascolarctobacterium, Pseudomonas, Veillonella, and Streptococcus and a marked depletion of Faecalibacterium, Blautia, and Coprococcus. In contrast with the nursing staff, the resident doctors showed a significant increase in Erysipelotrichaceae and Clostridium and a decrease in Bacteroides, Blautia, and Ruminococcus in the gut microbiome. Moreover, we found that the microbiota of hospital environments potentially correlated with the workers' gut microbiota. Conclusions Our findings demonstrated structural changes in the gut microbial community of medical workers.

To screen and identify key genes as potential biomarkers of lung cancer using bioinformatics analysis.Observational study.Department of Critical Care Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China, from August 2018 to April 2021.Independent microarray datasets (GSE85841 and GSE118370) were downloaded from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were screened using GEO2R. Cytohubba was employed to identify the hub genes. Cellular component analysis, hierarchical clustering, and survival analyses of hub genes were performed via BiNGO, UCSC, and cBioPorta. A series of analyses of FGF2 and PIK3R1 were conducted using Oncomine.A total of 463 DEGs were identified and 11 hub genes were determined. BDNF, FGF2, JAK2, NCAM1, CAV1, TJP1, and PIK3R1 may affect the survival probability and life expectancy of lung cancer patients, but the p-values were not statistically significant. FGF2 and PIK3R1 had the highest node degrees, 40 and 32 respectively. The expression of FGF2 and PIK3R1 were significantly lower in the 4 lung cancer data sets compared with non-lung cancer tissues. And the low expression of FGF2 and PIK3R1 is related to tumor grades, family history of cancer, multiple tumors present, and prior therapy of lung cancer.Evaluation of FGF2 and PIK3R1 as potential biomarkers can contribute to the subsequent theoretical analysis of potential molecular mechanisms and development of lung cancer, so that the diagnosis of lung cancer may be more accurate, and it is possible to provide therapeutic and prognostic medicine targets.Lung neoplasms, Differentially expressed genes, Bioinformatical analysis, Microarray analysis, biomarkers.

Objective To investigate nutritional treatment in the intensive care unit (ICU) of the mainland China. Methods A cross-sectional study was conducted in 116 ICUs of 118 mainland hospitals on April 26th, 2017. All patients of these ICUs were investigated at 0 o'clock on April 26th. Demographic and clinical parameters of those patients on April 25th (the investigation day) were recorded, including the dates of hospitalization, ICU admission and nutrition initiation and clinical outcome on 28 days after the investigation day. Results A total of 1953 patients were collected, including 631 females and 1306 males. The mean age was (64.1±19.3) years old (1950 cases). The means of Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) scores were (10.76±4.35)(1749 cases), (5.65±3.52)(1783 cases), (17.14±7.31)(1792 cases), respectively. The outcomes of 28 days after the investigation day were 1483 survivors (75.9%), 312 non-survivors (16.0%) and 158 cases (8.1%) being lost to follow-up. There were no significant differences between the males and the females in age, severity of disease and clinical outcomes of 28 days but in height and weight. There were 73.7%(1440 cases) of patients with normal or mildly injured gastrointestinal function, 10.8%(210 cases) with moderately or severely injured function, 1.7%(33 cases) with gastrointestinal failure and 13.2%(258 cases) without evaluation. To the investigation day, enteral nutrition (EN) had been initiated in 69.4%(1356 cases) of patients and parenteral nutrition (PN) in 36.4%(711 cases) of patients. There were 1720(88.1%) patients with EN administration on the investigation day. The proportion of patients with nausea, vomit/regurgitation, aspiration, abdominal pain, abdominal distention and diarrhea was 4.8%(93 cases), 5.4%(105 cases), 0.9%(17 cases), 8.7%(170 cases), 27.5%(538 cases) and 4.3%(84 cases) respectively, while that of patients using EN was 3.1%(40 cases), 4.25%(54 cases), 0.79%(10 cases), 4.41%(56 cases), 26.85%(341 cases) and 5.43%(69 cases) correspondingly. The proportion of cases starting EN within 24, 48 and 72 hours after ICU entry was 22.4%(437/1953), 38.6%(754/1953) and 46.6%(911/1953), respectively. The proportion of cases receiving ≥80% estimated energy target (=past body weight ×25 kcal/kg.d) within 3, 7 and 14 days after ICU entry was 12.9%(78/607), 18.7%(189/1010) and 23%(305/1325) respectively, while that of cases with EN was 9.9%(60/607), 15.0%(151/1010) and 18.6%(246/1325) correspondingly. Conclusions Nowadays, most of patients in the mainland ICUs receive nutrition therapy and the EN usage rate is much higher than the PN rate. However, the time of EN initiation and the target-reaching rate of energy are suboptimal and an individualized plan of nutrition therapy is still missing. Details of energy delivery still need to be improved. DOI: 10.11855/j.issn.0577-7402.2019.05.05

