ObjectiveTo investigate the characteristics and differences of immune cell infiltration between different SDHx gene expression and pheochromocytoma/paraganglioma(PPGL).MethodsRNAseqdata of PPGL were downloaded and organized from The Cancer Genome Atlas(TCGA) database. Spearman correlation analysis was performed to assess the relationship between the expression of SDHx family genes(SDHA, SDHB, SDHC, SDHD, and SDHAF2) and the infiltration of 24 types of immune cells. Analyze the infiltrating immune cells in PPGL tumors caused by mutations in each gene in the SDHx family and the differences in immune cell infiltration of different genes.ResultsCompared to the other four syngeneic genes, SDHA exhibited unique immune cell infiltration characteristics, with dendritic cells(r=0.157, P=0.034) and immature dendritic cells(r=0.150, P=0.043) showing positive correlations with its expression in the tumor microenvironment. SDHB displayed unique immune cell infiltration features, including positive correlations with eosinophils(r=0.192, P=0.009) and Th17 cells(r=0.230, P=0.002), and negative correlations with regulatory T cells(r=-0.160, P=0.030) and CD8+ T cells(r=-0.147, P=0.047). SDHC showed unique immune cell infiltration characteristics, with positive correlations with effector memory T cells(r=0.196, P=0.008), Th2 cells(r=0.171, P=0.020), T cells(r=0.149, P=0.043), and neutrophils(r=0.149, P=0.043). SDHD exhibited unique immune cell infiltration features, with negative correlations with natural killer cells(r=-0.173, P=0.019) and NK CD56bright cells(r=-0.162, P=0.028). SDHAF2 demonstrated unique immune cell infiltration characteristics, with positive correlations with plasmacytoid dendritic cells(r=0.152, P=0.039) and negative correlations with macrophages(r=-0.187, P=0.011) and Th2 cells(r=-0.264, P < 0.001). In PPGL with SDHB, SDHC, and SDHD mutations, plasmacytoid dendritic cells were significantly negatively correlated with gene expression(all P < 0.05).ConclusionsEach gene mutation in the SDHx gene family leads to distinct immune cell infiltration characteristics in PPGL, providing a feasible research direction for exploring targeted immunotherapies based on the unique immune cell infiltration patterns.

BACKGROUND:This study aims to identify a pathogenic SDHD mutation associated with hereditary head and neck paraganglioma (HNPGL) in a Chinese family and to explore its implications for genetic counseling. METHODS:The study involved a family with 15 members spanning three generations. A 31-year-old patient (II-4) was diagnosed with a left parotid gland tumor and a right carotid body tumor, while both the father and elder sister had right carotid body tumors, and the third sister had bilateral carotid body tumors. Whole exome sequencing and Sanger sequencing were employed to identify candidate pathogenic variants. Genetic counseling was conducted for third-generation descendants to assess the likelihood of carrying the mutation and to guide future diagnosis and treatment. RESULTS:A nonsense mutation in the SDHD gene (NM_001276503:exon2:c.C64T: p.R22X) was identified in the patient and three other affected family members. Genetic counseling for the third generation revealed that only one child (III-4) carried the pathogenic mutation inherited from the patient's third sister. CONCLUSION:We identified a pathogenic mutation in SDHD in a Chinese HNPGL family, which is the second reported case of its kind. Our genetic counseling analysis for the third generation provided important information for the family and guidance for future diagnosis and treatment.

