SLA-3d printed building and characteristics of GelMA/HAP biomaterials with gradient porous structure.

Developing a gradient porous scaffold similar to bone structure is gaining increasing attention in bone tissue engineering. The GelMA/HAP hydrogel has demonstrated potential in bone repair. Although 3D printing can build GelMA/HAP with porous structure, fabricating porous GelMA/HAP with gradient porosity and pore size in one step remains challenging. In this paper, a gradient porous structure with controllable pore size, based on gelatin methacryloyl (GelMA) and hydxroxyapatite (HAP), was engineered and printed using stereolithography. Firstly, the GelMA and HAP were mixed to prepare a hydrogel with a solid content ranging from 10 wt% to 50 wt% for stereolithography. Taking advantage of the sol-gel characteristics of GelMA/HAP hydrogel, GelMA/HAP was fed on the workbench through a combination of extrusion and paving to form a thin layer. During the curing of each layer, the hydrogel exposed to the curing of a single UV beam immediately solidified, forming a highly interconnected porous structure. Additionally, the hydrogel outside the scanning range could be further polymerized to form a relatively dense structure due to the residual laser energy. Finally, without gradient structural design or changing printing parameters, the gradient porous structure of bone-like could be printed in a single-step process. By adjusting the curing parameters of the single UV beam and the concentration and size of ceramic in the hydrogel, the printed pore diameter of the spongy structure could be controlled within the range of 50-260 µm, while the thickness of the compact area could be adjusted within 130-670 µm.

Identification and validation of the necroptosis-related gene signature related to prognosis and tumor immune in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer, which is characterized by complicated etiology, excessive heterogeneity, and poor prognosis. Necroptosis is a new kind of programmed cell death, which is intently associated with the occurrence and development of tumors. Although researchers have had a deep understanding of necroptosis in recent years, the expression level of necroptosis-related genes in HCC and its relationship with the survival time of HCC patients are not clear. METHODS: According to the expression of necroptosis-related genes and the survival of HCC patients, HCC patients in the TCGA database were divided into 2 groups that were relatively independent of each other. The genes related to the survival time of HCC patients were screened from the 2 groups of differentially expressed genes. By using the Least Absolute Shrinkage and Selection Operator Cox regression analysis, the optimal λ value was obtained, and the 10-gene signature model was established. RESULTS: According to the median risk score of the TCGA cohort, HCC patients were averagely divided into high- and low-risk groups. Compared with the low-risk group, the death toll of the high-risk group was relatively higher and the survival time was relatively shorter. Principal component analysis and t-distributed stochastic neighbor embedding analysis showed that there was a significant separation between high- and low-risk groups. Through Kaplan-Meier analysis, it was found that the survival time of HCC patients in the high-risk group was significantly shorter than that in the low-risk group. Through receiver operating characteristic analysis, it was found that the sensitivity and specificity of the model were good. We also make a comprehensive analysis of the international cancer genome consortium database as a verification queue and prove the reliability of the 10-gene signature model. Gene Ontolog, Kyoto Encyclopedia of Genes and Genomes, and single-sample gene set enrichment analysis showed that many biological processes and pathways related to immunity had been enriched, and the antitumor immune function was weakened in the high-risk population. CONCLUSION: The risk score can be considered as an independent prognostic factor to predict the prognosis of patients with HCC, and necroptosis-related genes are also closely related to tumor immune function.

Identification of the ferroptosis-related ceRNA network related to prognosis and tumor immunity for gastric cancer.

Gastric cancer (GC) is a highly invasive course and has a very poor prognosis. Because there are no obvious symptoms in the early stage, most patients with GC are diagnosed in the late stage. The effective diagnosis, prognosis biomarkers and treatment targets of GC can solve this problem to a great extent. Although researchers have done a lot of research on GC in recent years, the relationship between the competing endogenous RNA (ceRNA) network of ferroptosis-related genes and the GC remains to be explored. Therefore, the research done in this paper has become particularly important. Download the expression data and clinical survival data about stomach adenocarcinoma from UCSC Xena and The Cancer Genome Atlas (TCGA) platform. Using bioinformatics tools to screen lncRNAs, miRNAs and mRNAs that are differentially expressed in GC samples and normal samples and related to the prognosis of GC. Then, screening lncRNAs, miRNAs and mRNAs with targeted relationships from the Starbase database. Subsequently, correlation analysis and survival analysis were carried out respectively. Finally, we get a ceRNA network related to the prognosis of GC patients. Cell experiments confirmed the results obtained by bioinformatics. This is critical for the discovery of the diagnosis, prognosis biomarkers and treatment targets.

