Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To explore the diagnostic key points, treatment strategies, and prognosis of graft-versus-host disease (GVHD) after liver transplantation.Methods:The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed. The causes, onset, diagnosis, treatment, and prognosis of GVHD after liver transplantation were summarized and analyzed. Literature was searched in CNKI, Wanfang, VIP, Chinese Medical Journal Full-text Database, PubMed, Web of Science, and Google Scholar using the Chinese keywords "移植物抗宿主病+肝移植", and the English keywords "graft versus host disease + liver transplantation". The search time ranged from January 1988 to January 2025. Inclusion criteria for the literature: (1) meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation; (2) recipient age >18 years; (3) case number ≥2. Exclusion criteria: incomplete clinical data such as incidence, mortality, and clinical manifestations of GVHD after liver transplantation. The retrieved literature was reviewed.Results:All 5 recipients were male. Among them, 4 cases underwent liver transplantation at this center. The incidence of GVHD after liver transplantation in this center was 0.46% (4/872). All 5 cases developed symptoms such as fever, rash, diarrhea, oral ulcers, and pancytopenia on the 19th (5-21) day after liver transplantation. One case had gastrointestinal bleeding. Two cases were diagnosed by skin pathological biopsy, and three cases were diagnosed based on clinical manifestations such as fever, rash, diarrhea, and bone marrow suppression. One case discontinued immunosuppressants, and four cases reduced the dosage of immunosuppressants. Four cases were treated with high-dose glucocorticoids, four with intravenous immunoglobulin (IVIG), three with ruxolitinib, and three with hematopoietic factors. All five cases received protective isolation, anti-infection, and symptomatic supportive treatment. Among the three recipients treated with ruxolitinib, body temperature returned to normal, rash gradually faded, oral ulcers gradually healed, blood cells returned to normal, and they were eventually discharged after recovery. The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure. Literature review A total of 34 articles were included. The incidence of GVHD after liver transplantation was 1.03% (279/27 018), and the onset time ranged from 7 to 1,865 days post-transplantation; 272 cases (97.49%) occurred within 1-8 weeks. The main clinical manifestations included fever (195 cases, 69.89%), rash (267 cases, 95.70%), diarrhea (173 cases, 62.01%), and bone marrow suppression (214 cases, 76.70%). Treatment mainly involved adjustment of immunosuppressants (201 cases, 72.04%), high-dose corticosteroids (215 cases, 77.06%), and IVIG pulse therapy (146 cases, 52.33%). In the end, 83 cases (29.75%) recovered and were discharged, while the mortality rate was 70.25% (196/279), with causes of death including infection, gastrointestinal bleeding, and multiple organ failure.Conclusions:GVHD after liver transplantation has a low incidence, high mortality, and poor prognosis. Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy. Early administration of high-dose corticosteroids combined with IVIG pulse therapy, timely reduction or discontinuation of immunosuppressants, use of ruxolitinib, active infection management, and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.

Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To explore the diagnostic key points, treatment strategies, and prognosis of graft-versus-host disease (GVHD) after liver transplantation.Methods:The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed. The causes, onset, diagnosis, treatment, and prognosis of GVHD after liver transplantation were summarized and analyzed. Literature was searched in CNKI, Wanfang, VIP, Chinese Medical Journal Full-text Database, PubMed, Web of Science, and Google Scholar using the Chinese keywords "移植物抗宿主病+肝移植", and the English keywords "graft versus host disease + liver transplantation". The search time ranged from January 1988 to January 2025. Inclusion criteria for the literature: (1) meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation; (2) recipient age >18 years; (3) case number ≥2. Exclusion criteria: incomplete clinical data such as incidence, mortality, and clinical manifestations of GVHD after liver transplantation. The retrieved literature was reviewed.Results:All 5 recipients were male. Among them, 4 cases underwent liver transplantation at this center. The incidence of GVHD after liver transplantation in this center was 0.46% (4/872). All 5 cases developed symptoms such as fever, rash, diarrhea, oral ulcers, and pancytopenia on the 19th (5-21) day after liver transplantation. One case had gastrointestinal bleeding. Two cases were diagnosed by skin pathological biopsy, and three cases were diagnosed based on clinical manifestations such as fever, rash, diarrhea, and bone marrow suppression. One case discontinued immunosuppressants, and four cases reduced the dosage of immunosuppressants. Four cases were treated with high-dose glucocorticoids, four with intravenous immunoglobulin (IVIG), three with ruxolitinib, and three with hematopoietic factors. All five cases received protective isolation, anti-infection, and symptomatic supportive treatment. Among the three recipients treated with ruxolitinib, body temperature returned to normal, rash gradually faded, oral ulcers gradually healed, blood cells returned to normal, and they were eventually discharged after recovery. The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure. Literature review A total of 34 articles were included. The incidence of GVHD after liver transplantation was 1.03% (279/27 018), and the onset time ranged from 7 to 1,865 days post-transplantation; 272 cases (97.49%) occurred within 1-8 weeks. The main clinical manifestations included fever (195 cases, 69.89%), rash (267 cases, 95.70%), diarrhea (173 cases, 62.01%), and bone marrow suppression (214 cases, 76.70%). Treatment mainly involved adjustment of immunosuppressants (201 cases, 72.04%), high-dose corticosteroids (215 cases, 77.06%), and IVIG pulse therapy (146 cases, 52.33%). In the end, 83 cases (29.75%) recovered and were discharged, while the mortality rate was 70.25% (196/279), with causes of death including infection, gastrointestinal bleeding, and multiple organ failure.Conclusions:GVHD after liver transplantation has a low incidence, high mortality, and poor prognosis. Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy. Early administration of high-dose corticosteroids combined with IVIG pulse therapy, timely reduction or discontinuation of immunosuppressants, use of ruxolitinib, active infection management, and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.

BACKGROUND:The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways,augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells,osteocytes,osteoclasts,and osteoblasts,thus facilitating the process of periodontal remodeling. OBJECTIVE:To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS:The PubMed,Web of Science,China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy.And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION:Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause,leading to autophagy in periodontal tissue.Subsequently,autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B,Hippo,and mitogen-activated protein kinase pathways,promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability.Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side.Related targets have good prospects in the clinical application of orthodontic treatment.Orthodontics and autophagy have complex mechanisms.However,existing research has only focused on exploring the role of autophagy in orthodontic tooth movement.Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement,as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways.

Oral submucous fibrosis (OSF) can cause various oral dysfunctions in patients and can turn into oral cancer. The causes and processes of OSF malignant transformation involve betel nut chewing, vascular atrophy, tissue hypoxia, cell cycle changes, aging, autophagy, and changes in cancer/cancer suppressor genes and microRNAs. It is of great significance to study the causes and process of OSF malignant transformation for the treatment and prevention of OSF malignant transformation.

Forkhead box protein O1 (FOXO1) has been extensively studied as a tumor suppressor. In oral squamous cell carcinoma, studies have demonstrated that FOXO1 can inhibit tumor cell oxidative stress, stemness and epithelial-mesenchymal transition, and promote tumor cell autophagy and apoptosis. FOXO1 may serve as a potential target for the treatment of oral squamous cell carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.