Search

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Economic development has led to a rapid increase in urban water consumption. The number of cities with water shortages nationwide is increasing. The establishment of a water resource circulation system is conducive to solving the urban water shortage. This study aims to investigate the restoration of the urban water environment landscape system and the integration of SWMM technology in cities with scarce water resources. For this objective, the meteorological situation of a city with water shortage in central China was used to establish the surface water hydrological model of Teaneck Creek. By establishing a data collection system at each meteorological point of the city, the USEPA SWMM model was implemented to simulate the movement of the urban sub-base system. The relationship model between the surface water flow and groundwater flow was established, and then the relationship between vegetation and soil was determined to formulate a plan for the restoration of a benign and environmentally friendly urban water environment landscape system. The established model can solve the urban water shortage problem. The results showed that the developed model was increased the utilization rate of water resources by about 20% and the urban greening rate by about 15%. The system will bring China a sustainable and eco-friendly urbanization process, which is of guiding significance for the production and development of cities with water shortages in China.

Purpose The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design. Materials and Methods Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method. Results Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS. Conclusion NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

ObjectiveTo determine predictors of malignancy in surgically treated Bethesda category III nodules.MethodsPatients with surgically treated thyroid nodules classified as Bethesda category III were retrospectively enrolled. The association between clinical/sonographic features and postoperative pathology was evaluated using univariate and multivariate analyses.ResultsA total of 188 nodules from 184 patients were included. The overall malignancy rate was 54.3%. In univariate analysis, male sex, aspect ratio >1, microcalcification, unclear boundary, BRAFV600E mutation, and nuclear atypia were significantly associated with malignant disease in Bethesda category III nodules. Multivariate analysis confirmed that male sex, aspect ratio >1, microcalcification, and BRAFV600E mutation were independent predictors of malignant disease.ConclusionsMalignant disease was common in Bethesda category III nodules, and surgical treatment was strongly indicated in the presence of male sex, aspect ratio>1, microcalcification, and BRAFV600E mutation.

BackgroundThis study aims to assess the association between positron emission tomography-computed tomography (PET-CT) parameters and the response to immune checkpoint inhibitors in unresectable head and neck squamous cell carcinoma (HNSCC).MethodsA total of 105 patients receiving immunotherapy (pembrolizumab or sintilimab with/without cisplatin) were retrospectively enrolled in this study; pretreatment data regarding metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) were collected. The primary interest of the study was objective response rate (ORR), and the secondary was progression−free survival (PFS).ResultsThe mean total MTV was 40.6 cm3 (range: 8.5–100.3), ORRs in tumors with total MTV of ≥40.6 and 3 were 43.1% and 23.1%, respectively; the difference was statistically significant (p = 0.018). Survival analysis indicated similar PFS rates in the two groups (p = 0.057). The mean total SUVmax was 12.5, ORRs in tumors with total SUVmax ≥12.5 and p = 0.092). Survival analysis reported patients with total SUVmax of ≥12.5 had significantly worse PFS (p = 0.001) than patients with total SUVmax of ConclusionsIn HNSCC, total MTV ≥40.6 cm3 translated into improved clinical response but not into better PFS; total SUVmax had no effect on clinical response, but total SUVmax ≥12.5 was associated with worse PFS.

ObjectiveThe lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is an important part of the central lymph nodes (LNs). We aimed to explore the rate and predictors of LN-prRLN metastasis in cN0 papillary thyroid carcinoma (PTC) located at the left thyroid lobe.MethodsPatients with surgically treated primary left lobe PTC were retrospectively enrolled. The metastatic distribution of LN-prRLN and postoperative complications were assessed. The association between LN-prRLN metastasis and clinicopathological variables was evaluated by univariate and multivariate analyses.ResultsA total of 857 patients were included for the analysis. Central LN metastasis was noted in 310 (35.3%) cases. The most (27.6%) and least (1.7%) commonly involved LNs were the left paratracheal LN and the LN-prRLN. In the univariate analysis, the tumor size, multifocality, the extent of extrathyroidal extension (none vs. macroscopic vs. macroscopic maximal), and perineural invasion were associated with positive LN-prRLN. In the multivariate analysis, tumor size of >40.0 mm and macroscopic maximal invasion were found as the only two independent predictors. Transient and permanent hypoparathyroidism were noted in 90 (10.2%) and 13 (1.5%) patients, respectively. Voice change was noted in 40 (4.6%) patients, and 20 patients recovered.ConclusionsIn cN0 PTC located at the left lobe, LN-prRLN metastasis was very uncommon. We found that LN-prRLN dissection is not required routinely, but should be performed if the tumor size is >40.0 mm and macroscopic maximal extrathyroidal extension is present.