CILP, a Putative Gene Associated With Immune Infiltration in Breast Cancer Brain Metastases.

Breast cancer (BC) is the second leading cause of brain metastases (BM), with high morbidity and mortality. The aim of our study was to explore the effect of the cartilage intermediate layer protein (CILP) on breast cancer brain metastases (BCBM). Using a weighted gene coexpression network analysis (WGCNA) in GSE100534 and GSE125989 datasets, we found that the yellow module was closely related to the occurrence of BCBM, and CILP was a hub gene in the yellow module. Low CILP expression was associated with a poor prognosis, and it was an independent prognostic factor for stage III-IV BC determined using Cox regression analysis. A nomogram model including CILP expression was established to predict the 5-, 7-, and 10-year overall survival (OS) probabilities of stage III-IV BC patients. We found that CILP mRNA expression was downregulated in BCBM through GSE100534, GSE125989, and GSE43837 datasets. In addition, we found that CILP mRNA expression was negatively correlated with vascular endothelial growth factor A (VEGFA), which is involved in regulating the development of BM. UALCAN analysis showed that CILP expression was downregulated in HER2-positive (HER2+) and triple-negative breast cancer (TNBC), which are more prone to BM. The vitro experiments demonstrated that CILP significantly inhibited BC cell proliferation and metastasis. Western blot (WB) results further showed that the mesenchymal protein marker vimentin was significantly downregulated following CILP overexpression, suggesting that CILP could participate in migration through epithelial-mesenchymal transition (EMT). A comparison of CILP expression using immunohistochemistry in BC and BCBM showed that CILP was significantly downregulated in BCBM. In addition, gene set variation analysis (GSVA) revealed that CILP was associated with the T-cell receptor signaling pathway in BCBM and BC, indicating that CILP may be involved in BCBM through immune effects. BCBM showed lower immune infiltration than BC. Moreover, CILP expression was positively correlated with HLA-II, T helper cells (CD4+ T cells), and Type II IFN Response in BCBM. Collectively, our study indicates that CILP is associated with immune infiltration and may be a putative gene involved in BCBM. CILP offers new insights into the pathogenesis of BCBM, which will facilitate the development of novel targets for BCBM patients.

The shadow in the darkness: Case report on adhesive intestinal obstruction secondary to ventriculoperitoneal shunt catheter in an elderly patient.

Introduction: Shunt placement is an effective therapy for hydrocephalus. Ventriculoperitoneal shunt draining excess cerebrospinal fluid connects the cerebral ventricles to the abdominal cavity. However, intestinal obstruction may ensue as an infrequent complication of the shunt. Case presentation: A 65 years old female patient presented with abdominal pain, abdominal bloating, and ceased passage of flatus and stool for six days. She had a history of undergoing a VP shunt procedure due to midbrain obstruction and supratentorial hydrocephalus. Conservative treatment at another local hospital couldn't relieve her symptoms. Laboratory investigations revealed elevated CRP and neutrophils. CT scan showed distended small bowel loops with aerated effusion. Thus, she was admitted to our hospital and underwent an emergent laparotomy following diagnostic modalities completion. Discussion: Adhesive intestinal obstruction secondary to ventriculoperitoneal shunt is a rare but fatal shunt complication. The possible mechanisms involved include rubbing movements between the greater omentum and the catheter, cerebrospinal fluid reaction with abdominal organs, immunological rejection of the catheter, and deposition of brain tumor cells with the resultant abdominal metastatic lesions. Laparoscopic and laparotomy are warranted in the surgical management of the disease. Conclusion: A high index of suspicion for adhesive intestinal obstruction is key to timely diagnosis and treatment.

