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:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Objective:To investigate clinical treatment regimens for ocular lesions in patients with severe ocular rosacea.Methods:A total of 28 patients (34 eyes) with severe rosacea complicated by blepharokeratoconjunctivitis were collected from outpatient department of the Affiliated Eye Hospital of Nanjing Medical University from December 1, 2019 to May 30, 2021. They were randomly divided into two groups: group A (13 cases, 16 eyes) topically treated with sodium hyaluronate 0.3% eye drops and levofloxacin 0.5% eye drops, and group B (15 cases, 18 eyes) topically treated with sodium hyaluronate 0.3% eye drops alone. Patients in both groups also received oral minocycline hydrochloride 100 mg every day for the first 2 weeks, and then 50 mg every day for the next 6 weeks. Meanwhile, all patients received same physical therapies such as meibomian gland massage, eyelid hot compresses and eyelid margin cleaning. LogMAR visual acuity, tear break-up time (BUT) , ocular surface disease index (OSDI) score, and meibomian gland function grading examination results in the two groups were recorded before and 8 weeks after treatment. Paired t test was used to compare within-group differences in the parameters before and after treatment, and two-independent-sample t test to compare intergroup differences after treatment. Results:After 8-week treatment, both group A and group B showed significantly increased LogMAR visual acuity ( t = 3.10, 2.15, P = 0.007, 0.046, respectively) , improved BUT ( t = 3.44, 2.85, P = 0.003, 0.011, respectively) , but significantly decreased OSDI scores ( t = 7.12, 9.33, respectively, both P < 0.001) and meibomian gland function scores ( t = 13.73, 16.82, respectively, both P < 0.001) compared with those before treatment. After treatment, no significant differences were observed in the LogMAR visual acuity ( P = 0.721) , BUT ( P = 0.189) , OSDI scores ( P = 0.808) and meibomian gland function scores ( P = 0.191) between the two groups. No adverse drug reactions occurred during the treatment. During the follow-up period (8 months or shorter) , no recurrence of ocular lesions was observed. Conclusion:Without topical antibiotics, oral minocycline hydrochloride combined with topical sodium hyaluronate eye drops is still effective for the treatment and prevention of recurrence of ocular lesions in patients with severe ocular rosacea.

Marsupialization is effective in the treatment of cystic lesions of the jaw. It is a simple operation that can result in minimal trauma, the reduction of postoperative recurrence, and maximum preservation of the surrounding tissue structure and function. However, there is a certain failure rate in clinical treatment due to the improper grasp of indications and nonstandard operation. The highest failure rate reported in the literature is 32.6%. To further standardize the clinical application of marsupialization and improve the success rate of treatment, we put forward an expert consensus of marsupialization in the treatment of jaw cystic lesions by reviewing the domestic and foreign literature and summarizing the experience in marsupialization from some famous domestic experts. In this consensus, we propose three elements of marsupialization: the establishment of the opening, the maintenance of cyst plugs and regular washing. The scope of application of marsupialization includes jaw cysts and cystic ameloblastomas. It is necessary to standardize the position of the opening, the size of the opening and the manufacture of the cyst plug, and a panoramic film or cone beam computed tomography(CBCT) should be used to observe the changes in the cystic cavity before and after operation. A second-stage operation should be performed when the lesion is significantly reduced by more than 50% or at least 5 mm from important structures; furthermore, the teeth of focus should be treated according to the relationship between the lesion and tooth and the type of tooth.

Objective To investigate the relationship between electrolyte level change with prognosis in the patients with craniocerebral injury.Methods A total of 360 patients with craniocerebral injury in this hospital during 2012-2015 were selected as the research subjects and divided into the mild craniocerebral injury group (171 cases),moderate craniocerebral injury group(104 cases)and severe craniocerebral injury group(85 cases) according to the Glasgow coma scale.The severe craniocerebral injury group was further divided into the high level blood sodium subgroup(73 cases)and stable level blood sodium subgroup(12 cases)according to the lev-el of blood sodium,meanwhile 70 persons undergoing healthy physical examination were selected as the control group.The plasma electrolyte levels(blood sodium,potassium,chloride)in each group were detected within 5 d after admission.Then the results were statistically analyzed.Results Compared with the control group,the blood sodium,potassium and chloride levels had no statistical difference between the mild and moderate craniocerebral injury groups(P>0.05).The blood sodium and chloride levels in the severe craniocerebral inju-ry group were higher than those in the mild and moderate craniocerebral injury groups,the difference was sta-tistically significant(P<0.01).The blood potassium level had no statistical difference between the mild,mod-erate and severe craniocerebral injury groups with control group(P>0.05).In the severe craniocerebral injury group,there were 58 cases(79.45%)of death in the high level blood sodium subgroup and 4 cases(33.33%) of death in the stable level blood sodium subgroup,the difference was statistically significant(P<0.01).Con-clusion Clinically monitoring the blood sodium level change in the patients with craniocerebral injury,espe-cially severe craniocerebral injury,is conducive to the disease recovery.

Objective To study the effects of tonifying kidney therapy on pathology in chronic hepatitis B virus carriers.MethodsWith the multi-center, randomized, double-blinded and placebo-controlled methods, 600 cases of chronic hepatitis B virus carriers were divided intoBushen Qingtou group,Bushen Jianpi group and control group, 200 cases in each group, and were treated withBushen Qingtou prescription,Bushen Jianpi prescription and placebo prescription respectively for 52 weeks. The pathological changes of the liver biopsy were observed by liver biopsy examination before and after treatment. Inflammatory active degree and fibrosis were scored with Knodell HAI and Ishak.Results The number of decreasing more than 2 points on Knodell HAI inBushen Qingtou group,Bushen Jianpi group and control group was 21, 18, and 6 respectively (P<0.05); the number of increasing more than 2 points on Knodell HAI in three groups was 3, 2, and 8 respectively (P<0.05). The curative effect ofBushen Qingtou prescription,Bushen Jianpi prescription were significantly obviously better than control group, without statistical significnce between the two treatment groups (P>0.05). The number of decreasing more than 1 points on Ishak in Bushen Qingtou group,Bushen Jianpi group, and control group was 13, 12, and 9 respectively (P>0.05); the number of increasing more than 1 points on Ishak inBushen Qingtou group,Bushen Jianpi group and control group was 8, 3, and 11 respectively, with statistical significance betweenBushen Jianpi group and controlled group (P<0.01), without statistical significance betweenBushen Qingtou group and control group (P>0.05), which meantBushenJianpi prescription could prevent the deterioration of liver tissue fibrosis more significantly than placebo prescription did. ConclusionTonifying kidney therapy, includingBushen Qingtou prescription andBushen Jianpi prescription, can inhibit the inflammatory activity and slow down the fibrosis progression of the chronic HBV carriers.