HSP90AA1 promotes lymphatic metastasis of hypopharyngeal squamous cell carcinoma by regulating epithelial-mesenchymal transition

Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.

Hypopharyngeal cancer trends in a high-incidence region:A retrospective tertiary single center study

BACKGROUND Hypopharyngeal cancer has the bleakest prognosis among head and neck cancers due to its extensive submucosal involvement,advanced tumor stage,and limited surgical reconstruction options.Its primary causes include alcohol consumption,tobacco use,genetic predisposition,1`diet,and socioeconomic conditions.While squamous cell carcinoma(SCC)accounts for 95%of hypopharyngeal tumors,it remains a rare form,comprising only 3%-5%of all SCC cases in the head and neck region.Globally,Central and Eastern Europe have the highest incidence rates for males(3.9 per 100000)and the third highest for females(2.26 per 100000),underscoring the significance of this seemingly uncommon condition.In Romania,hypopharyngeal cancer ranked 24th in incidence rate,with 634 new cases in 2020.AIM To study the incidence,treatment and survival rates of hypopharyngeal tumor cases in a major ear,nose,throat(ENT)surgical center.METHODS A retrospective epidemiological clinical study was conducted on patients diagnosed and treated for hypopharyngeal cancer at the ENT department of"Carol Davila Central University Emergency Military Hospital"in Bucharest between January 2018 and August 2022.The study included 53 patients and was authorized by the Ethics Committee of Titu Maiorescu Doctoral School(Bucharest,Romania)and the Ethics Committee of Carol Davila Central University Emergency Military Hospital(Bucharest,Romania).Inclusion criteria required a positive histopathological diagnosis of hypopharyngeal cancer,tumor localization in the hypopharyngeal region,and informed consent for data usage.Exclusion criteria involved major psychiatric pathologies and disagreement for data usage.Diagnosis was based on ENT assessment,imaging reports,and laboratory data.Treatment methods were determined based on various factors.Additional tools,such as Adult Comorbidity Evaluation-27 and Karnofski Performance Status Scale,were used for risk assessment and functional capacity evaluation.Quality of life aspects were measured using the European Organisation for Reasearch and Treatment of Cancer Quality of Life Questionnaire Head and Neck-35 questionnaire.RESULTS Our retrospective study examined 53 patients with hypopharyngeal cancer between January 2018 and August 2022.The majority of patients were male(94.3%),with an average age at diagnosis of 62.5 years.Among the patients,20.75%were employed,66.03%were retired,and 9.43%were unemployed.Smoking was prevalent among 69.81%of patients,while alcohol consumption was frequent in 32.07%of cases.The tumors were mostly diagnosed at an advanced stage(stage IV)and were predominantly SCC.Comorbidities were present in 83.01%of patients,with cardiovascular diseases being the most common.Dysphagia and neck mass were the most common symptoms reported.Treatment methods included surgery,radiation therapy,and chemotherapy.A favorable treatment response was observed in 22.64%of cases,while relapse occurred in 6 cases.Follow-up data was unavailable for some patients.CONCLUSION In summary,our findings align with existing literature;however,we observed a higher severity.

Lentivirus-Mediated Short Hairpin RNA for Follistatin Downregulation Suppresses Tumor Progression in Hypopharyngeal Carcinoma

