BACKGROUND:Extracellular vesicles are secreted into the extracellular milieu by a wide range of cell types,including tumor cells,under different physiological and pathophysiological conditions,where a wide range of biological signals and cell-to-cell signaling exists.Tumor-derived extracellular vesicles may exacerbate cancer progression,survival,invasion,and promote angiogenesis. OBJECTIVE:To review the research progress of extracellular vesicles in the diagnosis and treatment of oral squamous cell carcinoma. METHODS:Literature search was performed by the first author in PubMed,WanFang,CNKI and other databases with the keywords"EVs,oral squamous cell carcinoma,diagnosis and treatment,biopsy,tissue engineering"in Chinese and English.Finally,63 articles were included for analysis. RESULTS AND CONCLUSION:(1)In oral squamous carcinoma saliva biopsies,extracellular vesicles play a crucial role in the progression of oral squamous cell carcinoma by acting as an information transfer tool between tumor cells and the surrounding microenvironment,carrying a wide range of biomolecules including soluble proteins,lipids,DNA,and RNA.These tiny vesicles not only play a key role in tumor growth and spread,but also provide important information about the biological properties of the tumor.(2)Saliva biopsy,as a non-invasive diagnostic method,can open up new possibilities for early diagnosis and targeted treatment of oral squamous cell carcinoma by analyzing the extracellular vesicles therein.(3)It has been found that bioactive molecules,such as microRNAs(miRNAs)and specific proteins,contained within extracellular vesicles can serve as biomarkers for oral squamous carcinoma and improve the accuracy of early diagnosis.Specific proteins in extracellular vesicles such as EHD2,CAVIN1,PF4V1,and CXCL7 show potential as novel predictive biomarkers.(4)In addition,this paper highlights the potential application of extracellular vesicles in the treatment of oral squamous carcinoma.Through engineering modifications,extracellular vesicles can serve as a new generation of nanoscale drug delivery systems to enhance the efficiency and specificity of targeted tumor therapy.(5)Future studies will further explore the effect and mechanism of extracellular vesicles in oral squamous cell carcinoma,which is expected to improve patients'survival and quality of life.

BACKGROUND:With the development and progress in the field of stomatology,oral implant technology has gradually become the mainstream alternative to traditional dentures.In recent years,the maturity of various bone increment techniques and the continuous development of the oral digital field have expanded the indications of dental implantation,and the success rate of implantation surgery is also increasing.However,it has become a difficult problem for some clinicians to use cone-beam computed tomography(CBCT)to accurately measure the residual alveolar ridge bone mass before implantation and to make a suitable implantation plan. OBJECTIVE:To measure the residual alveolar ridge bone mass in the proposed implant area of the mandibular first molar using the CBCT. METHODS:In a retrospective study design,the CBCT images of 205 patients with mandibular first molar loss were included to measure the height and width of the residual alveolar ridge in the proposed implant area of the mandibular first molar.The residual alveolar ridges were divided into four categories:Ⅰ,Ⅱ,Ⅲ and Ⅳ(Class Ⅱ,Ⅲ,and Ⅳ residual alveolar ridge defined as insufficient bone).Statistical analyses were conducted in terms of frequency distribution of residual alveolar ridge height,width,and morphology of the mandibular first molar,differences in residual alveolar ridge height and alveolar ridge crest width of the mandibular first molar in patients of different sexes,correlation of the residual alveolar ridge height with the crest width and bottom width of the residual alveolar ridge,as well as correlation of age with the width and height of the residual alveolar ridge crest. RESULTS AND CONCLUSION:(1)The average height of the residual alveolar ridge in the proposed implant area of the mandibular first molar was(12.14±2.96)mm,of which 43.41％(89/205)were less than 12 mm.The average width of the residual alveolar ridge in the proposed implant area of the mandibular first molar was(6.80±1.65)mm,of which 26.34％(54/205)were less than 6 mm.(2)The height of the residual alveolar ridge of the mandibular first molar was higher in males than in females,with no significant difference(P>0.05),and the width of the residual alveolar ridge of the mandibular first molar was significantly wider in males than in females(P<0.01).(3)The height of the residual alveolar ridge was negatively correlated with the top and bottom width of the residual alveolar ridge(P<0.01).Age showed a positive correlation with the residual alveolar ridge width(P<0.05)and no significant correlation with the residual alveolar ridge height(P>0.05).(4)The residual alveolar ridge of class Ⅰ accounted for 58.05％(119/205),class Ⅱ accounted for 9.27％(19/205),class Ⅲ accounted for 20.49％(42/205),and class Ⅳ accounted for 12.19％(25/205),most of which were class Ⅲ with insufficient remaining alveolar ridge bone mass.Clinicians need to individualize and design the optimal implantation plan based on the type of residual alveolar ridge.

