BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

Intestinal fibrosis in Crohn′s disease (CD) presents a significant clinical challenge, imposing a substantial burden on patients, their families and society. This article explores the histopathological and pathophysiological changes associated with intestinal fibrosis, providing a detailed summary of the related phenomena and processes. Additionally, we discuss the methods for detecting and assessing intestinal fibrosis, including radiological examinations, histopathological investigations, and the application of serum biomarkers. Finally, we delve into the therapeutic strategies for intestinal fibrosis in CD and the challenges faced in this realm, offering vital insights for further research and treatment of the disease.

Intestinal fibrosis in Crohn′s disease (CD) presents a significant clinical challenge, imposing a substantial burden on patients, their families and society. This article explores the histopathological and pathophysiological changes associated with intestinal fibrosis, providing a detailed summary of the related phenomena and processes. Additionally, we discuss the methods for detecting and assessing intestinal fibrosis, including radiological examinations, histopathological investigations, and the application of serum biomarkers. Finally, we delve into the therapeutic strategies for intestinal fibrosis in CD and the challenges faced in this realm, offering vital insights for further research and treatment of the disease.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Patients with Crohn's disease (CD) are often complicated with malnutrition and enteral nutrition is the preferred option for nutritional support. Enteral nutrition is the first-line therapy to induce remission of CD in children, but its application in adults has not been well established. In recent years, studies have found that enteral nutrition can not only improve the nutritional status in adult CD patients, but also induce and maintain CD remission through various mechanisms. Given its favorable nutritional efficacy and safety, enteral nutrition has been considered as the basic treatment for adult CD patients and often used in combination with other treatment approaches. However, any combination therapy should be assessed in terms of benefit and risk. This review aims to describe the efficacy and safety of enteral nutrition combined with other treatment approaches in adult CD patients and enumerate common applicable clinical settings, so as to better inform clinical treatment.

Objective:To compare the abilities of different neural networks to generate pseudo-computed tomography (CT) images from magnetic resonance imaging (MRI) images and to explore the feasibility of pseudo-CT for clinical radiotherapy planning.Methods:A total of 29 brain cancer patients with planning CT and diagnostic MRI were selected. 23 of these patients were used for training neural networks and 6 for testing pseudo-CT images. Cycle-consistent generative adversarial network (cycleGAN), contrastive learning for unpaired image-to-image translation (CUT), and improved network denseCUT proposed in this study were applied to generate pseudo-CT images from MRI images. The pseudo-CT images were imported into a clinical treatment planning system to verify the feasibility of applying this method to radiotherapy planning.Results:The comparison between the generated pseudo-CT images and real CT images showed that the mean absolute errors were (72.0±6.9), (72.5±8.0), and (64.6±7.3) HU for the cycleGAN, CUT, and denseCUT, respectively. Meanwhile, the structure similarity indices were 0.91±0.01, 0.91±0.01, and 0.93±0.01, respectively. The peak signal-to-noise ratios were (28.5±0.7), (28.5±0.7), and (29.5±0.7) dB, respectively. The 2%/2 mm γ passing rates were 98.05%, 97.92%, and 98.31% for the cycleGAN, CUT, and denseCUT, respectively.Conclusions:DenseCUT can generate more accurate pseudo-CT images and the pseudo-CT can meet the demand for the dose calculation of IMRT plan.

Innate lymphoid cells (ILC) are a type of innate immune cells with adaptive immune function, which can secrete a variety of cytokines and regulate immune response. In recent years, more and more studies have confirmed that there are abundant ILC in the lamina propria of the human intestinal mucosa, and are closely related to the occurrence and development of inflammatory bowel disease (IBD) . When intestinal inflammation occurs, the composition of ILC also appears abnormal. This article reviews the role of abnormal composition of ILC in the occurrence and development of IBD from the aspects of composition and function of ILC, the influence of its abnormal composition on IBD and possible mechanisms.

Innate lymphoid cells (ILC) are a type of innate immune cells with adaptive immune function, which can secrete a variety of cytokines and regulate immune response. In recent years, more and more studies have confirmed that there are abundant ILC in the lamina propria of the human intestinal mucosa, and are closely related to the occurrence and development of inflammatory bowel disease (IBD) . When intestinal inflammation occurs, the composition of ILC also appears abnormal. This article reviews the role of abnormal composition of ILC in the occurrence and development of IBD from the aspects of composition and function of ILC, the influence of its abnormal composition on IBD and possible mechanisms.

Objective:To evaluate the impacts of tissue heterogeneity on dose calculation of cervical brachytherapy by comparing the doses calculated by two clinically used dose calculation method and the CT image-based Monte Carlo (MC) method.Methods:This study retrospectively selected 11 patients with cervical cancer treated with 3D brachytherapy in Anhui Provincial Cancer Hospital from January 2018 to June 2020. The dose distribution of each plan was calculated via three methods, dose calculation method described in American Association of Physicist in Medicine(AAPM) Task Group No. 43 Report (TG43-BT), Acuros BV(BV-BT) used to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity, and CT image-based EGSnrc tool kit used to perform Monte Carlosimulation (MC-BT). The dose volumes( V3 Gy, V6 Gy, V9 Gy, and V12 Gy), target volume doses( D98, D90, D50), D2 cm 3 of organs at risk (OARs) calculated by the three methods were compared. Results:The HRCTV D90obtained by TG43-BT was 6.274 Gy, which was even overestimated by around 5% compared to the result calculated by MC-BT. Meanwhile, TG43-BT overestimated the dose volumesand the target volume doses compared to MC-BT.Except for D50 and V12 Gy, the differences between the doses to tumor calculated by BV-BT and MC-BT were not statistically significant( P>0.05). There was also no significant statistical difference between the D2 cm 3 of rectum, small intestine, and sigmoid calculated by BV-BT and MC-BT ( P>0.05). In contrast, the dose to D2 cm 3 of bladder determined by MC-BT was 4.609 Gy, which was notably higher than those deter mined by TG43-BT and BV-BT. Conclusions:TG43-BT overestimated the doses to tumor targets and most OARs since the effects of tissue heterogeneity were not taken into consideration. BV-BT performed efficient calculation and most of the dose distributionin target volume and OARs obtained by BV-BT were consistent with that calculated by MC-BT. Nevertheless, low accuracy occurred for the regions near the sources and full bladder, which warrants further caution in clinical evaluation.

Objective:To investigate the impacts of the composition and physical density of tissue on the dose distribution of implanted 125I seeds, in order to provide references for the clinical dose calculation and assessment of implanted radioactive particles. Methods:The OncoSeed 6711 physical model of 125I seeds was established using thes of twareegs_brachy and was validated through the calculation of dose rate constant and the radial dose function [ g( r)] in water. Then, based on the element composition and physical density of different types of tissue, the g( r) and absorbed dose ratein water, prostate, breast, muscle, and bone were calculated. Results:The calculated dose rate constant (0.950 cGy·h -1·U -1) and g( r)in water approached the values in related literature. The absorbed dose in bone was 6.042 times than that in water at a distance of 0.05 cm from the implanted source. The difference between the absorbed doses in breast and water was more than 10% at a distance of less than 1.7 cm from the implanted source. The difference between the absorbed doses in prostate/muscle and water was less than 5% at the same radial location. Conclusions:The dose distribution of 125I seeds in some types of human tissue is significantly different from that in water, which should be carefully considered in clinical dose calculation.