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Visceral adiposity index (VAI), an indicator of visceral fat, is associated with metabolic health and arterial stiffness. However, studies correlating VAI and stroke are limited. This study aimed to explore the association between VAI and incident stroke in the Chinese population.We retrospectively analysed the data of 9127 individuals enrolled in the China Health and Retirement Longitudinal Study. The first survey of the study was conducted during 2011-2012 and the individuals were followed up until Survey 4 (2017-2018). Multivariable-adjusted Cox regression models were used to evaluate the association between VAI and stroke. The mean age of the study population was 59.3 ± 9.5 years and 4938 (54.1%) participants were women. During the median follow-up of 5.2 [1.0-7.0] years, 833 (9.1%) participants developed stroke, and the cumulative incidence of stroke increased with increasing quartiles of VAI (8.6%, 8.7%, 9.2%, and 10.0%). Compared to those in the first quartile of VAI, individuals in the fourth quartile had an increased risk of stroke (adjusted hazard ratio, 1.45; 95% CI, 1.15-1.75). The results were stable in several sensitivity analyses.Our findings suggest a positive association between VAI and incident stroke in the Chinese population.

Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on colorectal peritoneal metastasis (CRPM) and provide more reliable evidence for clinical practice.Methods: We searched for relevant randomized controlled trials (RCTs), case-control studies and cohort studies in PubMed, Web of Science, Cochrane Library, and Embase databases from their inception to 1 January 2022. Hazard ratio (HR) and odd ratio (OR) with 95% confidence intervals (CIs) were performed a meta-analysis using RevMan 5.3 software.Results: A total of twelve studies, of which three RCTs, eight cohort studies and one case-control study were included, and 3605 participants were involved. The results showed that CRS plus HIPEC was better than other remedial measures at improving the overall survival (OS) (HR=0.46, 95% C1:0.35-0.61, P=0.02). However, the heterogeneity was obvious (P2=73%). According to different control measures, it is divided into three subgroups of CRS, CRS plus intraperitoneal chemotherapy (IPC) and palliative chemotherapy (PC). The results of subgroup analysis showed that CRS plus HIPEC was better than CRS plus IPC at enhancing the OS (HR=0.58, 95% CI :0.36-0.93, P=0.02) and was more effective than PC at improving the OS (HR=0.29, 95% CI :0.24-0.35, PP=0.06). In addition, CRS plus HIPEC had more adverse events than CRS (OR=1.69, 95% CI : 1.06-2.70, P=0.03). Conclusions: This systematic review and meta-analysis suggests that CRS plus HIPEC might be effective to CRPM in improving the OS. However, compared with CRS alone, the efficacy of CRS plus HIPEC has not improved much, and CRS plus HIPEC may bring more adverse events.

Background Natural compounds extracted from plants have been reported to have antitumor activity. A fungal metabolite from Phomopsis, identified as epoxycytochalasin H and isolated from the flowering plant Polygonatum sibiricum, was found to have significant antitumor activity. In this study, we report the antitumor effects and mechanism of action of epoxycytochalasin H in the ovarian cancer cell line A2780. Our data suggest that epoxycytochalasin H markedly reduces cell proliferation and induces apoptosis in ovarian cancer cells. Materials and methods The viability, apoptosis and colony formation of A2780 cells, treated with epoxycytochalasin H, were detected by MTT assay, nuclear staining, flow cytometry, and clone formation assay. MitoROS and mitochondrial membrane potentials were detected by MitoSOX staining and flow cytometry. The expression of proteins associated with apoptosis, autophagy, and endoplasmic reticulum stress, in A2780 cells treated with epoxycytochalasin H, was detected by Western blot. Effects of mitophagy were detected in Parkin-overexpressing 293T cells. Results Our data suggested that epoxycytochalasin H could strongly reduce cell proliferation and induce apoptosis in ovarian cancer cell line A2780. Epoxycytochalasin H induced apoptosis through mitochondrial injury, mitophagy, and endoplasmic reticulum stress. Specifically, epoxycytochalasin H increased ROS level in cells, and in mitochondria, it decreased mitochondrial membrane potential, caused mitochondrial injury, activated macroautophagy and mitophagy, and subsequently induced apoptosis via the mitochondrial pathway. Additionally, it was discovered that epoxycytochalasin H could induce apoptosis more significantly in 293T cells overexpressing Parkin than in the parental cells. Thus, the mitophagy activated by epoxycytochalasin H could promote apoptosis. In addition, epoxycytochalasin H mediated endoplasmic reticulum stress-related apoptosis. Conclusion Epoxycytochalasin H could promote apoptosis of human ovarian cancer A2780 cells by activating mitochondrial and endoplasmic reticulum stress-related apoptotic pathways.

