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 investigate the changes of 8 lipid biomarkers,4 complement biomarkers and albu-min(ALB)in serum of patients with colorectal cancer(CRC)and their value in CRC screening.Methods A total of 120 newly diagnosed CRC patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from August 2022 to January 2024 were selected as the CRC group,and 110 healthy subjects were selected as the healthy control(HC)group.A total of 8 lipid biomarkers including total cholesterol(TC),tri-glyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein(Apo)A1,ApoA2,ApoB and ApoE,4 complement biomarkers including complement C3(C3),complement C4(C4),complement C1q(C1q)and complement C1 inhibitor(C1INH),3 intestinal tumor markers including carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,CA19-9,and ALB levels were detected in serum of each group.Independent sample t test and Mann-Whitney U test were used for com-parison between groups,and stepwise Fisher discriminant algorithm was used to fit each marker to establish a screening model.Receiver operating characteristic curve was used to analyze the diagnostic efficacy of each marker and the model.Results The serum levels of ApoA1,ApoA2,HDL-C,TC and ALB in CRC group were lower than those in HC group(P<0.05),while the serum levels of C1INH,C4 and CEA were higher than those in HC group(P<0.05).Among the single biomarkers,ALB had the highest diagnostic efficiency,the area under the curve(AUC)was 0.909,the sensitivity was 77.50%,and the specificity was 94.55%.The AUC of the screening model composed of ApoA2,C1INH and ALB was 0.978,the sensitivity was 91.67%,and the specificity was 98.86%.The diagnostic efficacy was higher than any single biomarker.Conclusion ApoA2,C1INH and ALB are abnormally expressed in the serum of CRC patients.The screening model composed of ApoA2,C1INH and ALB can provide reference for CRC screening and clinical auxiliary diagnosis.

Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

AIM To investigate the therapeutic mechanism of tanshinone ⅡA in a mouse model of chronic colitis induced by trinitrobenzene sulfonic acid(TNBS).METHODS The BALB/c mice were randomly divided into the control group,the model group,and the low-dose and high-dose tanshinone ⅡA groups(10,20 mg/kg).Chronic inflammatory bowel disease(IBD)was induced in the model and tanshinone ⅡA groups by epicutaneous application of 3.75 mg TNBS(dissolved in 48％ethanol),followed by intrarectal administration of TNBS(0.75,1.5 and 2.25 mg in 40％ethanol)on days 7,14 and 21.Starting on day 7 post-modeling,the mice underwent their 14-day consecutive dosing of corresponding drugs by gavage.The mice had their disease activity index(DAI)assessed;their colon length and weight measured;and their levels of inflammatory factors IFN-γ and TNF-α in the colon mucosa detected by ELISA.The wild-type and PXR-/-mice were randomly divided into the control group,the model group,and the tanshinone ⅡA group(20 mg/kg).After modeling and drug administration using the aforementioned method,Masson staining was used to assess the intestinal fibrosis;immunohistochemistry was employed to detect the colon expression of ZO-1 and Occludin proteins;and immunofluorescence was used to detect the colon expression of NF-κB p65.RESULTS Tanshinone ⅡA(20 mg/kg)reduced DAI scores,colon weight/length ratio,and the colon levels of IFN-γ and TNF-α of the mouse models(P＜0.05,P＜0.01).Compared with the WT control group,the WT model group and PXR-/-control group exhibited increased colon histopathological scores and fibrosis areas(P＜0.01),decreased protein expressions of ZO-1 and Occludin(P＜0.01),and increased expression of p-NF-κB p65(P＜0.01).Compared with the WT model group,the WT tanshinone ⅡA group showed reduced colon weight/length ratio,histopathological scores,and fibrosis areas(P＜0.01);increased protein expressions of ZO-1 and Occludin(P＜0.05,P＜0.01);and decreased expression of p-NF-κB p65(P＜0.01).However,tanshinone ⅡA showed no significant therapeutic effect upon PXR-/-model mice(P＞0.05).CONCLUSION Tanshinone ⅡA(20 mg/kg)can effectively alleviate TNBS-induced chronic colitis in mice,and this protective effect may be exerted by the modulation of PXR/NF-κB signaling pathway.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Objective:To construct a risk prediction model for pulmonary infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on decision tree method, and analyze nursing strategies.Methods:From March 2022 to June 2024, convenience sampling was used to select 162 patients with AECOPD at the First Affiliated Hospital of Zhengzhou University as study subjects. Patients with AECOPD complicated by pulmonary infection were designated as infection group ( n=82), while patients without pulmonary infection were designated as non-infection group ( n=80). Relevant clinical data were collected, and multiple Logistic regression was used to analyze the influencing factors of pulmonary infections in AECOPD patients, and a decision tree prediction model was established. Results:Multivariate Logistic regression analysis showed that age, glucocorticoid use time, hospital stay, mechanical ventilation history, diabetes, C-reactive protein and procalcitonin were the influencing factors of AECOPD patients with pulmonary infection ( P<0.05). The risk decision tree model of AECOPD patients with pulmonary infection based on the above factors showed that procalcitonin, C-reactive protein, mechanical ventilation history and diabetes were nodes, with four layers, six terminal nodes and four explanatory variables. The area under the receiver operating characteristic curve was 0.929 [95% CI (0.889, 0.968) ], the sensitivity was 0.854, the specificity was 0.875, and the predictive performance was good. Conclusions:Age, glucocorticoid use time, hospital stay, mechanical ventilation history, diabetes, C-reactive protein and procalcitonin are independent risk factors for AECOPD patients with pulmonary infection. The decision tree prediction model constructed has good predictive performance and can be used as a basis for selecting nursing strategies.

