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BackgroundThis study aims to analyze the historical trends of inflammatory bowel disease (IBD) burden in the elderly from 1990 to 2021 and forecast future trends up to 2051.MethodsData from the Global Burden of Disease Study 2021 were utilized. Age-standardized rates (ASR) for incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated. Estimated annual percentage changes (EAPCs) were computed to quantify temporal trends. A Bayesian Age-Period-Cohort model was employed to project future trends.ResultsFrom 1990 to 2021, the global number of elderly IBD increased from 573,500 to 1,278,190. The age-standardized incidence rate (ASIR) rose from 8.01 to 8.77 per 100,000, while the age-standardized prevalence rate (ASPR) slightly decreased from 118.14 to 117.29 per 100,000. Death number increased from 14,400 to 33,490, but the age-standardized mortality rate decreased from 3.21 to 2.84 per 100,000. DALYs increased from 324,100 to 683,750, with the age-standardized DALYs rate declining from 68.78 to 60.88 per 100,000. Significant geographical variations were observed, with high Socio-demographic Index regions showing the highest burden. Projections suggest that by 2051, elderly IBD prevalence number may reach 2,316,000, with ASIR and ASPR potentially rising after 2035 and 2042, respectively. Deaths and DALYs are projected to increase to 75,000 and 1,401,000 respectively, despite continued declines in ASRs.ConclusionThe absolute burden of IBD in the elderly population is projected to increase substantially by 2051, despite decreasing ASRs. These findings underscore the need for tailored healthcare strategies and resource allocation to address the growing challenge of elderly IBD globally.

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment.

At present, with the original point cloud as input, most of the object detectors use Pointnet++ to extract features of the point cloud based on the Farthest Point Sampling (FPS). However, affected by FPS, feature extraction is incomplete and unstable. Moreover, high-level semantic features lack the internal vertex properties of Regions of Interest (RoI). In order to solve the above problems, we propose the Mask-SL RCNN (Mask-Spherical-neighborhood-global-feature-Layer Region-CNN), a feature-enhanced 3D object detection network. It improves sampling of the farthest point through point-level feature enhancement. In addition, we propose Spherical neighborhood global feature Layer (SL) to supplement the global features and improve the learning ability of network. At last, based on semantic-level feature enhancement, we design grid pooling layer based on vertex attention, which fully explores the boundary characteristics of RoI and increases ability to learn advanced features in RoI. Our network improves detection precision of small objects such as pedestrians. Compared with PointRCNN, it has improved the mAP of simple, medium, and difficult object detection in the KITTI dataset by 2.66%, 1.69%, and 0.67%, respectively.

ObjectivesTo explore the correlation between the incidence rates of depression and anxiety and cerebral glucose metabolism in cancer patients.MethodsThe experiment subjects consisted of patients with lung cancer, head and neck tumor, stomach cancer, intestinal cancer, breast cancer and healthy individuals. A total of 240 tumor patients and 39 healthy individuals were included. All subjects were evaluated by the Hamilton depression scale (HAMD) and Manifest anxiety scale (MAS), and were examined by whole body Positron Emission Tomography/Computed Tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG). Demographic, baseline clinical characteristics, brain glucose metabolic changes, emotional disorder scores and their relations were statistically analyzed.ResultsThe incidence rates of depression and anxiety in patients with lung cancer were higher than those in patients with other tumors, and Standard uptake values (SUVs) and metabolic volume in bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were lower than those in patients with other tumors. We also found that poor pathological differentiation, and advanced TNM stage independently associated with depression and anxiety risk. SUVs in the bilateral frontal lobe, bilateral temporal lobe, bilateral caudate nucleus, bilateral hippocampus, left cingulate gyrus were negatively correlated with HAMD and MAS scores.ConclusionThis study revealed the correlation between brain glucose metabolism and emotional disorders in cancer patients. The changes in brain glucose metabolism were expected to play a major role in emotional disorders in cancer patients as psychobiological markers. These findings indicated that functional imaging can be applied for psychological assessment of cancer patients as an innovative method.

BackgroundHuman papillomavirus (HPV) is a virus primarily transmitted through sexual contact. Little is known about the association between HPV infection or immunization and the risk for rheumatoid arthritis (RA). The purpose of this study was to evaluate whether HPV infection or immunization is related to the risk for RA in adults.MethodsData were obtained from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). We developed three independent multivariate logistic regression models to evaluate the association between HPV infection or immunization and the risk for RA in adults.ResultsFinally, we analyzed 15,677 and 8,944 subjects, respectively. In all models, HPV infection was positively associated with an increased prevalence of RA in adults aged 18-59 years, with the highest value of the odds ratio (OR) in model 2 (after weighting: OR 1.095, 95% CI 1.092, 1.097), whereas HPV immunization significantly reduced the prevalence of RA in adults aged 18-59 years, with the lowest OR in model C (after weighting: OR 0.477, 95% CI 0.472, 0.481). These associations persisted after correction for confounders such as age, sex, race, education level, marital status, smoking, diabetes, hypertension, hyperlipidemia, and BMI.ConclusionIn summary, our study suggests that HPV infection is positively associated with the prevalence of RA in adults, and HPV immunization can reduce the prevalence of RA in adults. However, our findings need more powerful to prove these associations through rigorously designed prospective studies.