Objective:Follistatin(FST)inhibits the action of activin by interfering with the binding of activin to its receptor.Although the prognostic value of FST in various cancers has been investigated previously,studies rarely focused on hypopharyngeal carcinoma(HPC).In our study,the effect of FST expression on HPC tissues and cell lines was investigated.Methods:A total of 60 patients with HPC were recruited for this study.Levels of FST mRNA and protein were measured by quantitative polymerase chain reaction(PCR)and immunohistochemistry in HPC tissue samples and by qPCR in the HPC FaDu cells,as well as immortal nasopharyngeal epithelial cell line NP-69 cells.After silencing the FST expression in FaDu cells using lentivirus-mediated siRNA that was specific for FST mRNA,cell proliferation was determined by a Celigo assay.Tumor growth was monitored in nude mice and viability was determined by a methylthiazoletetrazolium assay.The ratio of cell cycle arrest and apoptosis was evaluated by flow cytometry.The colony formation ability was performed using Giemsa staining.In addition,wound healing and Transwell migration and invasion assays were performed for the analysis of cell motility.Results:FST expression was significantly higher in human HPC tissue and FaDu cells than in normal tissue and NP-69 cells.A higher expression of FST in HPC samples was positively correlated with advanced tumors.Moreover,FST knockdown by shRNA significantly decreased cell growth,colony formation,migration and invasion.Furthermore,FST silencing increased the cell apoptosis percentage,and arrested cell cycle in the S phase in FaDu cells.In addition,FST silencing suppressed tumor growth in vivo.Conclusions:Our results indicated that the FST gene was associated with HPC progression and may serve as a potential therapeutic target for the treatment of HPC.

Surgical resection of a large hypopharyngeal hemangioma in an adult using neodymium-doped yttrium aluminum garnet laser: A case report

BACKGROUND Generally,hemangiomas do not require surgical intervention;however,cases of large hemangiomas,potentially involving the throat and trachea,necessitate surgical therapy.Here,we present a case of hypopharyngeal hemangioma in an adult that was successfully treated with neodymium-doped yttrium aluminum garnet(Nd-YAG)laser.CASE SUMMARY Laryngoscopic examination of a 61-year-old man demonstrated the presence of a large,submucosal vascular lesion that extended into the epiglottis,left arytenoid cartilage,lateral to the aryepiglottic fold,and pyriform sinus.The lesion was resected and photocoagulated with limited hemorrhage using Nd:YAG laser.The hypopharyngeal hemangioma was completely excised.The patient showed no recurrence of hypopharyngeal hemangioma during the 1.5-year follow-up period.CONCLUSION Laser therapy is one of the effective tools for treating hemangiomas with rapid,uncontrolled growth or in functional areas,with few side effects and complications.The present case of a male patient with a large hypopharyngeal hemangioma,treated with YAG laser,demonstrates the efficacy of laser photocoagulation in treating cases of hemangiomas,without the risk of bleeding or airway obstruction.The favorable postoperative outcomes demonstrated by our patient with Nd:YAG laser therapy indicate its consideration in the therapy of similar cases.

The Value of Magnetic Resonance Diffusion-Weighted Imaging in Evaluating the Efficacy of Concurrent Chemoradiotherapy in Patients with Hypopharyngeal Carcinoma

Objective: To investigate the application value of magnetic resonance diffusion-weighted imaging (DWI) combined with conventional magnetic resonance imaging (MRI) in evaluating the efficacy of concurrent chemoradiotherapy for hypopharyngeal carcinoma. Methods: A total of 20 patients with hypopharyngeal carcinoma diagnosed by pathological biopsy (who only received chemoradiotherapy without surgery) were collected. Before treatment, all patients underwent conventional MRI and DWI scanning, MRI characteristics of patients were analyzed, and maximum cross-sectional area of the tumor and average apparent diffusion coefficient (ADC) value were measured. One month after treatment, MRI was performed again to measure residual tumor area and ADC value, and the tumor remission rate was calculated. The changes in tumor ADC values before and after treatment were analyzed and their correlation with tumor remission rate was analyzed. The differences in ADC values and changes between complete response patients (CR group) and incomplete response patients (non-CR group) before and after treatment were analyzed. Results: The tumor area of 20 patients with hypopharyngeal cancer was 3.48 (0.93 - 5.6) cm2 before treatment and 0.24 (0 - 0.9) cm2 after treatment. There were 15 patients (15/20, 75%) in the CR group and 5 patients (5/20, 25.0%) in the non-CR group. The remission rate was 90.3% (6.0% - 100%). The average ADC value of the tumor before treatment was negatively correlated with the tumor remission rate after treatment (r = ?0.786, ?0.813, P Conclusion: The ADC value of tumor before treatment and the change of ADC value of tumor before and after treatment have a certain significance in evaluating the early remission rate of hypopharyngeal carcinoma after chemoradiotherapy.

