Background Currently, there is limited research on the impact of abdominal infection on intestinal damage under microgravity conditions. Cordyceps polysaccharide (CPS), the main active ingredient of Cordyceps, has demonstrated various pharmacological effects, including anti-inflammatory, antioxidant, and immunomodulatory properties. Moxifloxacin (MXF) is a fourth-generation quinolone antibiotic that is believed to have a dual regulatory effect on immune system activation and suppression. Our objective was to investigate the effects of MXF plus CPS on the intestinal barrier damage due to abdominal infection under microgravity. Methods The hindlimb unloading model in rats was employed to simulate microgravity. The rat model of abdominal infection was established by cecal ligation and puncture (CLP). MXF, CPS and the combination of the two drugs were used to treat CLP-rats in simulated microgravity. We assessed histopathological changes of ileum by hematoxylin and eosin staining. The intestinal ultrastructure was observed under transmission electron microscopy. Additionally, the expression of intestinal barrier proteins RegIII α/γ and MUC2 was detected by Western blot analysis, while the localization of these proteins within the ileum was examined using immunohistochemistry. Cytometric bead array (CBA) was employed to detect cytokine including IL-6, TNF-α, IL-1β, IL-1α, CXCL-1, MCP-1, IL-17A, IL-18, and IL-33. Flow cytometry analysis was conducted to determine the percentages of Treg cells, M1 macrophages, M2 macrophages, T cells and CD8+T cells. Results The results showed that compared with the normal gravity groups, the simulated microgravity groups exhibited a significant decrease in RegIII α/γ protein expression, an increase in M1 macrophage frequency, and elevated levels of TNF-α, IL-1α, MCP-1 and IL-6. Notably, the combined application of MXF and CPS effectively mitigated intestinal barrier damage in CLP-rats exposed to microgravity, as evidenced by alleviated ultrastructural and pathological impairments in ileum, along with increased expression of key intestinal barrier proteins MUC2 and RegIII α/γ. Furthermore, the combination therapy enhances the proportion of T cells, CD8+ T cells, and M2 macrophages in septic rats exposed to simulated microgravity while reducing the frequency of Treg cells and M1 macrophages. MXF plus CPS also led to a reduction of proinflammatory cytokines and chemokines, including IL-6, TNF-α, IL-1β, IL-1α, CXCL-1, MCP-1, IL18, and IL33. Conclusion Our study showed that MXF plus CPS exhibited a protective effect on intestinal barrier damage due to abdominal infection under microgravity, potentially attributed to its anti-inflammatory properties and immune regulatory mechanisms. These findings may provide insights into the development of drugs targeting abdominal infections in the space environment.

Benign prostatic hyperplasia (BPH) is a condition commonly observed in aging males. Inflammatory and metabolic factors are pivotal in the development and progression of BPH. The degree to which the effects of 91 inflammation-related proteins on BPH are mediated by 1400 plasma metabolites remains ambiguous. Our research analyzed the impact of these traits utilizing genetic evidence.Two-sample Mendelian randomization (MR) and multivariable MR (MVMR) were utilized in our study to infer the genetic causal effect of inflammation-related proteins on BPH, with metabolites serving as mediators. Increased levels of IL-2 were linked to a heightened incidence of BPH (beta = 0.071, OR:1.074, 95% CI [1.002-1.152], p = 0.045), whereas lower concentrations of N6,N6-dimethyllysine were associated with decreased risk (beta 1=-0.127, p = 0.02; beta 2=-0.039, p = 0.008). The mediation effect was 0.005 (95% CI [0.0004, 0.012], OR: 1.005, 95% CI [1.000, 1.012]), accounting for 7.04% of the total effect. subsequently, we examined the phenotypic co-localization of the two pairings independently, revealing that the posterior probability of rs145516501 associated with IL-2 and BPH was 80.7%, whereas the posterior likelihood of rs4917820 linked to N6,N6-dimethyllysine levels and BPH was 95.9%. The research indicated that N6,N6-dimethyllysine levels seem to influence the causative relationship between IL-2 and BPH. These results elucidate the complex interplay between inflammation-related proteins and metabolism in the context of BPH, offering novel diagnostic and therapeutic avenues and enhancing our comprehension of the disease's etiology for prospective research.

