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OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.

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PURPOSE: This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: In this single-center, single-arm, phase 2 trial, patients with resectable stage III-IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m2 (or docetaxel 75 mg/m2) plus cisplatin 75 mg/m2] and camrelizumab 200 mg on day 1 of each 21-day cycle for three cycles, followed by surgery, and adjuvant radiotherapy. Co-primary end points were pathological complete response (pCR) rate and safety. RESULTS: Thirty patients were enrolled and completed the neoadjuvant therapy, with an objective response rate (ORR) of 96.7% (29/30). Twenty-seven patients underwent surgery without delay, with an R0 resection rate of 92.6% (25/27). The clinical to pathological downstaging rate was 100% (27/27). The pCR rate was 37.0% [95% confidence interval (CI), 19.4%-57.6%], and the major pathological response (MPR) rate was 74.1% (95% CI, 53.7%-88.9%). The median follow-up duration was 16.1 months (range, 8.3-28.5), and the disease-free survival rate at 12 months was 95.8% (95% CI, 73.9%-99.4%). Grade 3 neoadjuvant therapy-related adverse events included rash (1; 3.3%), pruritis (1; 3.3%), and thrombocytopenia (1; 3.3%), and no grade 4 or 5 treatment-related events occurred. The most common surgical complication was delayed wound healing (5; 18.5%). CONCLUSIONS: Neoadjuvant chemotherapy plus camrelizumab for locally advanced HNSCC showed high ORR, pCR, and MPR rates, with an acceptable safety profile. These data support further evaluation of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.

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Endometriosis is a common gynecological disease characterized by diminished apoptosis, sustained ectopic survival of dysfunctional endometrial cells. Hypoxia has been implicated as a crucial microenvironmental factor that contributes to endometriosis. It has been reported that long non-coding RNA MALAT1 (lncRNA-MALAT1) highly expressed in endometriosis and up-regulated by hypoxia. Hypoxia may also induce autophagy, which might act as cell protective mechanism. However, the relationship between lncRNA-MALAT1 and autophagy under hypoxia conditions in endometriosis remains unknown. In the present study, we found that both lncRNA-MALAT1 and autophagy level were up-regulated in ectopic endometrium from patients with endometriosis, and its expression level correlates positively with that of hypoxia-inducible factor-1α (HIF-1α). In cultured human endometrial stromal cells, both lncRNA-MALAT1 and autophagy were induced by hypoxia in a time-dependent manner and lncRNA-MALAT1 up-regulation was dependent on HIF-1α signalling. Our analyses also show that knockdown of lncRNA-MALAT1 suppressed hypoxia induced autophagy. Furthermore, inhibiting autophagy with specific inhibitor 3-Methyladenine (3-MA) and Beclin1 siRNA enhanced apoptosis of human endometrial stromal cells under hypoxia condition. Collectively, our findings identify that lncRNA-MALAT1 mediates hypoxia-induced pro-survival autophagy of endometrial stromal cells in endometriosis.

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RATIONALE: Penetrating neck trauma has a mortality of 3% to 6% and is associated with serious complications, mainly due to the high density of vital structures in this area and the lack of corresponding protection from bone. PATIENT CONCERNS: A 55-year-old man who suffered neck trauma involving the parotid gland, caused by a rebar, after suffering a fall from the second floor of a building. DIAGNOSES: Penetrating neck trauma. INTERVENTIONS: The patient underwent a neck exploration under general anesthesia in the emergency operating room and tracheotomy was performed prophylactically. OUTCOMES: The foreign object was ultimately removed successfully with no complications. LESSONS: We concluded that computed tomography (CT) and three-dimensional reconstruction of the CT images can be a viable method to exclude macrovascular injury for patients who are in an emergency condition and are not eligible for computed tomography angiography (CTA). A chest tube could be used as an option for the removal of foreign bodies in the case of sharp or rough objects (such as spiral foreign bodies), when fully exposing the foreign body and its track.

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In this study, starch with porous structures derived from purple sweet potato was prepared and used as a food-grade polymer for the microencapsulation of olive oil. The optimal reaction conditions for preparing porous starch were determined to improve its adsorption capacity as effective microcapsule-wall materials. Olive oil was then impregnated in microspheres, and loading ratio was optimized by investigating the restrictive factors, including the mass ratio of olive oil to porous starch, as well as the embedding temperature and time. The presence of olive oil in the starch matrix was confirmed by SEM, FTIR, and TGA. Results demonstrated that the porous starch-based microencapsulation exhibit a stable olive oil loading ratio and a significant improvement in oxidative stability compared with free olive oil. The newly-proposed process used in this work was easy to scale up for developing a new and attractive method for oil protection in the food industry.

