Chronic pain exacerbates memory impairment and pathology of Aß and tau by upregulating IL-1ß and p-65 signaling in a mouse model of Alzheimer's disease.

BACKGROUND: Chronic pain is linked to cognitive impairment; however, the underlying mechanisms remain unclear. In the present study, we examined these mechanisms in a well-established mouse model of Alzheimer's disease (AD). METHODS: Neuropathic pain was modeled in 5-month-old transgenic APPswe/PS1dE9 (APP/PS1) mice by partial ligation of the sciatic nerve on the left side, and chronic inflammatory pain was modeled in another group of APP/PS1 mice by injecting them with complete Freund's adjuvant on the plantar surface of the left hind paw. Six weeks after molding, the animals were tested to assess pain threshold (von Frey filament), learning, memory (novel object recognition, Morris water maze, Y-maze, and passive avoidance), and depression-like symptoms (sucrose preference, tail suspension, and forced swimming). After behavioral testing, mice were sacrificed and the levels of p65, amyloid-ß (residues 1-42) and phospho-tau in the hippocampus and cerebral cortex were assayed using western blotting, while interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assay. RESULTS: Animals subjected to either type of chronic pain showed lower pain thresholds, more severe deficits in learning and memory, and stronger depression-like symptoms than the corresponding control animals. Either type of chronic pain was associated with upregulation of p65, amyloid-ß (1-42), and IL-1ß in the hippocampus and cerebral cortex, as well as higher levels of phosphorylated tau. CONCLUSIONS: Chronic pain may exacerbate cognitive deficits and depression-like symptoms in APP/PS1 mice by worsening pathology related to amyloid-ß and tau and by upregulating signaling involving IL-1ß and p65.

SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter.

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells. IMPLICATIONS: Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.

Inhalation of Carboxymethyl Chitosan Alleviates Posttraumatic Tracheal Fibrosis.

OBJECTIVES: The present study was performed to determine whether the inhalation of carboxymethyl (CM)-chitosan can alleviate tracheal fibrosis in a rabbit model. METHODS: We designed a rabbit model of tracheal stenosis involving electrocoagulation with a spherical electrode. Twenty New Zealand white rabbits were randomly divided into experimental and control groups (10 animals each). Tracheal damage was successfully established by electrocoagulation in all animals. The experimental group was given CM-chitosan (inhalation for 28 days), while the control group inhaled saline. The effects of CM-chitosan inhalation on tracheal fibrosis were analyzed. Laryngoscopy was performed to evaluate and grade tracheal granulation, while tracheal fibrosis was evaluated by histological examination. The effects of CM-chitosan inhalation on the tracheal mucosa were examined by scanning electron microscopy (SEM), and hydroxyproline content in tracheal scar tissue was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Laryngoscopy showed that the tracheal cross-sectional area was smaller in the experimental than control group. The amounts of loose connective tissue and damaged cartilage, as well as the severity of collagen and fibrosis, decreased following inhalation of CM-chitosan. According to the ELISA, the experimental group had low levels of hydroxyproline in the tracheal scar tissue. CONCLUSION: The findings presented here showed that inhalation of CM-chitosan mitigated posttraumatic tracheal fibrosis in a rabbit model, thus suggesting a potential new treatment for tracheal stenosis.

Evaluation of prescription review and feedback policy on rational antibiotic use in primary healthcare settings in Beijing, China: a qualitative study using the Theoretical Domains Framework and the behaviour change wheel.

Objectives: To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship. Methods: We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions. Results: Procedural knowledge (Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics (Social/professional role and identity) and believed that PRF could help to change inappropriate provider behaviours (Behavioural regulation) in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation (Goals). Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates (Goals), lack of resources (Environmental context and resources) and perceived pressure coming from patients (Social influences). Conclusions: Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation.

Rapid Separation of Asiatic Acid, Quercetin, and Kaempferol from Traditional Chinese Medicine Centella asiatica (L.) Urban Using HSCCC-Semi-Prep-HPLC and the Assessment of Their Potential as Fatty Acid Synthase Inhibitors.

