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.

BackgroundArrhythmia and obsessive-compulsive disorder （OCD） frequently co-occur in clinical and epidemiological settings， yet their shared genetic basis and potential heart-brain axis mechanisms remain unclear. ObjectiveTo systematically evaluate the genetic correlation between arrhythmia and OCD， and to elucidate their underlying molecular genetic mechanisms， so as to provide molecular evidence for the "heart-brain axis" to support risk assessment and integrated clinical strategies for these comorbidities. MethodsThe aggregated data from the genome-wide association study （GWAS） of arrhythmia in the UK Biobank （7 207 cases and 477 391 controls） and the GWAS data of OCD released by the Psychiatric Genomics Consortium （2 688 cases and 7 037 controls） were integrated， all of which were limited to individuals of European ancestry. The genome-wide genetic correlations were estimated using the linkage disequilibrium score regression （LDSC） and the high-definition likelihood （HDL）. Local genetic correlation analysis was conducted using the local analysis of variance annotation （LAVA）. Multi-trait analysis of GWAS （MTAG） was employed to identify pleiotropic loci. Shared risk genes were identified by combining summary-data based Mendelian randomization （SMR） and transcriptome-wide association study （TWAS）. Functional enrichment analysis was performed based on the functional mapping and annotation （FUMA） platform. ResultsBoth LDSC （r_g=0.248， 95% CI： 0.159–0.336， P=4.82×10^-3） and HDL （r_g=0.294， 95% CI： 0.237–0.351， P=5.87×10^-4） revealed significant positive genetic correlation between arrhythmia and OCD. LAVA identified 23 significantly local correlated regions in the genome （P<2.0×10^-5）. MTAG discovered 11 genome-wide significant pleiotropic SNPs， among which rs12754189 （intron of KCNN3） had potential functional harmfulness （CADD>12.37）. SMR and TWAS jointly identified 20 shared genes， enriched in neural-cardiovascular tissues such as the cerebral cortex， amygdala， and left ventricle， and involved in DNA damage response， RNA metabolism， transcriptional regulation， and FAS signaling pathway （FDR<0.05）. ConclusionArrhythmia and OCD share a common genetic basis. The co-morbidity mechanism may involve the common vulnerability of neurons and cardiac muscle cells in terms of gene expression regulation and stress response， supporting the role of the brain-heart axis in the pathophysiology of both conditions.

Objective　To analyze the clinical characteristics and prognostic factors for clinical cure in chronic hepatitis B virus (HBV) infected patients with pegylated interferon-α-2b (PEG-IFN-α-2b) based therapy. Methods　This is a retrospective study. Chronic HBV infected patients receiving PEG-IFN-α-2b therapy were enrolled in Yuncheng Central Hospital affiliated to Shanxi Medical University between August 2020 and November 2023. Treatment-naïve patients received PEG-IFN-α-2b monotherapy, while nucleoside (acid) analogs (NAs)-experienced patients received PEG-IFN-α-2b add-on therapy. The study endpoint was hepatitis B surface antigen (HBsAg) negative in accompany with HBV DNA below the detection limit (course of treatment < 48 weeks) or treatment for 48 weeks. The general characteristics, virological variables, blood routine test, and liver function of patients were collected at baseline and study endpoint. Student’s t test or Mann-Whitney U test was used for comparison. The prognostic factors of clinical cure were examined using univariate and multivariate stepwise logistic regression models. Results　A total of 61 chronic HBV infected patients were enrolled, including 39 males and 22 females. The age were (39.13±7.53) years. Twenty-one cases were treatment-naïve, while 40 patients were NAs-experienced. Nineteen cases were positive for HBV DNA at baseline. The baseline HBsAg levels were 211.30(50.93, 2 110.00) IU/mL. Thirty-four patients achieved clinical cure at the study endpoint with 25.50 weeks of median course of PEG-IFN-α-2b treatment. Twenty-seven patients did not achieve clinical cure at the study endpoint, and the course of treatment was 48 weeks. Clinical cure group had significant lower baseline HBsAg level when compared with non-clinical cure group [78.66(19.54, 204.60) IU/mL vs 2 078.00(442.20, 4 237.00) IU/mL, P<0.001]. At the study endpoint, the white blood cell, platelet, red blood cell, hemoglobin levels were lower than those in baseline (P<0.05), while alanine aminotransferase and asparatate aminotransferase levels were higher than those in baseline (P<0.05). There were no remarkable differences in blood routine tests or liver function between clinical cure and non-clinical cure group at either baseline or study endpoint (P>0.05). Baseline low HBsAg level was a predictor for clinical cure in patients receiving PEG-IFN-α-2b therapy (OR=0.998, 95%CI: 0.998-0.999). No severe adverse events were happened during therapy. Conclusion　PEG-IFN-α-2b-based therapy was well-tolerant, and could achieve high rate of clinical cure in chronic HBV-infected patients who had low baseline HBsAg level.

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

To explore the clinical efficacy of the modified segmented peroral endoscopic myotomy (POEM) for the treatment of achalasia (AC), AC patients admitted to the Jianhu People's Hospital from December 2019 to December 2021 were included in a retrospective cohort study. Patients received segmented POEM were included in the segmented POEM group, while patients treated with progressive POEM were included in the progressive POEM group. Perioperative indicators (including Eckardt scores preoperatively and at 6 months postoperatively), clinical efficacy, and complications were compared between the two groups. A total of 65 AC patients were included, among them, 28 patients were in the segmented POEM group, and 37 patients in the progressive POEM group. There were no significant differences in the general information of the two groups, including gender, age, lesion type, or Eckardt scores before the operation ( P>0.05). There were significant differences in the incidence of postoperative complications, including subcutaneous emphysema [3.6% (1/28) VS 24.3% (9/37), P=0.035] and small pleural effusion [7.1% (2/28) VS 27.0% (10/37), χ2=4.186, P=0.041] between the two groups. Postoperative chest pain duration (36.5±10.5 hours VS 44.3±11.8 hours, t=2.765, P=0.008), severity (4.1±2.1 VS 6.2±2.3, t=3.783, P<0.001), and fever days (2.1±1.3 days VS 3.1±1.5 days, t=2.816, P=0.007) also showed statistical difference. However, there was no significant difference in the incidence of postoperative pneumothorax between the two groups [0.0% (0/28) VS 2.7% (1/37), P=1.000]. At the 6-month follow-up, the segmented POEM group had a lower incidence of retrosternal pain and gastroesophageal reflux compared to the progressive POEM group ( P<0.05), and the Eckardt score was significantly improved (2.2±1.1 VS 2.9±1.3, t=2.294, P=0.025). Both segmented and progressive POEM are effective treatments for AC, but segmented POEM has higher safety, lower incidence of postoperative chest pain and gastroesophageal reflux complications, and better clinical efficacy.