Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Changing trends in Chlamydia and gonorrhea infections among female sex workers in Southern China: a surveillance data analysis spanning 2019 to 2022.

BACKGROUND: Female sex workers (FSW) are particularly vulnerable to chlamydia and gonorrhea infections. However, there were few studies that detail the evolving patterns of chlamydia and gonorrhea among Chinese FSW. Therefore, our study endeavors to assess the prevalence of chlamydia and gonorrhea epidemics within FSW, investigate their changing trends and scrutinize associated factors. METHODS: In 2019, China instituted a sentinel surveillance network focused on FSW in Guangdong Province. This network conducted an annual serial cross-sectional survey spanning from April to August. All analyses are predicated on surveillance data accumulated between 2019 and 2022. RESULTS: The prevalence of chlamydia increased from 10.1 to 12.3%, exhibiting an annual percentage shift of 6.8%. Conversely, the prevalence of gonorrhea dwindled from 2.0 to 1.3%, marking an annual percentage decline of 13.4% (P < 0.001). After adjusting for covariates, chlamydia exhibited associations with having household registration in other provinces (adjusted odds ratio (aOR = 0.55)), displaying symptoms of sexually transmitted infections (STIs) (aOR = 1.65) and infected with gonorrhea (aOR = 5.68). In parallel, gonorrhea demonstrated associations with providing oral sex to clients (aOR = 3.74), manifesting STIs symptoms (aOR = 4.27) and those infected with chlamydia (aOR = 5.43). CONCLUSIONS: Our observations underscore the imperative to implement a comprehensive intervention strategy concentrating on chlamydia, while simultaneously fortifying endeavors to expand the scope of gonorrhea prevention services.

Discovery and structural optimization of 3-O-ß-Chacotriosyl betulonic acid saponins as potent fusion inhibitors of Omicron virus infections.

The recent global Omicron epidemics underscore the great need for the development of small molecule therapeutics with appropriate mechanisms. The trimeric spike protein (S) of SARS-CoV-2 plays a pivotal role in mediating viral entry into host cells. We continued our efforts to develop small-molecule SARS-CoV-2 entry inhibitors. In this work, two sets of BA derivatives were designed and synthesized based on the hit BA-1 that was identified as a novel SARS-CoV-2 entry inhibitor. Compound BA-4, the most potent one, showed broad inhibitory activities against pOmicron and other pseudotyped variants with EC50 values ranging 2.73 to 5.19 µM. Moreover, pSARS-CoV-2 assay, SPR analysis, Co-IP assay and the cell-cell fusion assay coupled with docking and mutagenesis studies revealed that BA-4 could stabilize S in the pre-fusion step to interfere with the membrane fusion, thereby displaying promising inhibition against Omicron entry.

TRPV4 channel is involved in HSV-2 infection in human vaginal epithelial cells through triggering Ca2+ oscillation.

Herpes simplex virus (HSV) infection induces a rapid and transient increase in intracellular calcium concentration ([Ca2+]i), which plays a critical role in facilitating viral entry. T-type calcium channel blockers and EGTA, a chelate of extracellular Ca2+, suppress HSV-2 infection. But the cellular mechanisms mediating HSV infection-activated Ca2+ signaling have not been completely defined. In this study we investigated whether the TRPV4 channel was involved in HSV-2 infection in human vaginal epithelial cells. We showed that the TRPV4 channel was expressed in human vaginal epithelial cells (VK2/E6E7). Using distinct pharmacological tools, we demonstrated that activation of the TRPV4 channel induced Ca2+ influx, and the TRPV4 channel worked as a Ca2+-permeable channel in VK2/E6E7 cells. We detected a direct interaction between the TRPV4 channel protein and HSV-2 glycoprotein D in the plasma membrane of VK2/E6E7 cells and the vaginal tissues of HSV-2-infected mice as well as in phallic biopsies from genital herpes patients. Pretreatment with specific TRPV4 channel inhibitors, GSK2193874 (1-4 µM) and HC067047 (100 nM), or gene silence of the TRPV4 channel not only suppressed HSV-2 infectivity but also reduced HSV-2-induced cytokine and chemokine generation in VK2/E6E7 cells by blocking Ca2+ influx through TRPV4 channel. These results reveal that the TRPV4 channel works as a Ca2+-permeable channel to facilitate HSV-2 infection in host epithelial cells and suggest that the design and development of novel TRPV4 channel inhibitors may help to treat HSV-2 infections.

Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer.

BACKGROUND: Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients. METHODS: The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0). RESULTS: Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death. CONCLUSION: Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.

Fabrication of a Free-Standing MWCNT Electrode by Electric Field Force for an Ultra-Sensitive MicroRNA-21 Nano-Genosensor.

Abnormal expression of microRNA-21 (miR-21) is considered to be closely associated with the pathogenesis of colorectal cancer. However, great challenges do exist for the development of ultra-sensitive biosensors to detect the abnormal expression of miR-21 due to the low concentration in serum (fm level) at the early stage of colorectal cancer. Therefore, electric field force is used to rotate and rearrange random multi-walled carbon nanotubes (MWCNTs) at the microscale to improve the active sites of the electrode in this study. The free-standing MWCNTs are densely and high-orderly embedded into the bare electrode along the direction of the electric field. Compared to the bare electrode, the peak-current response of the free-standing MWCNT electrode improves by 150 times in cyclic voltammetric measurement. A nano-genosensor based on the free-standing MWCNT electrode is developed for measuring miR-21. The nano-genosensor for miR-21 shows an ultra-high sensitivity of 48.24 µA µm-1 , a wide linear range from 0.01 × 10-15 to 100 × 10-12 m, and a low detection limit of 1.2 × 10-18 m. The present nano-genosensor shows superior performance for miR-21 in human serum samples and demonstrates a potential application for the diagnosis of early stage colorectal cancer.

TLR1/2 Agonist Enhances Reversal of HIV-1 Latency and Promotes NK Cell-Induced Suppression of HIV-1-Infected Autologous CD4+ T Cells.

The complete eradication of human immunodeficiency virus type 1 (HIV-1) is blocked by latent reservoirs in CD4+ T cells and myeloid lineage cells. Toll-like receptors (TLRs) can induce the reversal of HIV-1 latency and trigger the innate immune response. To the best of our knowledge, there is little evidence showing the "killing" effect of TLR1/2 agonists but only a small "shock" potential. To identify a new approach for eradicating the HIV latent reservoir, we evaluated the effectiveness of SMU-Z1, a novel small-molecule TLR1/2 agonist, in the "shock-and-kill" strategy. The results showed that SMU-Z1 could enhance latent HIV-1 transcription not only ex vivo in peripheral blood mononuclear cells from aviremic HIV-1-infected donors receiving combined antiretroviral therapy but also in vitro in cells of myeloid-monocytic origin targeting the NF-κB and mitogen-activated protein kinase pathways. Interestingly, the activation marker CD69 was significantly upregulated in natural killer (NK) cells, B cells, and monocytes 48 h after SMU-Z1 treatment. Furthermore, SMU-Z1 was able to activate T cells without global T cell activation, as well as increasing NK cell degranulation and gamma interferon (IFN-γ) production, which further block HIV-1-infected CD4+ lymphocytes. In summary, the present study found that SMU-Z1 can both enhance HIV-1 transcription and promote NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells. These findings indicate that the novel TLR1/2 agonist SMU-Z1 is a promising latency-reversing agent (LRA) for eradication of HIV-1 reservoirs. IMPORTANCE Multiple in vivo studies showed that many LRAs used in the shock-and-kill approach could activate viral transcription but could not induce killing effectively. Therefore, a dual-function LRA is needed for elimination of HIV-1 reservoirs. We previously developed a small-molecule TLR1/2 agonist, SMU-Z1, and demonstrated that it could upregulate NK cells and CD8+ T cells with immune adjuvant and antitumor properties in vivo. In the present study, SMU-Z1 could activate innate immune cells without global T cell activation, induce production of proinflammatory and antiviral cytokines, and enhance the cytotoxic function of NK cells. We showed that SMU-Z1 displayed dual potential ex vivo in the shock of exposure of latently HIV-1-infected cells and in the kill of clearance of infected cells, which is critical for effective use in combination with therapeutic vaccines or broadly neutralizing antibody treatments aimed at curing AIDS.