The main objective of this study was to rapidly separate asiatic acid (AA), quercetin (QCN), and kaempferol (KPL) from Centella asiatica (L.) Urban using high-speed counter-current chromatography (HSCCC) in tandem with the UV detector of semipreparative high-performance liquid chromatography (Semi-Prep-HPLC) and to evaluate their potential as inhibitors of fatty acid synthetase (FAS). To efficiently prepare large amounts of AA, QCN, and KPL from Centella asiatica (L.) Urban, rapid and simple methods by HSCCC were established respectively based on the partition coefficients (K values) of crude samples. The conditions of HSCCC-Semi-Prep-HPLC for the large-scale separation of AA, QCN, and KPL from Centella asiatica (L.) Urban were established and optimized. This included selecting the solvent system, flow rate, rotation speed, and so on. HSCCC-Semi-Prep-HPLC was successfully applied to separate and purify AA, QCN, and KPL, with n-hexane-n-butanol-methanol-water (3 : 1 : 3 : 3, V : V : V : V) as the solvent system for AA, which was detected at a wavelength of 210 nm with the stationary phase retention of 70%, and with n-hexane-ethyl acetate-methanol-water (0.8 : 0.9 : 1.2 : 1, V : V : V : V) as the solvent system for the co-separation of QCN and KPL, which was detected at a wavelength of 254 nm with the stationary phase retention of 65%. AA could be isolated at a large scale with high purity (>91.0%) in only one-step HSCCC-Semi-Prep-HPLC separation (within 150 min) under the optimized conditions. Meanwhile, QCN and KPL could be simultaneously isolated at a large scale with high purity (>99.1%) by another one-step HSCCC-Semi-Prep-HPLC separation (within 240 min) under the optimized conditions. The assessment of inhibition potential revealed that AA exhibited the strongest inhibitory effect on FAS, with an IC50 of 9.52 ± 0.76 µg/mL. Madecassic acid (MA) followed closely with IC50 values of 10.84 ± 0.92 µg/mL. QCN and KPL showed similar and relatively weaker inhibitory effects on FAS, with IC50 values of 43.09 ± 2.98 µg/mL and 36.90 ± 1.83 µg/mL, respectively. Overall, the HSCCC-Semi-Prep-HPLC method proved to be a highly efficient and reliable technique for separating AA, QCN, and KPL from Centella asiatica (L.) Urban, and the isolated compounds showed potential as FAS inhibitors.

Evaluation of modified coblation endoscopic lingual lightening in multilevel surgery for obstructive sleep apnea hypopnea syndrome: an open intervention study.

PURPOSE: To evaluate the efficacy and safety of modified coblation endoscopic lingual lightening to address retrolingual obstruction in multilevel surgery for obstructive sleep apneae (OSA). METHODS: Patients with OSA due to retropalatal and retrolingual obstructions were enrolled. Group 1 consisted of patients who underwent modified coblation endoscopic lingual lightening combined with H-uvulopalatopharyngoplasty, while group 2 comprised patients treated by H-uvulopalatopharyngoplasty alone. Objective parameters and subjective evaluations were recorded preoperatively and at 6 months postoperatively. RESULTS: The mean (standard deviation) apnea-hypopnea index (AHI) declined from 51.5 (18.9) to 14.3 (7.2) in group 1, and from 51.7 (15.8) to 28.5 (16.9) in group 2. The mean (standard deviation) percentage change in AHI was higher in group 1 than in group 2 (73.2 [10.9] vs. 48.9 [22.4], P < 0.01). The surgical response rate differed significantly between groups 1 and 2 (88.5 [23/26] vs. 46.7 [14/30], P < 0.01). Other outcomes, including the lowest oxygen saturation, Epworth Sleepiness Scale score, snoring visual analog scale score, and subjective improvement rate, were also significantly better in group 1 than in group 2. CONCLUSION: Without increasing complications, modified coblation endoscopic lingual lightening significantly improved surgical outcomes as part of multilevel surgery in patients with OSA due to multilevel obstruction.