Toripalimab, a humanized IgG4 monoclonal antibody (mAb) against programmed death receptor-1, is being extensively studied to treat various malignancies. At present, there is no complete methodology reported for quantifying toripalimab, except for an electrochemiluminescence immunoassay (ECLIA) mentioned in several clinical studies. Therefore, a sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to accurately detect toripalimab levels, compared with the ECLIA. Plasma samples were pretreated by a five-step process, encompassing denaturation, reduction, alkylation, enzymatic hydrolysis and quenching. And a unique, sensitive and stable enzymatic peptide (ASGYTFTDYEMHWVR) selected as surrogate of toripalimab was eluted and monitored by UPLC-MS/MS system with the linear range of 5.0375-201.5 μg/mL. After fully validated, the UPLC-MS/MS method was applied to determine 77 plasma samples from 29 patients in a phase I clinical trial, and compared with ECLIA based on 56 samples. Wilcoxon paired samples test showed toripalimab levels by UPLC-MS/MS were significantly higher than that by ECLIA (p 0.001), though a strong correlation was observed (r = 0.96). Moreover, Passing-Bablok regression analysis exhibited constant and proportional biases: UPLC-MS/MS = 2.25 + 1.21 * ECLIA. This discrepancy could be mainly attributed to different forms determined: total mAb for UPLC-MS/MS and free mAb for ECLIA, respectively. As a result, this UPLC-MS/MS method may be complementary to ECLIA to monitor different forms of toripalimab. Beyond that, it can be easily modified to simultaneously quantitate multiple-analyte with a small volume of plasma.

ObjectiveThe association between metastasis to the lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) and cN0 papillary thyroid carcinoma (PTC) located in the thyroid isthmus remains unknown; therefore, our goal was to analyze the characteristics of LN-prRLN metastasis of cN0 PTCs of the thyroid isthmus and determine its potential predictors.Patients and methodsThis retrospective study included patients who underwent bilateral central neck dissection between January 2018 and January 2021. The specimen was divided into five groups of prelaryngeal lymph node (LN), pretracheal LN, left paratracheal LN, lymph node anterior to the right recurrent laryngeal nerve (LN-arRLN), and LN-prRLN. Univariate and multivariate analyses were used to assess the association between the clinical pathologic variables and LN-prRLN metastases. Surgical complications were presented descriptively.ResultsA total of 357 patients were included, LN-prRLN metastasis occurred in 23 (6.4%) patients, and LN-prRLN was positive only when there were other LN metastases, especially LN-arRLN metastases. Other independent risk factors for LN-prRLN included foci numbers ≥2, tumor size ≥5.0 mm, and extrathyroidal extensions. The rates of permanent hypoparathyroidism and vocal cord paralysis were 1.1% and 2.0%, respectively.ConclusionLN-prRLN metastases should not be ignored in cN0 PTC located in the thyroid isthmus; however, its dissection is a safe procedure, and the status of LN-arRLN can be a reliable predictor for LN-prRLN metastases.

Background This study aimed to explore the efficacy and safety of sintilimab combined with induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. Methods A total of 163 patients were prospectively enrolled; 98 patients received IC only, and 65 patients received IC with sintilimab. Following neoadjuvant therapy, patients either underwent surgery (31.9%) or chemoradiotherapy (68.1%). Objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicities between the two groups were compared. Results The ORR in the IC group was significantly lower than that in the IC with sintilimab group (68.4% vs 84.6%, P = 0.019). Grade 3 or higher acute toxicity occurred in 15 (15.3%) and 12 (18.5%) patients in the IC and IC with sintilimab groups, respectively. However, this difference was not significant (P = 0.596). After follow-up with a median time of 28.0 months, the IC group had a 2-year PFS rate of 27% (95%CI: 18–36%), whereas the IC with sintilimab group had a 2-year PFS rate of 44% (95%CI: 32–56%), and this difference was significant (P = 0.041). The 2-year OS rates in the IC and IC with sintilimab groups were 61% (95%CI: 52–70%) and 70% (95%CI: 60–80%), respectively, the difference was not significant (P = 0.681). Conclusions Addition of sintilimab to IC could provide longer PFS time than traditional chemotherapy regimen, without increasing the toxicity events.