Emerging antiviral therapies and drugs for the treatment of influenza.

INTRODUCTION: Both vaccines and antiviral drugs represent the mainstay for preventing and treating influenza. However, approved M2 ion channel inhibitors, neuraminidase inhibitors, polymerase inhibitors, and various vaccines cannot meet therapeutic needs because of viral resistance. Thus, the discovery of new targets for the virus or host and the development of more effective inhibitors are essential to protect humans from the influenza virus. AREAS COVERED: This review summarizes the latest progress in vaccines and antiviral drug research to prevent and treat influenza, providing the foothold for developing novel antiviral inhibitors. EXPERT OPINION: Vaccines embody the most effective approach to preventing influenza virus infection, and recombinant protein vaccines show promising prospects in developing next-generation vaccines. Compounds targeting the viral components of RNA polymerase, hemagglutinin and nucleoprotein, and the modification of trusted neuraminidase inhibitors are future research directions for anti-influenza virus drugs. In addition, some host factors affect the replication of virus in vivo, which can be used to develop antiviral drugs.

Sexual uses of drug and alcohol among men who have sex with men in China: implications for HIV prevention.

BACKGROUND: Sexual uses of alcohol and drugs are pervasive among men who have sex with men (MSM) and associated with increased risk of HIV infection. However, there are limited studies related to sexual uses of alcohol and drugs among MSM in China. This study aims to describe the pattern of alcohol use, drug use, and multi-drug use during sex among Chinese MSM and to examine the association between condomless anal intercourse, group sex, commercial sex and HIV infection. METHODS: We conducted an online cross-sectional survey in China. Characteristics on social-demographic, sexual behaviors, and sexual uses of alcohol and drugs were collected. The associations with high-risk sexual behaviors and HIV infection were analyzed with multivariable logistic regression. RESULTS: A total of 699 MSM were included in this study. About 39.5% (230/582) of men reported sexual alcohol use in the past three months and 50.8% (355/699) reported sexual drug use. Of those reporting sexual drug use, around 10.7% (38/355) reported having multi-drug use. Factors associated with both sexual uses of alcohol and drugs included: reporting more male sexual partners (alcohol: adjusted odds ratio [aOR] = 1.77; drug: aOR = 2.12), reporting condomless anal intercourse in the past three months (alcohol: aOR = 2.08; drug: aOR = 2.08), having ever engaged in group sex (alcohol: aOR = 2.04; drug: aOR = 5.22; multi-drug: aOR = 3.52) and commercial sex (alcohol: aOR = 4.43; drug: aOR = 4.22 multi-drug: aOR = 5.07). Sexual drug use was also correlated with reported HIV-positive status (drug: aOR = 2.53, 95% CI:1.31-4.90). CONCLUSION: Sexual uses of alcohol and drugs are prevalent among Chinese MSM. Interventions to reduce the sexual use of alcohol and other drugs may be warranted among MSM in China.

Ultrasonic surgical and electrosurgical system (USES) with conventional ultrasonic scalpel (CUS) in gastrectomy: a retrospective cohort study.

