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.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

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

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To synthesize a hydrolysis-resistant urushiol-modified monomer(UMM)to improve the hydrolysis resistance of light-cured composite resin,while reducing the volume shrinkage rate(VS),increasing the double bond conversion rate(DC),and mitigating the potential biosafety concerns of bisphenol A glycidyl methacrylate(Bis-GMA)monomer.Methods:UMM was synthesized by modifying urushiol via an acyl chloride reaction,and its structure was analyzed and characterized using Fourier transform infrared spectroscopy(FT-IR).Control group was consisted of Bis-GMA/triethylene glycol dimethacrylate(TEGDMA)without UMM,while 10%UMM,15%UMM,and 20%UMM groups were prepared by partially replacing Bis-GMA with UMM at mass fractions of 10%,15%,and 20%,respectively.The viscosity of UMM was measured using a rheometer.The DC of light-cured composite resin in various groups was detected by FT-IR spectroscopy,and the VS was calculated.The contact angle of light-cured composite resin in various groups was measured using the sessile drop method,and the water sorption and solubility values were calculated.The mechanical properties of light-cured composite resin in various groups were tested.The in vitro cytotoxicity of light-cured composite resin in various groups was evaluated using the cell counting kit-8(CCK-8)assay.Results:The FT-IR spectra results showed that the absorption peak of the hydroxyl group at 3 402 cm-1 disappeared,while characteristic absorption peaks of-C=O and-C=C appeared at 1 745 and 1 637 cm-1,indicating that urushiol successfully reacted with acryloyl chloride to form UMM.The viscosity of UMM ranged from 25.14 to 29.43 Pa·s.Compared with control group,the DC of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05),while the VS was significantly decreased(P<0.05),both in a dose-dependent manner.Compared with control group,the contact angle of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05).Compared with 10%UMM group,the contact angle of light-cured composite resin in 15%UMM and 20%UMM groups was further increased(P<0.05).Compared with control group,the water sorption and solubility values of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),showing a dose-dependent trend.After 24 h of water immersion,compared with control group,the flexural strength(FS)and elastic modulus(EM)of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),also in a dose-dependent manner.After 7 d of water immersion,compared with control group,the FS of light-cured composite resin in 10%UMM group was significantly increased(P<0.05),while that in 20%UMM group was significantly decreased(P<0.05).Compared with 10%UMM group,the FS of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),exhibiting a dose-dependent trend.Compared with control group,the EM of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),also in a dose-dependent manner.The relative growth rate(RGR)of the L929 cells in control,10%UMM,15%UMM,and 20%UMM groups was above 90%,with no statistically significant differences among groups(P>0.05),and all cytotoxicity results were qualified.Conclusion:A novel low-viscosity monomer UMM is successfully synthesized in this study.All UMM-containing light-cured composite resin formulations exhibit higher DC,lower VS,reduced water sorption and solubility values,improved hydrolysis resistance,and low cytotoxicity.UMM can serve as a potential resin monomer to enhance the hydrolysis resistance of light-cured composite resin.

Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.

Objective To investigate the distribution difference of T lymphocyte subsets in common and refractory mycoplasma pneumonia and its impact on treatment.Methods Two hundred children with mycoplasma pneumonia hospitalized from October 2023 to January 2024 were retrospectively reviewed and divided into common mycoplasma pneumonia group and refractory mycoplasma pneumonia group(n=100 each)according to the severity of disease and treatment.The distribution of T cell immunophenotypes CD4+,CD8+and CD4+/CD8+were compared between common mycoplasma pneumonia and refractory mycoplasma pneumonia.The predictive value of CD4+,CD8+counting,CD4+/CD8+and combined detection on the occurrence of refractory mycoplasma pneumonia were ana-lyzed.Results Compared with the common mycoplasma pneumonia group,the refractory mycoplasma pneumonia group had more school-age children,longer fever duration and hospital stay(P＜0.05).Compared with the common mycoplasma pneumonia group,CD4+expression was slightly decreased in the refractory mycoplasma pneumonia group,but there was no statistical significance between the two groups;CD8+expression was significantly increased while CD4+/CD8+expression was significantly decreased(P＜0.05).Receiver operating characteristic curve(ROC)showed that CD4+(AUC=0.532,95%CI=0.455-0.608),CD8+(AUC=0.592,95%CI=0.515-0.666),CD4+/CD8+(AUC=0.579,95%CI=0.502-0.653)and combined detection(AUC=0.607,95%CI=0.531-0.680).Conclusions Compared with the common mycoplasma pneumonia group,CD4+expression is slightly decreased,CD8+expression is significantly increased,and CD4+/CD8+expression is significantly decreased in the refractory mycoplasma pneumonia group.All these indicators hold certain value in predicting the occurrence of refractory mycoplasma pneumonia,with combined detection demonstrating higher predictive value.