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.

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.

Objective:To observe the clinical effect of free perforator flap of deep medial plantar artery and with sensory nerve in reconstruction of soft tissue defect in heel.Methods:From May 2022 to June 2023, a total of 15 patients with soft tissue defect of heels that caused by various reasons were admitted to the Department of Orthopedics, Zhengzhou Orthopaedic Hospital. The patients were 6 males and 9 females aged 21 to 45 years old, at 32 years old in average. The size of defects was 5 cm×8 cm-10 cm×14 cm. Free perforator flaps of deep medial plantar artery with cutaneous medial plantar nerve were used, at 5 cm×8 cm-11 cm×14 cm in size. Cover the first phase of VSD dressing in the supply site, remove it after 1 week, fill the wound with granulation tissue, and then perform full-thickness skin graft.Results:All 15 flaps survived after surgery. Postoperative outpatient follow-up lasted for 8 to 15 (average 12)months. Appearance and texture of the reconstructed heels were satisfactory, the affected feet were able to bear normal weight without obvious tenderness or ulcer formation. The reconstructed heals were resistant to wear and cold with good sensation. TPD of the flaps achieved 5 mm to 7 mm, without sense of heterotopia after rehabilitation. There was no obvious pigmentation or cicatricial contracture.Conclusion:It is satisfactory to apply a free perforator flap of deep medial plantar artery with sensory nerve in reconstruction of soft tissue defect of heel.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.
Activities of Daily Living ; Alzheimer Disease/genetics* ; Humans ; Mutation ; Neurodegenerative Diseases ; Presenilin-1/genetics* ; Presenilin-2/genetics*

Objective:To evaluate the performance and the accuracy of surgical robot for mandibular reconstruction based on intelligent surgical planning.Methods:115 CT scanning images of normal mandible (57 males, 48 females, 40.3±9.1 years old, from February 2010 to May 2019) and 115 CT scanning images of mandible with tumor (62 males, 53 females, 55.6±7.2 years old, from March 2008 to August 2019) from Shanghai Ninth People’s Hospital were selected. The surgical robot system including work station, UR robot, optical navigation system, 6 dimensional force senor and surgical instrument. A 3D V-Net for mandible preoperational segmentation from CT scans was proposed and used to segment the mandible of a 54-year-old male patient who received mandible reconstruction with fibular flaps. The machine learning algorithm was used to aid surgical planning for maxillo-mandibular defect by detecting landmarks. The accuracy was defined as the distance between corresponding landmarks on the intact mandible. The robot could locate the target according to surgical planning and perform fibula osteotomy through force-motion control. The CT scanning of limb and head from the patient (male, 54 years old) was used for phantom experiments. 30 osteotomies on 5 3D-priented resin phantom were carried out. The pre- and post-operative images were compared to calculate the accuracy. The descriptive results were in the format of Mean±SD.Results:The average accuracy of V-Net for mandible segmentation was 96.581% and the time cost was less than 30 seconds. The average error of feature points on mandible was (2.24±1.74) mm. The residual length error was (1.02±0.45) mm and angle error was (0.96±0.42) degree in robotic-assisted osteotomy according to 3 cases of phantom experiments. The surgical robot could perform osteotomy safely and steadily within 15 min.Conclusions:Intelligent surgical planning can precisely segment the mandible and determine its landmarks. Robot for mandibular reconstruction can perform fibular osteotomy precisely with the pre-operative planning.

Objective:To evaluate the performance and the accuracy of surgical robot for mandibular reconstruction based on intelligent surgical planning.Methods:115 CT scanning images of normal mandible (57 males, 48 females, 40.3±9.1 years old, from February 2010 to May 2019) and 115 CT scanning images of mandible with tumor (62 males, 53 females, 55.6±7.2 years old, from March 2008 to August 2019) from Shanghai Ninth People’s Hospital were selected. The surgical robot system including work station, UR robot, optical navigation system, 6 dimensional force senor and surgical instrument. A 3D V-Net for mandible preoperational segmentation from CT scans was proposed and used to segment the mandible of a 54-year-old male patient who received mandible reconstruction with fibular flaps. The machine learning algorithm was used to aid surgical planning for maxillo-mandibular defect by detecting landmarks. The accuracy was defined as the distance between corresponding landmarks on the intact mandible. The robot could locate the target according to surgical planning and perform fibula osteotomy through force-motion control. The CT scanning of limb and head from the patient (male, 54 years old) was used for phantom experiments. 30 osteotomies on 5 3D-priented resin phantom were carried out. The pre- and post-operative images were compared to calculate the accuracy. The descriptive results were in the format of Mean±SD.Results:The average accuracy of V-Net for mandible segmentation was 96.581% and the time cost was less than 30 seconds. The average error of feature points on mandible was (2.24±1.74) mm. The residual length error was (1.02±0.45) mm and angle error was (0.96±0.42) degree in robotic-assisted osteotomy according to 3 cases of phantom experiments. The surgical robot could perform osteotomy safely and steadily within 15 min.Conclusions:Intelligent surgical planning can precisely segment the mandible and determine its landmarks. Robot for mandibular reconstruction can perform fibular osteotomy precisely with the pre-operative planning.

