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.

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 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.

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.

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 analyze the clinical characteristics of solitary rectal ulcer syndrome (SRUS) .Methods:Retrospective analysis was performed on the data of 26 patients with SRUS diagnosed by pathology and admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2015 to November 2019. A descriptive method was used to collect the general information, clinical manifestations, endoscopy, pathological examination, treatment and prognosis of patients.Results:A total of 26 patients were enrolled, including 11 males and 15 females, with average age of (41.96±13.83) years old and median duration of 21 (0.2-480) months from onset to diagnosis. The main clinical manifestations were rectal bleeding in 15 (57.69%) cases, rectal prolapse in 9 (34.62%) , perianal pain in 6 (23.08%) , body mass loss in 6 (23.08%) and rectal mucus in 5 (19.23%) . Seventeen patients underwent endoscopic examination, endoscopic features included ulcer in 6 (35.29%) cases, rectal polyp in 5 (29.41%) , protuberance in 4 (23.53%) , hyperplasia and swelling in 4 (23.53%) , erosion in 3 (17.65%) , either alone or in combination. Histological examination of rectal biopsies revealed that the characteristic features were mucosal surface erosion and ulcer in 11 (42.31%) cases, lamina propria fibrosis in 8 (30.77%) , mucosal gland deletion or decreased secretion in 6 (23.08%) , inflammatory cell infiltration in 5 (19.23%) , vascular changes in 5 (19.23%) , and crypts alteration in 4 (15.38%) . Five patients (19.23%) received medical treatment and 21 patients (80.77%) received surgery. Symptoms except rectal prolapse disappeared or were improved in all the patients after treatment.Conclusion:The clinical and endoscopic features of SRUS are variable. Pathology is crucial for diagnosis and differential diagnosis. Both the medical and surgical treatment are effective for SRUS.

The pathogenesis of inflammatory bowel disease (IBD) , especially mucosal immunity, has made rapid progress, and the emergence of cytokine targets has greatly promoted the treatment of IBD. According to the different effects, biological agents targeting cytokines can be divided into anti-inflammatory cytokine-derived biological agents and pro-inflammatory cytokine-derived biological agents, which are currently in different stages of research. This article reviews the application and prospect of cytokine-derived biological agents in maintaining intestinal immune balance, and provides some reference for clinical treatment of IBD.