Slide Pharyngo-Esophagostomy Following Ablation of Hypopharyngeal Cancer

We describe a procedure of slide pharyngo-esophagoplasty for restoration following ablation of hypopharyngeal cancer in a 99 year-old man. The elderly presented to our hospital with 2-month dysphagia, occasional bloody salivation, and 2-day respiratory distress. To solve the problems of swallowing difficulty and dyspnea, he underwent laryngopharyngectomy, permanent tracheostomy, and slide pharyngo-esophagoplasty. The patient was uneventful after the restoration procedure.

Development of a Nomogram Based on Clinicopathological and Biological Features to Predict Neck Lymph Node Metastasis in Hypopharyngeal Squamous Cell Carcinoma

Background: Clinicopathological and biological features are associated with neck lymph node metastasis (LNM) of hypopharyngeal squamous cell carcinoma (HSCC). However, there is no complete nomogram combining multiple factors that can be used to accurately predict the neck LNM status for HSCC patients. Purpose: To guide the selection of surgical methods and radiotherapy areas for hypopharyngeal cancer. In this study, a nomogram was developed to combine these risk factors to predict neck LNM and guide the treatment of HSCC. Material and Methods: This retrospective study included 117 patients (training cohort, 64 patients;trial cohort, 53 patients). Biological characteristics of HSCC patients were assessed using immunohistochemical staining, and data of patient age, gender, and preoperative computed tomography (CT) scan reports were collected. Significant risk factors in univariate analysis were further identified to be independent variables in multivariate logistic regression analysis, which were then incorporated in and presented with a nomogram by using the rms package in R software. Receiver operating characteristic (ROC) curves and calibration curves were used to validate the discrimination and accuracy in the training and validation cohorts, respectively, and clinical usefulness was verified in decision curve analysis curves. Results: All variables with P-values < 0.2 in the univariate analysis were selected for multivariate logistic regression analysis to further identify independent risk factors for neck LNM. In multivariate logistic regression analysis, variables with P-values < 0.2 were identified as independent risk factors and then used to construct the nomogram. In total, five independent predictors, including the maximum tumor diameter in CT, tumor cell differentiation, LNM status in CT, Stathmin1 expression level, and lymphatic vessel invasion were included in the nomogram. The area under the ROC curve (AUC) was 0.916 (95% confidence interval [CI], 0.833 - 1.000) and AUC of 0.928 (95% CI, 0.864 - 1.000) in internal validation and the external validation. Conclusions: Both the internal validation in the training cohort and the external validation in the validation cohort showed that the nomogram had good discrimination, accuracy, and excellent clinical usefulness. The nomogram based on clinicopathological and biological features developed in this study has strong predictive power and could be used to predict neck LNM of HSCC in clinical practice.

Preservation of laryngeal function in treatment of hypopharyngeal carcinoma

OBJECTIVE: To study the surgical technique and results of laryngeal function preservation in treatment of hypopharyngeal carcinoma. METHODS: A retrospective review of 305 patients with malignant neoplasms of the hypopharynx (279 males, 26 females, age ranging from 14 to 77 years) was performed from 1978 to 1996. In the 305 patients (stage I, n = 6; stage II, n = 12; stage III, n = 82; stage IV, n = 205), the sites of origin were pyriform sinus (n = 234), postcricoid (n = 21), posterior pharyngeal wall (n = 35) and superior hypopharynx (n = 15). Of the 305 patients, 206 (67.54%, stage I, n = 6; stage II, n = 12; stage III, n = 65; stage IV, n = 123) were surgically treated with laryngeal function preserved and 99 (32.46%, stage III, n = 17; stage IV, n = 82) had no laryngeal function preserved.All had 55-75 Gy radiotherapy according to their need. RESULTS: A total of 206 patients (67.54%) were surgically treated with laryngeal function preserved, totally (voice, respiration and deglutition) in 139 (67.5%) and partially (voice and deglutition) in 67 (32.5%). 99 patients (32.46%) had no laryngeal function preserved. The overall 5-year survival rate of the 305 patients was 44.8%, which segregated to 83% (stage I), 71% (stage II), 58% (stage III), and 36% (stage IV). The 5-year survival of the laryngeal function preserved group was 48% (n = 66), the rate of complications 28% (n = 58) and the rate of residual tumor 5.8% (n = 12), compared with the no laryngeal function preserved group 37% (n = 20), 31.3% (n = 31), and 6% (n = 6) (P > 0.05). CONCLUSION: Only a small proportion of patients (31/305, 10%) with hypopharyngeal carcinoma who require total laryngectomy and preservation of the laryngeal function is feasible for eradication of tumor and preservation of laryngeal function.

