Simulated microgravity altered the proliferation, apoptosis, and extracellular matrix formation of L929 fibroblasts and the transforming growth factor-ß1/Smad3 signaling pathway.

Exposure to microgravity can adversely affect the fitness of astronauts. The integrity of the skin plays a crucial role in protecting against mechanical forces and infections, fluid imbalance, and thermal dysregulation. In brief, the skin wound may cause unknown challenges to the implementation of space missions. Wound healing is a physiological process that relies on the synergistic action of inflammatory cells, extracellular matrix (ECM), and various growth factors to maintain the integrity of skin after trauma. Fibroblasts are present almost throughout the entire process of wound repair, especially in the scar formation at the endpoint of wound healing. However, there is limited knowledge about the extent to which fibroblasts are affected by the lack of gravity during wound healing. In this study, we utilized the rotary cell culture system, a ground-based facility that mimics the weightless condition, to study the alterations of L929 fibroblast cells under simulated microgravity (SMG). Our results demonstrated that the SM condition exerted negative influences on the proliferation and ECM formation of the L929 fibroblast. Whereas, the apoptosis of fibroblast was significantly upregulated upon exposure to SMG conditions. Moreover, the transforming growth factor-ß1/Smad3 (TGF-ß1/smad3) signaling pathway of L929 fibroblast related to wound repair was also altered significantly under a weightless environment. Overall, our study provided evidence that fibroblasts are strongly sensitive to SMG and elucidated the potential value of the TGF-ß1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.

Autophagy in hepatic macrophages can be regulator and potential therapeutic target of liver diseases: A review.

Hepatic macrophages are a complex population of cells that play an important role in the normal functioning of the liver and in liver diseases. Autophagy, as a maintainer of cellular homeostasis, is closely connected to many liver diseases. And its roles are not always beneficial, but manifesting as a double-edged sword. The polarization of macrophages and the activation of inflammasomes are mediated by intracellular and extracellular signals, respectively, and are important ways for macrophages to take part in a variety of liver diseases. More attention should be paid to autophagy of hepatic macrophages in liver diseases. In this review, we focus on the regulatory role of hepatic macrophages' autophagy in a variety of liver diseases; especially on the upstream regulator of polarization and inflammasomes activation of the hepatic macrophages. We believe that the autophagy of hepatic macrophages can become a potential therapeutic target for management of liver diseases.

Jejunojejunal intussusception with chronic bleeding caused by gastrointestinal stromal tumor: a case report and literature review.

Background: Intussusception is a rare clinical condition in adults. The majority of patients present with symptoms of bowel obstruction. Intussusception is often misdiagnosed and the majority of cases are diagnosed intraoperatively. In this paper, we present a rare case of adult jejunojejunal intussusception with chronic bleeding caused by a gastrointestinal stromal tumor (GIST). We emphasize the role of contrast-enhanced computed tomography (CT) and enteroscopy in the presurgical diagnosis and the good prognosis in the high-risk GIST patient after surgery and targeted therapy. Case Description: Herein, we present the case of a 63-year-old female patient with small bowel intussusception with chronic bleeding caused by a GIST. Her main symptoms were intermittent melena and progressive anemia. She had a 20-year history of hypertension and had never undergone previous abdominal surgery. After failure of an esophagogastroduodenoscopy and colonoscopy to locate the hemorrhagic foci in the gastrointestinal tract, contrast-enhanced CT and enteroscopy were used and a small bowel intussusception and an intraluminal mass with a bleeding ulcer was identified. The patient underwent laparoscopic partial small bowel resection, and postoperative pathological examinations showed a small intestinal GIST with a high risk of recurrence. It was suggested that the patient take imatinib regularly for at least 3 years. At the time of writing, she has remained in good health without relapse for 24 months after discharge. We also review 20 published cases of intussusception caused by small bowel GIST in the PubMed database. Conclusions: Obscure gastrointestinal hemorrhage needs meticulous examinations to promptly determine the cause and location of bleeding. This case and literature review revealed that comprehensive surgical resection-centered treatment was the standard treatment for primary localized GISTs in patients at significant risk of relapse.

Proteomic analysis of the effects of simulated microgravity in human gastric mucosal cells.