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The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer and is associated with tumorigenesis and metastasis. However, the expression and function of miR-223 in nasopharyngeal carcinoma (NPC) remain unclear. The present study demonstrated that miR-223 was downregulated in NPC cell lines. The ectopic expression of miR-223 dramatically suppressed cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, a luciferase reporter assay identified the structure-specific recognition protein (SSRP1) as a novel direct target of miR-223. SSRP1 expression was upregulated in NPC cell lines and the overexpression of miR-233 markedly reduced the expression of SSRP1. Furthermore, SSRP1 was involved in miR-223-regulated NPC cell proliferation, invasion, and EMT. Taken together, these results indicate that miR-223 functions as a tumor suppressor miRNA in NPC and that its suppressive effects are primarily mediated by repressing SSRP1 expression and inhibiting EMT.

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The relationship between Kruppel-like factor 4 (KLF4) and the Notch pathway was determined to investigate the effect of KLF4 on the activation of hepatic stellate cells and underlying mechanisms. Fifty SPF BALB/c mice were randomly divided into two groups. A liver fibrosis model was established in 25 mice as the experimental group, and the remaining 25 mice served as controls. On the day 0, 7, 14, and 35, liver tissues were removed for immunofluorescent detection. The Notch pathway inhibitor DAPT was added to the primary original hepatic stellate cells, and KLF4 and Notch-associated factor expression was detected by qRT-PCR. Additionally, the hepatic stellate cell line LX-2 was used to establish control and experimental groups, and was cultured in vitro. LX-2 cells in the experimental groups were treated with DAPT and the Notch activator transforming growth factor-beta 1 separately, whereas those in the control group were given isotonic culture medium. After 48 h, KLF4 expression was examined by Western blotting. After transient transfection of LX-2 cells to increase KLF4, the expression of Notch factor was examined. Immunofluorescence analysis showed that, with the aggravation of liver fibrosis, the absorbance (A) values of KLF4 were decreased (day 0: 980.73±153.19; day 7: 1087.99±230.23; day 14: 390.95±93.56; day 35: 245.99±87.34). The expression of Notch pathway- related factors (Notch-1, Notch-2, and Jagged-1) in the hepatic stellate cell membrane was negatively correlated to KLF4 expression. With the increase of KLF4 expression, Notch-2 (0.73±0.13) and Jagged-1 (0.43±0.12) expression decreased, whereas Notch-1 level was not detectable. When the Notch pathway was inhibited, KLF4 levels generally increased (18.12±1.31). Our results indicate that KLF4 expression is negatively correlated to the Notch pathway in hepatic stellate cells, which may provide a reference for the treatment of hepatic fibrosis.

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BACKGROUND: The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. miR-205 was reported to be upregulated in laryngeal squamous cell carcinoma (LSCC) tissues, however, the mechanisms by which miR-205 functions as a regulator of LSCC are largely unknown. RESULTS: In this study, Real-time qPCR and Western blot assay showed that expression of miR-205 was upregulated and expression of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) was downregulated in LSCC tissues. The expression levels of miR-205 were negatively related to those of CDK2AP1 in LSCC tissues and cell lines. Moreover, we found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the CDK2AP1 expression in LSCC cells. 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyl-tetrazolium bromide assays and transwell invasion assay were performed to test the proliferation and invasion of LSCC cells. Gelatin zymography was used to detect the activity of MMP2 and MMP9. CDK2AP1, c-Myc and CyclinD1 expression in cells was assessed with Western blotting. We found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the expression of CDK2AP1 in LSCC cells. In addition, miR-205 significantly induced cell proliferation and invasion by suppressing CDK2AP1 expression. Consistent with miR-205 inhibitors, overexpressed CDK2AP1 suppressed the activity of MMP2 and MMP9 and c-Myc and CyclinD1 expression in LSCC cells. CONCLUSION: These findings help us to better elucidate the molecular mechanisms of LSCC progression and provide a new theoretical basis to further investigate miR-205 as a potential biomarker and a promising approach for LSCC treatment.

