Automated intelligent design of modified uni-traveling carrier photodectors.

This paper introduces an automatic intelligent design method for the modified uni-traveling carrier photodetector (MUTC-PD). The conventional photodetector design process often relies on the numerical solution of complex nonlinear partial differential equations to simulate and optimize device performance, which is not only computationally intensive but also inefficient. To overcome this challenge, we apply the charge control principle to calculate the photodetector bandwidth, which improves the computational speed by a factor of approximately 1800 compared to the numerical solution of nonlinear partial differential equations. To further optimize the structure of the photodetector, we incorporate the Velocity Varying Climbing Particle Swarm Optimization (VVCPSO) algorithm. This is an improved algorithm based on the traditional particle swarm algorithm, which is able to quickly find the optimal solution in a complex parameter space. By applying the VVCPSO algorithm, we successfully fine-tuned the photodetector structure and obtained structural parameters with optimal performance. Our thorough verification process confirms that the proposed method is consistent with the results of ATLAS simulation software. Automated design has resulted in a high-performance MUTC-PD with a responsivity of 0.52A/W and a bandwidth of 60 GHz (@-3 V) at a mesa diameter of 16µm. Compared to the pre-optimized device, the bandwidth is increased to three times the original. By reducing the mesa diameter to 4µm, the bandwidth can be further increased to 82 GHz (@-3 V). The proposed method's calculation speed is fast enough, enabling extensive parameter studies to optimize device performance.

Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.

BACKGROUND: Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis. METHODS: In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed. RESULTS: Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1ß, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss. CONCLUSIONS: Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.

Neoadjuvant chemoimmunotherapy followed by robot esophagectomy has no effect on short-term results compared with surgery alone.

BACKGROUND: To determine the safety and efficacy of robot-assisted minimally invasive esophagectomy (RAMIE) for locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoimmunotherapy (NCI). METHODS: Data from patients who underwent RAMIE between January 2020 and June 2022 were retrospectively analyzed. The oncological and operative outcomes of the NCI and surgery-only (S) groups were compared by both unmatched and 1:1 propensity score-matched (PSM) analysis. RESULTS: A total of 201 patients with ESCC who underwent three-incision RAMIE were included in this study (143 patients in the S group and 58 patients in the NCI group). Of the 58 patients who underwent NCI, a pathologically complete response (pCR) (ypT0N0) was identified in 14 (24.1%) patients. The patients in the NCI group were younger than those in the S group (p = 0.017), and had more advanced cT (p < 0.001) and cN stage diseases (p = 0.002). After 1:1 PSM of the confounders, 55 patients were allocated to each of the NCI and S groups. No significant differences were found in oncological and operative results, including surgical blood loss, operative time, and lymph node harvest (all p > 0.05). However, the NCI group exhibited a lower rate of pulmonary complications than the S group (3.6% vs. 14.5%, p = 0.047). No significant difference between the groups was found for other complications (all p > 0.05). CONCLUSION: These findings indicate that NCI could result in a high pCR rate without increased complications in locally advanced ESCC. RAMIE is safe and feasible in patients with ESCC after NCI.

Piezoelectrically-activated antibacterial catheter for prevention of urinary tract infections in an on-demand manner.

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

A Novel Multi-compartment Rotating Bioreactor for Improving ADSC--Spheroid Formation and its Application in Neurogenic Erectile Dysfunction.

OBJECTIVE: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED). METHODS: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment. RESULTS: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 µm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01). CONCLUSION: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device.

Device Structure, Light Source Height, and Sunset Time Affect the Light-Trap Catching of Tea Leafhoppers.

Device structure, light source height, and climatic factors can potentially affect the catching of target pests in light traps. In this study, the installation of an anti-escape cover in a newly designed light trap significantly increased the number of catches of tea leafhoppers, Empoasca onukii, an economically significant pest of tea gardens, and it prevented 97.95% of leafhoppers from escaping. A series of assessments were performed in the field and showed that the optimal trapping window of the light trap was between 1.5 and 2.5 h (2 ± 0.35 h) after sunset, and the starting time of the window was positively correlated with the sunset time. The number of leafhopper catches decreased sharply when the height of the light source was above the flight height range of E. onukii adults. The height of the light source was optimal between 20 and 40 cm above the tea canopy. The efficacy of the light traps for capturing leafhoppers decreased in the autumn peak period. High numbers of leafhopper catches by the newly designed light trap in the summer could reduce E. onukii population sizes in the autumn. Overall, the newly designed light trap can be used to reduce E. onukii adult populations in tea gardens.