Microgravity is an ecological factor that affects the environment of the body. In this study, quantitative isobaric labeling (tandem mass tag) method was used to study the changes in human gastric mucosal cells under simulated microgravity for the first time. Comparative proteomic analysis identified 394 (202 upregulated and 192 downregulated) and 542 (286 upregulated and 256 downregulated) proteins differentially regulated by simulated microgravity after 3 and 7 days, respectively. Then the identified proteins were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for further exploration. The results of the analysis showed that the ribosomes of gastric mucosal cells were significantly impacted after exposure to simulated microgravity for 3 days, and the cells appeared to be in a state of stress and inflammation. Exposure to simulated microgravity for 7 days significantly affected the mitochondria of the cells, oxidative stress became more evident, while inflammation and weakened connections were observed in the cells. The results of this study highlighted the temporal response trend of gastric mucosal cells to the stressor of microgravity at the two time points of 3 and 7 days. These findings will provide insights into the development of methods to protect the gastric mucosa during space flight.

Inflammation is involved in response of gastric mucosal epithelial cells under simulated microgravity by integrated transcriptomic analysis.

Astronauts suffer from inflammatory changes induced by microgravity during space flight. Microgravity can significantly affect the inflammatory response of various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and digestive system. The aim of this research was to identify the key genes and pathways of gastric mucosa affected by microgravity. Human gastric mucosal epithelial GES-1 cells were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The gene expression profiles of GES-1 cells were obtained using Illumina sequencing platform and differentially expressed genes were identified by DESeq2 software, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Subsequently, a protein-protein interaction (PPI) network was constructed. Compared with a normal gravity (NG) group, a total of 943 DEGs, including 192 downregulated genes and 751 upregulated genes, were identified. These DEGs were associated with findings that included response to interleukin-1, positive regulation of inflammatory response, and positive regulation of neuroinflammatory response. Furthermore, these DEGs were mainly enriched in herpes simplex virus 1 infection, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathway. Thus, 21 hub genes were identified from PPI network, including IL6, IL1B, ITGAM, CXCL8, ITGAX, CCL5, SERPINA1, APOE, CSF1R, VWF, GBP1, APOB, CYBB, HLA-DRB1, CD68, FGG, FGA, OASL, NOD2, OAS2 and FCGR2A. These findings suggested that simulated microgravity upregulated inflammation-related genes and pathways of GES-1 cells, which may play important roles in the response to microgravity and provide useful information for preventing mucosal damage in astronauts. In conclusion, this study revealed the key genes and pathways associated with simulated microgravity and indicated that simulated microgravity induced an inflammatory response in gastric mucosal epithelial cells.

Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target.

The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.

The effects of combined environmental factors on the intestinal flora of mice based on ground simulation experiments.

The composition and function of intestinal microbial communities are important for human health. However, these intestinal floras are sensitive to changes in the environment. Adverse changes to intestinal flora can affect the health of astronauts, resulting in difficulties in implementing space missions. We randomly divided mice into three groups and placed each group in either a normal environment, simulated microgravity environment or a combined effects environment, which included simulated microgravity, low pressure and noise. Fecal samples of the mice were collected for follow-up analysis based on metagenomics technology. With the influence of different space environmental factors, the species composition at the phylum and genus levels were significantly affected by the combined effects environment, especially the abundance of the Firmicutes and Bacteroidetes. Furthermore, screening was conducted to identify biomarkers that could be regarded as environmental markers. And there have also been some noticeable changes in the function of intestinal floras. Moreover, the abundance of antibiotic resistance genes (ARGs) was also found to be changed under different environmental conditions, such as bacitracin and vancomycin. The combined effects environment could significantly affect the species composition, function, and the expression of ARGs of intestinal flora of mice which may provide a theoretical basis for space medical supervision and healthcare.

Asymptomatic epiploic appendage with torsion in laparoscopic surgery: a case report and literature review.