Nucleic acid detection technology has been widely applied in fields such as pathogen detection due to its characteristics of rapidity,sensitivity,and specificity.With the numerous nucleic acid markers related to diseases,the demand for multiplex nucleic acid detection is gradually increasing.Multiplex polymerase chain reaction(PCR)can simultaneously amplify multiple targets,but there are problems such as easy contamination when opening the tube during the analysis process after amplification and high technical requirements.With the continuous advancement of detection technology,a series of simple,re-liable single-tube multiplex PCR detection technologies that do not require opening the tube have emerged successively.A common technology is the single-closed tube multiplex PCR detection method based on fluorescent probes,which mainly uses different fluorescent labels to distinguish multiple targets.Com-bined with different specific enzymatic digestion reactions,it can achieve multiplex detection of rare tumor mutations and single nucleotide-specific genotyping.In addition,the monochromatic melting curve analysis method based on differences in melting temperatures enables parallel detection of multiple targets within a single fluorescence channel.When performed within multiple fluorescence channels,it is called the multicolor melting curve analysis method,which can increase the number of detected targets to doz-ens,greatly breaking through the limitation of the number of fluorescence channels on the multiplexity of detection.At the same time,the fluorescence coding method using different combinations of fluorescent labels also provides new ideas for single-closed tube multiplex PCR detection.These include encoding the sequence of signals generated by different fluorescent labels corresponding to the same target,using a combination of two fluorescent labels to identify specific targets,and controlling the amplitude of fluores-cent signals of different targets,all of which can also improve the multiplexity of detection.This article summarizes and prospects the research progress of single-closed tube multiplex PCR detection technology in recent years from multiple dimensions such as principles,applications,and the advantages and disad-vantages of the methods,providing valuable references for subsequent scientific research exploration and application.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

OBJECTIVE: Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated. METHODS: This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011-2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use. RESULTS: We identified three frailty trajectories: low-stable ( n = 5,789), moderate-increasing ( n = 2,603), and fast-increasing ( n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing ( OR: 1.24, 95% CI: 1.08-1.42) and fast-increasing ( OR: 1.48, 95% CI: 1.14-1.92) trajectories. These associations were strengthened by longer solid fuel use ( P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group. CONCLUSION Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
Humans ; China/epidemiology* ; Cooking ; Male ; Female ; Middle Aged ; Aged ; Air Pollution, Indoor/adverse effects* ; Frailty/etiology* ; Longitudinal Studies ; Cohort Studies

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.