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 compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

AIM: To design and construct recombinant epitope nucleotides vaccine of glycoprotein B(gB)and glycoprotein D(gD)of herpes simplex virus type 1(HSV-1), and to investigate its immunoprotective effects and tissue expression in animal models.METHODS: The HSV-1 gB and gD epitope genes were selected and tandem assembled to construct the recombinant protein-coding gene X, which was transducted into the prokaryotic expression vector pET28(a). The recombinant protein was synthesized and utilized to generate monoclonal antibodies, which were subsequently used to immunize New Zealand white rabbits. The immunogenicity of the purified protein and the presence of polyclonal antibodies in the serum were tested through separating serum from cardiac blood, and the serum antibody titers were determined. The pcDNA3.1-X was successfully constructed as a eukaryotic expression vector and immunized the female BALB/c mice aged 4 to 6 wk via intramuscular injection. Serum antibodies and immune-related cytokines were quantified using enzyme-linked immunosorbent assay(ELISA). The expression of the X protein in the ocular, trigeminal ganglion, and brain tissues of the mice was assessed.RESULTS: The target polyclonal antibody was identified with a serum antibody titer of 1:3200 in the rabbit serum after immunized by recombinant protein X. Upon immunizing mice with the eukaryotic recombinant plasmid pcDNA3.1-X, the concentration of HSV-1 serum IgM antibodies of the experimental group was 12.13±0.85 ng/L, which was significantly higher than that of the vector control group(0.49±0.44 ng/L; t=21.07, P<0.001). The concentrations of cytokines interleukin IL-2, IL-4, IL-10, and IFN-γ in the experimental group were 11.63±0.60, 22.65±1.47, 85.75±14.12, and 114.90±6.39 ng/L, respectively, all of which were significantly higher than those in the vector control group and the blank control group(all P<0.05). Immunohistochemical staining revealed the presence of target protein X in the eyeball, trigeminal ganglion, and brain tissue.CONCLUSION: The HSV-1 gB and gD tandem epitope nucleotides vaccine pcDNA3.1-X was successfully constructed, which activates a remarkable immune response and is stably expressed in the eyeball, trigeminal ganglion, and brain tissue. This study provides a foundation for further research of an HSV-1 recombinant antigen epitope tandem vaccine.

Cataract surgery is one of the most common ophthalmologic procedures. Advances in technology and medical policies have made it more precise. Residual refractive errors and deviation of target diopters are a main cause of dissatisfaction among patients. Refractive enhancement after cataract surgery can correct or eliminate these errors, improving patients' visual quality of life. There are multiple options for correcting residual refractive errors. The best approach depends on factors like the cause of the error, degrees of residual refractive errors, type of intraocular lens, ocular comorbidities, and patient preference. This paper summarizes the incidence and types of residual refractive errors, advancements in refractive enhancement surgeries, and provides practical solutions for clinical practice.

Venous malformation is a common congenital, non-tumor vascular malformation, accounting for about 60% of all vascular malformations, of which 40% occur in the head and neck. Due to the complex anatomical structure of the oral and maxillofacial region and the diverse classification of venous malformations, their clinical treatment poses certain difficulties and challenges. This article systematically elaborates on the etiology, clinical manifestations, imaging features, and clinical treatment strategies of venous malformations in the oral and maxillofacial region. Molecular genetic studies have shown that the occurrence and development of venous malformations are closely related to abnormal activation of the ANGPT/TIE2/PI3K/AKT/mTOR signaling pathway; its clinical manifestations are gradually growing blue purple masses and its histological features are tortuous venous ducts; and clinical imaging examinations have high specificity, among which digital subtraction angiography classification has important clinical guidance value for the treatment of venous malformation sclerosis. According to different classifications, strategies, such as sclerosis treatment, surgical treatment, and laser treatment, can be applied separately or in combination. This article also explores the advantages and disadvantages of targeted therapy in the treatment of venous malformations, with a focus on improving clinical outcomes while reducing complications. At the same time, through the analysis of typical clinical cases, it summarizes the key points of diagnosis and treatment and treatment plans, in order to provide a reference for improving the clinical efficacy of venous malformation treatment and reducing treatment complications.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