BACKGROUND: Harmonic ACE +7 Shears with Advanced Hemostasis is an upgraded ultrasonic device, an ultrasonic surgical and electrosurgical system (USES). The study aimed to evaluate the economic and clinical effectiveness of the USES compared with the conventional ultrasonic scalpel (CUS) in gastrectomy. METHODS: We conducted a single-center, retrospective cohort study using the electronic medical records in China. We collected intraoperative and postoperative data from gastric cancer patients who underwent the endoscope-assisted distal gastrectomy from 2018 to June 30, 2019. Procedure-related costs were estimated. We used linear regression by controlling a set of covariates to assess the effect of USES on outcomes. RESULT: Out of 87 eligible patients, the USES group (40 patients) and CUS group (47 patients) were comparable in terms of age, medical history and stages of cancer. Compared with the CUS, the USES saved 4.27 hemoclips per person (95% CI 0.57-7.97, p < 0.05) and 34.18 ml intraoperative blood per person (95% CI 8.74-59.62 ml, p < 0.05), respectively. Postoperative length of stay (LOS) was shorter in the USES group (7.90 ± 1.95 vs. 9.26 ± 2.81 days) but the difference was not statistically significant (p = 0.05). CONCLUSIONS: The USES group was associated with fewer hemoclips use and intraoperative blood loss in patients undergoing laparoscopic gastrectomy at comparable costs.

An Automatic Defect Detection System for Petrochemical Pipeline Based on Cycle-GAN and YOLO v5.

Defect detection of petrochemical pipelines is an important task for industrial production safety. At present, pipeline defect detection mainly relies on closed circuit television method (CCTV) to take video of the pipeline inner wall and then detect the defective area manually, so the detection is very time-consuming and has a high rate of false and missed detections. To solve the above issues, we proposed an automatic defect detection system for petrochemical pipeline based on Cycle-GAN and improved YOLO v5. Firstly, in order to create the pipeline defect dataset, the original pipeline videos need pre-processing, which includes frame extraction, unfolding, illumination balancing, and image stitching to create coherent and tiled pipeline inner wall images. Secondly, aiming at the problems of small amount of samples and the imbalance of defect and non-defect classes, a sample enhancement strategy based on Cycle-GAN is proposed to generate defect images and expand the data set. Finally, in order to detect defective areas on the pipeline and improve the detection accuracy, a robust defect detection model based on improved YOLO v5 and Transformer attention mechanism is proposed, with the average precision and recall as 93.10% and 90.96%, and the F1-score as 0.920 on the test set. The proposed system can provide reference for operators in pipeline health inspection, improving the efficiency and accuracy of detection.

Hole Repairing Algorithm for 3D Point Cloud Model of Symmetrical Objects Grasped by the Manipulator.

For the engineering application of manipulator grasping objects, mechanical arm occlusion and limited imaging angle produce various holes in the reconstructed 3D point clouds of objects. Acquiring a complete point cloud model of the grasped object plays a very important role in the subsequent task planning of the manipulator. This paper proposes a method with which to automatically detect and repair the holes in the 3D point cloud model of symmetrical objects grasped by the manipulator. With the established virtual camera coordinate system and boundary detection, repair and classification of holes, the closed boundaries for the nested holes were detected and classified into two kinds, which correspond to the mechanical claw holes caused by mechanical arm occlusion and the missing surface produced by limited imaging angle. These two kinds of holes were repaired based on surface reconstruction and object symmetry. Experiments on simulated and real point cloud models demonstrate that our approach outperforms the other state-of-the-art 3D point cloud hole repair algorithms.

Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. METHODS: In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. RESULTS: 35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e-5), differentiation (1.9e-7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. CONCLUSIONS: We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.

Expression of Interleukin-6 and Integrin ανß6 in Colon Cancer: Association with Clinical Outcomes and Prognostic Implications.

As important factors in the tumor microenvironment, interleukin-6 (IL-6) and integrin ανß6 play significant roles in accumulating mutations that drive the progression and metastatic capacities of cancer. The aim of this study was to investigate the expression of IL-6 and integrin ανß6, their clinical significance, as well as their correlation in the colon cancer tissues of 145 cases using immunohistochemistry. Our results showed that IL-6 and integrin ανß6 are indicators of cancer progression and poor prognosis in patients with colon cancer. Moreover, their relationship may provide clues for further studies on how the tumor microenvironment mediates the development of colon cancer, as well as strategies for the identification of novel therapeutic targets in the prevention and treatment of colon cancer.

Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia.

