Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

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.

Humans ; Epstein-Barr Virus Infections ; Immune Checkpoint Inhibitors ; Herpesvirus 4, Human

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Abstract: Viral shedding of SARS-CoV-2 is a continuous dynamic process, which can be divided into latent stage, initial stage, peak stage and decreasing stage according to the characteristics of viral shedding. After being infected with SARS-CoV-2, the infected person generally stays in the latent period for 1-3 days, which is characterized by continuous negative nucleic acid test results and no infectiousness, and the risk of infection for close contacts is very low. At the initial stage of viral shedding is characterized by a rapid decline in the Ct value of nucleic acid tests in a short time, and clinical symptoms gradually appear. The infectiousness of the infected person gradually increases during this period, and the risk of infection for close contacts also gradually increases, but it is still in the early stage of infection, the possibility of viral shedding is low, and the risk of infection of secondary close contacts is low. The peak of viral shedding is characterized by low Ct value in nucleic acid test and obvious clinical symptoms; during this period, the infected person is the most infectious, and the risk of infection of the contact is the highest, so the scope of close contacts should be expanded appropriately. The decreasing period is characterized by the gradual increase of Ct value of nucleic acid test and the gradual disappearance of clinical symptoms; during this period, the infectiousness of the infected person gradually decreases to disappear. In an outbreak, an infected person in the decreasing phase is more likely to be an early infected person in the transmission chain. If infected individuals in the decreasing phase are found in an area without a SARS-CoV-2 epidemic, it suggests that the local outbreak epidemic has been spreading for some time and may be larger in scale. According to the characteristics of viral shedding, risk personnel can be determined more scientifically and accurately, so as to minimize the risk and reduce the waste of epidemic prevention resources.

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.
Male ; Humans ; Cohort Studies ; Chemoradiotherapy ; Carcinoma ; Hypopharyngeal Neoplasms/therapy* ; Induction Chemotherapy

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

Background/Aims: We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol. Methods: In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting. Results: One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the “4+2” protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0–5.0] vs 4.0 [4.0–5.0], p=0.266). No adverse events were observed during the study. Conclusions The “4+2” protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD.

Given the important position and function of the hypopharynx, the preservation of organ function and survival improvement are equally important. The optimal role of multi-disciplinary combined treatment modality becoming increasingly important. The optimal laryngeal preservation strategy for hypopharyngeal cancer is under continuous exploration. With the constant research of surgery, radiotherapy, chemotherapy, and molecular targeted therapy, new laryngeal preservation strategies continue to emerge. Herein, we primarily summarize the advances in multi-disciplinary combined treatment and the future direction in the treatment of hypopharyngeal carcinoma.

Objective:To evaluate the incidence, clinical characteristics and prognosis of second primary malignancies (SPMs) among patients with hypopharyngeal carcinoma (HPC) in real-world analysis.Methods:A total of 594 HPC patients admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2010 to 2018 were retrospectively analyzed.The incidence and clinical characteristics of HPC patients complicated with SPMs were analyzed. Clinical efficacy was compared among different groups.Results:With a median follow-up time of 66.9 months, SPMs were present in 36.4% (216/594) of HPC patients: 22.2% (132/594) were synchronous and 14.1% (84/594) were metachronous. The upper aerodigestive tract was the most common involved region. Compared with patients without SPMs, patients with synchronous and metachronous carcinoma in situ had similar 5-year overall survival (OS) of 42.2% vs. 44.5% ( P=0.958) and 62.2% vs. 44.5% ( P=0.240), respectively. Patients with synchronous invasive SPMs had a worse 5-year OS of 27.2% vs. 44.5% in their counterparts without SPMs ( P=0.001). Patients with metachronous invasive SPMs had similar 5-year OS of 50.2% vs. 44.5% in their counterparts without SPMs ( P=0.587). SPMs accounted for 42.5% of total death in metachronous invasive SPMs group. Conclusions:Patients with HPC have a high probability of developing SPMs. Moreover, the incidence of complicated with esophageal/gastric carcinoma in situ or metachronous SPMs exerts no effect on prognosis, while the occurrence of synchronous SPMs significantly affectes the prognosis of patients. However, the incidence of SPMs is still one of the main death causes in metachronous invasive SPMs group.