The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

Multiple system atrophy （MSA） is a rare degenerative disease of the nervous system and has diverse and atypical clinical manifestations， and it overlaps with other diseases in α-synuclein spectrum disease. There are great challenges in the diagnosis and early differential diagnosis of the disease， and missed diagnosis and misdiagnosis occur from time to time， thereby delaying the treatment of the disease.Videonystagmography （VNG） is currently the main noninvasive test used to assess vestibular function and can provide different eye movement parameters. Studies have shown the presence of abnormal eye movements in patients with MSA. From the perspective of vision-eye movement， this article reviews the current status of research on eye movements in patients with MSA and reveals the internal connection between them， in order to provide an important reference for the early diagnosis of MSA.
Saccades

Parkinson disease （PD） is the second most prevalent neurodegenerative disorder and predominantly impacts the extrapyramidal system. This condition arises from the degeneration of the dopaminergic nigrostriatal pathway. In recent years， studies have shown that PD pathology and lesions are not limited to the center nervous system， and that PD is a systemic and multisystem disease. The concurrence of PD with peripheral neuropathy （PN） has been increasingly acknowledged， although its pathogenesis remains elusive. The motor symptoms in PD patients often mask the symptoms of PN， leading to relatively low clinical recognition of PD coexisting with PN. This poses challenges in the clinical diagnosis and treatment of PD. This review comprehensively summarize the pathogenesis of PD coexisting with PN.
Parkinson Disease

Objective To observe the therapeutic effect of extracorporeal shock wave therapy combined withsurface electromyography biofeedback training(ESW-sEMGBF)on post-traumatic elbow joint stiffness.Methods A total of 80 patients with post-traumatic elbow stiffness admitted to the Rehabilitation Department of Hangzhou Fuyang Hospital of Orthopedics of Traditional Chinese Medicine from January 2021 to December 2021 were randomly assigned into control group(n = 40)and treatment group(n = 40)using a lottery method.The control group received conventional rehabilitation treatment(including soft tissue release,joint mobilization,continuous passive motion and cold therapy),and the treatment group received conventional treatment combined with ESW-sEMGBF.Both groups underwent training once daily for five days a week over eight weeks.The visual analogue scale(VAS),active range of motion(AROM)of the elbow joint,and Mayo Elbow Performance Score(MEPS)were evaluated before and after treatment.Results After 8 weeks of treatment,significant improvements were observed in all outcomes for both groups.The treatment group showed better improvements in VAS scores,AROM,and MEPS after treatment compared with the control group(P<0.05,P<0.001,P<0.001).No side effects or adverse reactions were observed in either group after treatment.Conclusion Extracorporeal shock wave therapy combined with surface electromyography biofeedback training effectively alleviated pain in patients with post-traumatic elbow joint stiffness,improved elbow joint function,and increased active range of motion of the elbow joint.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Objective:To explore the diagnostic efficacy of enhanced CT value in central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) with Hashimoto’s thyroiditis (HT) .Methods:The 209 central lymph nodes of 209 patients with PTC confirmed by surgery and pathology were retrospectively analyzed, and they were divided into HT group and non-HT group, including 77 lymph nodes (52 negative and 25 positive) in the HT-PTC group and 132 lymph nodes (74 negative and 58 positive) in the non-HT group. The CT values of lymph nodes were measured on enhanced CT images, and the optimal thresholds and corresponding sensitivity and specificity of enhanced CT values in the two groups were analyzed by the receiver operating characteristic curve.Results:The enhanced CT values of metastatic lymph nodes in the two groups were (103.2±21.1) Hu and (101.9±25.4) Hu, respectively ( t=0.23, P>0.05), and the enhanced CT values of benign lymph nodes were (72.0±15.8) Hu and (68.5±10.9) Hu, respectively ( t=-1.38, P>0.05). The area under the curve of enhanced CT values in the HT group and non-HT group were 0.882 and 0.918, respectively, and the optimal thresholds were 78.8 Hu and 74.7 Hu, respectively, with corresponding sensitivity of 92.0% and 91.4%, and specificity of 67.3% and 77.0%, respectively, for the diagnosis of CLNM in the two groups. Conclusion:The enhanced CT value has high and similar diagnostic efficiency for CLNM in HT group and non-HT group, providing a theoretical basis for the early clinical development of individualized treatment plans.