ObjectiveHospital environment has been implicated in enrichment and exchange of pathogens and antibiotic resistances, but its potential in shaping the symbiotic microbial community of the hospital staff is unclear. This study was designed to evaluate the alteration of gut microbiome in medical workers compared to non-medical controls.DesignProspective cross-sectional cohort study.SettingIntensive care unit (ICU) and other departments from a center in northeast China.Subjects175 healthy medical workers (1-3 months short-term workers, n = 80; >1 year long-term workers, n = 95) and 80 healthy normal controls.InterventionsNone.Measurements and Main ResultsFecal samples of all subjects were analyzed using the 16S rRNA gene sequencing. Medical workers exhibited remarkable deviation in gut microbial within-sample diversity and enterotypes stratification, and shift in overall microbial structure. Short-term workers were significantly more abundant in taxa including Lactobacillus, Butyrivibrio, Clostridiaceae_Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter and Desulfovibrio, and with lower abundances of Bacteroides and Blautia compared with the controls. While long-term workers were enriched in taxa including Dialister, Veillonella, Clostridiaceae_Clostridium, Bilophila, Desulfovibrio, Pseudomonas and Akkermansia, with lower abundances of Bacteroides and Coprococcus compared with the controls. In addition, medical worker’s working years (short-term vs. long-term), hospital department (resident doctor vs. nursing staff) and work position (ICU vs. not-ICU) revealed considerable effects on their gut microbiome. Moreover, by analyzing the environmental samples (n = 9) around the inpatient wards and the hospital, we showed that the gut microbiota of medical workers was closer to environmental microbiota than that of the normal controls, probably in correlation to lasting exposure to the pathogenic taxa (e.g. Pseudomonas) in health workers.ConclusionsOur findings demonstrated structural changes in the gut microbial community of the medical workers. Further studies are proposed for investigating the potentially physiological influence of the altered gut microbiome in medical participants.IMPORTANCEIn this study, we for the first time focused on the influence of hospital environmental factors on gut microbiota of medical workers. The significance of our study is not limited to revealing the remodeling effect of the hospital environment on the gut microbiota of medical workers. Based on these, we also propose targeted and operational recommendations that can promote the health of hospital staff.

Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy. The FDA approved flubendazole, has been widely used in the treatment of intestinal parasites. Here, we demonstrated a novel effect of flubendazole on breast CS-like cells. Flubendazole inhibited breast cancer cells proliferation in dose- and time-dependent manner and delayed tumor growth in xenograft models by intraperitoneal injection. Importantly, flubendazole reduced CD44high/CD24low subpopulation and suppressed the formation of mammosphere and the expression of self-renewal related genes including c-myc, oct4, sox2, nanog and cyclinD1. Moreover, we found that flubendazole induced cell differentiation and inhibited cell migration. Consistently, flubendazole reduced mesenchymal markers (β-catenin, N-cadherin and Vimentin) expression and induced epithelial and differentiation marker (Keratin 18) expression in breast cancer cells. Mechanism study revealed that flubendazole arrested cell cycle at G2/M phase and induced monopolar spindle formation through inhibiting tubulin polymerization. Furthermore, flubendazole enhanced cytotoxic activity of conventional therapeutic drugs fluorouracil and doxorubicin against breast cancer cells. In conclusion, our findings uncovered a remarkable effect of flubendazole on suppressing breast CS-like cells, indicating a novel utilization of flubendazole in breast cancer therapy.

Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3β (GSK3β). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy.

Background/Aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.