Learning Curve of Robot-Assisted Lymph Node Dissection of the Left Recurrent Laryngeal Nerve: A Retrospective Study of 417 Patients.

OBJECTIVE: Left recurrent laryngeal nerve (no.106recL) lymph node dissection is a challenging procedure, and robotic-assisted minimally invasive esophagectomy (RAMIE) may have some advantages. This study aimed to determine the learning curve of no.106recL lymph node dissection. METHODS: The data of 417 patients who underwent McKeown RAMIE between June 2017 and June 2022 were retrospectively analyzed. The lymph node harvest of no.106recL was used to determine the learning curve, and the cumulative sum (CUSUM) method was employed to obtain the inflection point. RESULTS: A total of 404 patients (404/417, 96.9%) underwent robotic surgery. Based on the number of no.106recL lymph nodes harvested, the CUSUM learning curve was mapped and divided into three phases: phase I (1‒75 cases), phase II (76‒240 cases), and phase III (241‒404 cases). The median (IQR) number of no.106recL lymph node harvests were 1 (4), 3 (6,) and 4 (4) in each phase (p < 0.001). The lymph node dissection rate gradually increased from 62.7% in phase I to 82.9% in phase III (p = 0.001). The total and thoracic lymph node harvest gradually increased (p < 0.001), whereas operation time (p = 0.001) and blood loss gradually decreased (p < 0.001). Moreover, the incidence of total complication (p = 0.020) and recurrent laryngeal nerve injury (p = 0.001) significantly decreased, and the postoperative hospital stay gradually shortened (p < 0.001). CONCLUSION: Robotic no.106recL lymph node dissection has some advantages for patients with esophageal cancer. In this study, perioperative and clinical outcomes were significantly improved over the learning curve. However, further prospective studies are required to confirm our results.

Simulation and design of a high-speed and high-power modified uni-traveling carrier photodiode based on the electric field distribution in the depletion region.

A modified uni-traveling carrier photodiode with an electric field control layer is proposed to achieve high-speed and high-power performance at a lower bias voltage. By inserting the 10 nm p-type InGaAs electric field control layer between the intrinsic absorption layer and space layer, the electric field distribution in the depleted absorption layer and depleted non-absorption layer can be changed. It is beneficial for reducing power consumption and heat generation, meanwhile suppressing the space-charge effect. Compared with the original structure without the electric field control layer, the 3 dB bandwidth of the 20 µm diameter novel structure, to the best of our knowledge, is improved by 27.1% to 37.5 GHz with a reverse bias of 2 V, and the RF output power reaches 23.9 dBm at 30 GHz. In addition, under 8 V bias voltage, the bandwidth reaches 47.3 GHz.

Multi-omics characterization of a scoring system to quantify hypoxia patterns in patients with head and neck squamous cell carcinoma.

BACKGROUND: The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains < 50%. Hypoxia patterns are a hallmark of HNSCC that are associated with its occurrence and progression. However, the precise role of hypoxia during HNSCC, such as the relationship between hypoxia, tumor immune landscape and cell communication orchestration remains largely unknown. The current study integrated data from bulk and single-cell RNA sequencing analyses to define the relationship between hypoxia and HNSCC. METHODS: A scoring system named the hypoxia score (HS) was constructed based on hypoxia-related genes (HRGs) expression. The predictive value of HS response for patient outcomes and different treatments was evaluated. Single-cell datasets and cell communication were utilized to rule out cell populations which hypoxia targeted on. RESULTS: The survival outcomes, immune/Estimate scores, responses to targeted inhibitors, and chemotherapeutic, and immunotherapy responses were distinct between a high HS group and a low HS group (all P < 0.05). Single-cell datasets showed different distributions of HS in immune cell populations (P < 0.05). Furthermore, HLA-DPA1/CD4 axis was identified as a unique interaction between CD4 + T Conv and pDC cells. CONCLUSIONS: Altogether, the quantification for hypoxia patterns is a potential biomarker for prognosis, individualized chemotherapeutic and immunotherapy strategies. The portrait of cell communication characteristics over the HNSCC ecosystem enhances the understanding of hypoxia patterns in HNSCC.