Objective:To summarize and analyze the effect of facial nerve decompression surgery for the treatment of Bell's palsy and Hunt syndrome. Methods:The clinical data of 65 patients with facial nerve palsy who underwent facial nerve decompression in our center from October 2015 to October 2022 were retrospectively analyzed, including 54 patients with Bell's palsy and 11 patients with Hunter syndrome. The degree of facial paralysis（HB grade） was evaluated before surgery, and ENoG, pure tone audiometry, temporal bone CT and other examinations were completed. All patients had facial palsy with HB grade V or above after conservative treatment for at least 1 month, and ENoG decreased by more than 90%. All patients underwent facial nerve decompression surgery through the transmastoid approach within 3 months after onset of symptoms. The recovery effect of facial nerve function after surgery in patients with Bell's palsy and Hunter syndrome was summarized and analyzed. In addition, 15 cases in group A（operated within 30-60 days after onset） and 50 cases in group B（operated within 61-90 days after onset） were grouped according to the course of the disease（the interval between onset of symptoms and surgery） to explore the effect of surgical timing on postoperative effect. Results:There was no significant difference between the two groups of patients with Chi-square test（P=0.54） in 42 patients（77.8%, 42/54） with Bell's palsy and 7 patients（63.6%, 7/11） in patients with Hunter syndrome who recovered to grade Ⅰ-Ⅱ. According to the course of the disease, 10 cases（66.7%, 10/15） in group A recovered to grade Ⅰ-Ⅱ after surgery. In group B, 39 patients（78.0%, 39/50） recovered to grade Ⅰ-Ⅱ after surgery, and there was no statistically significant difference between the two groups by Chi-square test（P=0.58）. Conclusion:Patients with Bell's palsy and Hunter syndrome can achieve good results after facial nerve decompression within 3 months of onset, and there is no significant difference in the surgical effect between the two types of patients.

目的 探讨岩骨次全切除术应用于多种侧颅底病变的治疗效果.方法 回顾性分析2007年7月—2019年9月行岩骨次全切除术的78例患者的临床资料,男40例,女38例;平均年龄(37.3±14.1)岁.其中岩骨胆脂瘤28例,慢性中耳炎术后感染20例,颞骨良性肿瘤19例,脑脊液耳漏11例.术前患者均行纯音测听、颞骨CT、内耳MRI,面神经功能评价House-Brackmann分级:Ⅰ级25例,Ⅱ级19例,Ⅲ级15例,Ⅳ级10例,V级5例,Ⅵ级4例;全聋21例,余者平均听力52.2 dB.术后复查颞骨CT、内耳MRI并评价面神经功能.结果 平均随访5.51年,术后无死亡、颅内出血、脑脊液耳漏等严重并发症.岩骨胆脂瘤、慢性中耳炎术后感染患者术后复发各2例,经再次手术治愈;颞骨良性肿瘤均完全切除肿瘤,其中14例面神经鞘瘤患者中9例行面神经-舌下神经吻合术.术后面神经功能评价:Ⅰ级28例,Ⅱ级20例,Ⅲ级17例,Ⅳ级7例,V级2例,Ⅵ级4例;所有患者均无实用听力.结论 岩骨次全切除术适用于广泛的岩骨胆脂瘤、慢性中耳炎术后感染及颞骨良性肿瘤的切除,也可用于防治脑脊液耳漏;此术式无法保留或重建听力,故仅适用于无听力重建条件者.

目的 探讨颞骨次全切除术在外耳道腺样囊性癌的临床应用效果.方法 回顾性分析2015-2019年收治的8例外耳道腺样囊性癌患者的临床资料,其中男2例,女6例;年龄33～76岁,平均年龄55.6岁.耳痛7例,外耳道肿块、耳溢液、听力下降各6例,面瘫1例;从最初出现症状到确诊平均为2.75年,5例曾被误诊,3例曾被误治手术;6例行颞骨次全切除+腮腺浅叶切除术,2例行颞骨次全切除+全腮腺切除术.结果 围手术期内1例患者出现局部切口感染,1例出现脑脊液漏.全部患者平均随访4.34年;6例患者无瘤存活;1例复发患者于我院二次手术后3年再次出现局部复发伴肺转移,接受放射治疗,目前带瘤生存;1例患者术后随访3.5年死于其他疾病.结论 外耳道腺样囊性癌早期症状不典型,容易误诊;确诊后应实施颞骨次全切除术以达到彻底切除肿瘤目的,术中应同时处理腮腺;术后放疗也是一种可选择的补充治疗手段.