Laryngeal and hypopharyngeal carcinoma: comparison of helical CT multiplanar reformation, three-dimensional reconstruction and virtual laryngoscopy

OBJECTIVE: To evaluate the clinical application of helical CT multiplanar reformation (MPR) three-dimensional reconstruction (3D) and virtual laryngoscopy (CTVL) in laryngeal and hypopharyngeal carcinoma. METHODS: Axial helical CT scans were performed in 22 patients with laryngeal or hypopharyngeal carcinoma, along with MPR, 3D and CTVL. These results were compared with the findings of fiber optic laryngoscopy and surgery. RESULTS: Combining axial and MPR images, both the accuracy in preoperative tumor staging and the diagnosis of metastatic lymph nodes were 95%. MPR demonstrated more information about the extent of tumor than axial images in 23% cases; 3D image displayed clearly the extension of tumor, the vessels and airway from multiple views. The location, size and extent of tumors found in cranio-caudal CTVL corresponded well with that of laryngoscopy, and CTVL demonstrated the relationship between the tumor and vocal cords and anterior commissure by caudo-cranial approach, which was inaccessible to fiber optic laryngoscopy in 3 cases. CONCLUSIONS: Axial images of helical CT clearly demonstrate the location, size and extent of laryngeal and hypopharyngeal carcinoma, while MPR and 3D images are useful in displaying the three-dimensional images and anatomical relation of the tumor. CTVL can clearly display the mucosal surface structures of the larynx and hypopharynx and is a good complementary method of laryngoscopy.

Survival differences between definitive radiotherapy and surgery followed by adjuvant radiotherapy in supraglottic and hypopharyngeal carcinoma

Background:Organ preservation has long been a consideration in the treatment of supraglottic and hypopharyngeal carcin improve the quality of life(QOL).Definitive radiotherapy(DRT)with or without systematic treatment,such as chemotherapy,is always the first choice to achieve improved QOL.This retrospective study focused on the survival differences between DRT and surgery followed by adjuvant radiotherapy(S+RT)in supraglottic and hypopharyngeal carcinoma.Methods:This study included adult patients with supraglottic or hypopharyngeal carcinoma undergoing single-modality treatment with either DRT or S+RT between January 2012 and August 2016.A total of 59 patients were identified,of whom 31 were treated with DRT,and 28 were treated with S+RT.In the 31 cases of DRT,23 cases were treated with concurrent chemoradiotherapy(CRT),one case was treated with DRT plus cetuximab,and seven cases were treated with DRT alone.Of the other 28 cases of S+RT,15 cases were treated with adjuvant concurrent CRT.Survival analysis was used to compare the overall survival(OS),local recurrence-free survival(LRFS)and distant metastasis-free survival(DMFS)between DRT and S+RT groups.Results:The median follow-up was 20 months(range,4-67 months).The patients of the two groups were similar with respect to mean age,original sites,and tumor stages.The 1-,2-,and 5-year OS rates were 80.6%,53.4%,and 24.7% for the DRT group and 85.7%,67.1%,and 24.7%for the S+RT group,respectively.There was no significant difference between the two groups(x^2=3.183,P=0.074).The 1-,2-,and 5-year LRFS and DMFS were 90.4%,61.7%,and 18.0%and 87.4%,49.2%,and 9.9%,respectively,and no statistical difference was observed between the two groups(LRFS:x^2=0.028,P=0.868;DMFS:x^2=3.347,P=0.067).No significant difference was found between the two groups in acute radiotoxicity.Conclusions:Without loss of laryngeal function,the survival of DRT is comparable to that of S+RT in supraglottic and hypopharyngeal carcinoma.

