Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

The working principle and development of flexible semiconductor devices based on organic field effect transistor(OFET)technology were introduced.The current research status of OFET-based wearable flexible monitoring devices were reviewed,including biomechanical monitoring devices,tattoo biomonitoring devices and cellular detection devices and etc.The deficiencies of OFET-based wearable flexible monitoring devices were analyzed,and it's pointed out that miniaturization,personalization and diversification were the directions for the development of the future OFET-based wearable flexible moni-toring devices.[Chinese Medical Equipment Journal,2024,45(1):93-100]

Objective To summarize the clinical characteristics and genetic variations in children with cystic fibrosis(CF)primarily presenting with pseudo-Bartter syndrome(CF-PBS),with the aim to enhance understanding of this disorder.Methods A retrospective analysis was performed on the clinical data of three children who were diagnosed with CF-PBS in Hunan Children's Hospital from January 2018 to August 2023,and a literature review was performed.Results All three children had the onset of the disease in infancy.Tests after admission showed hyponatremia,hypokalemia,hypochloremia,and metabolic alkalosis,and genetic testing showed the presence of compound heterozygous mutation in the CFTR gene.All three children were diagnosed with CF.Literature review obtained 33 Chinese children with CF-PBS,with an age of onset of 1-36 months and an age of diagnosis of 3-144 months.Among these children,there were 29 children with recurrent respiratory infection or persistent pneumonia(88％),26 with malnutrition(79％),23 with developmental retardation(70％),and 18 with pancreatitis or extrapancreatic insufficiency(55％).Genetic testing showed that c.2909G＞A was the most common mutation site of the CFTR gene,with a frequency of allelic variation of 23％(15/66).Conclusions CF may have no typical respiratory symptoms in the early stage.The possibility of CF-PBS should be considered for infants with recurrent hyponatremia,hypokalemia,hypochloremia,and metabolic alkalosis,especially those with malnutrition and developmental retardation.CFTR genetic testing should be performed as soon as possible to help with the diagnosis of CF.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Objective:To investigate the effect of tripartite motif-containing 23 (Trim23) on the differentiation and maturation of dendritic cells and the possible mechanism.Methods:Mouse bone marrow-derived dendritic cells (BMDCs) were prepared from bone marrow cells of C57BL/6 mice with the presence of Flt3L. Real-time quantitative PCR and Western blot were used to detect the expression of Trim23 in BMDCs after LPS stimulation. An overexpression vector for full-length Trim23 (Trim23 OE) was constructed and transfected into BMDCs, and the pcDNA3.1 empty vector was used as control. Flow cytometry was used to detect the expression of CD80, CD86, CD40 and MHCⅡ on the surface of vector-transfected BMDCs after LPS stimulation and ELISA was used to detect the secretion of IL-12p40, TNF-α, IL-6 and IL-10 by these cells. CD8 + and CD4 + T cells were isolated from spleen and lymph nodes of OT-Ⅰ and OT-Ⅱ mice by magnetic beads and co-cultured with LPS-treated BMDCs in the presence of ovalbumin (OVA). Flow cytometry was used to detect the proliferation and differentiation of CD8 + and CD4 + T cells. Western blot was performed to analyze the phosphorylation of p38, ERK1/2 and AKT in BMDCs. Two overexpression vectors for Trim23 mutants lacking RING or ARF domain (Trim23 ΔRING and Trim23 ΔARF) were constructed and transfected into BMDCs. Then flow cytometry and ELISA were used to detect the expression of surface molecules and cytokines. Results:The expression of Trim23 in BMDCs was significantly down-regulated after LPS stimulation. The expression of MHCⅡ, CD86 and CD80 and the secretion of TNF-α and IL-6 decreased significantly in BMDCs overexpressing Trim23. Furthermore, overexpression of Trim23 inhibited the ability of BMDCs to induce the proliferation and differentiation of CD4 + T cells and the proliferation of CD8 + T cells. Western blot showed that the phosphorylation of p38 and ERK1/2 decreased significantly in Trim23-overexpressing BMDCs. Compared with wildtype Trim23, overexpression of Trim23 ΔRING had no significant influence on the expression of surface molecules (MHCⅡ and CD86) and the secretion of cytokines (TNF-α and IL-6) in BMDCs stimulated by LPS. Conclusions:Trim23 overexpression inhibited the maturation and immune activation of BMDCs via MAPK signal pathway and its RING domain. This study provided reference for targeting Trim23 to improve the immune response of dendritic cell-based tumor vaccines.