Context Bell's palsy is a form of idiopathic, facial nerve palsy. Initial treatment includes the use of oral corticosteroids and/or antiviral agents, but facial paralysis may persist. Some surgeons suggest that surgical decompression of the facial nerve can be a beneficial, but the optimal surgical approach, extent of nerve decompression, and timing of surgery remain unclear. Objective This study intended to evaluate the efficacy of delayed, facial nerve decompression for severe Bell's palsy (BP) and to explore the relationship of opportunity timing for operations, with postoperative recovery for facial nerve function. Design The research team performed a retrospective study. Setting The study took place at Beijing Tiantan Hospital of Capital Medical University in Beijing, China. Participants Participants were 45 patients who had been diagnosed with BP between 2015 and 2021 and who had undergone facial nerve decompression using the transmastoid approach, between 30 and 180 days after the onset of BP. According to the operation's timing, the research team divided the participants into three groups, consisting of participants who underwent surgery: (1) at 30-60-days after BP onset-19 participants, (2) at 61-90 days after BP onset-18 participants, and (3) at more than 90 days after BP onset-8 participants. Outcome Measures The research team: (1) analyzed participants' demographic and preoperative and postoperative clinical characteristics, (2) compared the surgical outcomes with participants' House-Brackmann (HB) scales, and (3) analyzed the factors affecting the recovery of facial nerve function using logistic regression. Results Decompression surgery was effective for 29 participants (64.4%), with similar rates for participants who underwent surgery after 30-60 days (73.7%) and 61-90 days (77.8%), but the surgery' success was significantly higher for those groups than for participants who underwent surgery after >90 days (12.5%), with P = .008 and P = .003, respectively. Multivariate logistic regression analysis showed that disease duration was the only factor significantly associated with the effectiveness of surgery (odds ratio = 120.337; 95% confidence interval 2.997-4832.267, P = .011). Conclusions For patients with severe Bell's palsy with ineffective conservative treatment, surgery performed 30 to 90 days after the onset of paralysis can have therapeutic benefits, whereas surgery performed after 3 months is relatively ineffective.

ObjectiveTo investigate the relationship between the thresholds of intraoperative facial nerve response and postoperative facial nerve function recovery in patients with Bell's palsy.MethodsClinical data from Bell's palsy patients who underwent facial nerve decompression surgery at Beijing Tiantan Hospital from October 2015 to October 2022 were collected. The patients selected for analysis had intraoperative facial nerve monitoring with accurate recording of the facial nerve direct stimulation threshold and at least 1 year of detailed follow-up. The patients with postoperative facial nerve function recovery to grade Ⅰ-Ⅱ (HB grading) were defined as having good recovery, while those recovering to grade Ⅲ or higher were defined as having poor recovery. The patients were divided into two groups (A and B) according to facial nerve reaction excitability, with group A having a direct stimulation threshold of ≤1.5 mA and group B having a direct stimulation threshold of > 1.5 mA or a stimulation volume up to 3 mA without being able to record neural response waveform. The relationship between postoperative facial nerve function recovery and facial nerve direct stimulation threshold was analyzed.ResultsA total of 36 Bell's palsy patients were included in this study, who underwent facial nerve decompression surgery through the transmastoid-epitympanum approach within 1-3 months after onset. Of the 36 patients, 24 (66.7%) had good recovery and 12 (33.3%) had poor recovery. Only 20 (55.6%, 20/36) patients had facial nerve direct stimulation threshold recorded during the operation, and all were ≤1.5 mA(0.1-1.5 mA). The reaction waveforms of 16 (44.4%, 16/36) patients could not be recorded even when facial nerve stimulation increased to 3 mA. There was no significant difference in age, gender, lateral discourse, timing of surgery, and preoperative electroneurography (ENoG) between the two groups(all P > 0.05), but the good recovery rate of the patients in group A was significantly higher than that in group B, and the difference was statistically significant ( P=0.009). ConclusionFor patients with Bell's palsy undergoing decompression surgery of the facial nerve, the intraoperative direct stimulation threshold of the facial nerve may have some predictive value for postoperative facial nerve function recovery.