Objectives: Osteoarthritis (OA) is a joint disease characterized by degeneration of joint cartilage and is a significant cause of severe joint pain, physical disability, and impaired quality of life in the aging population. Celastrol, a Chinese herbal medicine, has attracted wide interests because of its anti-inflammatory effects on a variety of diseases. This study aimed to investigate the effect of celastrol on OA as well as the mechanisms in vivo and in vitro.Methods: A rat knee OA model was established using “medial collateral ligament transection (MCLT) + partial meniscectomy (pMMT)”. Eight weeks after surgery, the OA rats started to receive intra-articular injection of celastrol (1 mg/kg) once a week. Safranin O-fast green (S&F) and hematoxylin and eosin (H&E) staining were used to estimate histopathological changes. Micro-CT was used to evaluate bone volume of the subchondral bone of the knee joint. Chondrocytes were isolated from the knee cartilage of rats and OA patients. Enzyme linked immunosorbent assay (ELISA), Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemistry (IHC) were used to detect the expression of inflammatory factors and stromal proteins, respectively.Results: We found that celastrol treatment significantly delayed the progression of cartilage damage with a significant reduction in osteophyte formation and bone resorption in OA rat model. In IL-1β-stimulated rat chondrocytes, celastrol significantly suppressed the production of inflammatory factors such as cyclooxygenase-2 (COX2), interleukin-6 (IL-6), and prostaglandin E2 (PEG2), and reduced IL-1β-induced matrix degradation by down-regulating the expression of matrix metalloproteinase 13 (MMP13). In addition, we found that toll-like receptor 2 (TLR2) was up-regulated in OA patients and rat knee OA models, while celastrol inhibited TLR2 signal and its downstream nuclear factor-kappa B (NF-κB) phosphorylation.Conclusion: In summary, celastrol may improve OA by inhibiting the TLR2/NF-κB signaling pathway, which provides innovative strategies for the treatment of OA.

Objective This study investigated the association between soluble scavenger receptor differentiation antigen 163 (sCD163) and the severity and prognosis of renal injury in lupus nephritis (LN). Methods Serum sCD163 levels in 121 Eastern Chinese patients with LN who underwent renal biopsy were determined by enzyme-linked immunosorbent assays. Clinical data were collected, and the glomerular filtration rate and disease activity score of lupus were calculated. Pathological classification was performed, and renal pathological scores were assessed by the activity index (AI) and chronic index (CI). Kaplan–Meier survival curves were drawn to evaluate prognosis. Results The pathological classification, AI and CI scores in the high sCD163 group were increased. The sCD163 levels were positively correlated with serum creatinine, blood urea nitrogen, AI scores and CI scores and negatively correlated with the estimated glomerular filtration rate. Kaplan–Meier survival analysis showed that the incidence of renal endpoint events was increased in the high sCD163 group compared with the normal sCD163 group. Conclusion The serum sCD163 level correlates with the severity of LN and is an important indicator of poor renal prognosis in patients with LN.

Purpose: To investigate the effect of the hedgehog (Hh) pathway inhibitor, cyclopamine, and activator purmorphamine on articular cartilage cell proliferation. Methods: Rats were subjected to AA and CIA models. Secondary paw swelling was measured at 12, 15, 18, 21, 24, 27, and 30 days. The rats were sacrificed on day 30. Tissues from the cartilage and knee joints were collected. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay while cell apoptosis was determined by annexin V-fluorescein isothiocyanate/propidium iodide assay. Protein expression levels of Shh, Ptch1 and Gli1 were determined by Western blotting. Results: Compared with the control group, arthritis index and secondary foot swelling of the adjuvant arthritis (AA) and collagen-induced arthritis (CIA) groups deteriorated significantly (p < 0.05). MTT data revealed that cyclopamine promoted articular cartilage cell proliferation of the AA and CIA groups. The cell proliferation rates of AA and CIA groups were significantly higher than that of control group (p < 0.05). Flow cytometry showed that the cell apoptosis rates of AA and CIA groups were significantly lower than that of control group (p < 0.05). Compared with control, cyclopamine decreased the protein expression levels of sonic Hh, patched homologue 1 and glioma-associated oncogene homologue, but the effect of purmorphamine was the reverse. Conclusion: Hh pathway inhibitor (cyclopamine) and activator (purmorphamine) affect the expression of Hh pathway. Disruption of the Hh pathway may be of potential therapeutic significance in protecting articular cartilage from rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of recombinant human brain natriuretic peptide rhBNP on myocardial enzymes and cardiac function following percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) subjects. Methods: Patients with AMI (124 cases) subjected to PCI for 2 years were used as subjects in this investigation. Two groups of patients were used (62 patients per group). One group received rhBNP while the other group served as control. The patients consisted of 76 males and 48 females (mean age, 63.54 ± 12.31 years). The two groups of patients received 75 mg/kg body weight of clopidogrel orally and aspirin (300 mg/kg) 2 h before PCI. The peaks of creatine kinase (CK), creatine kinase MB (CKMB), and the levels of troponin I (cTnI) were assayed at pre-determined intervals with an automated biochemical analyzer, and changes in the enzyme levels were recorded. Echocardiography (ECG) parameters were also measured. Results: Lower peaks of CK, CK-MB and levels of cTnI were seen in rhBNP-treated patients, when compared with controls (p < 0.05). Total effectiveness was markedly higher in rhBNP-treated group than in control group (p < 0.05). Moreover, myocardial infarct size was significantly lower in rhBNP treatment group than in control group (p < 0.05). Conclusion: Treatment with rhBNP before PCI in patients with AMI increases coronary blood flow, ameliorates perfusion injury, inhibits left ventricular remodeling, reduces myocardial cell necrosis, and improves cardiac function and prognosis. [ABSTRACT FROM AUTHOR]

Background: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. Results: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of 'DNA methylation entropy' to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. Conclusion: Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy. [ABSTRACT FROM AUTHOR]