Anatomy and assessment of a modified technique during totally robotic distal gastrectomy: A retrospective cohort study.

Background: Robotic surgery has potential benefits in the management of gastric cancer patients. This study compares the outcomes between totally robotic distal gastrectomy (TRDG) with modified port placement and arm positioning technique and conventional totally laparoscopic distal gastrectomy (CTLDG). Materials and methods: Fifty-two patients were enrolled into the study following a retrospective review of an in-patient database between January 2019 and June 2021. Patients who underwent gastric resection with the modified robotic technique were recruited into the study. Patients who did not receive treatment using the modified technique were excluded from the study. Data on demographic, clinical data and surgical outcomes were collected, analyzed, and presented. All statistical analyses were done using IBM SPSS statistical software. Results: Nineteen patients were in the TRDG group, and their mean age was 60.42 ± 11.53 years. There were no differences in demographic characteristics (all p > 0.05); nonetheless, laparoscopic patients had a significantly higher preoperative albumin level (p = 0.000). The operative time was longer in the TRDG group (223min), but the difference was insignificant. The reconstruction time was significantly shorter for the laparoscopic group (p = 0.000). Except for a significantly higher value of postoperative albumin level (p-value = 0.005) in the robotic group, there were no significant differences in all other surgical outcomes between the two groups. One (5.3%) patient had a severe complication in the robotic group compared to four (12.1%) in the laparoscopic group. Nevertheless, the differences in complications were statistically insignificant. Conclusion: The modified approach is a safe and feasible in totally robotic distal gastrectomy for the treatment of gastric cancer patients.

Revisiting the 8th AJCC system for gastric cancer: A review on validations, nomograms, lymph nodes impact, and proposed modifications.

Gastric cancer is the fifth most frequently diagnosed cancer worldwide, behind breast, lung, colorectal, and prostate cancers. In gastric cancer, multimodality treatment shows prospective benefits and also improves survival. Surgery, however, is the mainstay of curative treatment. The staging of gastric cancer patients is critical for harmonization of care. Accurate stages assure that informed clinical decisions are timely made. The American Joint Committee on Cancer (AJCC) staging system is the most widely applied system in to determine the disease's prognosis and survival prediction. The recently adopted 8th AJCC TNM staging system has been revised to enhance its survival predictive power. Subsequent studies have established the validity of the current edition, demonstrating improved stage stratification, discriminatory power, and survival prediction. However, other studies have cast doubt on the superiority of the new edition. Innovations aimed at further improving its prognosis have resulted in developing of novel models. Advances in our understanding of the tumor microenvironment and molecular categorization of cancer have resulted in proposals for their inclusion in TNM staging as potential complementary factors that enhance survival prediction and prognostic assessment ability. The purpose of this study is to conduct a review of the published literature regarding the validity of the 8th AJCC TNM staging system, proposed modifications, and nomograms.

Initial experience of single-incision plus one port left-side approach totally laparoscopic distal gastrectomy with uncut Roux-en-Y reconstruction.

