Objective To study the therapeutic effects of Yigan Fupi decoction(YGFP)on irritable bowel syndrome(IBS)and its mechanism of action in repairing the intestinal barrier and reducing IBS sensitivity through the PKA/PKC-CREB pathway.Methods Baby rats separated from their mother were randomly divided into a model control(M)and a YGFP group,while baby rats without maternal separation were used as a normal control(N)group.The YGFP group was given YGFP for 4 weeks.Abdominal withdrawal reflux was used to evaluate intestinal sensitivity.Liquid chromatography tandem mass spectrometry and ELISA were used to detect bile acid metabolite concentrations and serum levels of interleukin(IL)-6 and CXCL1,respectively.HE staining was used to observe pathological changes in the colon,and Western Blot and immunohistochemistry were used to analyze the relative protein expression levels of PKA,PKC,CREB,5HT2AR,5-HT7R,ZO-1,and Claudin 1.Results Compared with the normal control group,the M group showed a significantly decreased visceral pain threshold,significantly increased levels of total bile acid metabolites,IL-6,and CXCL1,significantly increased relative expression of PKA,PKC,CREB,5HT2AR,and 5-HT7R,and significantly decreased relative expression of ZO-1 and Claudin 1.Compared with the M group,the YGFP group showed a significantly increased visceral pain threshold,significantly reduced levels of total bile acid metabolites,IL-6,and CXCL1,significantly reduced relative expression of PKA,PKC,CREB,5HT2AR,and 5-HT7R,and increased relative expression of ZO-1 and Claudin 1.Conclusions YGFP effectively improved IBS through a mechanism that may involve repair of the intestinal barrier and reduced sensitivity through the PKA/PKC-CREB pathway.

Melanoma is characterized with high heterogeneity and invasiveness. The advent of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors have shown the obvious therapeutic efficacy in the treatment of melanoma patients, which promotes the progression of melanoma immunotherapy. However, therapy resistance caused by immune escape of melanoma and immune-related adverse events caused by treatment have limited the therapeutic effects of CTLA-4 inhibitors, which have become a clinical challenge. This article reviews the current role of CTLA-4 inhibitors in melanoma therapy, aiming to provide references for clinical immunotherapy strategies for melanoma.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective To study the therapeutic effects of Yigan Fupi decoction(YGFP)on irritable bowel syndrome(IBS)and its mechanism of action in repairing the intestinal barrier and reducing IBS sensitivity through the PKA/PKC-CREB pathway.Methods Baby rats separated from their mother were randomly divided into a model control(M)and a YGFP group,while baby rats without maternal separation were used as a normal control(N)group.The YGFP group was given YGFP for 4 weeks.Abdominal withdrawal reflux was used to evaluate intestinal sensitivity.Liquid chromatography tandem mass spectrometry and ELISA were used to detect bile acid metabolite concentrations and serum levels of interleukin(IL)-6 and CXCL1,respectively.HE staining was used to observe pathological changes in the colon,and Western Blot and immunohistochemistry were used to analyze the relative protein expression levels of PKA,PKC,CREB,5HT2AR,5-HT7R,ZO-1,and Claudin 1.Results Compared with the normal control group,the M group showed a significantly decreased visceral pain threshold,significantly increased levels of total bile acid metabolites,IL-6,and CXCL1,significantly increased relative expression of PKA,PKC,CREB,5HT2AR,and 5-HT7R,and significantly decreased relative expression of ZO-1 and Claudin 1.Compared with the M group,the YGFP group showed a significantly increased visceral pain threshold,significantly reduced levels of total bile acid metabolites,IL-6,and CXCL1,significantly reduced relative expression of PKA,PKC,CREB,5HT2AR,and 5-HT7R,and increased relative expression of ZO-1 and Claudin 1.Conclusions YGFP effectively improved IBS through a mechanism that may involve repair of the intestinal barrier and reduced sensitivity through the PKA/PKC-CREB pathway.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Melanoma is characterized with high heterogeneity and invasiveness. The advent of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors have shown the obvious therapeutic efficacy in the treatment of melanoma patients, which promotes the progression of melanoma immunotherapy. However, therapy resistance caused by immune escape of melanoma and immune-related adverse events caused by treatment have limited the therapeutic effects of CTLA-4 inhibitors, which have become a clinical challenge. This article reviews the current role of CTLA-4 inhibitors in melanoma therapy, aiming to provide references for clinical immunotherapy strategies for melanoma.