To explore the clinical effect of microsurgery in the treatment of the tumor which was diagnosed with the plexiform neurofibroma (PN) of the forearm and palm. Methods From January, 2014 to June, 2017, 6 cases of the PN in the forearm and palm were removed by microsurgery such as neurovascular transplantation, separation and anastomosis under microscope, etc. There were 4 males and 2 females, with an average age of 9.2 (range, 2-18 )years. There was 1 case with PN of the median nerve, ulnar nerve and their branches in the right fore-arm and palm, 2 cases with PN of the median nerve and its branches in the right forearm and palm, 2 cases with PN of the median nerve and its branches in the left forearm and palm, and 1 case with PN of the ulnar nerve and its branches in the left forearm and palm.The postoperative function and feeling of the patients were evaluated by outpa-tient followed-up. Results The pathological results of 6 patients all showed PN, and their incisions healed primari-ly.The patients were followed-up for 6 to 36 months, with an average of 18 months. No obvious scar formation was observed in all incisions. Among them, PN of the palmar of the youngest patient recurred after the operation, and it was resected in a second operation.The remaining 5 patients had no recurrence during follow-up.The 2 point resolu-tion of each fingertip of the affected limb of the patients who had median and ulnar PN was 2-5 mm, with an average of 3.30 mm; the 2 point resolution of the thumb, indicator, middle and ring fingers of the affected limbs of the patients who had median PN was 2-5 mm, with an average of 2.95 mm; the 2 point resolution of the ring and little fingers of the affected limbs of the patients who had ulnar PN was 3-4 mm, with an average of 3.50 mm.According to the related evalu-ation criteria made by the American Orthopedic Foot and Ankle Surgery Society (AOFAS), the results of the forearm and hand functions were excellent in 5 cases, good in 1 case. Conclusion The application of microsurgical techniques in the treatment of PN in the forearm and palm can be effective separation of tumor and nerve fibers, effectively protect the branches of the median nerve and ulnar nerve and their blood circulation, prevent recurrence and reduce nerve damage after operation.

Objective:To investigate the potential prognostic value of cyclin D1 expression in patients with locally advanced oral squamous cell carcinoma (OSCC) and its relationship with taxol (Docetaxel)/cisplatin plus 5-fluorouracil (TPF) induction chemothera-py. Methods:A total of 256 patients with locally advanced OSCC were selected from Shanghai Ninth People's Hospital of Shanghai Ji-ao Tong University School of Medicine between March 2008 and December 2010 as the objects of study in this prospective randomized clinical trial. The effect of TPF induction chemotherapy was investigated. Immunohistochemical staining against cyclin D1 was per-formed in the pretreatment biopsy specimen of the patients. The relationship between cyclin D1 expression and prognostic data of the TPF induction arm and control arm was analyzed. Results:Cyclin D1 expression was detected in 232 out of the 256 patients. Patients with low cyclin D1 expression showed significantly better overall survival (OS) (P=0.001), disease-free survival (DFS) (P=0.003), lo-coregional recurrence-free survival (LRFS) (P=0.004), and distant metastasis-free survival (DMFS) (P=0.001) than those with high cy-clin D1 expression. No significant differences existed in OS, DFS, LRFS, or DMFS between the patients with TPF induction chemother-apy and the control. Cyclin D1 expression levels were not predictive of the benefit from TPF induction chemotherapy in the overall pop-ulation. However, patients with nodal stage cN2 and high cyclin D1 expression, who were undergoing TPF chemotherapeutic regimen, showed significantly higher OS (P=0.024) and DMFS (P=0.024) than cN2 patients with high cyclin D1 expression but undergoing stan-dard surgical treatment. Conclusion:Cyclin D1 can be used as a prognostic biomarker for patients with locally advanced OSCC. Fur-thermore, cN2 OSCC patients with high cyclin D1 expression can receive long-term benefit from the addition of TPF induction chemo-therapy to standard surgical treatment.

Objective:To review our patients who underwent cranio-maxillofacial resection in the recent 10 years and explore the indication of the operation. Methods:From 2003 to 2013, 116 patients underwent cranio-maxillofacial resection in our department for the treatment of tumors involving the skull base. Tumors that involved the skull base were divided into 3 types according to skull base invasions shown in the coronal planes of CT and MRI scans. Type 1 tumor was adjacent to the skull base with free bone (n=45), type 2 tumor involved the skull base with intact dura (n=30), and type 3 tumor involved dura with free brain (n=41). All patients underwent cranio-maxillofacial resection by oral and maxillofacial surgeons and neurosurgeons. The defects after cranio-maxillofacial resection were reconstructed immediately with adjacent local or regional flaps (n=62) and free vascularized flap (n=54) according to different de-fects, respectively. Results:Cranio-maxillofacial resection was successfully performed in all patients. No intraoperative complication was found. The overall success rate of soft tissue flaps and free flaps was 98.3%and 96.4%, respectively. Three patients with intracrani-al infection (n=2) and bleeding in the internal carotid artery were dead postoperatively even though they underwent salvage surgery. The overall rate of complications was 14.7%, and the dead rate was 2.6%. Recurrence or distant metastasis was found in 36 patients dur-ing the follow-up period. Conclusion: For the indication of cranio-maxillofacial resection, the balance between tumor resection and postoperative function, survival rate, and quality of life should always be considered. This technique includes the balance between func-tion and form, survival and quality of life, donor and recipient sites, and primary and secondary functions.