[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

[Preliminary experience of gasless transoral vestibular robotic thyroidectomy].

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

[Preliminary experience of robotic lateral neck dissection via combined axillary-retroauricular approach for N1b papillary thyroid carcinoma].

Objective: To evaluate the feasibility, safety, and short-term efficacy of robotic lateral neck dissection via combined axillary-retroauricular approach for N1b papillary thyroid carcinoma (PTC). Methods: Thirty patients with cT1-2N1bM0 PTC who received robotic lateral neck dissection via combined axillary-retroauricular approach were included in the Department of Otorhinolaryngology of Sun Yat-sen Memorial Hospital from December 2016 to December 2020. There were 10 males and 20 females, with a median age of 34.5 years and a median body mass index of 25.55 kg/m2. The clinical, surgical, complications, pathology and follow-up data were analysed with SPSS 25.0 software package. Results: The median operative time of 30 patients was 255.50 min, the median operative blood loss was 69.00 ml, and the median postoperative hospital stay was 6.00 days. The incidence of postoperative temporary recurrent laryngeal nerve paralysis was 3.33% (1/30), temporary hypoparathyroidism was 16.67%(5/30), temporary accessory nerve injury was 3.33% (1/30), hematoma was 3.33% (1/30) and chylous leakage was 3.33% (1/30). The median visual analogue scale (VAS) score was 8.00, and the follow-up time was 13-38 months, with a median of 25.5 months. One case showed cervical lymph node recurrence 14 months after surgery. The most recent dynamic recurrence risk stratification showed 21 patients (70.00%) had excellent responses. Conclusions: Robotic lateral neck dissection via combined axillary-retroauricular approach for unilateral cN1b PTC is safe, feasible and aesthetic. The short-term efficacy and dynamic recurrence risk stratification results of short-term follow-up are satisfactory. It can provide a surgical option for cN1b PTC patients.

[Transoral robotic nasopharyngectomy for local recurrent nasopharyngeal carcinoma].

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.

Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.

In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.

Long noncoding RNA GAS5 attenuates cardiac fibroblast proliferation in atrial fibrillation via repressing ALK5.

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have caught more attention for their role in the progression of many diseases. Among them, lncRNA GAS5 (Growth Inhibition Specificity 5) was studied in this research to identify how it affects the progression of atrial fibrillation (AF). PATIENTS AND METHODS: In 40 patients with AF and 30 patients with sinus rhythm (SR), the GAS5 expression of the right atrial appendage (RAA) tissues was detected by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the cell proliferation assay was conducted in AC16 cells transfected with GAS5 inhibitor and mimics, respectively. Furthermore, the qRT-PCR was performed to uncover the mechanism. RESULTS: In the research, the expression of GAS5 in RAA tissues was decreased significantly in AF patients than that in SR ones. Moreover, overexpression of GAS5 inhibited cell growth in AC16 cells, while knockdown of GAS5 promoted cell growth in AC16 cells. In addition, further experiments revealed that ALK5 was a target of GAS5 and its expression in AF tissues negatively correlated to GAS5 expression. CONCLUSIONS: These results indicate that GAS5 could inhibit cell proliferation of AF via suppressing ALK5, which may offer a new vision for interpreting the mechanism of AF development.

[Gasless endoscopic selective lateral neck dissection via an anterior chest approach for papillary thyroid carcinomas].

Objective: To assess the safety and curative effect of gasless endoscopic selective lateral neck dissection (GESLND) via an anterior chest approach for papillary thyroid carcinoma (PTC). Methods: Eighteen patients with PTC(T1-2N1bM0, size<3.0 cm), having GESLND via an anterior chest approach, were included from November 2008 to December 2016. Results: GESLND via an anterior chest approach was successfully performed in all 18 PTC patients (seven male and eleven female) with 83.3% of T1 and 16.7% of T2. The mean operative time of selective lateral neck dissection was 73 min (range 51-92 min). The mean of intraoperative bleeding was 61.1 ml (range 30-120 ml). No major complications occurred except one transient hypoparathyroidism. No residual thyroid glands were detected on ultrasonography and thyroglobulin was(0.73±0.16)ng/ml three months postoperatively. The median of follow-up was 54.5 months (range 6-104 months). No recurrence disease was observed in any patient on ultrasonography, computer tomography, thyroglobulin or selective iodine-131 scan during the follow-up period. The cosmetic result and functional preservation was excellent, when the assessments were performed three months postoperatively. Conclusion: GESLND via an anterior chest approach is feasible and safe for selected PTCs, with superior appearance.

