Highly efficient clustering of long-read transcriptomic data with GeLuster.

MOTIVATION: The advancement of long-read RNA sequencing technologies leads to a bright future for transcriptome analysis, in which clustering long reads according to their gene family of origin is of great importance. However, existing de novo clustering algorithms require plenty of computing resources. RESULTS: We developed a new algorithm GeLuster for clustering long RNA-seq reads. Based on our tests on one simulated dataset and nine real datasets, GeLuster exhibited superior performance. On the tested Nanopore datasets it ran 2.9-17.5 times as fast as the second-fastest method with less than one-seventh of memory consumption, while achieving higher clustering accuracy. And on the PacBio data, GeLuster also had a similar performance. It sets the stage for large-scale transcriptome study in future. AVAILABILITY AND IMPLEMENTATION: GeLuster is freely available at https://github.com/yutingsdu/GeLuster.

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

TGF-ß1 and TGF-ßR1 variants are associated with clinical outcomes in smoking-related head and neck cancer patients treated with chemoradiation through modulating microRNA-mediated regulation.

TGF-ß1 and TGF-ßR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-ß1 rs1800470 and TGF-ßR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-ß1 rs1800470 and TGF-ßR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-ß1 and TGF-ßR1 and survivals. Patients with TGF-ß1 rs1800470 CT or CC genotype had 30-35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-ßR1 rs334348 GA or GG genotype had significant 50-60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60-70%. The TCGA dataset was used for validation. These findings suggest that TGF-ß1 rs1800470 and TGF-ßR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life.

Potentially functional variants of CHMP4A and PANX1 in the pyroptosis-related pathway predict survival of patients with non-oropharyngeal head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC). METHODS: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the pyroptosis-related genes and survival of patients with NON-ORO HNSCC. Bayesian false discovery probability (BFDP) was used for multiple testing correction. Functional annotation was applied to the identified survival-associated genetic variants. RESULTS: There are 8254 single-nucleotide polymorphisms (SNPs) located in 82 pyroptosis-related genes, of which 202 SNPs passed multiple testing correction with BFDP < 0.8 in the discovery and six SNPs retained statistically significant in the replication. In subsequent stepwise multivariable Cox regression analysis, two independent SNPs (CHMP4A rs1997996 G > A and PANX1 rs56175344 C > G) remained significant with an adjusted hazard ratios (HR) of 1.31 (95% confidence interval [CI] = 1.09-1.57, p = 0.004) and 0.65 (95% CI = 0.51-0.83, p = 0.0005) for overall survival (OS), respectively. Further analysis of the combined genotypes revealed progressively worse OS associated with the number of unfavorable genotypes (ptrend < 0.0001 and 0.021 for OS and disease-specific survival, respectively). Moreover, both PANX1 rs56175344G and CHMP4A rs1997996A alleles were correlated with reduced mRNA expression levels. CONCLUSIONS: Genetic variants in the pyroptosis pathway genes may predict the survival of NON-ORO HNSCC patients, likely by reducing the gene expression, but our findings need to be replicated by larger studies.

Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

Involvement of M2 macrophages polarization in PM2.5-induced COPD by upregulating MMP12 via IL4/STAT6 pathway.

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

scQA: A dual-perspective cell type identification model for single cell transcriptome data.

Single-cell RNA sequencing technologies have been pivotal in advancing the development of algorithms for clustering heterogeneous cell populations. Existing methods for utilizing scRNA-seq data to identify cell types tend to neglect the beneficial impact of dropout events and perform clustering focusing solely on quantitative perspective. Here, we introduce a novel method named scQA, notable for its ability to concurrently identify cell types and cell type-specific key genes from both qualitative and quantitative perspectives. In contrast to other methods, scQA not only identifies cell types but also extracts key genes associated with these cell types, enabling bidirectional clustering for scRNA-seq data. Through an iterative process, our approach aims to minimize the number of landmarks to approximately a dozen while maximizing the inclusion of quasi-trend-preserved genes with dropouts both qualitatively and quantitatively. It then clusters cells by employing an ingenious label propagation strategy, obviating the requirement for a predetermined number of cell types. Validated on 20 publicly available scRNA-seq datasets, scQA consistently outperforms other salient tools. Furthermore, we confirm the effectiveness and potential biological significance of the identified key genes through both external and internal validation. In conclusion, scQA emerges as a valuable tool for investigating cell heterogeneity due to its distinctive fusion of qualitative and quantitative facets, along with bidirectional clustering capabilities. Furthermore, it can be seamlessly integrated into border scRNA-seq analyses. The source codes are publicly available at https://github.com/LD-Lyndee/scQA.

Numerical Simulation and Parameter Optimization for Water-to-CO2 Flooding in a Strongly Water-Sensitive Reservoir.