Objective:To investigate the effect and mechanism of Sufentanil (Suf) on oxidative stress injury in osteoporosis (OP) rats.Methods:Rats were randomly separated into normal group, OP group, low concentration Suf group, high concentration Suf group, alendronate sodium group, and high concentration Suf+AMPK inhibitor (Dorsomorphin) group, with 12 rats in each group. The normal group of rats only removed a small amount of adipose tissue around the ovaries. Except for the normal group, rats in other groups constructed OP models by removing both ovaries. After successful modeling, they were administered once a day for 12 weeks. Micro CT scanners were applied to measure bone density and trabecular structure parameters in rats, including trabecular quantity, trabecular thickness, and trabecular separation. ELISA was applied to detect levels of osteocalcin, alkaline phosphatase (ALP), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) in rat serum. HE staining was applied to detect pathological changes in femoral tissue. Reagent kit was applied to detect levels of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) in femoral tissue. Western blot analysis of phosphorylated adenylate activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), silence-information regulatory factor2-associated enzyme 1 (SIRT1) proteins in femur tissue.Results:Compared with the normal group, the bone trabecular structure of rats in the OP group was thin and scattered, with fewer bone trabeculae and widened trabecular gaps, mainly in the form of rods, the bone density, number of trabeculae, thickness of trabeculae, levels of ALP, osteocalcin, OPG in serum, the level of SOD, and p-AMPK, PGC-1α, and SIRT1 proteins in femoral tissue decreased ( q=38.00, 67.81, 47.91, 48.32, 28.42, 21.23, 52.22, 30.86, 24.11, 24.55, P all<0.001), the bone trabecular separation, level of RANKL in serum, and the levels of MDA and ROS in femoral tissue increased ( q=42.00, 37.97, 50.56, 72.01, P all<0.001). Compared with the OP group, the number of bone trabeculae in rats in the low concentration Suf group, high concentration Suf group, and alendronate sodium group increased, the gap decreased, and the bone trabecular structure gradually recovered to a plate-like shape, the bone density, number of trabeculae, thickness of trabeculae, levels of ALP, osteocalcin, OPG in serum, the level of SOD, and p-AMPK, PGC-1α, and SIRT1 proteins in femoral tissue increased ( F=214.40, 889.60, 396.10, 480.30, 168.60, 38.09, 367.80, 187.70, 91.17, 101.00, P all<0.001), the bone trabecular separation, level of RANKL in serum, and the levels of MDA and ROS in femoral tissue decreased ( F=174.10, 173.40, 298.90, 607.10, P all<0.001). Dorsomorphin reversed the improvement effect of high concentration of Suf on oxidative stress injury in OP rats. Conclusion:The inhibitory effect of Suf on oxidative stress injury in OP rats may be related to the activation of the AMPK/SIRT1/PGC-1α signaling pathway.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.