Conventional two-dimensional (2D) cell culture techniques may undergo modifications in the future, as life scientists have widely acknowledged the ability of three-dimensional (3D) in vitro culture systems to accurately simulate in vivo biology. In recent years, researchers have discovered that microgravity devices can address many challenges associated with 3D cell culture. Stem cells, being pluripotent cells, are regarded as a promising resource for regenerative medicine. Recent studies have demonstrated that 3D culture in microgravity devices can effectively guide stem cells towards differentiation and facilitate the formation of functional tissue, thereby exhibiting advantages within the field of tissue engineering and regenerative medicine. Furthermore, We delineate the impact of microgravity on the biological behavior of various types of stem cells, while elucidating the underlying mechanisms governing these alterations. These findings offer exciting prospects for diverse applications.

Objective In this study, we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model. GO and KEGG analyses were conducted using the DAVID database. GSEA was performed using the R language. The STRING database was used to conduct PPI analysis. qPCR was used to measure the IL1B, TNFA, CASP3, CASP9, and BCL2L11 mRNA expressions. Western Blotting was performed to detect the level of proteins CASP3 and CASP 9. Flow cytometry was used to detect apoptosis and mitochondrial membrane cells. Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells. Simulated microgravity improved the CASP3, CASP9, and BCL2L11 expressions in Kupffer cells. Annexin-V/ PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells. Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization, which can secrete TNFA to promote apoptosis.

Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the “gut-organ” axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as “detecting agents” for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may also present a potential therapeutic approach to attenuate damage in other organs. Studies have demonstrated that diverse signaling pathways and their corresponding key molecules are extensively involved in the pathophysiological regulation of the intestinal barrier. Aberrant activation of these signaling pathways and dysregulated expression of key molecules play a pivotal role in the process of intestinal barrier impairment. Microgravity, being the predominant characteristic of space, can potentially exert a significant influence on diverse intestinal barriers. We will discuss the interaction between the “gut-organ” axes and intestinal barrier damage, further elucidate the signaling pathways underlying intestinal barrier damage, and summarize alterations in various components of the intestinal barrier under microgravity. This review aims to offer a novel perspective for comprehending the etiology and molecular mechanisms of intestinal barrier injury as well as the prevention and management of intestinal barrier injury under microgravity environment.

Benign prostatic hyperplasia (BPH) is a chronic disease that pretends to occur in elderly men. Inflammatory and metabolic factors play a key role in the pathogenesis and progression of BPH. The extent to which effects of 91 inflammation-related proteins on BPH are mediated by 1400 plasma metabolites is unclear. In our study we examined the effects of these traits using genetic evidence. We used two-sample Mendelian randomization ( two-sample MR) and Multivariable MR (MVMR) to determine:there is a genetic causal relationship between Interleukin-2 levels (IL-2)and BPH,N6,N6-dimethyllysine levels play a mediation role:higher IL-2 was associated with higher risk of BPH(β = 0.071, OR:1.074,95%CI[1.002–1.152],p = 0.045 and lower levels of N6,N6-dimethyllysine levels (β1=-0.127 p = 0.02).The N6,N6-dimethyllysine levels (β2=-0.039,p = 0.008) was negatively genetic associated with the risk of BPH.The mediation effect was 0.005,95% confidence interval(CI) [0.0004,0.012],odds-ratio (OR) :1.005,95%CI[1.000,1.012].Then,we analyzed the phenotypic co-localization of the two pairs : IL-2—BPH and N6,N6-dimethyllysine levels—BPH, which showed that IL-2 and BPH co-locate the SNP of rs145516501 on the NO. 13 chromosome. N6,N6-dimethyllysine levels, and BPH are co-located to the SNP of rs4917820 on the NO. 10 chromosome.The mediation proportion is 7.04%.The study suggested that N6,N6-dimethyllysine levels appear to mediate the causal effect of IL-2 on BPH.

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‐β1/Smad3 (TGF‐β1/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‐β1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.