Background siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells. Materials and methods The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays. Results The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%. Conclusion FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.

Background An intro-abdominal hernia through the lesser omentum is a rare but severe condition that can cause intestinal obstruction and other life-threating complications. Until now, only a handful of cases have been reported worldwide. The diagnosis of lesser omental hernia remains challenging for emergency surgeons because of the unspecific symptoms. Therefore, there is a need for a better understanding of the characteristics of this condition. Case presentation In this report, we described the case of a 73-year-old female patient who was diagnosed with a lesser omental hernia caused by previous total colectomy. The patient underwent emergency surgery, and the intraoperative findings revealed a 200-cm segment of the small intestine was herniated through a defected lesser omentum (approximately 3 × 4 cm) from the lesser retrogastric curvature of the stomach. Besides, we summarize the specific abdominal computed tomography (CT) findings of lesser omental hernia by reviewing the literature. Conclusion The lesser omental hernia is extremely rare but can cause serious complications. The cause of lesser omental hernia can be congenital or acquired. Careful examination of the small omentum before the closure of the abdomen is expected to reduce the occurrence of these abdominal surgery-associated complications. The specific features of abdominal CT in cases of lesser omental hernia, which are summarized in this article, can help other clinicians to obtain accurate diagnoses of lesser omentum hernia in the future.

Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.

DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5 mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5 mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.

The study reports on a case of primary angiosarcoma of the small intestine in a 43-year-old woman presenting with intestinal perforation and metastasis to the peritoneum, along with a pertinent literature review. After hospitalization, an exploratory laparotomy was undertaken to aid in her diagnosis, followed by palliative intestinal resection with enteroenterostomy. The pathological examination and immunohistochemistry of resected tumor tissues confirmed the diagnosis. Moreover, analysis of seven reported cases of primary intestinal angiosarcoma in the literature revealed that patients often present with abdominal pain or recurrent gastrointestinal (GI) bleeding, dying within six months of diagnosis or resection surgery. Altogether, these findings illustrate that, despite volume-reducing palliative surgery, the prognosis of primary angiosarcoma of the small intestine remains poor for the majority of patients.

Background and aims We aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences. Methods and results The China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05–1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98–1.29). In addition, the positive dose–response relationship between BMI increase and stroke was observed only in men. Conclusion Among middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.

Background Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. Methods We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein–protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. Results Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. Conclusion The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.

This study aimed to identify prognostic epigenetic biomarkers for colon cancer (CC). Methylation and mRNA expression in CC samples with clinical characteristics that corresponded to those in The Cancer Genome Atlas were analyzed. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were screened between matched tumor and nontumor tissues. Among the 415 DEGs and DMGs that significantly correlated between cytosine-phosphate-guanine (CpG) methylation and gene expression, unc-5 netrin receptor C (UNC5C), solute carrier family 35 member F (SLC35F)1, Ly6/Neurotoxin (LYNX)1, stathmin (STMN)2, slit guidance ligand (SLIT)3, cell adhesion molecule L1 like (CHL1), CAP-Gly domain containing linker protein family member 4 (CLIP4), transmembrane protein (TMEM) 255A, granzyme B (GZMB), and brain expressed X-Linked (BEX)1 were promising epigenetic biomarkers. Prediction was more accurate when models were based on the expression and/or methylation of GZMB rather than clinical stage. Comparisons of tissues with high or low GZMB expression significantly associated the DEGs with natural killer-mediated cytotoxicity, cytokine-cytokine receptor interactions, and chemokine signaling pathways. From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.

