Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To explore the correlation between c-myc and glutaminase(GLS)and glutamine synthase(GS)in oral epider-moid carcinoma cells in animal models.Methods:Immunohistochemistry was used to detect the expression of c-myc,GLS and GS in clinical samples of oral cancer.KB cell model with stable and high expression of c-myc was established and verified,then the KB cells were transplanted into nude mice to establish mouse tumorigenic models.The cells and nude mouse models were respectively diveded into 3 groups(n=6):normal cotnrol,empty vector and c-myc overexpression groups.The tumor growth was observed.The expression of c-myc,GLS and GS in the cells and the tumor samples was detected by immunohistochemistry.Results:c-myc,GLS and GS were highly expressed in clinical samples of oral cancer.In the cells of c-myc overexpression group c-myc mRNA expression level was sig-nificantly higher than that of empty vector control group.The tumorigenic models were formed in all nude mice of the groups,and the volume and weight of the c-myc overexpression group increased more significantly(P＜0.01),in the c-myc overexpression group c-myc was overexpressed,the expression of GLS and GS was significantly higher than that in the other 2 groups.Conclusion:c-myc is highly expressed in oral cancer,and may up-regulate GLS and GS expression.

Protein S-palmitoylation is a reversible post-translational modification of lipids that regulates protein localization, stability and protein-protein interactions. The thioesterification of palmitate to internal cysteine residues is catalyzed by palmitoyltransferase, while the removal of palmitate is mainly catalyzed by acyl-protein thioesterase. The S-palmitoylation of some tumor-related proteins is abnormally altered in tumor, which is closely related to the biological processes such as tumor cell proliferation, invasion, metastasis, drug resistance and immune response. Furtherly, exploring the characteristics of protein S-palmitoy-lation and its role in tumor progression could deliver new ideas in targeting protein S-palmitoylation for tumor therapy.

With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.
Humans ; Tandem Mass Spectrometry/methods* ; Irritable Bowel Syndrome/drug therapy* ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Glycosides ; Chromatography, High Pressure Liquid/methods*

Objective : To investigate the effect of adeno⁃associated virus ( AAV) delivery of short hairpin RNA ( shRNA) against the Ptger3 gene in the lateral parabrachial nucleus (LPB) on the fever induced by microinjection of prostaglandin E2 (PGE2 ) into the LPB and the intraperitoneal injection of lipopolysaccharide (LPS) . Methods: AAV2⁃shRNA⁃Ptger3(EP3) ⅣEGFP ( shRNA⁃EP3) and AAV2⁃ CMV⁃ EGFP ( shRNA⁃control) viruses were constructed and transfected the rat LPB by stereotaxic injection. Four weeks later, the transfection efficiency of AAV viruses was observed by fluorescence microscopy , and the knockdown efficiency was determined by real⁃time PCR of EP3 receptor mRNA on the LPB. The effects of microinjection of saline or PGE2 in the LPB or intraperitoneal injection of LPS on body temperature (Tcore ) and energy expenditure (EE) of shRNA⁃control group and shRNA⁃EP3 group were monitored using an animal monitoring system with temperature telemetry. Results : AAV virus transfecnificant difference in basal body temperature between shRNA⁃control group and shRNA⁃EP3 group. Tcore and EE were briefly and slightly increased after microinjection of saline in the LPB , but there was no significant difference between the two groups. Compared with the shRNA⁃control group , the febrile response induced by LPB PGE2 was attenuated in the shRNA⁃EP3 group (P < 0. 05) . Furthermore , the knockdown of EP3 receptor of LPB also attenuated the LPS⁃induced fever, and the Tcore 5. 5 h post⁃LPS in the shRNA⁃EP3 rats increased compared with the baseline (P < 0. 05) , which was lower than that in the shRNA⁃control rats ( P < 0. 01) . Conclusion EP3 receptor knockdown in LPB attenuates the febrile response induced by microinjection of PGE2 in the LPB and intraperitoneal injection of LPS , suggesting that EP3 receptors of LPB mediate the pyrogenic action of LPB PGE2 and partly participate in LPS⁃induced fever.

Radiotherapy is an essential part of comprehensive treatment, as well as a radical treatment for head and neck cancer (HNC). The COVID-19 has continued so far, imposing a great impact on cancer care. Since conventional fractionated radiotherapy (CFRT, 2 Gy/F) requires as long as more than six weeks of treatment time, a huge challenge for epidemic control is created for both hospitals and patients. Hypofractionated radiotherapy (Hypo-RT) may be more suitable than CFRT for patients during pandemic by increasing the fraction size, thus reducing fraction number and treatment duration. Early studies have explored the application of Hypo-RT in HNC in palliative setting, which partially proved its safety and effectiveness. Recently, the efforts have been made in definitive treatment using hypofractionated regimen, as well as its combination with systemic treatment and immunotherapy. Indeed, regarding the pandemic of COVID-19, Hypo-RT has been recommended by several expert consensus in the HNC. In this review, relevant research progress was summarized and clinical implication of Hypo-RT in COVID-19 pandemic era was discussed.

Gene editing technology CRISPR/Cas9 and its derivative editing technologies including base editor and prime editor can precisely edit the target genome sequences, having been widely used in tumor therapy and achieved remarkable clinical results in tumor immunotherapy, human papilloma virus infection treatment and oncolytic virotherapy, providing a new means for tumor therapy.

Objective To investigate etiology and pathological morphological characteristics of sudden death caused by non-atherosclerotic aortic dissection. Propose accurate diagnosis of non-atherosclerotic aortic dissection by a proper method to autopsy. Methods A total of 8 cases of non-atherosclerotic aortic dissection from 2007 to 2015 were evaluated and analyzed in the present study. Results Non-atherosclerotic aortic dissection rupture is more common in men under the age of 40. It is lack of a typical clinical symptoms and had no marked history of hypertension. There are no related pathological changes of hypertension observed in autopsy. The pathological type is mainly DeBakey 1, in the main arteries,where it was found that decrease of elastic fibers and smooth muscle, cystic degeneration, inflammatory cell infiltration and other changes in media membrane. These changes were also found in the media arteries in 5 cases. Conclusion The etiology of non-atherosclerotic aortic dissection is complex, which is closely associated with many factors, such as genetics and inflammation. It affects the vessels systemically. In addition, systematic examination of large vessels is necessary as well as the examination of the middle arteries during autopsy. It is suggested that genetic tests are carried out for definite diagnosis.