Objective To analyze the epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan during 2016-2020, and to provide a basis for formulating effective prevention and control strategies and measures. Methods Using the National Tuberculosis Information Management System, a descriptive statistical analysis was performed on the medical records of elderly (≥60 years old) pulmonary tuberculosis patients registered in Wuhan from 2016 to 2020. Results A total of 9 427 elderly pulmonary tuberculosis patients were registered in Wuhan during 2016-2020, accounting for 32.07% of the total number of registrations in the whole population. The reported incidence rate of tuberculosis in the elderly was significantly higher than that in the total population, and the reported incidence rates in both the elderly and the general population showed declining trends (whole population χ²_trend=216.97, P<0.05, elderly population χ²_trend=153.57, P<0.05). The time distribution showed that more cases occurred from April to November (70.90%). The top three districts with the largest number of registered cases were far urban areas, namely Huangpi District (13.81%), Xinzhou District (11.55%), and Jiangxia District (9.82%). The ratio of male to female with pulmonary tuberculosis in elderly patients was 2.85:1. Among the elderly pulmonary tuberculosis, the most registered cases were in the age group of 60 ~ years old, followed by 65 ~ years old. The proportion of smear-positive in elderly patients with pulmonary tuberculosis retreatment was 16.83%. Conclusion From 2016 to 2020, the epidemic situation of elderly pulmonary tuberculosis showed a downward trend in Wuhan. However, the elderly population with tuberculosis registrations still accounted for a relatively high proportion of the total population. According to the epidemiological characteristics of pulmonary tuberculosis among the elderly, the city should carry out tuberculosis prevention and control work in a timely, appropriate and focused manner.

Objective     To summarize the characteristics of children diagnosed with secondary subaortic stenosis after the surgical closure for ventricular septal defect and explore its potential mechanism. Methods     We retrospectively collected patients aged from 0 to 18 years, who underwent ventricular septal defect closure and developed secondary subaortic stenosis, and subsequently received surgical repair from 2008 to 2019 in Fuwai Hospital. Their surgical details, morphological features of the subaortic stenosis, and the follow-up information were analyzed. Results     Six patients, including 2 females and 4 males, underwent the primary ventricular septal defect closure at the median age of 9 months (ranging from 1 month to 3 years). After the first surgery, patients were diagnosed with secondary subaortic stenosis after 2.9 years (ranging from 1 to 137 months). Among them, 2 patients underwent the second surgery immediately after diagnosis, and the other 4 patients waited 1.2 years (ranging from 6 to 45 months) for the second surgery. The most common type of the secondary subaortic stenosis after ventricular septal defect closure was discrete membrane, which located underneath the aortic valve and circles as a ring. In some patients, subaortic membrane grew along with the ventricular septal defect closure patch. During the median follow-up of 8.1 years (ranging from 7.3 to 8.9 years) after the sencond surgery, all patients recovered well without any recurrence of left ventricular outflow tract obstruction. Conclusion     Regular and persistent follow-up after ventricular septal defect closure combining with or without other cardiac malformation is the best way to diagnose left ventricular outflow tract obstruction in an early stage and stop the progression of aortic valve regurgitation.

Non-alcoholic fatty liver disease (NAFLD) is a very common chronic liver disease in clinic, which can further develop into liver fibrosis, cirrhosis, eventually hepatocellular carcinoma and liver failure. Limonin is a natural triterpenoid compound containing furan rings. Previous studies have found that limonin has good anti-inflammatory, analgesic and liver protective functions. However, the mechanism of action of limonin on NAFLD has not been clarified. Based on the background, C57BL/6J male mice were fed with high fat diet (HFD) to establish NAFLD model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220429001), and limonin was added to the mice for administration by intragastric administration (i.g.). The results showed that HFD can induce typical NAFLD phenotypes, including impaired liver function, increased fat accumulation, and increased serum aspartate amino transferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels in mice. Mice were treated with limonin (50 and 100 mg·kg^-1) for 10 weeks, and it was found that limonin could restore dyslipidemia and improve fat accumulation in liver cells of mice. In addition, we conducted in vitro experiments with human hepatoma cell line HepG2 cells, and found that limonin can promote the expression of oxidative metabolism and autophagy related genes and inhibit apoptosis in HepG2 cells. Mechanistically, limonin improves high-fat food-induced NAFLD by promoting the expression of oxidative metabolism genes transcriptional coactivator of peroxisome proliferator activating receptor γ (PPARγ) (PGC1α) and carnitine palmitoyl transferase 1 alpha (CPT1α) through peroxisome proliferator activates receptor alpha (PPARα). These results indicate that limonin can inhibit apoptosis, promote autophagy and improve NAFLD by promoting oxidative metabolism of fatty acids through PPARα.

Objective To investigate the occurrence and clinical characteristics of the adverse reactions of hyperammonemic encephalopathy caused by sodium valproate and provide reference for the safe clinical use of the drug.Methods CNKI,WanFang Data,VIP,PubMed and Web of Science databases were electronically searched to collect case reports on valproate-induced hyperammonemic encephalopathy from the inception to March 2023.The extracted data was conducted for statistical analysis.Results A total of 37 documents with 41 patients were finally included.Among them,28 patients(68.3%)were males and 13 patients(31.7%)were females,aged 5 to 78 years,the median age was 41 years;most of the patients had no underlying diseases but the blood ammonia concentrations of them were abnormally high in laboratory tests,and the main clinical manifestations were neurological impairment such as cognitive impairment,drowsiness,coma and other disorders of consciousness.After drug discontinuation,drug switch and symptomatic treatment,they gradually recovered consciousness and the blood ammonia concentrations returned to normal.Conclusion It is not easy to recognize and detect the high blood ammonia encephalopathy caused by the application of sodium valproate in clinical practice,so the clinical performance and blood concentration of this drug should be closely monitored,and once the abnormalities are detected,patients should be treated symptomatically in time to ensure the safety of the drug use.