To assess the efficacy and safety of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H(2)RA) in intensive care unit patients for stress ulcer prophylaxis.A systematic search of MEDLINE (1966 to March 2009), Ebsco and CNKI was made. Two reviewers were assigned to assess the quality of studies and extracted data independently. Six items were evaluated for each trial (patient selection, patient characteristics, randomization, blinding, definition of bleeding and of pneumonia). Disagreements were resolved through discussion. RevMan 4.2.2 software developed by the cochrane collaboration was used for Meta-analysis.Four series of clinical use involving 771 patients were included. Meta-analysis showed that the incidence of clinically significant bleeding was significantly lower in the PPI group (2.2% vs. 6.8%) as compared to H(2)RA group [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.21 to 0.96, P=0.04]. There was no significant difference of the incidence of nosocomial pneumonia (10.0% vs. 9.9%, OR 1.03, 95%CI 0.63 to 1.70, P=0.89) and mortality (14.5% vs. 14.3%,OR 1.17, 95%CI 0.76 to 1.80, P=0.47) between two groups.In comparison with H(2)RA, PPI is more effective in the prevention of stress ulcer bleeding (SUB) in patients under intensive care. There is no significant difference in the incidence of nosocomial pneumonia and mortality between two groups. There were very few randomized controlled clinical trials on prevention of stress ulcer, and these findings were based on a small number of patients, therefore a steadfast conclusion cannot presently be reached. More randomized, multicenter studies with sufficient sample size are warranted.

It is recognized that lung fibroblasts (LF) act as a common pathway in the development of fibrosis from alveolitis of whatever etiology. The study was undertaken to identify the modulating effects of insulin-like growth factor-1 (IGF-1) on LF glucose metabolism and functions, to explore possible therapeutic targets through modulating LF for the treatment of pulmonary fibrosis.Human embryonic lung (HEL) diploid fibroblast cells were cultured for 24 h with blank control, 100 ng/ml IGF-1, 200 ng/ml IGF-1, 100 ng/ml IGF-1 + 100 ng/ml insulin, 100 ng/ml IGF-1 + 200 ng/ml insulin, 100ng/ml insulin, 200 ng/ml insulin, respectively. The culture supernatants and cell pellets were collected to extract proteins and mRNAs. After quantitated with ultraviolet spectrometer, RT-PCR and Northern blotting were performed to determine the content of glucose transporter-4 (Glut-4), hexokinase II, elastin and collagen-IV.RT-PCR showed that the general mean absorbance ratios of Glut-4 and HK-IImRNA in IGF-1 group were (0.67 +/- 0.25) and (0.60 +/- 0.19), significantly increased as compared with that of control group [(0.61 +/- 0.12), (0.55 +/- 0.19)]; but decreased as compared with that of insulin group [(0.74 +/- 0.26), (0.71 +/- 0.23)]. The expression of elastin, collagen protein in IGF-1 group [(174.3 +/- 4.2), (142.1 +/- 1.0)] were significantly stronger than that of insulin group.IGF-1 can stimulate LF glucose metabolism, companied with increased expression of elastin and collagen IV in a concentration-dependent manner. IGF-1 can decrease the effect of insulin on LF glucose metabolism, whereas insulin can attenuate the effect of IGF-1 on LF in elastin and collagen expression.

To investigate the protective effect of glutamine in rats with pseudomonas pneumonia receiving total parenteral nutritional (TPN) therapy.Forty Sprague-Dawley rats were randomly divided into 4 groups (Group A, B, C and D). Rats in Group A received, by intra-tracheal route, infusion of 0.3 ml normal saline. Rats in Group B received, also by intra-tracheal route, infusion of 0.3 ml pseudomonas aeruginosa soliquoid so that the bacteria entered the lungs directly. A standard TPN solution not containing glutamine was administered intravenously to rats in Group C (160 ml/kg) for 5 days, and a TPN solution containing glutamine was administered intravenously to rats in Group D (160 ml/kg) for 5 days. On day 6, 0.3 ml pseudomonas aeruginosa soliquoid was administered by intra-tracheal route to rats in Group C and D. The weight of rats, their activity and mortality were recorded. 48 h after intratracheal administration, blood and bronchoalveolar lavage fluid (BALF) samples were collected for measurement of white blood cell count, TNFalpha, IL-1, IL-10 and total protein of BALF. Segments of the lung, the liver and the ileum tissues were collected for HE pathological slice.(1) Initially there was no difference in weight between the four groups, but on day 8 the weights of rats in Group B, C, and D were significantly decreased compared with that in Group A (P0.05). The mortality of rats in Group C was significantly higher than that in Group B and D (P0.05). (2) There were significant differences between Group C and D in white blood cell count, blood TNFalpha and IL-10 level, BALF, and total protein of BALF (P0.05). (3) Pathological changes of the lung, the liver and ileum in Group C were more severe than that in Group B and D. Group A was basically normal.Glutamine is able to protect gastrointestinal tract function in rats receiving TPN, to improve pulmonary anti-infection ability, and to alleviate injuries of important organs caused by severe infection.