BACKGROUND: Single incision plus one port left-side approach (SILS+1/L) totally laparoscopic distal gastrectomy (TLDG) is an emerging technique for the treatment of gastric cancer. Reduced port laparoscopic gastrectomy has a number of potential advantages for patients compared with conventional laparoscopic gastrectomy: relieving postoperative pain, shortening hospital stay and offering a better cosmetic outcome. Nevertheless, there are no previous reports on the use of SILS+1/L TLDG with uncut Roux-en-Y (uncut R-Y) reconstruction. AIM: To investigate the initial feasibility of SILS+1/L TLDG with uncut Roux-en-Y digestive tract reconstruction (uncut R-Y reconstruction) to treat distal gastric cancer. METHODS: A total of 21 patients who underwent SILS+1/L TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at The Second Hospital of Shandong University. Reconstructions were performed intracorporeally with 60 mm endoscopic linear stapler and 45 mm no-knife stapler. The clinicopathological characteristics, surgical details, postoperative short-term outcomes, postoperative follow-up upper gastrointestinal radiography findings and endoscopy results were analyzed retrospectively. RESULTS: All SILS+1/L operations were performed by SILS+1/L TLDG successfully. The patient population included 13 men and 8 women with a mean age of 48.2 years (ranged from 40 years to 70 years) and median body mass index of 22.8 kg/m2. There were no conversions to open laparotomy, and no other port was placed. The mean operation time was 146 min (ranged 130-180 min), and the estimated mean blood loss was 54 mL (ranged 20-110 mL). The mean duration to flatus and discharge was 2.3 (ranged 1-3.5) and 7.3 (ranged 6-9) d, respectively. The mean number of retrieved lymph nodes was 42 (ranged 30-47). Two patients experienced mild postoperative complications, including surgical site infection (wound at the navel incision) and mild postoperative pancreatic fistula (grade A). Follow-up upper gastrointestinal radiography and endoscopy were carried out at 3 mo postoperatively. No patients experienced moderate or severe food stasis, alkaline gastritis or bile reflux during the follow-up period. No recanalization of the biliopancreatic limb was found. CONCLUSION: SILS+1/L TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery.

Overcoming Radioresistance in Tumor Therapy by Alleviating Hypoxia and Using the HIF-1 Inhibitor.

Radiotherapy has been extensively used to treat cancer patients because it can effectively damage most solid tumors without penetration limits. A hypoxic microenvironment in solid tumors leads to severe radioresistance and expression of hypoxic inducible factor-1 (HIF-1), which results in poor efficacy of radiotherapy alone. Herein, we report the excellent efficacy of radiotherapy achieved using a new type of yolk-shell Cu2-xSe@PtSe (CSP) nanosensitizer functionalized with the HIF-1α inhibitor acriflavine (ACF). We prepare the CSP nanosensitizer through the interfacial redox reactions between chloroplatinic acid and Cu2-xSe nanoparticles (CS) and then functionalize the nanosensitizer with ACF through their electrostatic interactions. We show that the synthesized CSP nanosensitizer can arrest the cell cycle (i.e., at the gap 2/mitosis (G2/M) phases) of tumor cells to enhance their sensitivity to X-rays and decompose endogenous H2O2 into O2 to reduce hypoxia and increase the production of reactive oxygen species, which leads to severe damage to DNA double strands and apoptosis of tumor cells. We also show that the ACF on the surface of CSP nanoparticles can effectively reduce the expression of HIF-1α. All these effects lead to a low vascular endothelial growth factor, low density of microvessels in tumor, decreased cell proliferation, and increased cell apoptosis, which synergistically and drastically enhance the efficacy of radiotherapy. This work provides insights and guidance for developing novel nanosensitizers to enhance the efficacy of radiotherapy.

Ultra-Sensitive Detection and Inhibition of the Metastasis of Breast Cancer Cells to Adjacent Lymph Nodes and Distant Organs by Using Long-Persistent Luminescence Nanoparticles.

The metastasis of breast cancer mainly occurs through the axillary lymph node and blood circulation systems. It is extremely difficult to know when the cancer cells start to metastasize; however, early detection of breast cancer metastasis is crucial and challenging to enable surgical removal of the primary tumor and perform a systematic lymphadenectomy to eliminate invasion of the tumor. Herein, we report real-time tracking of the metastasis of orthotopic breast cancer with background-free near-infrared long-persistent luminescence (NIR-PL) imaging, and its guidance for the surgical removal of lymph nodes. The NIR-PL imaging is based on Cr3+/Nd3+ codoped ZnGa2O4 (A-ZGCN) nanoparticles with a superlong afterglow time of more than 15 days. We show that the detection sensitivity of metastasis of cancer cells with the NIR-PL imaging is higher than the classic bioluminescence imaging. We find that the metastasis of breast cancer cells to lymph nodes occurred as early as on the third day after orthotopic inoculation of breast cancer cells and followed an order of the proper axillary lymph node (PALN, day 3) > accessory axillary lymph node (AALN, day 6) > accessory mandibular lymph node (AMLN, day 9) > mandibular lymph node (MLN, day 25). In addition, we show that the NIR-PL nanoprobes (i.e., A-ZGCN NPs) displayed 17% radioenhancement, which was used for radiotherapy of orthotopic breast cancer to further prevent and reduce its metastasis to other organs. The radiotherapy treatment is superior to surgery for removal of the tumor accompanied by a NIR-PL imaging-guided lymphadenectomy. Our work demonstrates the great potential of NIR-PL imaging and the corresponding nanoprobes for tracking metastasis of cancer cells and for radiotherapy.