Leakage Dynamics of Glass Bottles on Container Closure Integrity Testing: Influence of Different Laser-Drilled Microhole Geometries.

Container closure integrity testing (CCIT) is a critical step in ensuring package integrity and providing feedback on package designs. In practical applications, CCIT methods, namely physical and probabilistic methods, must be appropriately selected and validated to ensure their suitability for the intended use. However, the industry still lacks practical recommendations regarding the choice of CCIT methods and artificial leaks to set the acceptance criteria. The main reason is the lack of correlation between testing methods. Artificially introduced leak microholes are the only way to determine the sensitivity of a CCIT method and to implement the method correlation. However, the type of artificial leakage is a key factor because in most studies, leakage is described and valued using a single parameter, such as size. This can significantly affect the credibility of the relevant test results, especially in the case of microbial invasion, where the difference in test conditions and samples will severely affect the probability of microbial invasion. Therefore, it is vital to conduct a systematic study on the influence of leakage conditions on CCIT methods. In this study, the influence of the shapes of artificial leaks on the two kinds of testing methods was systematically studied based on a laser-drilled microhole-a highly potential and non-exogenous artificial leak manufacturing method that can fabricate different leakage geometries. The reason for the influence of the shape of an artificial leak on the CCIT is that the deterministic method takes defects as an idealized model and ignores the influence of the leak shape, wall thickness, and other factors on leakage and pollution risks. However, these factors seriously affect the dynamic process of leakage and microbial invasion. The pressure decay method is used to test the leakage flow rate of conical and straight holes. Microbial challenge tests are then used to verify the impact of leakage shapes on the pollution risk. The results of the tests indicated that the probability of microbial invasion in the conical holes is much higher than that in straight holes with the same flow test results and that the wall thickness can also affect microbial invasion. Thus, it can be proven that the risk of leakage and invasion or the sensitivity of different methods cannot only be compared through the leak diameter. Numerous influencing factors, including leakage geometry (e.g., shape and thickness), must be considered in practical applications.

Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut-microbiota-related tryptophan metabolites.

BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS: The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR. CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiota-related tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs. © 2022 Society of Chemical Industry.

[A case report of giant vagal schwannoma in the right neck and literature review].

Vagal nerve-derived schwannomas are rare, especially those with huge tumors. This paper reports a case of giant tumor in the right neck. The patient was misdiagnosed as pleomorphic adenoma before operation, and was diagnosed as schwannoma during operation. The clinical manifestations, diagnosis, differential diagnosis, treatment and prognosis are discussed in this paper based on the history and related literature.

Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats.

BACKGROUND: Berberine (BBR) has been found to have antiobesity effects, and obesity can lead to adipose tissue degeneration. As a special adipose tissue, perivascular adipose tissue (PVAT) is closely related to vascular function and affects vasoconstriction and relaxation. What happens to PVAT in the early stages of diet-induced obesity and how BBR affects vascular function is the focus of our experimental study. METHODS: Sprague-Dawley rats were fed a high-fat diet (fat 34% kcal) for 4 weeks to simulate early obesity. Obese rats were treated with BBR (200 mg/kg) or metformin (MET, 100 mg/kg) by gavage for 2 weeks. The mesenteric arterioles were studied by atomic force microscopy (AFM). The force vs. time curves were observed and analysed to indicate vascular function. Nitric oxide (NO) and noradrenaline (NA) release was quantified using an organ bath with fluorescence assays and ELISA, respectively. Network pharmacology was used to analyse the overlapping targets related to BBR and obesity-related diseases, and the expression of NOS in mesenteric PVAT was further analysed with immunohistochemistry and real-time PCR. The serum inflammatory factor levels were tested. RESULTS: BBR significantly reduced the levels of blood glucose, blood lipids and inflammatory factors in serum. It also effectively improved abnormal mesenteric vasoconstriction and relaxation in obese rats. There was no significant change in mesenteric vascular structure, but NO production and eNOS expression were significantly increased in mesenteric PVAT (P < 0.01), and NA was decreased (P < 0.05) in obese rats. All these changes in the mesenteric arterioles and PVAT of obese rats were reversed by treatment with BBR and MET. CONCLUSIONS: In diet-induced obesity in rats, the function of vasoconstriction and relaxation in mesenteric arterioles is altered, NO is increased, and NA is decreased in mesenteric PVAT. All these changes were reversed by BBR, suggesting a novel effect of BBR in ameliorating mesenteric vascular dysfunction by regulating PVAT.