A combination of Beers and STOPP criteria better detects potentially inappropriate medications use among older hospitalized patients with chronic diseases and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Research on potentially inappropriate medications (PIM) and medication-related problems (MRP) among the Chinese population with chronic diseases and polypharmacy is insufficient. OBJECTIVES: This study aimed to investigate the prevalence of PIM and MRP among older Chinese hospitalized patients with chronic diseases and polypharmacy and analyze the associated factors. METHODS: A retrospective cross-sectional study was conducted in five tertiary hospitals in Beijing. Patients aged ≥ 65 years with at least one chronic disease and taking at least five or more medications were included. Data were extracted from the hospitals' electronic medical record systems. PIM was evaluated according to the 2015 Beers criteria and the 2014 Screening Tool of Older Persons' Prescriptions (STOPP) criteria. MRPs were assessed and classified according to the Helper-Strand classification system. The prevalence of PIM and MRP and related factors were analyzed. RESULTS: A total of 852 cases were included. The prevalence of PIM was 85.3% and 59.7% based on the Beers criteria and the STOPP criteria. A total of 456 MRPs occurred in 247 patients. The most prevalent MRP categories were dosages that were too low and unnecessary medication therapies. Hyperpolypharmacy (taking ≥ 10 drugs) (odds ratio OR 3.736, 95% confidence interval CI 1.541-9.058, P = 0.004) and suffering from coronary heart disease (OR 2.620, 95%CI 1.090-6.297, P = 0.031) were the influencing factors of inappropriate prescribing (the presence of either PIM or MRP in a patient). CONCLUSION: PIM and MRP were prevalent in older patients with chronic disease and polypharmacy in Chinese hospitals. More interventions are urgently needed to reduce PIM use and improve the quality of drug therapies.

There is no fusion fascia in the abdomen and extraperitoneal fascia always surrounds the mesentery.

Toldt's fascia has always been described as a fusion fascia formed by two layers of visceral peritoneum when the mesentery attaches to the posterior abdominal wall. However, there is still no consensus about the mesentery and its surrounding fascia based on the current anatomic theories. This study aimed to determine the anatomical structures of the abdomen and provide a correct surgical plane for mesenteric-based surgery. Surgical videos of 121 patients who underwent laparoscopic operations of the digestive tract were reviewed to identify and compare the anatomical structures of the mesentery and associated fascia. Twenty-one postoperative specimens were stained with hematoxylin and eosin to indicate the histological appearance of the mesentery and its surrounding fascia. Furthermore, dynamic models had been established to explain the formation mechanism of the associated histological structures in different regions during the progression of mesenteric attachment. The fasciae surrounding the mesentery, including the submesothelial connective tissue, the subserosal connective tissue, Toldt's fascia, and "angel hair," have the same histological characteristic to extraperitoneal fascia. The general anatomical structure of the abdomen can be divided into three layers (abdominal wall, urogenital system, and digestive system) and two interlayers (transversalis fascia and extraperitoneal fascia). The extraperitoneal fascia surrounds the entire digestive system and is the natural layer separating adjacent structures from each other. Typical histological structures in the regions of posterior attachment include the fascia propria of the mesentery, mesofascial plane, extraperitoneal fascia, retrofascial plane, and anterior renal fascia. The urogenital system is surrounded by similar histological structures. There is no fusion fascia in the abdomen due to retreat of the visceral peritoneum, and all of the fasciae surrounding the mesentery are extraperitoneal fascia. This study demonstrates that the typical histological structures in the regions of attachment and mesofascial plane are the correct anatomic interface for mesenteric-based surgery.

The Bridging Effect of Controlled-Release Glial Cell-Derived Neurotrophic Factor Microcapsules within Nerve Conduits on Rat Facial Nerve Regeneration.