Propofol can suppress renal ischemia-reperfusion injury through the activation of PI3K/AKT/mTOR signal pathway.

INTRODUCTION: Renal ischemia/reperfusion injury (IRI) remains one of the most diseases in clinic. The purpose of this study was to investigate the potential role and mechanism of propofol in protecting mice kidney from IRI. METHODS: Renal I/R model was established in C57/BL6 mice by clamping bilateral renal pedicles for 35 min. The mice were randomly divided into four groups: sham group, IR group, IR + Propofol group, and IR + Propofol+LY294002 group. Histological assessment of kidney was conducted by HE staining and the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) of each group were measured. Expressions of inflammatory factors (IL-6, TNF-α) were detected by qRT-PCR and immunoblotting. The expression levels of cleaved Caspasse-3, PI3K, Akt, p-Akt, mTOR, and p-mTOR within renal tissue samples were measured by Western Blot. RESULTS: The levels BUN, Cr and morphological damage score increased significantly after renal IRI. However, such changes could be prevented by propofol. Besides, IRI reduced renal expressions of PI3K, p-Akt, p-mTOR, and increased the levels of IL-6, TNF-α，cl-caspase-3 in kidney, After propofol treatment, these changes were significantly alleviated, but the use of PI3K inhibitor LY294002 could reverse the effects of propofol. CONCLUSION: Propofol can protect renal IRI partially by reducing apoptosis and release of inflammatory cytokines, which is possibly involved in the modulation of the PI3K/AKT/mTOR signaling pathway. Our data suggested that propofol may play certain positive roles in protecting the kidney from IRI.

[Synergic effects of synthesis arecoline in combination with snail-killing drugs niclosamide].

OBJECTIVE: To prove that synthetic Are combination with snail-killing drug Nic can increase the effects of snail-killing remarkably. METHODS: In indoor immersing experimentation, the experiments were divided into 4 groups, 30 snails in each group, to observe the rate of opening operculum, the rate of climbing adhesion and the rate of death at 3, 6 and 24 hours respectively. In field experimentation, we intermixed 0.1 mg/L Are with 0.2 mg/L Nic as sample as contrasted with 2 mg/L Nic and non-drug group. Immersing method (we chose three slots each size were 10 m x 2 m x 1 m.) and insufflation method (we chose three patch of bottomlands each area were 10 m x 5 m.) were used to kill snails separately and the death rate of fish, at the same time was observed. RESULTS: In the room, as we added 0.1 mg/L Are to the solution of 0.1 mg/L and 0.2 mg/L Nic separately, the opening operculum rate for 6 hours was increased from 20% and 12% to 100% and 95%, the climbing adhesion rate for 6 hours decreased from 17% and 53% to 3% and 5%, the death rate for 24 hours increased from 25% and 40% to 90% and 100%. In the field, the snails death rate in sample group and in contrastive group applied with immersing method and insufflation method for 72 hours were 95.9%, 93.3% and 100%, 95.8%; only one small fish (2 cm long) died in sample group, and all fishes died in Nic group, and all fish were alive in non-drug group. CONCLUSION: It proved that synthetic Are combination with snail-killing drug Nic might decrease Nic dosage and toxicity and increase the effects of snail-killing.

[A novel synthesized Schistosoma japonicum miracidium attractant imprinted polymer].

A novel molecularly imprinted polymer with adequate attractability for Schistosoma japonicum miracidia was prepared. When adulterated with polyvinyl alcohol (PVA), the fabricated film with good swelling property was formed which can suspend on water and slowly release XF (a chemical to be published). This reusable film can well attract Schistosoma japonicum miracidia, and hopefully be used in the prevention of schistosome infection.