Compound glycyrrhiza oral solution alleviates oxidative stress and inflammation by regulating SRC/MAPK pathway in chronic obstructive pulmonary disease.

OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) suffer from persistent cough and breathlessness, which can be ameliorated by the Chinese herbal medicine glycyrrhiza. Furthermore, the SRC/MAPK pathway is activated in the process of oxidative stress and inflammation, which afflict COPD progression. Thus, this research aimed at dissecting the mechanism of compound glycyrrhiza oral solution (CGOS) relieving oxidative stress and inflammation in COPD via the SRC/MAPK pathway. METHODS: After a COPD rat model was established using lipopolysaccharide and cigarette smoke, rats underwent intragastric administration with CGOS and intratracheal injection with LV-NC and LV-SRC lentivirus into lungs. Then, pulmonary function-related indexes were evaluated, followed by analyses of arterial blood and inflammatory cell number in prepared bronchoalveolar lavage fluids. Meanwhile, the contents of oxidative stress-related indicators (malondialdehyde, 3NT, 8-Isoprostane, glutathione, NO, and SOD) in pulmonary tissues were measured, along with RT-qPCR and ELISA detection of the expression of inflammatory factors (TNF-α, IL-1ß, IL-4, and IL-10). Moreover, western blot assay was utilized to assess p-SRC/SRC and p-p38/p38 ratios in pulmonary tissues. RESULTS: CGOS treatment enhanced PaO2 and reduced PaCO2 in COPD rats, accompanied by declines in the number of total cells, neutrophils, and macrophages. CGOS improved pulmonary function, decreased malondialdehyde, 3NT, 8-Isoprostane, TNF-α, and IL-1ß levels, and increased GSH, NO, IL-4, and IL-10 levels and SOD activity. Mechanistically, CGOS suppressed the SRC/MAPK pathway, and SRC overexpression reversed the alleviating function of CGOS in COPD rats. CONCLUSIONS: In conclusion, CGOS might alleviate oxidative stress and inflammation in COPD rats by inhibiting the SRC/MAPK pathway.

Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002).

Background: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC). Methods: This study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4-6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life. Discussion: This is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years. Trial Registration: This prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

Inverse design of sub-wavelength convergent grating based on the "stepped particle swarm algorithm".

In this Letter, a novel "stepped particle swarm optimization" (SPSO) based on field intensity adjustment is proposed. After that, we used this algorithm to design a sub-wavelength converging grating that could be integrated with the detector on the back. Firstly, the advantages of reverse design in the process of two-dimensional or multi-element grating pattern design were summarized by comparing the theory of forward and reverse design. Then, the common "particle swarm optimization" (PSO) and our proposal were compared in the reverse design process; we found that the field strength at the focal point obtained by the improved algorithm was approximately twice of the conventional PSO, and the SPSO had higher computational efficiency and better global convergence. The value of the SPSO had been steadily enlarged, which significantly improved the performance of the sub-wavelength convergent grating. Finally, the property of the sub-wavelength converging grating was simulated, and we found that the grating could achieve good convergence in the focal length range of 100-150 µm, and had a strong ability to compensate for the position deviation of the incident light. In actual optical communications, this sub-wavelength converging grating will play an important role in alleviating the bandwidth and quantum efficiency, improving the performance of the detectors.

Safety and effectiveness of pembrolizumab combined with paclitaxel and cisplatin as neoadjuvant therapy followed by surgery for locally advanced resectable (stage III) esophageal squamous cell carcinoma: a study protocol for a prospective, single-arm, single-center, open-label, phase-II trial (Keystone-001).