Applied anatomy of the submental island flap and its clinical application in the repair of defects following hypopharyngeal carcinoma resection

Objective: To explore the feasibility of the submental island flap in the repair of hypopharyngeal defects.Methods: We collected wet specimens of fresh cadaveric heads from the Han Chinese adult population for applied anatomy of the submental island flap, and followed five patients with pyriform sinus carcinoma after reconstruction surgery using submental island flaps.Results: We found that the average length and width of the submental island flaps were (65.20 ± 11.69) mm and (46.70 ± 6.59) mm, respectively.The skin flap in all five patients survived after surgery, and tracheal tubes and gastric tubes were removed 7-36 days after surgery.Patients were followed up for 24-42 months, pharyngeal flaps grew well, and speech and swallowing functions were satisfactory.Conclusion: The submental island flap is a preferred material for the repair of hypopharyngeal defects after hypopharyngeal carcinoma resection, because of good blood supply, easy harvesting, and high survival rate.

Decellularized small intestine submucosa/polylactic-co-glycolic acid composite scaffold for potential application in hypopharyngeal and cervical esophageal tissue repair

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid,which resembled the layered architectures of its intended tissues.The decellularized small intestine submucosa contained minimal residual DNA(52.5±61.2 ng/mg)and the composite scaffold exhibited satisfactory mechanical properties(a tensile modulus of 21.1±64.8 MPa,an ultimate tensile strength of 14.0±62.9MPa and a failure strain of 26.9±65.1%).The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays,immunostaining and Western blotting.Desirable cell proliferation and phenotypic behaviors were observed.These results have provided an important basis for the next-step in vivo studies of the scaffold,and bode well for its future clinical applications.

Prognostic value of lymph node ratio in hypopharyngeal squamous cell carcinoma after chemoradiotherapy

Background Lymph node ratio （LNR） has recently been reported as a potential prognostic marker in many malignant diseases. We aimed to analyze the potential prognostic effect of LNR on hypopharyngeal squamous cell carcinoma （HPSCC） after neoadjuvant therapy in our institution.

Ultrastructural features of the hypopharyngeal glands in the social wasp Polistes versicolor （Hymenoptera： Vespidae）

The wasps of the genus Polistes have been considered the key to understanding the evolution of social behavior in Hymenoptera. Several studies have shown that the development of organized insect societies was accompanied by the evolution of structures like exocrine glands, which became specialized to perform specific functions. This article investigates the ultrastructural and cytochemical features of the hypopharyngeal glands of Polistes versicolor. These glands have been studied in depth in social bees, where they occur only in nurses and produce the royal jelly. Our results＇ revealed that these glands basically did not vary among individuals or between sexes. They are constituted by spherical cells, each with a large nucleus and well-developed rough endoplasmic reticulum. Secretion vesicles are abundant, but lipid droplets were not observed, indicating that these glands may not have a role in pheromone synthesis. Acid phosphatase was detected in lysosomes, and also flee in the cytosol, but did not seem to be related with cell death. Thus, our results suggest that the hypopharyngeal glands ofP. versicolor may not have a specialized social role, but could produce digestive enzymes.