Torsion of an epiploic appendage may result in epiploic appendagitis, which is a rare cause of acute abdominal pain. However, no previous reports have described an asymptomatic twisted epiploic appendage found during laparoscopaic surgery to the best of our knowledge. This case describes a 66-year-old man who was admitted to our medical center with yellowness of the skin and eyes that had lasted over two months. Physical examination showed slight yellow staining of the skin and sclera. Blood analysis indicated liver dysfunction and jaundice. Routine blood, C-reactive protein (CRP), and levels of tumor markers were normal. The contrast-enhanced abdominal and pelvic computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed gallbladder atrophy and choledocholithiasis. The patient underwent laparoscopic surgery for the removal of the choledocholithiasis. The laparoscopic exploration unexpectedly revealed a twisted and ischemic epiploic appendage, which was surgically removed. The postoperative pathological examination uncovered necrosis of adipocytes and vascular obstruction, but there was no inflammation of the epiploic appendage. The patient had a satisfactory recovery during the 16-month follow-up period. This case describes and provides a feasible management approach for an asymptomatic twisted epiploic appendage discovered during surgery and highlights its pathological characteristics, reflecting the early stage of epiploic appendagitis.

Correction to: Simulated microgravity significantly altered metabolism in epidermal stem cells.

The affiliation given for Yan Cui in this article is not correct. The following is the correction affiliation.

Effect of simulated microgravity on metabolism of HGC-27 gastric cancer cells.

The understanding into the pathogenesis and treatment of gastric cancer has improved in recent years; however, a number of limitations have delayed the development of effective treatment. Cancer cells can undergo glycolysis and inhibit oxidative phosphorylation in the presence of oxygen (Warburg effect). Previous studies have demonstrated that a rotary cell culture system (RCCS) can induce glycolytic metabolism. In addition, the potential of regulating cancer cells by targeting their metabolites has led to the rapid development of metabolomics. In the present study, human HGC-27 gastric cancer cells were cultured in a RCCS bioreactor, simulating weightlessness. Subsequently, liquid chromatography-mass spectrometry was used to examine the effects of simulated microgravity (SMG) on the metabolism of HGC-27 cells. A total of 67 differentially regulated metabolites were identified, including upregulated and downregulated metabolites. Compared with the normal gravity group, phosphatidyl ethanolamine, phosphatidyl choline, arachidonic acid and sphinganine were significantly upregulated in SMG conditions, whereas sphingomyelin, phosphatidyl serine, phosphatidic acid, L-proline, creatine, pantothenic acid, oxidized glutathione, adenosine diphosphate and adenosine triphosphate were significantly downregulated. The Human Metabolome Database compound analysis revealed that lipids and lipid-like metabolites were primarily affected in an SMG environment in the present study. Overall, the findings of the present study may aid our understanding of gastric cancer by identifying the underlying mechanisms of metabolism of the disease under SMG.

Simulated microgravity significantly altered metabolism in epidermal stem cells.

Simulated microgravity can significantly affect various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and immune system, and is known to cause anemia and loss of electrolyte and fluids. Epidermal stem cells (EpSCs) were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The metabolites of EpSCs were identified by liquid chromatography-mass spectrometry (LC-MS). Compared with normal gravity (NG) group, a total of 57 different metabolites of EpSCs were identified (P < 0.05, VIP > 1), including lipids and lipid-like molecules (51 molecules), amino acids (5 molecules), nucleosides, nucleotides, and analogues (1 molecule). According to the partial least squares discriminant analysis (PLS-DA) score plot, a VIP > 1 and P < 0.05 were obtained for the 57 different metabolites, of which 23 molecules were significantly downregulated and 34 were significantly upregulated in simulated microgravity (SMG) group. These results showed that SMG has a significant impact on different pathways, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that multiple pathways were involved, mainly the amino acid metabolism pathway, lipid metabolism pathway, membrane transport pathway, and cell growth and death pathways. Thus, the metabolic profile of EpSCs was changed under SMG. Exploring the metabolic profile of EpSCs would be helpful to further understand the growth characteristics of EpSCs under SMG, which will provide a new approach to explore the metabolomics mechanism of stress injury and repair trauma under SMG.

Minimally invasive surgery for appendiceal intussusception caused by mucocele of the appendix: case report and review of the literature.

