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.

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective:To summarize the clinical symptoms of cyclic vomiting syndrome（CVS）in children and investigate its association with small intestinal bacterial overgrowth（SIBO）.Methods:A total of 89 children who were diagnosed as CVS and improved lactulose hydrogen breath test (LHBT) in the Pediatric Department of Beijing Tsinghua Changgung Hospital from June 2020 to June 2023 were selected as CVS group.Simultaneously，50 healthy children with physical examination in our hospital were selected as the control group. According to the results of LHBT,the children with CVS were divided into SIBO group (LHBT positive) and non-SIBO group (LHBT negative). The clinical data of children in each group were compared.Results:Among the 89 CVS patients，there were 42 males and 47 females，with a mean age of（7.50±3.54）years.Common accompanying symptoms included excessive sleepiness（76 cases，85.39%），anorexia(62 cases，69.66%），constipation（55 cases，61.80%），abdominal pain（34 cases,38.20%）and so on. There were no significant differences in age and gender between children in CVS group and control group ( P>0.05). The body mass index of CVS group was lower than that of control group.The positive rate of LHBT was higher than that of the control group (56.18% vs. 8.00%),the difference was statistically significant ( P<0.05),and the concentrations of hydrogen and methane in CVS group were higher than those of the control group at different time points( P<0.05).Among 89 children with CVS,there were 50 cases in SIBO group and 39 cases in non-SIBO group. There were no significant differences in gender,age and body mass index between the two groups ( P>0.05). The constipation rate and moderate/severe disease rate in SIBO group were higher than those in non-SIBO group (88.00% vs. 28.21%,94.00% vs. 43.59%),and the differences were statistically significant ( P<0.05). Conclusion:The incidence of SIBO in children with CVS is higher,and SIBO may play a key role in CVS. CVS children with SIBO have higher disease severity.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.