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.

In recent years, the incidence of myopia has been increasing alongside the growing global population, emerging as a significant public health challenge worldwide. Individuals with myopia exhibit an elongated axial length, which leads to various structural and functional ocular changes, resulting in the risk of related eye diseases and, in severe cases, blindness. Unfortunately, once myopia develops, it is irreversible. The only way to prevent or slow its progression is through appropriate treatment. The current focal point in myopia prevention and control is the peripheral myopic defocus theory. This paper summarizes the relevant research on defocus incorporated multiple segments(DIMS)lenses, following a systematic analysis of the literature. It analyzes the advantages and disadvantages of DIMS compared to other myopia control methods, and discusses the application prospects and future directions of defocus lenses represented by DIMS, aiming to provide reference and guidance for the control of myopia progression in children and adolescents.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

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*

Objective: The purpose of this study was to investigate the different categories of males within two groups, namely a community male sample who engaged in online sexual activities (OSAs) and a subclinical male sample who were out of control in viewing pornography and had sought help. Additionally, the study aimed to determine the threshold for excessive OSAs in both samples. Methods: A total of 568 community adult males who engaged in OSAs and 567 adult males seeking help for pornography use were recruited online. A latent profile analysis (LPA) was used to identify potential profiles within the samples. Cut-point analyses were conducted to determine optimal cutoff scores for OSAs in each sample. Results: The LPA revealed two categories with different cutoff scores for OSAs within each sample. Excessive OSA can be a screening tool for detecting out-of-control behavior. More stringent criteria for identifying excessive OSAs can aid in distinguishing problematic pornography use (PPU) from impaired control in viewing sexually-explicit materials (SEMs). Two subcategories of loss of control emerged: high OSAs frequency impaired control and high viewing SEMs impaired control. Conclusion The threholds of excessive OSAs varies among community and sub-clinical male samples; this knowledge can assist in screening out individuals with impaired control and selecting individuals with PPU from the subclinical sample.

Objective To explore the correlation between the change of the serum levels of thyroid hormone and the severity of anxiety symptoms in patients with generalized anxiety disorder after treatment with paroxetine hydrochloride.Methods 76 patients with generalized anxiety disorder treated in the Third People's Hospital of Huzhou from January to August 2023 were collected as study group,and they were divided into mild group(n=23),moderate group(n=30),and severe group(n=23),according to degree of anxiety by Hamilton anxiety scale(HAMA),69 healthy examination subjects in the same period were selected as control group.Patients in study group were treated with paroxetine hydrochloride tablets for 8 weeks,patients were evaluated anxiety symptoms,the serum levels of thyroid hormone were measured at baseline and 8 weekend,including triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),antithyroglobulin antibody(TG),anti-thyroid peroxidase antibody(TPO).Results After 8 weeks of paroxetine hydrochloride treatment,the significant efficacy rates of mild group,moderate group,and severe group were 73.9％,76.7％,and 73.9％,with no statistically significant difference in efficacy among three groups(x2=0.073,P＞0.05).In the baseline period,FT4 levels of patients in moderate group and severe group were significantly higher than those in mild group and control group,and the difference was statistically significant(P＜0.05).The severity of anxiety symptoms in the baseline period of patients in moderate group and severe group showed a low positive correlation and a significant positive correlation with FT4 levels(r=0.382、0.610,P＜0.05).After 8 weeks treatment,the FT4 levels of patients in moderate group and severe group decreased significantly compared to the baseline period,and the difference was statistically significant(t=2.847,3.042,P＜0.05).The reduction rate of HAMA score in severe group was positively correlated with the change in FT4 level during the baseline period and at the end of 8 weeks of treatment(r=0.517,P＜0.05).By a binary Logistic regression analysis showed that the higher levels of FT4 in the baseline period with the worse efficacy in moderate group and severe group.Conclusion The improvement of anxiety symptoms could be affected by high baseline levels of FT4 in generalized anxiety disorder patients with moderate to severe anxiety.