SURGICAL MANAGEMENT OF THE HYPOPHARYNGEAL AND CERVICAL ESOPHAGEAL CANCER

Between December 1979 and December 1992, 15 patients with hypopharyngeal and cervical esophageal cancer were treated surgically. Total pharyngolaryngectomy and partial cervical esophagectomy were performed and the defects were reconstructed with cervical skin flaps in 2 cases. The free jejunal segments were used in 6 cases following total pharyngolaryngectomy and cervical esophagectomy, cervical esophagectomy (larynx preserved) was repaired with free jejunal graft in 1 case. The pharyngogastric anastomosis following total pharyngolaryngoesophagectomy were performed in 4 cases, one of them, used pectoralis major myocutaneous flap for resection of soft tissue and skin of the neck. The pectoralis major myocutaneous flap and forearm free flap in 1 case respectively were used to reconstruct the deficits of total laryngectomy and partial pharyngectomy, and partial pharyngolaryngectomy. In our series, 1, 3, 5 years survival rates were 73.3% (11 / 15), 50% (6 / 12) and 55.6% (5 / 9), respectively. The advantages and disadvantages of a variety of operative procedures and the cervical lymph nodes management will be discussed.

磷脂酶C1基因rs2274223位点多态性与下咽癌临床病理特征及预后的相关性分析

目的 探讨磷脂酶C1(phospholipase C1,PLC1)基因rs2274223位点多态性与下咽癌临床病理特征及预后的相关性。方法 收集2016年1月~2022年12月间浙江大学医学院附属金华医院耳鼻咽喉头颈外科收治的42例下咽癌患者,所有患者均行根治手术,记录临床病理数据,并均取全血3 ml作DNA提取,Sanger法测序检测PLCE1基因rs2274223位点单核苷酸多态性,分析其与下咽癌临床病理特征及预后的相关性。结果 PLCE1基因rs2274223位点在42例下咽癌患者中有16例突变为AG,位点突变与肿瘤分化程度相关(χ^(2)=5.301,P=0.021),K-M生存分析提示rs2274223位点突变与未突变的下咽癌患者3年生存率分别为75.0%和83.1%,5年生存率分别为18.8%和31.2%,差异有统计学意义(χ^(2)=5.475,P=0.019)。结论PLCE1基因rs2274223位点突变与下咽癌低分化相关,该位点突变的下咽癌患者预后更差。

喉癌喉咽癌的辅助与综合治疗

喉癌喉咽癌的辅助与综合治疗在喉癌喉咽癌治疗中占有越来越重要的位置。其主要目的是补充外科手术的缺点和不足,增强外科手术的治疗效果;提高喉器官功能保留率和患者的生存质量;作为晚期喉癌喉咽癌治疗的姑息性方法,延长患者的生存时间。本文系统论述了放疗、化疗、联合放化疗(包括同步放化疗)和分子靶向治疗在喉癌喉咽癌治疗中的作用及近年的发展和现状。

p21活性蛋白激酶在喉癌和喉咽癌中的表达及临床意义

p21活性蛋白激酶（p21-activated kinase 1,PAK1）是一种保守的丝氨酸/苏氨酸蛋白激酶,是Rho家族小鸟苷三磷酸酶（Rho-GTPase）Cdc42和Rac1下游的重要靶蛋白,参与调节细胞骨架的重组,提高细胞的运动性和侵袭力,有助于肿瘤的恶性进展.本研究采用免疫组化Envision二步法检测喉癌和喉咽癌组织中PAK1蛋白的表达情况,并探讨其临床病理学意义.

喉癌与下咽癌同时性多原发癌2例

多原发癌（multiple primary carcinoma,MPC）是指两种或两种以上原发恶性肿瘤发生在一个患者的相同器官或不同器官,分为同时性多原发癌（多种恶性肿瘤同时发生或发生间隔≤6个月）和异时性多原发癌（多种恶性肿瘤的发生间隔〉6个月）[1]。在临床工作中,同时性多原发癌的发生易与转移癌相混淆,但其治疗方法和预后却截然不同。对于转移癌,属于恶性肿瘤的晚期病变,

喉及喉咽癌喉功能保全性治疗动向

临床医学近年来的发展有两个主要倾向[1]：贯彻医学人道主义和循证医学原则。前者要求医师尊重患者的个人价值观、期望和意愿,进一步体贴患者。后者要求把医疗放在坚实的科研基础上。医师一定要从患者的利益着想,根据有实证的科技成果,设计出完善的治疗方案。