Objectives: The study is aimed at exploring the effect of the controlled release of the glial-derived neurotrophic factor (GDNF) on nerve regeneration. Methods: The PLGA/chitosan composite nerve conduit was used to bridge the dissected trunk of the rat facial nerve. GDNF microcapsules were loaded into the nerve conduit. Nine weeks after surgery, the facial nerve zygomatic and buccal branches were labeled with fluorescent indicators. The incorrectly grown facial neurons were reversed and counted. The facial nerve functional recovery was assessed by measuring the maximum evoked potential. Results: The nerve conduit was filled with different regenerating factors, such as the GDNF, GDNF microcapsules, or saline (control). The number of incorrectly regenerated neurons was lower with the nerve conduits filled with GDNF microcapsules than with those supplied with just the GDNF. However, neither the GDNF nor GDNF microcapsules affected the number of regenerated neurons. The functional recovery of the facial nerve was the best, with the nerve conduit filled with GDNF microcapsules closest to the healthy uncut facial nerve. Conclusion: The stable slow-release GNDF microcapsule inside the biodegradable nerve conduit can reduce the extent of incorrect growth of the facial nerve neuron when bridging the dissected rat facial nerve trunk. The technique has a good effect on functional nerve recovery.

LncRNA CASC15 upregulates cyclin D1 by downregulating miR-365 in laryngeal squamous cell carcinoma to promote cell proliferation.

BACKGROUND: This study investigated the role of lncRNA CASC15 in laryngeal squamous cell carcinoma (LSCC). METHODS: This study included 58 LSCC patients. Both tumor (LSCC) and adjacent (within 3 cm around tumors) non-tumor tissues from 3 different sites of each patient were collected. CCK-8 assay was used to determine cell proliferation. The expression levels of proteins and mRNAs were determined by Western blotting analysis and qRT-PCRs, respectively. RESULTS: CASC15 was upregulated in LSCC and high expression levels of CASC15 predicted poor survival. In LSCC tissues, CASC15 was negatively correlated with miR-365 but positively correlated with cyclin D1. In LSCC cells, overexpression of CASC15 resulted in downregulation of miR-365 and upregulation of cyclin D1. Overexpression of miR-365 did not affect the expression of CASC15 but downregulated cyclin D1. Overexpression of Cyclin D1 did not affect the expression of miR-365 and CASC15. Overexpression of CASC15 and cyclin D1 led to promoted, while overexpression of miR-365 led to inhibited LSCC cell proliferation. In addition, overexpression of miR-365 reduced the effects of overexpression of CASC15. CONCLUSION: Therefore, CASC15 upregulates cyclin D1 by downregulating miR-365 in LSCC to promote cell proliferation.

Comparison of the prevalence and nature of potentially inappropriate medication use in geriatric outpatients between tertiary and community healthcare settings: a multicenter cross-sectional study.

Background Geriatric outpatients with polypharmacy have a high risk of potentially inappropriate medication (PIM) use. Aim To identify differences in both prevalence and patterns of PIMs and drug-related problems (DRPs) in older outpatients who visited the tertiary hospitals (THs) and community health centers (CHCs) and analyze associated factors. Method A prospective cross-sectional study was conducted in five THs and five CHCs from September 2018 to November 2019 in Beijing, China. Data were collected from outpatients aged ≥ 65 years with chronic diseases and polypharmacy. PIMs were evaluated using the 2015 and 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) criteria. DRPs were classified using the Helper-Strand DRP Classification. The prevalence and types of PIMs and DRPs were compared, and relevant factors were analyzed. Results The prevalence of PIMs based on the 2015 Beers Criteria was higher in patients from the THs, while PIMs based on the 2019 Beers Criteria did not show a significant difference. PIM prevalence based on STOPP Criteria and DRPs was higher in patients from CHCs. Visiting CHCs was an independent factor of PIMs based on the 2015 Beers Criteria (OR 0.774, 95% CI 0.604-0.992) and the STOPP Criteria (OR 2.427, 95% CI 1.883-3.128), and DRPs (OR 3.612, 95% CI 2.682-4.865). Conclusion Differences in PIM and DRP might be due to the patients and settings. Specific measures to improve the appropriateness of medications in both settings should be used.

CircRNA circSEPT9 Downregulates miR-10a through Methylation to Promote Cell Proliferation in Laryngeal Squamous Cell Carcinoma.

