BACKGROUND:Quercetin has anti-inflammatory,anti-cancer,anti-oxidation,anti-aging,anti-depression and other pharmacological effects,and has high medicinal value.Quercetin can promote wound healing in normal rats,but few drugs with quercetin as the main component have been developed,which limits its wide application in clinical practice. OBJECTIVE:To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material. METHODS:(1)Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively,and the micromorphology and in vitro drug release properties of the hydrogels were characterized.(2)Cell experiment:Mouse L929 fibroblasts were cultured in four groups.The blank control group was cultured conventionally.Carboxymethyl chitosan hydrogel,quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively,to detect cell proliferation and migration ability.(3)Animal experiments:Diabetic models were established in 80 SD rats.After successful modeling,full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats,and these models were randomly divided into four groups.Normal saline,carboxymethyl chitosan hydrogel,quercetin solution,and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group,pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively.Each group contained 20 animals,which were bound with sterile gauze.Wound healing,pathological morphology,expression of inflammatory factors,and angiogenesis were observed after operation. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the microstructures of the two hydrogels were similar,both showed loose porous network structure,and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro.(2)Compared with blank control group,the cell proliferation and mobility of the other three groups were increased(P<0.05).The cell proliferation and mobility of drug-loaded hydrogel group were higher than those of pure hydrogel group and drug group(P<0.05).(3)The wound healing rate of the drug-loaded hydrogel group was higher than that of the other three groups at 5 and 11 days after operation.The wound healing rate of rats in the hydrogel group,pure hydrogel group,and drug group reached 100%18 days after operation,which was higher than that in the blank control group(P<0.05).Hematoxylin-eosin staining showed that intact skin and skin appendages were visible on the wounds of rats in the drug-loaded hydrogel group 18 days after surgery,while intact skin and skin appendages were visible on the wounds of rats in the blank control group,pure hydrogel group,and drug group 25 days after surgery.The levels of tumor necrosis factor α and interleukin-6 in the drug-loaded hydrogel group were lower than those in the blank control group at 5,11,and 18 days after surgery(P<0.05),and the levels of transforming growth factor β1 at 11 and 18 days after surgery were lower than those in the blank control group(P<0.05).The mRNA expressions of CD31 and vascular endothelial growth factor α in the drug-loaded hydrogel group were higher than those in the other three groups at 11 and 18 days after operation(P<0.05).(4)These findings indicate that quercetin in quercetin carboxymethyl chitosan hydrogel can regulate inflammatory response,accelerate angiogenesis,promote the proliferation and migration of fibroblasts,and enhance the healing of diabetic wounds in rats.

Tumor immunotherapy has revolutionized the treatment prospects for various malignant tumors. Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T) , as representative of tumor immunotherapy, have achieved tremendous success in clinical practice and have become the first-line clinical treatment options for certain tumors. This article summarizes the progress and challenges of immune checkpoint inhibitors and CAR-T therapy in tumor treatment, and discusses the future direction of tumor therapeutic vaccines development. Identifying novel therapeutic targets within the realm of tumor immunology, engineering innovative drug delivery systems, and employing combinatorial therapeutic strategies are poised to enhance therapeutic efficacy and patient outcomes in oncology, thereby extending benefits to a broader patient population.
Humans ; Neoplasms/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy/methods* ; Immunotherapy, Adoptive/methods* ; Animals ; Cancer Vaccines/therapeutic use*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Wumeiwan are recorded in the Jueyin chapter of Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）， and many doctors in the past dynasties believed that they had the effects of calming intestinal ascarid by warming Zang organs. The clinical application was limited. Since KE Qin， a doctor in the Qing dynasty， proposed that Wumeiwan were the primary prescription against Jueyin diseases， Wumeiwan have been valued by doctors， and their clinical application has also been expanded. The syndrome indicated for Wumeiwan is attributed， not only to the ascarid internal harassment， but to the abnormal Qi movement of wind and wood in Jueyin and the dysfunction of Yin and Yang. According to the functions of six meridians based on the theory of "open-close axis" in Huangdi's Internal Classic （《黄帝内经》） and the original texts of Treatise on Cold Damage and Miscellaneous Diseases， Yinshu refers to Jueyin. Wumeiwan， the primary prescription against Jueyin diseases， have the function of connecting Yin and Yang， and they can treat diseases caused by Qi disturbance of Jueyin and cold and heat in complexity. Sharing the same resource， the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） and Treatise on Cold Damage and Miscellaneous Diseases both consult Models of the Classic of Decoction （《汤液经方》）. The formulation rules of tonic/purgative and collapse-saving prescriptions in Secrets for Auxiliary Cultivation Life follow the recorded "Tang Ye Jing Fa Tu" （an image revealing the compatibility principles of Chinese herbal drugs） and are closely related to the five elements theory. By exploring the formulation rules in "Tang Ye Jing Fa Tu" and the five elements of drugs， this study analyzed Wumeiwan and proved that Wumeiwan mainly acted on the liver， spleen， and heart. According to the Five Zang-organs Storing Spirit theory from Huangdi's Internal Classic， the above three organs are closely related to emotional adjustment. Therefore， the treatment of emotional disorders caused by qi disturbance of Jueyin and cold and heat in complexity with Wumeiwan is supported by evidence. At the end of this article， the reports on the treatment of emotional disorders with Wumeiwan in recent years were listed and reviewed. This article provides new ideas for the clinical application of Wumeiwan in the treatment of emotional disorders and expands the application range.

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*

Objective:To evaluate the efficacy and safety of nimotuzumab in the treatment of advanced head and neck tumors by using meta-analysis.Methods:Randomized controlled trials (RCT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with nimotuzumab were searched from databases (Cochrane Library, PubMed, Embase, Wanfang Data and CNKI) for meta-analysis. The efficacy evaluation indexes included overall survival, progression-free survival, disease-free survival, objective response rate, and complete response rate. Adverse reactions were analyzed for safety evaluation. The heterogeneity results were evaluated by Chi-square test, the degree of heterogeneity was evaluated by I2, and the literature was statistically analyzed by random effects model. Results:A total of 11 RCT were included, consisting of 1 202 patients (602 in the intervention group and 600 in the control group). Compared with the control group, the overall survival was significantly prolonged, death risk was decreased by 22% ( HR=0.78, 95% CI=0.63-0.95, P=0.014), the progression-free survival was prolonged and the risk of disease progression was declined by 35% ( HR=0.65, 95% CI=0.53-0.81, P<0.01), and the disease-free survival was prolonged and the risk of recurrence was decreased by 29% ( HR=0.71, 95% CI=0.55-0.91, P<0.01), the objective response rate ( RR=1.37, 95% CI=1.20-1.55, P<0.01) and complete response rate ( RR=1.30, 95% CI=1.15-1.46, P<0.01) were significantly improved in the intervention group. In addition, adding nimotuzumab did not increase the incidence of adverse reaction ( RR=0.98, 95% CI=0.93-1.03, P=0.41). Conclusion:Nimotuzumab can significantly prolong long-term survival and improve short-term efficacy with high safety in LA-HNSCC patients.