[The significance of preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach].

Objective: To evaluate the significance for the preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach. Methods: We retrospectively evaluated 168 patients who underwent unilateral endoscopic thyroidectomy via gasless anterior chest approach, with preservation of the medial branch of the supraclavicular nerve in 110 patients and not in other 58 patients. Semmes-Weinstein monofilament (SWM) test and a visual analogue scale (VAS) were used to assess the recovery of sensation in anterior chest within 1-12 months postoperatively. Difference in the scores of SWM or VAS between groups was tested with Mann-Whitney U test, and the rates of SWM and VAS scores returning to normal levels in individual periods after surgery was compared with Chi-square test. Results: The preserved group showed more favorable results than the non-preserved group in both SMW and VAS scores. Compared to control group, SWM score in preserved group possessed a higher rate recovery to normal level at any period after operation, which was close to complete normality in 7-9 months postoperatively, and SWM score in non-preserved group was still partially normal in 10-12 months from surgery. Preferable results for VAS were also found in the preserved group, except no significant difference in VAS between groups in1-3 months or 10-12 months after operation. Conclusion: Preservation of the medial branch of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach can improve sensation recovery in anterior chest, thus improving postoperative quality of life of patients.

Comparison of two stroke volume variation-based goal-directed fluid therapies for supratentorial brain tumour resection: a randomized controlled trial.

Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100ß, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05). Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration: NCT02113358.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 µM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 µM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 µM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 µM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 µM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 µM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.

Macrophages and control of granulomatous inflammation in tuberculosis.

The granuloma that forms in response to Mycobacterium tuberculosis must be carefully balanced in terms of immune responses to provide sufficient immune cell activation to inhibit the growth of the bacilli, yet modulate the inflammation to prevent pathology. There are likely many scenarios by which this balance can be reached, given the complexity of the immune responses induced by M. tuberculosis. In this review, we focus on the key role of the macrophage in balancing inflammation in the granuloma.

BK virus infection in renal transplant recipients.

BK virus (BKV) is increasingly being recognized as an important pathogen among renal transplant recipients. To date, only limited information is known about BKV infections in this population; definitive data regarding the epidemiology, diagnosis, treatment, and outcome of BKV infection are lacking. Therefore, further investigations are needed. This article reviews our current understanding of BKV infections among renal transplant patients.

Inhibition by magnolol of formylmethionyl-leucyl-phenyl alanine-induced respiratory burst in rat neutrophils.

The influence of the plant product magnolol on neutrophil superoxide anion (O2-*) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30mg kg(-1)) significantly inhibited the formylmethionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat whole blood ex-vivo. Magnolol also inhibited the 02-* generation with an IC50 (concentration resulting in 50% inhibition) of 15.4+/-1.6 microM and O2 consumption in rat neutrophils in-vitro. Magnolol weakly inhibited the O2-* generation in the xanthine-xanthine oxidase system, decreased cellular cyclic AMP level and had no effect on cyclic GMP levels. It weakly inhibited neutrophil cytosolic protein kinase C activity but did not alter porcine heart protein kinase A activity. Magnolol attenuated fMLP-induced protein tyrosine phosphorylation with an IC50 of 24.0+/-1.9 microM and the phosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 28.5+/-4.5 microM. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphatidyl-ethanol in the presence of ethanol. In the presence of NADPH, the arachidonate-activated NADPH oxidase activity in a cell-free system was weakly suppressed by magnolol. These results suggest that the inhibition of respiratory burst in fMLP-activated neutrophils by magnolol is probably attributable mainly to the attenuation of protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinase activation, and partly to the suppression of protein kinase C and NADPH oxidase activities.

Comparison of neuromuscular action of rocuronium, a new steroidal non-depolarizing agent, with vecuronium.