The oncogenic functions of circRNA circSEPT9 have been characterized in triple-negative breast cancer. We analyzed its role in laryngeal squamous cell carcinoma (LSCC). Quantitative reverse-transcription PCR (RT-qPCR) was used to analyze the expression of circSEPT9 and miR-10a in paired LSCC and nontumor tissues donated by 50 patients with LSCC. Methylation-specific PCR (MSP) was performed to analyze the role of circSEPT9 in miR-10a RNA gene methylation. circSEPT9 or miR-10a were overexpressed in LSCC cells to explore the interaction between them. The regulatory role of circSEPT9 and miR-10a in cell proliferation was studied with cell counting kit-8 (CCK-8) assay. CircSEPT9 was highly expressed in LSCC, whereas miR-10a was expressed at a lower level in LSCC. CircSEPT9 and miR-10a were closely correlated across LSCC tissue samples. In LSCC cells, circSEPT9 overexpression increased the methylation of the miR-10a gene and decreased the expression of miR-10a. CircSEPT9 overexpression increased LSCC cell proliferation, whereas miR-10a overexpression decreased cell proliferation. Co-transfection experiments showed that circSEPT9 overexpression attenuated the effects of miR-10a overexpression on cell proliferation. We conclude that circSEPT9 may increase miR-10a methylation to increase cell proliferation in LSCC.

Outpatient Antibiotic Prescribing Patterns and Appropriateness for Children in Primary Healthcare Settings in Beijing City, China, 2017-2019.

(1) Background: Few studies have focused on antibiotic use and appropriateness in children in primary health institutions (PHIs). This study aimed to identify the patterns and appropriateness of antibiotic use for children in PHIs in Beijing, China. (2) Methods: Outpatient prescriptions of 327 PHIs from 2017 to 2019 for patients <18 years old were collected. Prescriptions were described using quantity indicators. Antibiotics were categorized according to ATC classification J01 and Access, Watch, Reserve grouping. Appropriateness was reviewed by experts using three subtypes of irrational prescriptions (irregular, inappropriate, and abnormal). (3) Results: 20,618 prescriptions were collected in total. The antibiotic prescription rate (APR) was 15.1% (N = 3113). Among antibiotic prescriptions, J01FA Macrolides were the most used (N = 1068, 34.9%). The Watch group constituted 89.0% (N = 2818) of total antibiotic use. Bronchitis (N = 1059, 35.2%) was the most common diagnosis. A total of 292 instances of irrational antibiotic use were identified, with inappropriate prescriptions being the most prevalent subtype (N = 233, 79.8%). (4) Conclusion: Although APR for children in PHIs in Beijing was relatively low, the pattern of antibiotic use differed from other countries. Further studies are needed to optimize antibiotic use for children in PHIs under different levels of economic development.

Sensorimotor nerve lesion of upper airway in patients with obstructive sleep apnea.

The pathogenesis of obstructive sleep apnea (OSA) remains controversial. The role of anatomic stenosis is indisputable, and neural regulation of the upper airway remains to be elucidated. The upper airway maintains patency through the upper airway reflex. Lesions in any link of the reflex can increase the collapsibility of the upper airway. In this study, we investigated sensorimotor nerve lesions and their possible relationship with OSA. Tissue samples were obtained from the pharyngopalatine arch in 47 patients with OSA and 45 control participants to examine changes in the expression levels of myelin basic protein (MBP) and agrin through immunohistochemistry and western blotting. Downregulation of MBP in the mucosa reflects myelinated degeneration of mucosal sensory nerve axons, whereas upregulation of agrin in the neuromuscular junction reflects synaptic regeneration following denervation. The two neural factors correlate significantly with polysomnographic parameters, such as the apnea hypopnea index and lowest oxygen saturation. Our findings suggest that sensorimotor nerve damage in the upper airway of patients with OSA may be associated closely with the mechanism of OSA.

The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.

BACKGROUND: This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. METHODS: Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. RESULTS: During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). CONCLUSIONS: The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

[Analysis of the effect of one-stage revascularization with internal carotid artery resection on cervical metastatic carcinoma in advanced head and neck carcinomas].