BACKGROUND: We investigated the effects of glutamine (Gln)-enriched nutritional therapy during chemotherapy on the nutritional status and immune function of children with acute lymphoblastic leukemia (ALL). METHODS: We enrolled 48 children who were newly diagnosed with ALL in our department during the period of 2013.1-2014.12. The patients (follow random number table) were randomly divided into the control group (peptamen) and the treatment group (peptamen + glutamine), 24 cases in each group. The remission induction regimens were all based on VDLP (D) chemotherapy (VCR (Vincrisstine), DNR (Daunomycin), L-ASP (L-Asparagiase), Prednisolone and Dexamethasone). The treatment group received Gln-enriched nutritional therapy every day during the full course of chemotherapy,and the control group is as same as the treatment group except without glutamine. The indicators of general nutritional status, such as weight, height, and triceps skinfold thickness, and the indicators of biochemical tests, such as serum albumin, prealbumin, creatinine-height index, retinol binding protein, and urinary hydroxyproline index, were compared between the two groups at the end of the first, second, third and the fourth week when the chemotherapy was completed. And in the fourth week, flow cytometry was applied to detect the levels of T cell subsets and the activities of natural killer (NK) cells in peripheral blood of the two groups. RESULTS: 1. after 4 weeks nutritional therapy, there is no significant difference (p > 0.05) between the two groups of children in weight, height and other indicators. 2. At the end of 2 weeks treatment, the level of prealbumin (PA) and retinol-binding protein (RBP) is higher in treatment group than that in the control group (P <0.05), at the end of 3 weeks treatment, the thickness of triceps skinfold is higher (P <0.05) than that in the control group; 3. At the end of 3 and 4 weeks, the concentrations serum ALB, PA, RBP and UHI were higher than in the control group (P <0.05); 4. There is statistically significant (p < 0.05) between the two groups in edema incidence; 5. At the end of treatment (4 weeks), the percentages of CD3 +, CD4 +, CD4 +/CD8 +, NK cell are significantly decreased in the two groups (P <0.05). CONCLUSION: Gln-enriched nutritional therapy can effectively improve the systemic nutritional status of children with leukemia, improve immune function.

MiR-492 is functionally involved in Oxaliplatin resistance in colon cancer cells LS174T via its regulating the expression of CD147.

Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumors. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. To develop novel-targeted therapy holds promise for conquering chemotherapy resistance, one of the major hurdles in current colon cancer treatment. Previous studies indicate that CD147 is involved in the progression of chemotherapy resistance in breast cancer and ovarian cancer cells and its expression is negative regulated by miR-492 in muscles cells. In the present study, we found that lower level of miR-492 is accompanied with increased expression of CD147 in Oxaliplatin-resistant colon cancer cell line LS174T/L-OHP as compared with its parental cell line LS174T. Exogenous expression of miR-492 in LS174T/L-OHP could sensitize its reaction on the treatment of Oxaliplatin, which is coincided with its directly reducing the expression of CD147. Furthermore, we found that knockdown of CD147 in LS174T/L-OHP could also sensitize its reaction of the treatment with Oxaliplatin. Besides, intratumoral delivering of miR-492 could also restore Oxaliplatin treatment response in Oxaliplatin-resistant xenografts in vivo. These findings provide direct evidences that the miR-492/CD147 axis might play an essential role in the Oxaliplatin resistance of colon cancer cells, suggesting that the miR-492/CD147 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in colon cancer.

Application of Bioinformatics in Predicting the Efficacy of Digestive Tumour Immunotherapy Target TIM-3 and its Inhibitors.

Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.

Internal Carotid Artery Dissecting Aneurysm Associated with Persistent Trigeminal Artery: A Case Report.