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OBJECTIVE: To study the treatment effect of CO2 laser and self-made laryngeal dilator on the laryngeal stenosis. METHOD: Twenty-five patients with laryngeal stenosis were treated with CO2 laser and self-made laryngeal dilator. The laryngeal cavity scar was resected as much as possible by using CO2 laser and the laryngeal cavity was exposed by placing laryngeal dilator under general anesthesia. RESULT: The 24 cases of all were successfully decanulated 1 to 12 months after operation and could breathe freely. One case had second operation and was successfully decanulated 9 months after operation. The follow-up for 1 to 2 years showed all cases speaking well and 3 cases recurrence. CONCLUSION: The method for treating laryngeal stenosis using CO2 laser and self-mande laryngeal dilator is effective, fewer complication, less invasive, and faster recovery. The laryngeal dilator is made simply and conveniently.

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BACKGROUND: The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. miR-205 was reported to be upregulated in laryngeal squamous cell carcinoma (LSCC) tissues, however, the mechanisms by which miR-205 functions as a regulator of LSCC are largely unknown. RESULTS: In this study, Real-time qPCR and Western blot assay showed that expression of miR-205 was upregulated and expression of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) was downregulated in LSCC tissues. The expression levels of miR-205 were negatively related to those of CDK2AP1 in LSCC tissues and cell lines. Moreover, we found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the CDK2AP1 expression in LSCC cells. 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyl-tetrazolium bromide assays and transwell invasion assay were performed to test the proliferation and invasion of LSCC cells. Gelatin zymography was used to detect the activity of MMP2 and MMP9. CDK2AP1, c-Myc and CyclinD1 expression in cells was assessed with Western blotting. We found that miR-205 was the upstream regulator of CDK2AP1 and could suppress the expression of CDK2AP1 in LSCC cells. In addition, miR-205 significantly induced cell proliferation and invasion by suppressing CDK2AP1 expression. Consistent with miR-205 inhibitors, overexpressed CDK2AP1 suppressed the activity of MMP2 and MMP9 and c-Myc and CyclinD1 expression in LSCC cells. CONCLUSION: These findings help us to better elucidate the molecular mechanisms of LSCC progression and provide a new theoretical basis to further investigate miR-205 as a potential biomarker and a promising approach for LSCC treatment.

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OBJECTIVE: To evaluate the utilization of functional neck dissection for treatment of recurrent branchial cleft anomalies. METHOD: Fifteen patients with recurrent branchial cleft anomalies (fistula and cyst) undergoing functional neck dissection were retrospectively analyzed. RESULT: Complications included 2 incisions secondary healing, 1 postoperative choking persisting for 1 months and 1 Horner's syndrome. There was no recurrence after a follow up from 2 months to 6 years,except 2 cases were lost to follow-up. CONCLUSION: Functional neck dissection is an effective and safe surgical management for recurrent second and third branchial cleft anomalies(fistula and cyst).

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CONCLUSION: A trans-superior meatus endoscopic approach to treat diseases in the sphenoid sinus and sellar area is a safe, minimally traumatic, and effective method. OBJECTIVE: To avoid complications, we explored the use of the superior meatus and superior turbinate in the endoscope approach to the sphenoid sinus and sellar area. PATIENTS AND METHODS: This was a retrospective analysis of the curative effect of the trans-superior meatus approach for diseases in the sphenoid sinus and sellar area in 138 cases. RESULTS: All of 138 patients had successful operations and no serious complication occurred. All cases were followed up for a period of 1-3 years. No recurrence was found in 94 patients with isolated sphenoid sinus disease (sinusitis, mucoceles, or mycosis). Of 24 patients with pituitary adenoma, 17 patients had entire resection and no recurrence was found. Four patients had subtotal resection and three patients had partial resection with postoperative radiotherapy, and preoperative symptoms were improved. Of 13 cases of cerebrospinal rhinorrhea in the sphenoid sinus, 12 cases were successfully repaired by a single operation and 1 case was successfully repaired by a repeat operation. Among seven cases with decompression of the optic canal, four had obvious effect, two cases showed improvement, and there was no improvement in one case.