ObjectivesTo analyze the diagnostic benefit of fine needle aspiration biopsy cytology (FNAB-C) and core needle biopsy tissue (CNB-T) with the addition of thyroglobulin (Tg) in the washout of the needle or BRAF V600E mutation assessment in assessing cervical lymph node metastasis (LNM) in papillary thyroid carcinoma.Materials and MethodsA total of 186 lymph nodes were punctured by fine or core needle. The diagnostic performance of FNAB-C and CNB-T with Tg in the washout or BRAF V600E mutation assessment was compared.ResultsThe optimal cutoff value of FNAB-Tg was 1.0 ng/ml, with an AUC of 0.976. The sensitivity and specificity of FNAB-C in predicting cervical LNM were 97.4% and 71.4%, respectively, and the addition of FNAB-Tg could contribute to a sensitivity of 100% and a specificity of 95%, but the introduction of BRAF V600E mutation assessment was associated with a decreased sensitivity of 96.3% and a decreased specificity of 50.0%. The FNAB-Tg level showed a comparable distribution in malignant lymph nodes with different TgAb statuses, serum TSH levels, and serum Tg levels. The sensitivity and specificity of CNB-T in predicting cervical LNM were 98.9% and 100%, respectively. The addition of CNB-Tg did not alter the diagnostic ability, but the introduction of BRAF V600E mutation assessment obtained the best performance, with a sensitivity of 100% and specificity of 100%.ConclusionThe sensitivity and specificity of FNAB-C could be increased if combined with FNAB-Tg. CNB-T alone could provide satisfactory diagnostic reliability.

Taking the small watershed in Tanxia town as an example, the classified investigation of agricultural non-point source pollution in the tributaries of Lijiang River was carried out, the sources of local agricultural non-point source pollution were analyzed, and the surface water environmental quality standard and Nemero index method were used to evaluate the water quality of the basin. The results show that the water quality of the basin is poor and the pollution exceeds the standard all the year round, and the source of agricultural non-point source pollution mainly depends on the pollution of agricultural chemical fertilizer. Improving the use of local chemical fertilizer and rational application of chemical fertilizer are the key factors to improve local agricultural non-point source pollution.

Background The prevalence of potential risk factors for postoperative cough after thyroidectomy remain unknown. The current study aimed to research postoperative cough in patients undergoing thyroid surgery prospectively. Methods Adult patients who underwent primary thyroid surgery were selected prospectively. Data regarding age, sex, BMI, pathology and surgical procedure were collected and analyzed. The Leicester Cugh Questionnaire (LCQ) was required to be completed by all patients before operation, 2 weeks and 4 weeks after operation. Results There were 1264 patients enrolled in total. Eleven patients with vocal cord paralysis were excluded. In patients with benign disease, postoperative cough occurred in 61 patients, with an prevalence rate of 17. 0% compared to an prevalence rate of 33.1% in patients with malignant disease; the difference was significant. For benign patients, the factors of smoking and operation time were independently related to the occurrence of postoperative cough. For malignant patients, the factors of smoking, operation time, operation extent, and the number of positive nodes at level 6 were independently related to the occurrence of postoperative cough. There was no significant difference regarding the LCQ score in patients with benign or malignant disease at the preoperative and the postoperative 4-week time periods. Patients with malignant disease had a significantly lower LCQ score than patients with benign disease at the postoperative 2-week time point (p = 0.004). Conclusions Patients undergoing thyroid cancer surgery had a higher incidence of postoperative cough and were also associated with a decreased cough-related quality of life. The factors of smoking and operation time were the most important predictors for postoperative cough after thyroidectomy.

