Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Aim To investigate the regulation of death-associated protein kinase 1(DAPK1)on seizure-in-duced Alzheimer's disease(AD)-like pathology.Methods Two-month old C57BL/6 mice were given intraperitoneal injection of 25 mg·kg-1 kainic acid(KA)to establish a temporal lobe epilepsy(TLE)model,and control mice were injected with an equal a-mount of saline.The expression of key proteins in the amyloid metabolic pathway,the secretion of soluble am-yloid β-protein(Aβ),the high phosphorylation of tau,and the activation of DAPK1 pathway were detected in hippocampus of mice.WT mice and Dapk1 KO mice were given intraperitoneal injections of KA,then the effect of DAPK1 on seizure-induced AD-like pathology was examined.Results The secretion of soluble Aβ,the expression of key proteins in the amyloid metabolic pathway,the level of phosphorylation of tau,and the ex-pression and activity of DAPK1 were higher in the hip-pocampus of TLE mice than in the control mice.Com-pared with WT mice,KA-induced Aβ secretion and tau phosphorylation were significantly reduced in hippo-campus of Dapk1 KO mice.Conclusion TLE in-duces AD-like pathology in mice,and DAPK1 knockout alleviates symptoms of aging in mouse brain.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.
Humans ; Rivers ; Virulence Factors/genetics* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Anti-Bacterial Agents ; Drug Resistance, Microbial/genetics*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Hemophagocytic syndrome (HPS) is a severe disease characterized by excessive release of inflammatory cytokines caused by abnormal activation of lymphocytes and macrophages, which can cause multiple organ damage and even death. Panniculitis is a disease characterized by inflammation of subcutaneous adipose tissue. We effectively treated 2 patients with panniculitis-associated HPS with ruxolitinib. Case 1: A 70-year-old male started with intermittent plantar swelling and pain, and then developed leukocytosis, mild anemia, multiple red maculopapules with painless subcutaneous nodules on the forehead, neck and bilateral lower legs. The patient was treated with prednisone and leflunomide for improvement. After that, repeated fever and rash occurred again. After admission to our hospital, we found his leukocyte and hemoglobin decreased, ferritin raised, fibrinogen and natural killer (NK) cell activity decreased, and hemophagocytic cells were found in bone marrow aspiration. The skin pathology was consistent with non-suppurative nodular panniculitis. He was diagnosed with nodular panniculitis associa-ted HPS. He was treated with glucocorticoid, cyclosporine, etoposide and gamma globule, but the disease was not completely controlled. After adjusting etoposide to ruxolitinib, his symptoms and abnormal laboratory findings returned to normal. After 2 months he stopped using ruxolitinib due to repeated infections. During the follow-up, though the prednisone dose was tapered, his condition was stable. Case 2: A 46-year-old female patient developed from intermittent fever, erythematous nodular rash with tenderness, leukopenia, and abnormal liver function. antibiotic therapy was ineffective. She improved after glucocorticoid treatment, and relapsed after glucocorticoid reduction. There were fever, limb nodules, erythema with ulcerative necrosis, intermittent abdominal pain when she came to our hospital. Blood examination showed that her white blood cells, red blood cells and platelets were decreased, fibrinogen was decreased, triglyceride was increased, ferritin and soluble interleukin-2 receptor(SIL-2R/sCD25) were significantly raised, and hemophagocytic cells were found in bone marrow aspiration. It was found that Epstein-Barr virus DNA was transiently positive, skin Staphylococcus aureus infection, and pulmonary Aspergillus flavus infection, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were normal, and no evidence of tumor and other infection was found. Skin pathology was considered panniculitis. The diagnosis was panniculitis, HPS and complicated infection. Antibiotic therapy and symptomatic blood transfusion were given first, but the disease was not controlled. Later, dexamethasone was given, and the condition improved, but the disease recurred after reducing the dose of dexamethasone. Due to the combination of multiple infections, the application of etoposide had a high risk of infection spread. Ruxolitinib, dexamethasone, and anti-infective therapy were given, and her condition remained stable after dexamethasone withdrawal. After 2 months of medication, she stopped using ruxolitinib. One week after stopping using ruxolitinib, she developed fever and died after 2 weeks of antibiotic therapy treatment in a local hospital. In conclusion, panniculitis and HPS are related in etiology, pathogenic mechanism and clinical manifestations. Abnormal activation of Janus-kinase and signal transduction activator of transcription pathway and abnormal release of inflammatory factors play an important role in the pathogenesis of the two diseases. The report suggests that ruxolitinib is effective and has broad prospects in the treatment of panniculitis associated HPS.
Humans ; Male ; Female ; Middle Aged ; Aged ; Lymphohistiocytosis, Hemophagocytic/drug therapy* ; Glucocorticoids/therapeutic use* ; Epstein-Barr Virus Infections/complications* ; Etoposide/therapeutic use* ; Prednisone/therapeutic use* ; Herpesvirus 4, Human ; Panniculitis/complications* ; Dexamethasone/therapeutic use* ; Exanthema/complications* ; Ferritins/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Fibrinogen/therapeutic use*

Objective:To analyze the correlations between the prognosis of patients with pancreatic cancer and macrophage infiltration, and to find the differential gene correlated with macrophage infiltration in patients with pancreatic cancer through bioinformatics.Methods:A total of 32 patients with pancreatic cancer admitted to the First Hospital of Lanzhou University from June 2015 to December 2018 were selected as the research objects, including 19 males and 13 females, with the age of (61.8±2.8) years. Cancer tissues, adjacent tissues, and related clinical data were collected. F4/80 (macrophage marker) immunohistochemical staining was performed on the samples. The survival time was followed up and its correlation with the above indexes was analyzed. The pancreatic cancer data from The Cancer Genome Atlas (TCGA) database was used for bioinformatics analysis.Results:The survival time of pancreatic cancer patients was negatively correlated with degree of macrophage infiltration in cancer tissues ( r=-0.522, P=0.002), but not with adjacent tissues ( r=0.168, P=0.358). The degree of macrophage infiltration in cancer tissue combined with preoperative serum carbohydrate antigen 19-9 (CA19-9), tumor TNM stage and vascular invasion can predict survival up to 47.4% of the survival time ( R2=0.474). TCGA database bioinformatic analysis showed that in pancreatic cancer there were 95 differentially expressed genes significantly correlated with M2 macrophage infiltration, among which JPH3 (positive correlation) and IL17REL (negative correlation) were the main genes. Conclusion:The degree of macrophage infiltration in cancer tissue can be used as a prognostic factor for patients with pancreatic cancer, and the combination with preoperative serum CA19-9, tumor TNM stage and vascular invasion is more accurate in predicting the prognosis. The related mechanism of M2 macrophage infiltration can be studied around the differential genes such as JPH3 and IL17REL.

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human/genetics* ; Humans ; Immunophenotyping ; Killer Cells, Natural ; Lymphoproliferative Disorders ; Male