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OBJECTIVE: To investigate the optimal surgical approach for resecting infratemporal fossa-pterygomaxillary fossa-parapharyngeal space tumor. The aim of this study is to enhance therapeutic effect and reduce complications and sequelae. METHOD: Sixty-six patients with infratemporal fossa-pterygomaxillary fossa-parapharyngeal space tumor were analyzed retrospectively from 1998-2004, including complains, symptoms, physical signs; histodiagnosis, image examinations and surgical approaches. RESULT: No recurrence was found in fifty benign tumor cases after 2 to 5 years, while in 16 cases with malignant tumor, four patients died in one year, 8 cases died in 2 to 4 years, and only 4 patients' survival time exceeded 4 years. CONCLUSION: Extended maxillectomy is suitable for resecting primary carcinoma of maxillary sinus invading pterygomaxillary fossa, infratemporal fossa and /or parapharyngeal space tumor. also midface degloving approach is suitable for nasal primary cavity, nasal sinuses, nasopharynx and/or pterygomaxillary fossa tumor and localized malignant tumor. Trans-cervical combining mandibular split swing approach is suitable for parapharyngeal space tumor invading pterygomaxillary fossa and/or infratemporal fossa tumor. Trans-cervical jaw combining mandibulotomy is suitable for resecting parapharyngeal space, infratemporal fossa tumor for invading lateral skull base and pterygomaxillary fossa tumor.

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OBJECTIVE: The aim of this study was to discuss the diagnosis and treatment of special airway foreign body. METHOD: Clinical data of 69 patients with airway foreign body were analyzed,of which 45 patients underwent rigid bronchoscopy while another 24 patients underwent tracheotomy. RESULT: The operations succeeded in 43 of the 45 patients who underwent rigid bronchoscopy, while the other 2 patients died of respiratory failure because of the foreign body slipping off at the level of the glottis. All of the 24 other patients were cured, in which continuous saturation of blood oxygen below 90% occurred in 8 patients and turned normal after positive airway pressure in intensive care unit (ICU). The total cure rate reached 97.1%. CONCLUSION: Most of special foreign body in the airway can be taken out through tracheotomy under general anesthesia. If the foreign body is too big and irregularly, or the patients is too young or have the pulmonary atelectasis, it is much safer to remove foreign body by tracheotomy.

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OBJECTIVE: To explore the reason and correct management of trachea cannula exodus in the patient who had been executed tracheotomy, and reduce the occurrence of trachea cannula exodus and its complication. METHOD: To analysis retrospectively 23 cases of trachea cannula exodus after executed tracheotomy in patients who had been obstructed in upper respiratory. RESULT: In 23 cases of trachea cannula exodus, 21 cases were rescued succeeded, 1 case death, 1 case became plant man. CONCLUSION: Occurrence of trachea cannula exodus after executed tracheotomy was correlated with operative procedure, postoperative care and suitable selection of tracheal cannula. Quick-witted ability of doctor and correct management is a key that rescued succeeded.

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OBJECTIVE: The purpose of this study was to describe the changes of resonance characteristics of the nasal cavity (including nasal sinuses) and nasal airway resistance (NAR) after endoscopic sinus surgery (ESS), through objective measurement of nasality and NAR before and after ESS. METHOD: Sixty- eight patients received the examinations of nasality and NAR using Nanometer and Atmos Rhinomanometry before and after ESS separately. RESULT: The nasality of patients with type III and type II stage 2, stage 3 chronic sinusitis was obviously improved ( P <0. 05), but still below the normal range 1 month after ESS. The nasality didn't recover to the normal level 3 months postoperatively. However the total NAR apparently decreased 1 months after ESS ( P <0. 01) and returned to normal 3 months postoperatively. Nasality and the total NAR of patients in type II stage 1 turned to normal 1 month after ESS. There are no distinctive changes in nasality and total NAR of type I stage 1 patients. CONCLUSION: The total NAR significantly decreased close to normal among the patients with severe sinus or/and nasal lesions after ESS, however nasality continued aberrant for a relatively long period. It is suggested that nasality can't be ameliorated immediately after ESS. On the contrary, it is possible to bring some undesirable effects to the professional voice users, such as announces, for the changed resonance characteristics of the nasal cavity due to the excessive destruction of its normal structure.