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most refractory malignant tumors. Esophageal cancer (EC) is a malignant tumor with a high incidence worldwide, and over 50% of EC cases occur in China. Under the National Comprehensive Cancer Network (NCCN) guidelines, concurrent chemoradiotherapy is the only standard neoadjuvant treatment for locally advanced ESCC. In the first-line treatment of advanced ESCC, the efficacy of immune checkpoint inhibitors (ICIs) combined with systemic chemotherapy is significantly better than that of chemotherapy alone. Paclitaxel and cisplatin (TP), as one of the neoadjuvant chemotherapy regimens for locally advanced ESCC, have been widely used in China in recent years. ICIs combined with TP as neoadjuvant therapy seems promising. Methods: This is an open-label, single-arm, single-center, phase-II trial. Locally advanced resectable (stage III) ESCC patients who have not undergone previous systemic treatments will be enrolled in this study. All the subjects will intravenously receive 3 cycles of pembrolizumab (200 mg) on day 1, paclitaxel (135 mg/m2) on day 2, and cisplatin (20 mg/m2) on days 2-4, every 3 weeks. After an efficacy evaluation, the subjects will undergo Da Vinci robot-assisted radical resection. If the postoperative pathologic results do not reveal a complete response, pembrolizumab will be administrated for at least 6 cycles as an adjuvant therapy with the same usage as before. The primary endpoints are the major pathological response and safety. The secondary endpoints include the objective response rate (ORR), overall survival (OS), disease-free survival (DFS), the R0 resection rate, and perioperative complications. The exploratory endpoint is to examine the correlation between related biomarkers and tumor responses to this neoadjuvant treatment regimen. Discussion: This trial is the first enrolled study to evaluate the safety and efficacy of pembrolizumab combined with TP as neoadjuvant therapy for locally advanced ESCC. Currently, under the NCCN guidelines, neoadjuvant chemoradiotherapy (nCRT) is the only recommended treatment for locally advanced ESCC. This phase-II study will provide preliminary evidence of the efficacy of pembrolizumab combined with TP as novel neoadjuvant therapy for patients with locally advanced ESCC. Trial Registration: Clinicaltrials.gov (Identifier: NCT04389177).

Systematic analysis of the function and prognostic value of RNA binding protein in head and neck squamous cell carcinoma.

OBJECTIVE: Dysregulation of RNA binding proteins (RBPs) plays an important role in controlling processes in cancer development. However, the function of RBPs has not been thoroughly and systematically documented in head and neck cancer. We aim to explore the role of RPB in the pathogenesis of HNSC. METHODS: We obtained HNSC gene expression data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and the GEO databases, and identified aberrantly expressed RBPs between tumors and normal tissues. Meanwhile, we performed a series of bioinformatics to explore the function and prognostic value of these RBPs. RESULTS: A total of 249 abnormally expressed RBPs were identified, including 101 downregulated RBPs and 148 upregulated RBPs. Using least absolute shrinkage and selection operator (LASSO) and univariate Cox regression analysis, the 15 RPBs were identified as hub genes. With the 15 RPBS, the prognostic prediction model was constructed. Further analysis showed that the high-risk score of the patients expressed a better survival outcome. The prediction model was validated in another HNSC dataset, and similar findings were observed. CONCLUSIONS: Our results provide novel insights into the pathogenesis of HNSC. The fifteen RBP gene signature exhibited the predictive value of moderate HNSC prognosis, and have potential application value in clinical decision-making and individualized treatment.

Risk factors for lymph node metastasis of the left recurrent laryngeal nerve in patients with esophageal squamous cell carcinoma.

BACKGROUND: The factors for left recurrent laryngeal nerve (RLN) lymph node (LN) metastasis have important guiding significance for whether the left RLN LNs should be dissected in patients with esophageal squamous cell carcinoma (ESCC), but few studies are currently available. To analyze the risk factors of LN metastasis of the left RLN area and to assess which LNs should be dissected in ESCC. METHODS: This was a retrospective study of patients who underwent McKeown minimally invasive esophagectomy (MIE) (no neoadjuvant therapy) at Tianjin Medical University Cancer Institute and Hospital (from January 2016 to December 2019). The detection of left RLN LNs using enhanced computed tomography (CT) was compared with the pathological examination. RESULTS: Of the total 94 participants, 43 had LN metastasis. The metastatic LNs were mainly located next to left (18.1%) and right (14.9%) RLN, and the left gastric artery (13.8%). Tumor size, LN size, tumor invasion (T stage), N stage, and tumor node metastasis (TNM) stage were associated with left RLN LNs metastasis, while LN size was the only independently associated factor [odds ratio (OR) =1.569, 95% confidence interval (CI): 0.259-1.956, P=0.0012]. The area under receiver operating characteristic (ROC) curve (AUC) reached 0.877, with 64% sensitivity and 75% specificity using a cutoff of 5.5 mm LN size. CONCLUSIONS: The size of left RLN LN is independently associated with metastasis. Left RLN LNs >5.5 mm at CT examination are more likely to be positive and should probably be dissected.