Lian Duan,1 Jianlin Zuo,2 Fuqiang Zhang,1 Binxi Li,3 Zhonghang Xu,4 Hao Zhang,3 Bai Yang,3 Wenzhi Song,5 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Stomatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jinlan Jiang; Wenzhi SongChina-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun, Jilin, People’s Republic of ChinaTel|Fax +86 431-84995432Email jiangjinlan@jlu.edu.cn; songwz@jlu.edu.cnPurpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.Keywords: SPION@PDA NPs, HU-MSCs, GC-ONFH, apoptosis

In this study, 5-fluorouracil (5-FU) and LY294002 (LY)-loaded PEGylated nanoliposome was prepared to target esophageal squamous cell carcinoma (ESCC). The particles were characterized in terms of physicochemical and biological parameters. The co-delivery of autophagy inhibitor and chemotherapeutic drug in a single carrier was successfully accomplished. The two components from 5-FU and LY-loaded PEGylated nanoliposome (FLNP) released in a controlled manner with LY relatively released faster compared to that of 5-FU. FLNP showed a receptor-mediated cellular uptake that will allow the gradual release of drug in the acidic environment. The cellular uptake of nanoparticles (NP) was further confirmed by FACS analysis. The combination of 5-FU and LY resulted in higher cytotoxic effect compared to that of individual drugs. Most importantly, FLNP exhibited a significantly higher anticancer effect in cancer cells compared to that of free cocktail combinations. The faster release of LY from FLNP leads to autophagy inhibition that improves the sensitivity of cancer cells towards 5-FU, resulting in more cell death. Consistently, FLNP induced a greater apoptosis (~ 48%) of cancer cells compared to that of any other groups. Western blot analysis clearly showed that 5-FU and LY individually increased the expression of caspase-3 and PARP, while as expected FLNP induced a remarkable expression of these protein markers indicating the superior anticancer effect. We believe that the programmed release of autophagy inhibitor and chemotherapeutic drug from a single nanocarrier will increase the prospect of anticancer therapy in ESCC.

Transforming growth factor beta (TGF-β) plays key roles in regulating cellular proliferation and maintaining tissue homeostasis. TGF-β exerts tumor-suppressive effects in the early stages of carcinogenesis, but it also plays tumor-promoting roles in established tumors. Additionally, it plays a critical role in cancer radiotherapy. TGF-β expression or activation increases in irradiated tissues, and studies have shown that TGF-β plays dual roles in cancer radiosensitivity and is involved in ionizing radiation-induced fibrosis in different tumor microenvironments (TMEs). Furthermore, TGF-β promotes radioresistance by inducing the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs), suppresses the immune system and facilitates cancer resistance. In particular, the links between TGF-β and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) axis play a critical role in cancer therapeutic resistance. Growing evidence has shown that TGF-β acts as a radiation protection agent, leading to heightened interest in using TGF-β as a therapeutic target. The future of anti-TGF-β signaling therapy for numerous diseases appears bright, and the outlook for the use of TGF-β inhibitors in cancer radiotherapy as TME-targeting agents is promising.

Epidemiological studies in recent years have found that the incidence of gastric signet ring cell carcinoma (SRCC) has increased significantly. In this paper, we first reviewed cell origin and biomarkers of SRCC, and the relationship between SRCC and various pathological types of gastric cancer. The early diagnosis rate of gastric SRCC is low, which may be due to the unclear mechanism of pathology and precancerous lesions. In clinical practice, SRCC has the characteristics of low differentiation and high degree of malignancy. Most of patients with gastric cancer Borrmann IV(diffuse infiltrative type) are gastric SRCC, and their prognosis is poor. The average age of gastric SRCC was 55 to 61 years old. Besides, in female, the incidence of SRCC was significantly higher than that of non-SRCC gastric cancer. It is found that the expressions of estrogen and progesterone receptors in SRCC tissues are high. The relationship between gastric SRCC and sex hormones may be the cause of gender differences in the pathogenesis of gastric SRCC. Due to the low risk of lymph node metastasis in early SRCC, endoscopic mucosal resection and endoscopic submucosal dissection can be performed for3 cm, submucosal invasive, medium differentiated tumors, or3 cm, highly differentiated, ulcerative and submucosal lesions. For non-metastatic advanced gastric SRCC, surgical resection and adequate lymph node dissection should be performed owing to the high risk of lymph node metastasis. Adjuvant chemotherapy is also considered to improve the long-term prognosis of patients. Taxane therapy may be more effective in gastric SRCC. Recent data show that gastric SRCC and diffuse gastric cancer are more sensitive to mitomycin C, doxorubicin and docetaxel than intestinal type gastric cancer, but are not sensitive to fluorouracil and cisplatin. These treatment perspectives still need to be confirmed in future studies.