Objective To analyze the clinical effects of modified infratemporal fossa type A approach for glomus jugulare tumors. Methods The clinical data of patients with glomus jugulare tumors who received modified infratemporal fossa approach type A from May 2014 to December 2019 were retrospectively collected in the Beijing Tiantan Hospital, Capital Medical University. Modified infratemporal fossa approach type A was performed and improved on two aspects: anterior transfer of facial nerve and management of sigmoid sinus. CT was performed 6 hours after surgery to exclude intracranial hemorrhage. MRI was reviewed 2 weeks after surgery to define residual tumor, and every year to determine recurrence. Follow-up was conducted to assess the facial nerve function. Results A total of 39 patients were included in this study. Patients' grades of preoperative facial nerve function according to House-Brackmann (HB) were as following: grade Ⅰ in 12 patients, grade Ⅱ in 6 cases, grade Ⅲ in 8 cases, grade Ⅳ in 9 cases, grade Ⅴ in 3 cases, and grade Ⅵ in 1 case. All 39 patients successfully completed surgery, and there were no deaths and no severe complications such as hemiplegia, or intracranial infections. Cerebrospinal fluid leakage occurred in 1 case and drainage was performed. There was no intracranial hemorrhage in the CT exam 6 hours after surgery. Total resection was performed in 37 cases (94.9%) and nearly total resection in 2 cases (5.1%). The postoperative facial function after 1 year was HB grade Ⅰ in 8 patients, grade Ⅱ in 16 cases, grade Ⅲ in 9 cases, grade Ⅳ in 4 cases, grade Ⅴ in 2 cases. The facial function was improved after the surgery(P < 0.05). One year after surgery, tumor recurrence occurred in 1 patient and radiotherapy was performed. There was no significant tumor enlargement during follow-up. Conclusions The modified infratemporal fossa approach type A keeps the advantage of classical approach. By adjusting the anterior transfer of the facial nerve, the preservation of facial nerve function was improved. By compressing the sigmoid sinus instead of ligation, the occurrence of brain injury and cerebrospinal fluid leakage were reduced.

Acoustic neuroma is the most common benign tumor in the internal auditory canal and cerebellopontine region． Its common clinical symptoms include unilateral sensorineural hearing loss, tinnitus and so on． Surgical resection is the predominant treatment of acoustic neuroma. The common approaches dominated by otologists include translabyrinthine approach, enlarged translabyrinthine approach, transotic approach, modified transotic approach, and middle cranial fossa approach; the approach dominated by neurosurgeons is retrosigmoid (suboccipital) approach.. For small tumors with intact hearing, it is recommended to choose the middle cranial fossa approach. Those with large tumors who wish to preserve their hearing can adopt the suboccipital retrosigmoid approach; those who do not consider retaining hearing and have medium or small acoustic neuromas can adopt the translabyrinthe approach or through the transotic approach. With the development of microsurgical technology and the wide application of intraoperative nerve monitoring equipment, the retention rate of facial/cochlear nerve function for surgery of small and medium-sized acoustic neuroma has been significantly improved. In the future, more patients with acoustic neuroma are expected to be completely cured on the basis of preserving facial/cochlear nerve function.