ObjectiveTo explore the exposure-lag-response relationship between temperature and risk of varicella incidence，and to provide a scientific evidence for early warning and precise prevention and control of varicella epidemic. MethodsDaily varicella cases and daily meteorological data were collected in Minhang District， Shanghai from 2010 to 2022. A distributed lag nonlinear model was used to determine the exposure-lag-response relationship between temperature and risk of varicella incidence. Furthermore， effect of temperature on the incidence risk was determined across different age groups. ResultsIn 2010‒2022， the total number of notified varicella cases was 26 207 in Minhang District， with the highest incidence in the group aged 3‒14 years （50.35%）. The seasonal pattern of daily varicella cases showed a double peak. The large peak was found in November and December， followed by a smaller peak in May and June. Moreover， the distributed lag nonlinear model showed a unimodal curve in the relationship between temperature and varicella incidence. The RR value reached its maximum peak of 1.90 （95%CI： 1.25‒2.87） at 7 ℃. A reverse U-shape was found in the lag-response curves between temperature and varicella incidence. Furthermore， the effect of temperature on the varicella incidence showed a unimodal pattern in the varicella cases aged 3‒14 years. The RR value reached its peak at 11 ℃ （RR=2.89， 95%CI： 1.33‒6.24）. In contrast， the effect of temperature on the varicella incidence in the cases aged 15 years and above showed a unimodal pattern， with RR value reaching the peak at 5 ℃ （RR=2.14， 95%CI： 1.33‒3.44）. ConclusionThe unimodal curve is found in the relationship between temperature and varicella incidence. Low temperature is associated with increased risk of varicella incidence. Children aged 3‒14 years are more susceptible to the effect of temperature on the varicella incidence.

Objective To investigate the safety and efficacy of mitral valve replacement combined with cryoablation Maze surgery in patients with atrial functional mitral regurgitation (AFMR). Methods From January 2014 to June 2020, patients with AFMR who underwent mitral valve replacement in our department were enrolled. They were divided into two groups, a cryoablation Maze group who received cryoablation Maze surgery during mitral valve replacement, and a non-cryoablation Maze group who did not receive cryoablation Maze surgery. The baseline data, surgical data, efficacy, and prognosis between the two groups were compared. Results Finally 85 patients were enrolled. There were 16 males and 24 females with an average age of 58.65±6.86 years in the cryoablation Maze group, and 24 males and 21 females with an average age of 61.29±8.30 years in the non-cryoablation Maze group. There was no statistical difference in baseline data between the two groups (P＞0.05). The aortic occlusion time and extracorporeal circulation time of the cryoablation Maze group were longer than those of the non-cryoablation Maze group with statistical differences (P＜0.01). There was no statistical difference in postoperative ICU retention time, ventilator assistance time, length of hospital stay, intraoperative blood loss, drainage volume on the first day or occurrence rate of complications (temporary pacemaker application, electrical cardioversion, thoracic puncture drainage, hospitalization death) between the two groups (P＞0.05). At the time of discharge, postoperative 3-month, 6-month, 12-month, and 24-month, the maintenance rates of sinus rhythm in the non-cryoablation Maze group were statistically different from those of the cryoablation Maze group (P＜0.001). Compared with the non-cryoablation Maze group, the decrease values of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and pulmonary artery systolic pressure were statistically different (P＜0.05). Postoperative cardiac function grading of both groups was grade Ⅰ or Ⅱ, which was significantly improved compared with preoperative level, but there was no statistical significance between the two groups (P＞0.05). There was no statistical difference in the incidence of adverse events during follow-up (P＞0.05). Conclusion Cryoablation Maze surgery combined with mitral valve replacement is safe and effective in the treatment of AFMR patients, which is conducive to the recovery and maintenance of sinus rhythm, and is beneficial to the remodeling of the left atrium and left ventricle, the reduction of pulmonary systolic blood pressure, and the improvement of life quality of the patients.