Objective:To evaluate the clinical efficacy of modified all-arthroscopic reconstruction of medial patella femoral ligament (MPFL) for the treatment of recurrent patellar dislocation.Methods:A retrospective case series study was conducted to analyze the clinical data of 38 patients (46 knees) with recurrent patellar dislocation, who were treated at First Affiliated Hospital of Shenzhen University from January 2017 to January 2020. The patients included 12 males (12 knees) and 26 females (34 knees), aged 14-40 years [(24.6±5.4)years]. All patients underwent the modified all-arthroscopic MPFL reconstruction procedure. The femoral tunnel locations were assessed by 3D-CT immediately after surgery. The MRI was performed at 6 and 12 months after operation to assess the healing morphology of the reconstructed MPFL. The Lysholm score and Kujala score were used to assess the knee function before operation, at 6 months after operation, at 12 months after operation and at the last follow-up. The time to return to sports as well as complications were observed.Results:All patients were followed up for 26-48 months [(32.4±8.6)months]. Postoperative 3D-CT examination showed that the femoral tunnels were located in the groove area of the medial epicondyle of the femur and the adductor tubercle. At 6 and 12 months after operation, MRI T2 images showed that the reconstructed MPFL had a low signal and well tensioned ligament tissue, indicating that the MPFL was healed well. The Lysholm scores at 6 and 12 months postoperatively and at the last follow-up were (81.1±12.0)points, (91.2±3.8)points, and (92.2±9.8)points, respectively, being significantly higher than the preoperative (52.4±10.6)points (all P<0.01). The Kujala scores at 6 and 12 months postoperatively and at the last follow-up were (85.4±3.9)points, (91.4±3.6)points, and (93.1±8.5)points, respectively, being significantly higher than the preoperative (55.2±6.8)points (all P<0.01). Compared with 6 months postoperatively, the Lysholm score and Kujala score were significantly improved at 12 months postoperatively and at the last follow-up (all P<0.05). All patients returned to sports, with the time to return to sports for 3-12 months [(8.7±2.3)months] after operation. One patient had poor wound healing but was healed after dressing changes. No wound infection, nerve injury, joint stiffness, patella re-dislocation or other complications occurred. Conclusion:For recurrent patellar dislocation, the modified all-arthroscopic MPFL reconstruction has advantages of accurate bone tunnel positioning, good ligament healing, good function recovery, early return to sports, and less postoperative complications.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Gout is a common metabolic disease. Gouty arthritis is associated with the deposition of urate crystals in the synovial fluid or para-articular soft tissues, which often affects the hands, feet, wrists, ankle and knees joints. However, the shoulder joint is unusual involved. In the present study, a 49-year-old male patient complained of right shoulder pain for 9 months and aggravating with limited range of motion for 2 weeks. Physical examination showed that the external rotation was 10° and hand back was S 5 of the right shoulder. The MRI showed shoulder joint effusion and intra-articular loose bodies. The patient was admitted to the hospital with the diagnosis of "loose bodies of the right shoulder with synovial chondromatosis possibly". Arthroscopic examination revealed that a lots of urate crystals were deposited on synovium, cartilage and rotator cuff. Loose bodies removal and joint debridement were performed. Histopathologic examination of the specimen demonstrated synovitis hyperplasia with urate crystals deposition. Shoulder gouty arthritis characterized by pain and limited movement. The imaging of tophi depends on the calcium-containing deposits. Tophus with calcium deposits can be found on X-ray and CT. MRI can not only evaluate the tophus but also the evaluate the other intra-articular pathologies. Due to no typical manifestations and specific images of shoulder gouty arthritis, pathological diagnosis is the "gold standard". Shoulder arthroscopy provide a minimal invasive technique in diagnosing and treating of the shoulder disease. Undoubtedly, it could be a reliable diagnosis and treatment method for shoulder gouty arthritis.