Objective. Recurrence is common after inappropriate surgical procedures for parotid pleomorphic adenoma (PA). However, there are some controversies regarding intraoperative tumor rupture and disease recurrence; therefore, our goal was to clarify this relationship by describing our experience with 128 cases of recurrent parotid PA. Methods. Patients suffering from a first recurrence of parotid PA were prospectively enrolled, and data regarding the operation, pathology, immunohistochemistry, and recurrence pattern (outside the previous surgical field vs. inside the previous surgical field) were extracted and analyzed. The recurrent lesions were divided into two groups based on the location of nodularity. Results. Thirty-five patients had recurrent disease outside the previous surgical field; there were 105 nodules with a mean size of 1.0 (range: 0.4–3.0) cm and 983 nodules with a mean size of 1.55 (range: 0.5–4.5) cm within the field, and the difference was significant ( p = 0.001 ). The mean values of Ki-67 in nodules outside of and within the previous surgical field were 4.7% (range: 2%–10%) and 2.1% (range: 1%–7%), respectively, and the difference was significant ( p < 0.001 ). In nodules outside the previous surgical field, cell-rich nodules were noted in 71.6% of cases; in nodules within the previous surgical field, cell-rich nodules were found in 30.4% of cases, and the difference was significant ( p < 0.001 ). Conclusion. Tumor rupture is not the only cause of disease recurrence, and recurrent PAs outside the previous surgical field are smaller in size, have higher Ki-67 expression, and have more cell-rich nodules than those within the surgical scar.

Objectives: Sarcomatoid carcinoma (SaCa) of the hypopharynx is rare, and its clinical pathologic characteristics and prognosis remain unknown. Therefore, the study aimed to analyze the oncologic outcomes of patients with SaCa of the hypopharynx. Methods: Patients with SaCa of the hypopharynx who were surgically treated in the period from January 1985 to December 2018 were enrolled from two clinical centers. A matched pair study was also performed, and each patient with SaCa of the hypopharynx was matched with one patient with squamous cell carcinoma of the hypopharynx. The main study endpoint was disease-specific survival (DSS). Results: A total of 62 patients (all male) were enrolled. Compared to patients with traditional squamous cell carcinoma of the hypopharynx, patients with SaCa of the hypopharynx were older and had higher rates of perineural invasion, lymphovascular invasion and cancer cachexia. The 5-year DSS rate was 20% in patients with SaCa compared to 34% in patients in the matched group, and the difference was significant (p=0.016). According to the univariate analysis, tumor stage, lymph node stage, disease stage, and cachexia were associated with DSS. According to the Cox model, neck lymph node metastasis and disease stage were independent predictors for worse DSS. Conclusion: The prognosis of patients with SaCa of the hypopharynx is dismal, and this type of SaCa is associated with more aggressive biological behavior than traditional squamous cell carcinoma of the hypopharynx; neck lymph neck node metastasis and disease stage were the most important predictors of disease-specific survival.

Objectives/hypothesis To analyze the prognostic value of a family cancer history for predicting survival in patients with oral tongue squamous cell carcinoma (SCC). Study design Retrospective case series. Methods Each patient with a family history was paired with one patient with sporadic oral tongue SCC without a family history. The primary endpoint was disease-specific survival (DSS). Results In total, 124 patients were enrolled as participants with a family cancer history, and the 5-year DSS rate was 51%. In the matched group, the 5-year DSS rate was 40%. The difference was significant (P = .032). In the smoking patients with a family history, the 5-year DSS rate was 43%. In the smoking patients from the matched group, the 5-year DSS rate was 17%; the difference was significant (P = .028). In nonsmoking patients with a history of cancer, the 5-year DSS rate was 51%; in nonsmoking patients in the matched group, the 5-year DSS rate was 40%; the difference was not significant (P = .141). Conclusions A family cancer history is associated with improved DSS in surgically treated oral tongue SCC patients. Level of evidence 4 Laryngoscope, 130:E605-E610, 2020.

Taking the planning and construction of Nanping Mountain Park in Chuzhou as an example, the ecological sponge system is constructed, and the urban ecological corridor formed by the green area formed by the park green area is used to construct the internal and external links in the park, and the natural resources and artificial facilities are used to construct the ecological system of road, green belt and water system. The park is fully integrated inside and outside the matrix, focusing on the construction of pervious pavement, grass planting ditch, rainwater garden, subsidence green space and vegetation buffer zone, using the rainwater strategy, purification strategy, conservation strategy, restoration strategy and plant ecological community strategy in the sponge system to achieve sustainable development in the green space environment of the public garden. It embodies the tolerance and development of “reciprocal symbiosis”.