BACKGROUND: Rocuronium is a new nondepolarizing muscle relaxant. It features a rapid onset and lack of histamine release: It has an intermediate onset of action as vecuronium. The purpose of this study was to compare the neuromuscular action and condition of intubation after a bolus dose of rocuronium or vecuronium (2 x ED90). We also compared the duration of relaxation after intubation and maintenance doses of each drug. METHODS: Sixty male or female patients, age 18-65, scheduled for elective surgery under general anesthesia were divided randomly into two groups (rocuronium and vecuronium group). All patients were ASA class I-II and pre-operative laboratory data were normal. Anesthesia was performed with fentanyl, isoflurane and O2. Rocuronium 0.6 mg/kg (2 x ED90) or vecuronium 0.1 mg/kg (2 x ED90) was given during induction of anesthesia. The response of adductor pollicis was measured with acceleromyography. Neuromuscular block was maintained by bolus injection of rocuronium 0.15 mg/kg or vecuronium 0.025 mg/kg when T1 reached 25% of control. Onset time, duration, recovery indices, intubation condition and T4/T1 ratio to 70% were recorded. Side effects were recorded during the study. RESULTS: The onset time was significantly longer in vecuronium group than that of rocuronium group (102.8 +/- 26.9 s vs. 54.9 +/- 10.9 s, p < 0.05). The clinical durations of action were respectively 44.2 +/- 13.2 min in rocuronium group and 42.5 +/- 9.1 min in vecuronium group (T1 to 25%). The duration of the maintenance were respectively 28.8 +/- 9.5 min in rocuronium group and 26.1 +/- 6.8 min in vecuronium group (T1 to 25%). No adverse effect occurred with either drug. The intubation condition was similar in both groups. CONCLUSIONS: We conclude that rocuronium provides a more rapid onset of action than that of vecuronium. Rocuronium is an intermediate-acting muscle relaxant as vecuronium with good to excellent intubation condition. It may be an useful alternative to vecuronium for rapid tracheal intubation.

Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.

BACKGROUND: Conventional and modified ultrafiltration was used in pediatric cardiac operations to reduce volume overload and total body water. The purpose of this study was to compare the efficacy of these techniques in removing inflammatory mediators during cardiopulmonary bypass. METHODS: Fifty pediatric patients undergoing cardiac operations were randomized into a modified or conventional ultrafiltration group. Blood samples were obtained before and after ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS: Except for plasma concentrations of tumor necrosis factor-alpha in the modified ultrafiltration group, the plasma concentrations of all the mediators measured increased after ultrafiltration in both groups of patients. The volume of ultrafiltrate and the total amounts of tumor necrosis factor-alpha and interleukin-6 removed by ultrafiltration were significantly greater in the modified group. The concentrations of mediators in the ultrafiltrate and the ratio of ultrafiltrate to plasma concentrations of the mediators did not differ between the groups. Ultrafiltration was more efficient in removing tumor necrosis factor-alpha than the other mediators. CONCLUSIONS: The efficacy in removing the inflammatory mediators generated during cardiopulmonary bypass did not differ between modified and conventional ultrafiltration.

Suppression of pulmonary metastases of rat mammary cancer by recombinant urokinase plasminogen activator inhibitor.

A pivotal point in the process of invasion and metastasis of cancer cells rests on the capability of those cells to present a proteolytic interface to the surrounding tissue matrix as well as to the lymphovascular channels supplying the tumor. The MATB rat mammary cancer cells used in this study, along with a number of cancers of epithelial cell origin, provide that proteolytic interface by cell surface-bound plasmin. Inhibition of tumor cell surface plasmin formation in this study was achieved through the addition of the urokinase plasminogen activator inhibitor (PAI-2) to the infusion of rat mammary cancer cells introduced into the pulmonary arterial circulation of female Fisher 344 rats. The results show a significant decrease in the numbers of pulmonary metastases in those rats receiving the inhibitor. This effect was demonstrable for cells delivered as a bolus as well as for those delivered slowly over a 7-day period via an osmotic pump. Delivery of the inhibitor was by osmotic pump in each instance. The evidence suggests a basis for an additional approach to control the spread of selected cancers.