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OBJECTIVE: To study the expressions and biological behavior of Survivin and VEGF in squamous cell carcinoma of larynx (LSCC) and the correlation between Survivin and VEGF. METHOD: The expressions of Survivin and VEGF in LSCC tissues of 40 cases and normal mucosa of larynx tissues of 5 cases were studied by immunohistochemical staining. RESULT: The expressions of Survivin and VEGF in LSCC tissues were higher than those in normal mucosa of laryngeal cavity (P <0.01). The expressions of the two marks in LSCC with the metastasis of lymph nodes were higher than those without metastasis (Survivin: P <0.05, VEGF: P <0.01). Age and sex did not change the expressions obviously (P > 0.05). There was a negative correlation between T-stage and Survivin expressions (P < 0.05). There was also a negative correlation between T-stage and VEGF expressions (P < 0.05). But, there was a positive correlation in staining intensity between Survivin and VEGF (r = 0.676, P < 0.01). CONCLUSION: Significant correlation between Survivin/VEGF expression and T-stage (P <0.05), lymph node metastasis (P <0.05) and prognosis (P <0.01) was revealed in squamous cell carcinoma of larynx. The high expression of it suggests bad prognosis. The up-regulate of the two genes suggest that they play important roles in the formation and metastasis of LSCC.

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OBJECTIVE: To evaluate the image feature of the X-ray plain film, the spiral computed tomography (CT) scans and three dimension reconstruction of inner ear with implanted electrode. METHODS: Eighteen patients of cochlear implant (MEDEL Combi 40+) recipients were involved in this study. The implanted electrode of all patients were examined on the fifth to seventh postoperative day, by the use of X-ray plain film with either anteroposterior transorbital projection (nine cases) or lateral position with coronal 60 degrees away from the examine table (nine cases). Three of the cochlear implant recipients were examined by the way of spiral CT scans with axial 1 mm image slices. The data of the CT scans was transferred to workstation for three-dimensioned reconstruction (direct volume rendering) of the inner ear. RESULTS: The X-ray plain film from both of anteroposterior projection and lateral with coronal 60 degrees projection provide satisfactory image of implanted electrode including the shape and the position in the temporal bone. The insertion depth of the electrode can be evaluated indirectly. In contrast, the images from CT scans with 3D reconstruction of the inner ear demonstrate more accurately the shape, the position, and the insertion depth of the electrode. Moreover, each of the electrode pairs can be identified clearly. CONCLUSIONS: X-ray plain film can meet the routine needs of postoperative evaluation of the implanted electrode with several kinds of head position of projection. But CT scans with 3D reconstruction of inner ear provide more accurate image of the spacial relationship of the electrode in the cochlear canal with direct demonstration of electrode insertion depth in the cochlea.

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OBJECTIVE: To evaluate the benefit of bilateral cochlear implants (BCIs) in prelingually deafened children on hearing rehabilitation as well as on speech and language development. METHOD: Two cases of congenital profound deaf children, who received unilateral cochlear implantation (CI, MEDEL C40+) on the age of 2 and 7.5, respectively, were performed secondary CI in the contralateral ear on their age of 5 and 9.5, respectively. One year after the secondary CI, the cochlear implant aided hearing threshold and speech discrimination rate were tested for both ears separately and together. The pronounce/speech distinct rate of the BCIs users were evaluated by their parents, surgeon and audiologist. RESULT: In comparison to unilateral aided ear, the mean hearing threshold at the frequency 250-4,000 Hz of the 2 cases with BCIs decreased by 13 dB and 11 dB, respectively. The speech discrimination rate of the BCIs users increased by 9% and 10%, respectively. The speech recognition in noise was improved. And their pronounce/speech distinct was improved. CONCLUSION: BCIs can provide a significant benefit in hearing, speech understanding, language development and pronounce/speech rehabilitation for prelingually deafened children.

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OBJECTIVE: To evaluate the feasibility and value of integrated methods to assess auditory pathway integrity. METHOD: Twenty-four cases of bilateral profoundly-deafened individuals who were considered as the candidates of cochlear implantation were included in this study. Auditory pathway integrity from these candidates of cochlear implantation were assessed with the integrated methods established by our team, which consist of 5 categories including 1. audiological test; 2. radiological imaging study; 3. ear-canal electric audiometry; 4. response to sound in daily life; and 5. speech development. RESULT: Twenty-three candidates who meet the criteria of auditory nerve-auditory pathway integrity received cochlear implantation with improved hearing and speech development postoperatively. The remainder one of the 24 candidates was diagnosed as bilateral absence of auditory nerve. The fault of cochlear implantation was avoided. CONCLUSION: The integrated methods for assessing auditory pathway integrity is feasible and valuable. Auditory nerve-auditory pathway integrity should be considered and included as one of the most important criteria for cochlear implantation candidate.

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