Reservoir resettlement is accompanied by the construction of water conservancy and hydropower projects, which is closely related to the population, resources and environment problems facing the world today. Tibet is the only minority Tibetan inhabitant-dominated area in China. At present, the resettlement problem of land expropriation and resettlement brought about by hydropower projects is one of the difficulties affecting hydropower development in Tibet. Taking the Luola Hydropower Station in Tibet as an example, we analysis and evaluate the resettlement mode and suitability of the resettlement mode, and get corresponding conclusions.

Water resource scheduling is a key way to efficiently allocate regional water resources and enhance water use efficiency. This study takes the optimal scheduling of water resources in a certain area as an example. Aims to enhance the ecological, social and economic benefits in the scheduling area, and establish SD-MOP water resources optimal dispatch model. The results show that compared with the traditional SD model, the SD-MOP model predicts that the dispatch result in 2025 is closer to the actual water demand of the city, and saves the cost of 2.053 million yuan, and the pollutant discharge is only 0.891t, which brings considerable economic and environmental benefits.

To develop a 1,4-α-glucan branching enzyme (BE) without homology to known allergens, the glgB gene from Bifidobacterium longum was overexpressed under the control of BLMA promoter in Escherichia coli. B. longum BE (BlBE) had a molecular weight of 86.1 kDa and a specific activity of more than 18.5 U/mg protein at 25–35 °C and pH 5.5–7.0, and exhibited 30% of the maximum activity at 10 °C. The cold-active BlBE preferred to transfer maltohexaose and introduced DP 4–36 branches into amylose. BlBE also increased the proportion of DP 2–10 branches in amylopectin and decreased its Mw from 1.39 × 106 to 1.16 × 105 g/mol. As the BlBE concentration increased from 0.0 to 0.5 U/mg substrate, the retrogradation enthalpy of BlBE-modified wheat starch decreased from 4.50 to 1.83 J/g (p

Zhang, C.; Tang, X.; Dai, L.; Zhang, P., and Chi, Y., 2020. Application of sponge urban design concept in river watercourse landscape renovation. In: Yang, Y.; Mi, C.; Zhao, L., and Lam, S. (eds.), Global Topics and New Trends in Coastal Research: Port, Coastal and Ocean Engineering. Journal of Coastal Research, Special Issue No. 103, pp. 590–595. Coconut Creek (Florida), ISSN 0749-0208.With the rapid development of China's social economy, the urbanization process is accelerating, people's living standards are improving day by day, and the demand for resources is increasing. Especially water resources, which are closely related to people's lives, the development of water resources has been intensified. As an important way to store water resources, if it is not effectively managed, it will seriously affect the quality of water resources. Therefore, efforts should be made to improve river courses, the ecological restoration of river should be done well to ensure the stable and healthy development of the whole ecosystem. The concept of sponge urban design is an innovative understanding and development of the theory of rain-flood utilization. It is the improvement and enrichment of water environmental treatment methods and ideas under the new situation of our country. The planning and implementation of sponge city construction provides new ideas and methods to help solve urban water environment problems, it plays an important role in solving urban water environment problems. This article has made the preliminary explanation and the analysis, it mainly aims at the connotation, target and function of sponge city. And taking Luotian water comprehensive treatment as an example, the importance of developing and constructing sponge city in China under the new situation is analyzed in detail.

Gantangjiang River Basin was took as the object of study on non-point source pollution to establish a non-point source pollution model applicable to Gantangjiang River Basin based on SWAT model theory and make assess the applicability of the model. The relative error Res of monthly mean value was less than 25%, the monthly correlation coefficient R2 ranged from 0.72 to 0.89, and the monthly efficiency coefficient Ens was not less than 0.5, with a good fitting effect. This study demonstrated that it was feasible to simulate the non-point source pollution along the Gantangjiang River Basin, based on SWAT model. The simulation result showed that the load capacity of non-point source pollution in knowable basin changed in an irregular "W" trend as months went by. The rainfall intensity and capacity influence the pollution load in a certain extent.