The infratemporal fossa approach was designed for the removal of large tumors located at the temporal bone and lateral skull base.[1] This approach has several subtypes, including types A, B, C, and D. The infratemporal fossa type B (ITFB) approach exposes the petrous apex, clivus, and horizontal segment of the internal carotid artery (ICA) and is used to remove tumors in this area.[2] The classical ITFB approach to fully exposing the horizontal segment of the ICA includes subtotal resection of the petrous bone, removal of the anterior wall of the external auditory canal and zygomatic arch, resection of the articular disc and condylar process of the mandible, downward traction of the mandible, and transection of the mandibular branch of the trigeminal nerve and middle meningeal artery.[3] Clinical practice has shown that some patients have lesions mainly located in the zygomatic arch and middle ear cavity. These lesions may extend downward into the temporomandibular joint or upward into the middle skull base or temporal lobes, and may not extend deep into the horizontal segment of the ICA. A modified ITFB approach has been proposed to remove tumors at these sites, while retaining the integrity of the mandibular branch of the trigeminal nerve and the middle meningeal artery, and not exposing the horizontal section of the ICA. This report describes our experience using the modified ITFB approach to resect lateral skull base tumors, and explores the surgical indications for use of the modified ITFB approach in lateral skull base surgery and outcomes of its application. This study was approved by the Review Committee of Beijing Tiantan Hospital and conforms to the principles of the Declaration of Helsinki. The modified ITFB approach was utilized by surgeons in the Department of Otolaryngology Head and Neck Surgery of Beijing Tiantan Hospital to remove lateral skull base tumors from six patients between August 2014 and August 2017. Patients were included if they had lesions located in the middle ear cavity, zygomatic arch, temporomandibular joint, middle skull base, or temporal lobes, but not invading the horizontal segment of the ICA. Before surgery, all patients underwent routine examination of the ear, head and neck, including the external auditory canal, tympanic membrane, and movements of the facial expression muscles. Facial nerve (FN) function was assessed using the House-Brackmann (HB) scale. Auditory function was evaluated by pure tone audiometry (PTA) at thresholds of 500, 1000, 2000, and 4000 Hz. The level of hearing was classified based on pure tone average (the average air conduction hearing thresholds across the four frequencies) according to the standards recommended by the World Health Organization in 1997.[4] Normal hearing was defined as 0 to 25 dB hearing level (HL), mild hearing loss as 26 to 40 dB HL, moderate hearing loss as 41 to 60 dB HL, severe hearing loss as 61 to 80 dB HL and extremely severe hearing loss as >80 dB HL. Each patient underwent computed tomography and enhanced magnetic resonance imaging (MRI) of the temporal bone. All operations were performed under general anesthesia; the surgical procedure is shown in Figure 1 and Supplementary Video https://links.lww.com/CM9/A316. The modified ITFB approach was utilized in six patients for tumor removal during the study period. The six patients included four males and two females, of mean age 37.5 years (range, 3.0–65.0 years). Before surgery, all six patients showed hearing loss, including one with mild (PTA 35 dB HL) and three with moderate conduction hearing loss (PTA 50, 50, 55 dB HL, respectively) and two with extremely severe sensorineural hearing loss (both PTA >80 dB HL). In addition, three patients had tinnitus, one had purulent ear discharge, one had facial paralysis (HB grade II), and one had headache.Figure 1: Operation procedure diagram. (A) The skin incision was C-shaped, starting above and posterior to the lateral orbital corner, extending 3 to 4 cm behind the postauricular sulus and ending inferiorly at the angel of the mandible. (B) The external auditory canal was closed as cul-de-sac. (C) The temporalis muscle is detached from its bed to be further reflected anteriorly and inferiorly, to expose the mastoid, the scale of the temporal bone and the zygomatic arch. Then a subtotal petrosectomy was performed. ∗1 showed the tumor and ∗2 showed zygomatic arch. (D) The capsule of the temporo-mandibular joint was separated, and the articular disk was then removed, exposing the mandibular condyle. The Fisch infratemporal fossa retractor was applied, with inferior displacement of the head of the mandible. ∗1 shows the dura mater of middle skull base. ∗2 shows the tumor. ∗3 shows mandibular condyle. ∗4 shows the inferior fossa retractor. (E) Radical resection of tumor. (F) Obliteration of the cavity with fat.All six patients underwent microscope-guided radical resection of the tumor, with enhanced MRI 1 week after surgery confirming the absence of residual tumor in all six patients. Pathologic examination showed that two patients had giant cell reparative granulomas and that the other four patients had giant cell tumor of the bone, epidermoid cyst, squamous cell