The increasing number of astronauts entering microgravity environments for long-term space missions has resulted in serious health problems, including accidental injury and trauma. Skin, as the largest organ and outermost layer of the human body, has the ability to self-renew and withstand a variety of harmful biological and environmental influences. Recent spaceflight experiments and simulated studies have begun to concern the effects of microgravity on the growth of skin cells and the process of cutaneous wound healing. However, the mechanisms of the adverse effects of microgravity on skin cells and potential intervention measures are still limited. Stem cells and their exosomes provide unique opportunities for the cutaneous wound healing as they have been used to improve skin repair. This review discusses the effects of microgravity on wound healing, from cell morphological changes to molecular level alterations. Furthermore, the current research on wound healing treatment utilizing stem cells and their exosomes on the ground is summarized. Finally, this review proposes promising therapeutic strategies using stem cells or exosomes for wound healing in the microgravity environment.

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.

Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) “untouchable” for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.

虽然腹腔镜手术已成为临床常规技术,但其所引起的胆管损伤一直是困扰临床的一个魔咒.胆管损伤是腹腔镜胆囊切除术(laparoscopic cholecystec-tomy,LC)中最严重的并发症.文献报道,LC术中胆管损伤发生率为0.3％～0.5％[1-2],一旦发生,可引发胆漏、胆道梗阻、胆汁性腹膜炎、化脓性胆管炎、脓毒血症、多器官功能障碍综合征(multiple organ dys-function syndrome,MODS)等严重后果[3],大多需要行胆道重建手术,而术后仍可能会反复发作的胆管炎、胆汁性肝硬化,以至导致终末期肝病,严重者需要行肝移植术,甚至引起死亡.笔者就LC术中胆管损伤的主要原因、分型、治疗和预防作一综述.

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.

Objective To investigate the effects of simulated microgravity (SMG) environment by rotary cell culture system (RCCS) on metabonomics of human gastric epithelial GES-1 cells. Methods Human gastric epithelial GES-1 cells were cultured in vitro. Three to ten generations of cells in logarithmic growth phase were selected and randomly divided into SMG group and normal gravity group (NG group. Cells in different groups were cultured for 1，3，and 5 d，and then subjected to non-targeted LC/MS based metabolomics analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) and two sample independent t-test were used to find the differential metabolites of the two groups of cells，and then the differential metabolites were input into KEGG database to construct metabolic pathways and conduct functional analysis. Results GES-1 cells in both groups had 151 differential metabolites after 1 d of RCCs culture，113 of which were up-regulated and 38 down-regulated;134 of which were up-regulated and 25 down-regulated after 3d of RCCS culture; 154 of which were up-regulated and 23 down-regulated after 5 d of RCCS culture. Seventy-four kinds of common differential metabolites (variable importance>1 and P<0.05) at 1，3 and 5 <1 in two groups were screened out by Venn diagram, among which 57 were up-regulated and 17 were down-regulated. KEGG database analysis found that there were 44 differential metabolites with specific names and related functions，mainly including phospholipids，amino acids，cofactors and carboxylic acids，mainly involving lipid metabolism, amino acid metabolism, coenzyme and vitamin metabolism, neurotransmitter metabolism，carbohydrate metabolism, cell proliferation and apoptosis，tumor regulation，membrane transport and signal transduction pathways. Conclusion SMG environment by RCCS can significantly affect the metabolism of GES-1 cells，which mainly involves lipid metabolism, membrane structure damage, cell proliferation and apoptosis，and tumor regulation.

门静脉海绵样变性（cavernous transformation of portal vein,CTPV）是指门静脉主干或其分支受阻后,机体为维持肝脏血流灌注,在肝门区代偿性形成的大量海绵样侧支血管丛.该病较罕见,临床实践中缺乏对其病因及诊疗原则的认识.对于出现门静脉高压相关症状的患者需要采取积极治疗措施.治疗的主要目的是防治门静脉高压引起的上消化道出血和脾功能亢进,以及恢复肝脏门静脉血流灌注.需要在充分了解患者病情及每种治疗方式最佳适应症的基础上,采用个体化综合治疗策略.本文就CTPV的病因、诊断、分型、治疗方面的最新进展作一综述.