BACKGROUND: Persistent trigeminal artery (PTA) is the most common vascular anastomosis between the carotid artery and vertebrobasilar systems. We report a very rare case of dissecting aneurysm in the right internal carotid artery (ICA) with ipsilateral PTA and discuss its clinical importance. CASE REPORT: A 38-year-old male presented to the emergency department with paroxysmal dysphasia for 6h. Brain magnetic resonance (MR) imaging showed acute cerebral infarction of the right corona radiata and right parietal lobe. Three-dimensional time-of-flight MR angiography (3D TOF MRA) revealed severe stenosis of the petrous segment (C1 portion) of the right internal carotid artery and a PTA originating from the right ICA cavernous segment (C4 portion), with a length of approximately 1.8cm and a diameter of approximately 0.2cm. The ICA segments are all named according to the Bouthilier classification. The basilar artery (BA) under union was well developed. The bilateral posterior communicating arteries were also present. One day later, the high-resolution vessel-wall MR demonstrated a dissecting aneurysm in the C1 portion of the right ICA. The length of the dissecting aneurysm is approximately 4.4cm, the diameter of the true lumen at the most severe stenosis is approximately 0.2cm, and the diameter of the false lumen is approximately 0.8cm. Subsequent digital subtraction angiography (DSA) confirmed a dissecting aneurysm in the C1 portion of the right ICA. The patient was treated conservatively and did not undergo interventional surgery. Four months later, head and neck MRA showed that the right ICA blood flow was smooth and that the dissecting aneurysm had disappeared. The Ethics Committee of Liaocheng People's Hospital approved the research protocol in compliance with the Helsinki Declaration. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. CONCLUSION: Flow alteration with PTA may have influenced the formation of ICA dissection in this patient. Awareness of this is crucial in clinical practice because it can influence treatment options and intervention procedures.

Considerations when treating influenza infections with oseltamivir.

INTRODUCTION: Since the coronavirus disease 2019-mandated social distancing policy has been lifted worldwide, the circulation of influenza is expected to resume. Currently, oseltamivir is approved as the first-line agent for influenza prevention and treatment. AREAS COVERED: This paper reviews the updated evidence in the pharmacology, resistance mechanisms, clinical pharmacy management, and real-world data on oseltamivir for influenza. EXPERT OPINION: Oseltamivir is an oral prodrug of oseltamivir carboxylate, an influenza A and B neuraminidase inhibitor. Recently, the therapeutic efficacy of oseltamivir has been demonstrated in several trials. Oseltamivir is generally well-tolerated but may lead to neuropsychiatric events and bleeding. Oseltamivir-resistant influenza virus has been associated with the H275Y mutation in the influenza A(H1N1)pdm09 virus, while most strains are still sensitive to oseltamivir. Dose adjustment for oseltamivir should be based on creatinine clearance and body weight in pediatric patients with renal failure. According to real-world data from Nanfang Hospital, the annual number of patients prescribed oseltamivir declined from 35,711 in 2019 to 8,971 in 2020, with marked increases in 2022 (20,213) and 2023 (18,071). Among the 206 inpatients, children aged < 6 years who were treated with oseltamivir had the shortest duration to defervescence.

Dynamic role of CUL4B in radiation-induced intestinal injury-regeneration.

CUL4B, a crucial scaffolding protein in the largest E3 ubiquitin ligase complex CRL4B, is involved in a broad range of physiological and pathological processes. While previous research has shown that CUL4B participates in maintaining intestinal homeostasis and function, its involvement in facilitating intestinal recovery following ionizing radiation (IR) damage has not been fully elucidated. Here, we utilized in vivo and in vitro models to decipher the role of CUL4B in intestinal repair after IR-injury. Our findings demonstrated that prior to radiation exposure, CUL4B inhibited the ubiquitination modification of PSME3, which led to the accumulation of PSME3 and subsequent negative regulation of p53-mediated apoptosis. In contrast, after radiation, CUL4B dissociated from PSME3 and translocated into the nucleus at phosphorylated histones H2A (γH2AX) foci, thereby impeding DNA damage repair and augmenting p53-mediated apoptosis through inhibition of BRCA1 phosphorylation and RAD51. Our study elucidated the dynamic role of CUL4B in the repair of radiation-induced intestinal damage and uncovered novel molecular mechanisms underlying the repair process, suggesting a potential therapeutic strategy of intestinal damage after radiation therapy for cancers.