carcinoma, and mature teratoma, respectively. None of the patients experienced vascular injuries, including those of the ICA, jugular bulb, and sigmoid sinus, with mean blood loss being <100 mL. After the surgery, four patients with mild or moderate conductive hearing loss before operation experienced severe conductive hearing loss (PTA increased to 60 dB HL for the patient with mild conduction hearing loss and by 10 to 15 dB HL for the three patients with moderate conduction hearing loss before the surgery) and two still had severe sensorineural hearing loss (both PTA >80 dB HL, identical to those before the surgery). One patient, with normal FN function before surgery, developed facial paralysis due to tumor invasion and resection of the FN during the operation, resulting in a postoperative FN function of HB grade VI. The patient having preoperative FN function of HB grade II showed worsening of FN function one week after surgery to HB grade III, but recovered to HB grade II after one year. The FN function of the other four patients was normal after surgery. Because the lesions in three patients had invaded the dura mater of the middle cranial fossa, and even involved the temporal lobe, the invaded dura and intracranial tumors were removed, and artificial dura was used to repair the defective dura. Head computed tomography 6 h after surgery showed that none of the patients experienced intracranial hemorrhage, with follow-up for 2 to 6 years showing no leakage of cerebrospinal fluid. All patients were evaluated by enhanced MRI once yearly after surgery. None of the patients experienced tumor recurrence or serious postoperative complications, such as cerebrospinal fluid otorrhea, intracranial hemorrhage, intracranial infection, hemiplegia, and death. Although the ITFB approach was originally designed for the removal of epidural lesions, it has also been used to remove intracranial lesions.[5] In this study, the lesions in three patients invaded the dura or even the temporal lobe and were successfully removed using the modified ITFB approach. This approach was especially suitable for removal of tumors located in the middle skull base and temporal lobe and invading the middle ear and temporomandibular joint. In addition, the routine closure of the external auditory canal and eustachian tubes, and packing the operative cavity with fat could reduce the likelihood of cerebrospinal fluid leakage or intracranial infection. Similar to classic ITFB, modified ITFB allows direct microscopic exposure of the lesions, as well as maximally protecting the dura mater, ICA, FN, and other important structures during removal of the lesions. Compared with the classic ITFB approach, the modified ITFB approach results in better retention of the mandibular nerve and middle meningeal artery, without exposing the horizontal segment of the ICA. The modified ITFB approach also avoids facial numbness in the innervated area of the mandibular nerve and delayed bleeding resulting from the resection of the middle meningeal artery, as well as maximally protecting the ICA from injury. This approach also reduces the occurrence of cerebrospinal fluid leakage and intracranial infection. The major disadvantages of the modified ITFB approach include the need to sacrifice hearing function and the temporomandibular joint, similar to those encountered using the classic ITFB approach. In summary, the modified ITFB approach has great advantages in the resection of lateral skull base lesions involving the petrous apex, zygomatic arch, temporomandibular joint, and even the temporal lobe. This approach can also reduce complications associated with the classic ITFB approach, such as damage to the horizontal segment of the ICA, mandibular nerve, and middle meningeal artery. Conflicts of interest None.

Objective To study the effects of phenylalanine ammonia-lyase(PAL) extract from gene engineering Lactococcus Lactis(NZ3900/pNZ8149-palart) on proliferation and apoptosis of human multiple myeloma cell line U266.Methods A new method was established with many techniques of physics,chemistry and biology to extract PAL from gene engineering L.L,then the activities and purities of the extraction were detected and analyzed.The proliferation inhibition rate of U266 cells was assayed by MTT analysis.Cell apoptosis were evaluated by flow cytometry(FCM) and phenylalannie(phe) concentration of cell curture were measured by HPLC.Result The PAL enzyme activities of the extraction were 92.5% of the same weight living gene engineering L.L.After U266 cells were treated with PAL extraction(the concentration from 0.1 U/ml to 2.0U/ml) for 24h,the cell proliferation was markedly inhibited with a dose related manner.When U266 cells were treated with 0.1 U/ml、0.2U/ml、2.0 U/ml PAL for 24h,the early apoptosis rate revealed by Annexin V/PI were 21.92%、50.64% and 90.86% respectively,being higher than that of the blank controls(0.88% and 1.12%±0.15%,P<0.01).The phe concentration of cell curture was reduced after treated with PAL.Conclusion The PAL extract from gene engineering L.L could obviously inhibit the proliferation and induce the apoptosis of U266 cells,which maybe attributed to the reduction of phe concentration.