Objective:To investigate the relationship between body weight and surgical outcome in patients undergoing radical resection of colorectal cancer.Methods:From January 2010 to October 2014, clinical data of 246 patients who underwent radical resection of colorectal cancer were analyzed retrospectively. All enrolled patients received radical resection of colorectal cancer and were followed up for 5 years until November 2019. According to body mass index (BMI), the patients were divided into normal group, super recombination group and obesity group, 96 cases, 80 cases and 70 cases respectively. Statistical analysis were performed by using SPSS 22.0 software. Kaplan-Meier survival analysis method was used for the 5-year disease-free survival rate (DFS) of patients. BMI and clinically relevant data were analyzed by using Cox regression.Results:The 5-year DFS was 78.13% (75/96), 62.05% (50/80) and 55.71% (39/70) in the normal group, the super recombination group and the obese group respectively. Cox regression analysis showed that high BMI, positive preoperative CEA, low differentiation, high pT staging and high pN staging were risk factors for prognosis of colorectal cancer patients after radical resection (P<0.05), and postoperative chemoradiotherapy was a protective factor for prognosis (P<0.05).Conclusion:Obesity is a major risk factor of poor prognosis in patients with colorectal cancer.

门静脉高压性胆病(PHB)是一种由肝外门静脉阻塞引起的胆道继发性改变,临床罕见;患者大多无明显自觉表现,少数病史较长者可出现腹痛、发热、黄疸等症状.目前对其治疗方案尚无统一意见,有症状的患者往往需要接受综合治疗.该文报告了1例门静脉海绵样变(PVCT)发展为PHB的病例.患者辗转多家医院就诊,因PVCT不宜手术,多次内镜下胆管支架植入及更换,症状反复,最终行腹腔镜下胆囊切除、小切口辅助胆总管切开取石、胆肠Roux-en-Y吻合术,术后黄疸、腹胀、发热等症状得到有效缓解.

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.

目的:探讨旋转细胞培养系统(RCCS)模拟失重环境对人SK-BR-3乳腺癌细胞生物学行为的影响.方法:体外培养人SK-BR-3乳腺癌细胞,将实验细胞随机分为模拟微重力组(SMG)和正常重力对照组(NG).应用RCCS模拟微重力环境.培养第3 d收取SMG组与NG组细胞进行检测:CCK-8法检测吸光度值,比较两组细胞增殖能力;流式细胞仪技术检测细胞周期和细胞凋亡变化;透射电镜观察细胞超微结构变化.结果:CCK-8检测结果显示,SMG组乳腺癌细胞的吸光值显著低于NG组(0.522±0.060 vs 1.327±0.090,P<0.001).流式细胞仪检测发现,SMG和NG组乳腺癌细胞的凋亡细胞率分别为(33.233±5.537)％和(5.500±1.572)％,差异有统计学意义(P=0.001);SMG组人SK-BR-3乳腺癌细胞G0/G1期、S期和G2/M期比例分别为(52.734±3.264)％、(36.864±2.918)％和(10.402±0.881)％,与NG组细胞G0/G1期、S期和G2/M期的对应比例(32.534±1.741)％、(53.924±3.215)％和(13.542±2.451)％相比,差异均有统计学意义(P<0.05).透射电镜结果显示,与NG组比较,SMG组人SK-BR-3乳腺癌细胞经RCCS模拟失重环境培养3 d后,线粒体水肿,次级溶酶体增多,细胞超微结构发生明显改变.结论:RCCS模拟失重环境下人SK-BR-3乳腺癌细胞凋亡增加,增殖受抑制,细胞周期和超微结构发生明显改变.

哺乳动物的表皮中存在多种不同类型的表皮干细胞(epidermal stem cells,EpSCs),EpSCs拥有自我更新和分化的潜能,在维持表皮组织结构稳定和皮肤创伤愈合及皮肤疾病发生、发展过程中发挥重要作用.本文就EpSCs的特性、信号调节、在创伤愈合过程和抗衰老中的作用以及与皮肤癌的关系做一综述.