Objective: The purpose of this study was to investigate the different categories of males within two groups, namely a community male sample who engaged in online sexual activities (OSAs) and a subclinical male sample who were out of control in viewing pornography and had sought help. Additionally, the study aimed to determine the threshold for excessive OSAs in both samples. Methods: A total of 568 community adult males who engaged in OSAs and 567 adult males seeking help for pornography use were recruited online. A latent profile analysis (LPA) was used to identify potential profiles within the samples. Cut-point analyses were conducted to determine optimal cutoff scores for OSAs in each sample. Results: The LPA revealed two categories with different cutoff scores for OSAs within each sample. Excessive OSA can be a screening tool for detecting out-of-control behavior. More stringent criteria for identifying excessive OSAs can aid in distinguishing problematic pornography use (PPU) from impaired control in viewing sexually-explicit materials (SEMs). Two subcategories of loss of control emerged: high OSAs frequency impaired control and high viewing SEMs impaired control. Conclusion The threholds of excessive OSAs varies among community and sub-clinical male samples; this knowledge can assist in screening out individuals with impaired control and selecting individuals with PPU from the subclinical sample.

Objective To explore the effect of the astigmatism precise positioning marker used in small incision lent-icule extraction(SMILE)to correct myopic astigmatism.Methods A total of 120 patients(120 right eyes)with myopic astigmatism between-5.00 D and-1.25 D,who underwent SMILE in our hospital from January to December 2022,were selected in this study.According to the random number table,the patients were divided into the marking group(60 eyes)and the non-marking group(60 eyes).The patients in the marking group were marked by surgeons using the astigmatism precise positioning marker developed by our department.All patients were examined before operation and at 1 day,1 week and 3 months after operation,and the data such as uncorrected visual acuity(UCVA),best corrected visual acuity(BC-VA),and computer optometry results were collected before and 3 months after operation.The vector analysis tools were used to calculate the relevant astigmatism evaluation indicators:absolute value of the difference vector(|DV|),correction index(CI),and absolute value of the angle of error(|AofE|).Higher-order aberrations,including spherical aberration,coma aberration and clover aberration,were measured by Nidek refractive analyzer.Relevant data of patients in the two groups were statistically analyzed using the SPSS 26.0 software.Results There was no significant difference in the BC-VA,spherical and cylindrical power between the two groups before operation(all P＞0.05).At 3 months after operation,the UCVA(logMAR)in the marking group was better than that in the non-marking group(P＜0.05),while the spherical and cylindrical power showed no significant difference between the two groups(both P＞0.05).There was no significant difference in|DV|and CI between the two groups at 3 months after operation(both P＞0.05).The|AofE|in the marking group was significantly lower than that in the non-marking group at 3 months after operation(P＜0.05).There was no sig-nificant difference in coma,trefoil and spherical aberrations between the two groups before operation(all P＞0.05).The coma,trefoil and spherical aberrations in the two groups significantly increased at 3 months after operation(all P＜0.05).The coma aberration in the marking group was smaller than that in the non-marking group at 3 months after operation(P＜0.05).Conclusion SMILE with the marking by the astigmatism precise positioning marker can better correct astigma-tism,optimize the coma aberration caused by SMILE,and improve the visual quality of patients.

AIM:To explore the promotion of ferroptosis by artesunate(Art)and its underlying mechanism in osteosarcoma.METHODS:Human osteosarcoma U-2 OS cells were divided into 4 groups:control,ferrostatin-1(Fer-1),Art,and Art+Fer-1 groups.Cell viability was measured by CCK-8 assay,while reactive oxygen species(ROS),Fe2+,and glutathione(GSH)levels were measured using biochemical assays.Mitochondrial morphology was evaluated by trans-mission electron microscopy.The mRNA and protein levels of p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were determined by RT-qPCR and Western blot,respectively.RESULTS:It was found that Art significantly reduced the growth of U-2 osteosarcoma cells,as well as inducing ferroptosis by promoting the accu-mulation of Fe2+and ROS and reducing GSH levels,while the ferroptosis inhibitor ferrostatin-1 inhibited ferroptosis.It was also observed that Art affected mitochondrial morphology,resulting in smaller mitochondria,higher mitochondrial mem-brane density,and reduced numbers of cristae.Treatment with Art also downregulated both the mRNA and protein expres-sion of the ferroptosis-associated genes SLC7A11 and GPX4,while upregulating expression of p53,an upstream regulator of ferroptosis,thus inducing ferroptosis.CONCLUSION:Artesunate induces ferroptosis in osteosarcoma cells through the p53/SLC7A11/GPX4 signaling pathway.