Appendiceal intussusception caused by mucocele of the appendix is extremely rare. In the current study, a 32-year-old woman was admitted to the department of general surgery of our hospital, complaining of persistent right, lower quadrant pain without an obvious cause for 17 hours. Physical examination indicated significant pain and tenderness in the right, lower abdominal quadrant. Blood analysis indicated that leukocyte count, the percentage of neutrophils and the serum C-reactive protein were increased. Abdominal and pelvic computed tomography revealed a well-encapsulated cystic mass surrounded by the caecum and intussusception. The appendiceal intussusception caused by mucocele of the appendix was revealed during the laparoscopic exploration. Appendectomy and partial cecectomy were conducted using the laparoscopic approach. Postoperative pathological examinations showed ileocecal intussusception and chronic inflammation, appendiceal mucocele and acute suppurative appendicitis. The patient showed satisfactory recovery that was observed during 15-months of follow-ups. This case highlights that laparoscopic appendectomy and partial cecectomy may be a beneficial, minimally invasive approach for appendiceal intussusception caused by mucocele of the appendix.

The effects of microgravity on the digestive system and the new insights it brings to the life sciences.

BACKGROUND: Weightlessness is a component of the complex space environment. It exerts adverse effects on the human body, and may pose unknown challenges to the implementation of space missions. The regular function of the digestive system is an important checkpoint for astronauts to conduct missions. Simulated microgravity can recreate the changes experienced by the human body in a weightless environment in space to a certain extent, providing technical support for the exploration of its mechanism and a practical method for other scientific research. METHODS AND MATERIALS: In the present study, we reviewed and discussed the latest research on the effects of weightlessness or simulated microgravity on the digestive system, as well as the current challenges and future expectations for progress in medical science and further space exploration. RESULTS: A series of studies have investigated the effects of weightlessness on the human digestive system. On one hand, weightlessness and the changing space environment may exert certain adverse effects on the human body. Studies based on cells or animals have demonstrated the complex effects on the human digestive system in response to weightlessness. On the other hand, a microgravity environment also facilitates the ideation of novel concepts for research in the domain of life science. CONCLUSION: The effects of weightlessness on the digestive system are considerably complicated. The emergence of methods that help simulate a weightless environment provides a more convenient alternative for assessing the impact and the mechanism underlying the effect of weightlessness on the human body. In addition, the simulated microgravity environment facilitates the ideation of novel concepts for application in regenerative medicine and other fields of life science.

Contrast-enhanced computed tomography findings of a huge perianal epidermoid cyst: A case report.

BACKGROUND: Epidermoid cysts can be found at any location in the human body. However, perianal epidermoid cysts are extremely rare and only a few cases have been reported. As far as we know, there is no special literature on the value of contrast-enhanced computed tomography (CT) for the diagnosis of perianal epidermoid cysts. CASE SUMMARY: A 60-year-old male patient presented to the department of general surgery of PLA Strategic Support Force Characteristic Medical Center with the chief complaint of a mass in the perianal region gradually expanding for more than 30 years and perianal discomfort upon sitting for a preceding period of 2 mo. Physical examination revealed a painless mass in the left perianal region. Contrast-enhanced CT was used for preoperative diagnosis. The patient was treated by total mass excision under epidural anesthesia. Postoperative pathological examination revealed the presence of a perianal epidermoid cyst. The patient showed a satisfactory recovery during the 6-month follow-up period. CONCLUSION: Contrast-enhanced CT may be a beneficial, useful, and convenient approach for assistance for preoperative diagnosis and surgical decision-making for patients with perianal epidermoid cysts.

[Predictors of local recurrence and survival in primary retroperitoneal leiomyosarcoma].

OBJECTIVE: To investigate the predictors of local recurrence and survival in primary retroperitoneal leiomyosarcoma (PRLS). METHODS: A retrospective analysis was conducted on 46 cases of PRLS between August 2006 and April 2012. There were 9 male and 37 female patients, and they were 30-79 year old (median 49 year old). Kaplan-Meier estimations and Cox regression analyses were performed. RESULTS: The tumor size were 5-36 cm, and 29 cases (63.1%) of this group was more than 10 cm. Local 3- and 5-year control rates after complete resection were 47% and 30%. FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grading (RR = 3.10, 95%CI: 1.59-6.04), gender (RR = 5.30, 95%CI: 1.64-17.13) and blood loss (RR = 3.12, 95%CI: 1.28-7.60) were independent prognostic factor of local recurrence in multivariable analysis (P < 0.05). The 5-year disease-free survival rates after complete resection of PRLS was 26%; and the 5-year disease-specific survival (DSS) rates after complete resection was 48%. The median DSS was 60 months in negative margin of resection and 50 months in positive margin. However, by multivariate analysis, only FNCLCC grading was significant independent predictors of DSS (RR = 2.01, 95%CI: 1.16-3.49, P = 0.013). CONCLUSIONS: Gender, FNCLCC grading and blood loss were independent prognostic factor of local recurrence. The disease-specific survival in PRLS varied significantly according to FNCLCC grading.

Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model.

Due to the anatomical structure of the rectum, the treatment of rectal cancer remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1 promoter, can selectively replicate within and kill cancer cells derived from solid tumors. Thus, this virus provides a novel approach for the treatment of rectal cancer. Given the poor efficacy and possible adverse reactions that arise from the use of oncolytic virus alone and the results of our analysis of the efficacy of Ad-E2F in the treatment of rectal cancer, we investigated the use of oncolytic adenovirus in combination with adoptive immunotherapy using cytokine-induced killer (CIK) cells as a therapeutic treatment for rectal cancer. Our results illustrated that E2F-1 gene expression is higher in rectal cancer tissue than in normal tissue. Furthermore, the designed oncolytic adenovirus Ad-E2F is capable of selectively killing colorectal cell lines but has no significant effect on CIK cells. The results of in vitro and in vivo experiments demonstrated that combined therapy with Ad-E2F and CIK cells produce stronger antitumor effects than the administration of Ad-E2F or CIK cells alone. For low rectal cancers that are suitable for intratumoral injection, local injections of oncolytic viruses in combination with CIK cell-based adoptive immunotherapy may be suitable as a novel comprehensive therapeutic approach.

[Assessment value of preoperative neutrophil-lymphocyte ratio for the prognosis of patients with colorectal cancer after radical operation].

OBJECTIVE: To assess the value of preoperative neutrophil-lymphocyte ratio (NLR) for prognosis in patients with colorectal cancer after radical operation. METHODS: Clinical data of 140 patients with colorectal cancer undergoing radical operation in the Department of General Surgery of General Hospital of PLA from July 2005 to July 2011 were analyzed retrospectively. According to preoperative NLR, patients were divided into the low NLR group (NLR<5, n=105) and the high NLR group (NLR≥5, n=35). The overall 5-year survival rates of two groups were compared and the independent risk factors were examined by univariate analysis and Cox model. RESULTS: The overall 5-year survival rates of the low and high NLR groups were 74.8% and 54.7% respectively with significant difference (P=0.03). Univariate analysis revealed depth of tumor, lymph nodes metastasis, TMN stage and NLR were associated with survival (P<0.05, P<0.01). Cox model showed that NLR was independent risk factor of prognosis (RR=1.068, 95%CI:1.009-1.129, P=0.02). CONCLUSION: Preoperative NLR≥5 predicts poorer prognosis of colorectal cancer patients.

[Analysis of treatment and prognosis in 34 patients with anorectal malignant melanoma].

OBJECTIVE: To explore the prognostic factors of anorectal malignant melanoma (ARMM). METHODS: Medical records and follow-up data of 34 patients with ARMM treated in the Chinese PLA General Hospital from March 1993 to November 2011 were analyzed retrospectively. RESULTS: There were 26 abdominoperineal resections(APR) and 8 wide local excisions (WLE). Twenty patients underwent postoperative adjuvant therapy, including chemotherapy in 14 cases, radiotherapy in 2 cases, traditional Chinese medicine therapy in 4 cases and immunotherapy in 16 cases. Postoperative follow-up was carried out in all the patients and the mean follow-up period was 27 months. The 1-, 3- and 5-year overall survival rates were 76.3%, 39.6% and 20.6% respectively, while the 1-, 3- and 5-year disease-free survival rates were 60.6%, 30.8% and 12.8% respectively. APR and postoperative immunotherapy could significantly reduce the local recurrence rate. According to the Kaplan-Meier method, gross type of tumor, mural involvement, lymph metastasis, and clinical staging had significant effects on overall survival, while lymph metastasis and postoperative immunotherapy on disease-free survival. Cox proportional hazards model indicated that the clinical staging and postoperative immunotherapy were significant predictive factors. CONCLUSIONS: Early diagnosis and correct choice of surgical method are the keys to the treatment. Postoperative immunotherapy can prolong disease-free survival.