Objective:To analyze the therapeutic effect of internal carotid artery resection and one-stage revascularization in advanced cervical metastatic carcinoma. Method:Twenty-one patients with advanced head and neck malignant tumors who underwent internal carotid artery resection and one-stage revascularization were analyzed retrospectively. Among those, 11 patients suffered from hypo-pharyngeal carcinomas, 5 laryngeal carcinomas, 2 external auditory carcinomas, 1 middle ear carcinoma, and 2 parotid gland carcinomas. All patients received CT, MRI, DSA and other examinations before operation. It was found that all the internal carotid artery walls had been invaded by tumors, and there were different degrees of lumen stenosis. Autogenous saphenous vein grafts were used in 18 cases; artificial vessels were used in 3 cases. After revascularization, pedicled or free flaps were used to protect the anastomotic areas. All patients were treated with radiotherapy and chemotherapy according to different situations. Result:Among the 21 cases, 16 cases underwent reconstruction of cervical segment internal carotid and 5 cases were the skull base segment internal carotid. Twenty patients were successfully reconstructed in the first stage, and no vascular reconstruction-related nervous system complications occurred after operations. Postoperative imaging showed that the reconstructed blood vessels were well recanalized, with a success rate of 95.2%（20/21）. Only 1 case received ligation of internal carotid artery after the failure of vascular reconstruction. Among all the cases, the 1-year survival rate and 3-year survival rate were 90.5% and 40.4%, respectively. Conclusion:In patients with advanced head and neck malignant tumors with cervical metastatic cancer invading the internal carotid artery, one-stage revascularization after radical resection of the tumor and the internal carotid can achieve good therapeutic effect. Careful preoperative evaluation, proficient vascular anastomosis technology, adequate risk assessment and prevention are the key to the success of the operations.

Using low concentration sodium hypochlorite to improve colorectal surgical specimen lymph node harvest.

Lymph node (LN) retrieval is a critical procedure to determine the pathological stage and adjuvant therapy for colorectal cancer. The present study aimed to recommend a novel method by using sodium hypochlorite to improve colorectal surgical specimen LN harvest. Dissolving time of mesenteric LNs and fat tissue was firstly investigated in different concentrations of sodium hypochlorite. In the sodium hypochlorite group, 65 patients with colorectal cancer who underwent curative surgery were included. After standard manual gross dissection, the mesenteric tissue was subsequently immersed in 1% sodium hypochlorite for ~30 min, and then manual dissection was again applied for additional LN harvest. In the manual method group, 68 patients with colorectal cancer were selected and only manual dissection method was applied for LN harvest. The number of LNs in both groups were recorded for each case. Sodium hypochlorite could dissolve fat tissue significantly faster than LNs and the low concentration sodium hypochlorite had the maximum dissolving time difference between fat tissue and LNs (P<0.001). After sodium hypochlorite treatment, more LNs were identified when compared with the manual dissection method (28.2±12.1 vs. 16.5±8.7; P=0.010), whereas the number of positive LNs had no significant statistical difference between the two groups (P=0.181). After sodium hypochlorite immersion, 818 additional LNs (12.5±4.8 per case) were identified and LNs ≤2 mm were 58.4% (478/818). Moreover, 16 additional metastatic LNs were found in 10 patients. A total of 7 of them were upstaged, including 2 initially N0 cases. Using sodium hypochlorite at low concentrations may be the most simple, rapid, cost-saving, nontoxic and effective technique to improve LN harvest in colorectal carcinoma specimens so far. This method should be used routinely regardless of whether the number of LNs is <12 or not.

Immediate Ansa Cervicalis-to-Recurrent Laryngeal Nerve Anastomosis for the Management of Recurrent Laryngeal Nerve Infiltration by a Differentiated Thyroid Carcinoma.

OBJECTIVES: The optimal surgical approach to treat recurrent laryngeal nerve (RLN) infiltration by differentiated thyroid cancer (DTC) remains a subject of debate. This study explored the feasibility and efficiency of immediate ansa cervicalis nerve (ACN)-to-RLN anastomosis for the management of RLN infiltration by DTC. MATERIAL AND METHODS: Fifty-three patients who underwent immediate ACN-to-RLN anastomosis during DTC extirpation were enrolled in the present study. Thirty-seven cases presented with unilateral vocal cord paralysis before the operation (Group A), and another 16 patients presented with normal vocal cord mobility preoperatively (Group B). Multidimensional assessments, videostroboscopy, voice assessment, and laryngeal electromyography (LEMG) were performed preoperatively and postoperatively. RESULTS: All videostroboscopy, voice assessment and LEMG parameters in Group A deteriorated 1 month after the operation and improved 1 year after the operation compared with preoperative data. In Group B, all parameters 1 year after the operation improved significantly compared with the corresponding parameters 1 month after the operation. LEMG in Group A and B provided substantial evidence for the maturation of neural regeneration from ACN and demonstrated that the laryngeal muscles were reinnervated successfully by this procedure. CONCLUSIONS: If the RLN is infiltrated by DTC, immediate ACN-to-RLN anastomosis during complete excision of DTC could restore satisfactory phonatory function and does not compromise oncological radicality.

Main branch of ACN-to-RLN for management of laryngospasm due to unilateral vocal cord paralysis.

OBJECTIVES/HYPOTHESIS: This study explored the feasibility and efficiency of main branch of ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) anastomosis for management of paroxysmal laryngospasm due to unilateral vocal cord paralysis (UVCP). METHODS: Thirteen patients who underwent main branch of ACN-to-RLN anastomosis for management of paroxysmal laryngospasm due to UVCP were enrolled in the present study. Multidimensional assessments, including videostroboscopy, voice assessment, and laryngeal electromyography (LEMG), were performed preoperatively and postoperatively. RESULTS: This series was limited to UVCP with iatrogenic causes, including thyroidectomy, cervical spine surgery, and thoracic surgery. After main branch of ACN-to-RLN anastomosis, all cases showed significant airway improvement, and laryngospasm was completely abolished in 92.3% (12 of 13) of cases. Videostroboscopy showed that the bulging and paradoxical adduction of the affected vocal cord during a sniff were abolished immediately after operation, and there was no significant difference in vocal fold position or glottal closure before versus after the operation. LEMG showed that the postoperative recruitment and amplitude of voluntary motor unit potential in the affected thyroarytenoid muscle during a sniff were significantly decreased compared to preoperative values, and postoperative recruitment showed significant improvement during phonation compared to that preoperatively. Voice assessment showed that there were no significant differences in overall grade, roughness, breathiness, jitter (local), shimmer (local), noise-to-harmonics ratio, or maximum phonation time after the operation compared to the preoperative values. CONCLUSIONS: Main branch of ACN-to-RLN anastomosis could have long-lasting efficacy in the management of paroxysmal laryngospasm due to UVCP, with no apparent compromise of voice quality. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2412-2419, 2020.

MicroRNA-98-HMGA2-POSTN signal pathway reverses epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma.

It has been widely considered that reversing epithelial-to-mesenchymal transition (EMT) is a potential access to restrain cancer progression and therapeutic resistance. Here, we aim to uncover the novel mechanisms by which we can reverse EMT and inhibit metastasis in laryngeal squamous cell carcinoma (LSCC). We show that miR-98 is significantly reduced in both LSCC specimens and cell lines. Over-expression of miR-98 inhibits the EMT-related gene expression and metastasis and invasive behavior in LSCC in vitro, as well as reduces lung metastasis in mouse model. In the mechanistically study, miR-98 directly targets HMGA2 in mediating EMT. HMGA2 knock down by si-RNA method declines several EMT-related genes expression and LSCC migration and invasion. In parallel, overexpression of HMGA2 transforms LSCC cells to acquire stem cell-like features. Furthermore, we reveal that HMGA2-mediated EMT is closely linked with the expression of POSTN that inhibits EMT, as a tumor suppressor, by gene profiling analyses. POSTN is transcriptionally repressed by HMGA2. In clinic, the HMGA2 mRNA level is negatively correlated with the miR-98 level in LSCC patient cohort. In conclusion, our study confers a powerful signal: miR-98-HMGA-POSTN in LSCC, which is able to reverse EMT and inhibit metastasis, underlining the therapeutic potential of this signal.