Carbon dioxide flooding can accelerate the development of low-permeability reservoirs of the Kexia group in the K region of the T oil field, thus resolving the issue of inadequate water drive effects. This study was focused on the well group 80513 in the K region, and based on the reservoir and fluid parameters, a simulation model of water-sensitive post-CO2 flooding was constructed to refine the gas injection strategy gradually. The injection rate of the continuous gas injection stage was preferred based on the degree of recovery. Multiindicator and multifactor injection and extraction schemes were established to optimize and analyze the key controlling factors, including the gas injection rate, gas injection period, gas-to-water ratio, and bottom-hole flow pressure, in the carbon dioxide gas-to-water alternation process. Recovery efficiency, oil exchange rate, formation pressure, and carbon dioxide storage rate were used as indicators. After 5 years of continuous CO2 flooding, the results indicated that switching to CO2 gas-water alternating flooding was more appropriate for the target block's environment. The best development plan was achieved when the gas injection rates were 1.0 and 1.25 × 104 m3·d-1 for continuous gas injection and CO2 gas-water alternating flooding, respectively, with a gas-water ratio of 1:1, a gas injection cycle of 90 days, and a bottom-hole flow pressure of 25 MPa in the production wells. A comparison between the results revealed that the formation pressure and oil recovery efficiency of this well group significantly increased upon CO2 flooding, and the parameter optimization results were well suited for controlling the gas flurry, offering a versatile model for future development of the block.

Epitaxial growth of Bi4Ti3O12-BiPO4 Z-scheme heterojunction to promote carrier transfer for photocatalytic oxidation of NO.

The lack of compactness in heterojunction interfaces and poor charge separation is a great challenge in developing high-efficiency heterojunction photocatalysts. Herein, a novel Bi4Ti3O12-BiPO4 heterojunction was successfully prepared for the first time by epitaxial growth of BiPO4 on the surface of Bi4Ti3O12 nanosheets. The optimized Bi4Ti3O12-BiPO4-0.5 increased the NO oxidation efficiency to 73.05%, surpassing pure Bi4Ti3O12 (63.45%) and BiPO4 (8.35%). Experiments and theoretical calculations indicated that the closely contacted heterointerface between BTO and BPO promoted the generation of the built-in electric field, which led to the formation of the Z- scheme transfer pathway for the photogenerated carriers. Therefore, the separation of photogenerated carriers was facilitated while retaining high redox potential, generating more ·O2- and ·OH to participate in NO oxidation. Furthermore, the adsorption of NO and O2 was enhanced by introducing BiPO4, further improving the photocatalytic NO oxidation performance. This work emphasizes the critical role of heterointerface in accelerating charge transfer, providing a basis for the design and construction of tightly contacted heterojunction photocatalysts.

FP-Zernike: An Open-source Structural Database Construction Toolkit for Fast Structure Retrieval.

The release of AlphaFold2 has sparked a rapid expansion in protein model databases. Efficient protein structure retrieval is crucial for the analysis of structure models, while measuring the similarity between structures is the key challenge in structural retrieval. Although existing structure alignment algorithms can address this challenge, they are often time-consuming. Currently, the state-of-the-art approach involves converting protein structures into three-dimensional (3D) Zernike descriptors and assessing similarity using Euclidean distance. However, the methods for computing 3D Zernike descriptors mainly rely on structural surfaces and are predominantly web-based, thus limiting their application in studying custom datasets. To overcome this limitation, we developed FP-Zernike, a user-friendly toolkit for computing different types of Zernike descriptors based on feature points. Users simply need to enter a single line of command to calculate the Zernike descriptors of all structures in customized datasets. FP-Zernike outperforms the leading method in terms of retrieval accuracy and binary classification accuracy across diverse benchmark datasets. In addition, we showed the application of FP-Zernike in the construction of the descriptor database and the protocol used for the Protein Data Bank (PDB) dataset to facilitate the local deployment of this tool for interested readers. Our demonstration contained 590,685 structures, and at this scale, our system required only 4-9 s to complete a retrieval. The experiments confirmed that it achieved the state-of-the-art accuracy level. FP-Zernike is an open-source toolkit, with the source code and related data accessible at https://ngdc.cncb.ac.cn/biocode/tools/BT007365/releases/0.1, as well as through a webserver at http://www.structbioinfo.cn/.

Built-in electric field mediated S-scheme charge migration and Co-N4(II) sites in cobalt phthalocyanine/MIL-68(In)-NH2 heterojunction for boosting photocatalytic nitric oxide oxidation.

The efficiency of photocatalytic Nitric Oxide(NO) oxidation is limited by the lack of oxygen(O2) active sites and poor charge carrier separation. To address this challenge, we developed a molecular Cobalt Phthalocyanine modified MIL-68(In)-NH2 photocatalyst with a robust Built-in electric field(BIEF). In the 2 % CoPc-MIN sample, the BIEF strength is increased by 3.54 times and 5.83 times compared to pristine CoPc and MIL-68(In)-NH2, respectively. This BIEF facilitates the efficient S-scheme charge transfer, thereby enhancing photogenerated carrier separation. Additionally, the Co-N4(II) sites in CoPc can effectively trap the separated photoexcited electrons in the S-scheme system. In addition, the Co-N4(II) sites can also serve as active sites for O2 adsorption and activation, promoting the generation of superoxide radical (O2-), thereby driving the direct conversion of NO to nitrate(NO3-). Consequently, the 2 % CoPc-MIN sample exhibits a remarkable photocatalytic NO removal efficiency of 79.37 % while effectively suppressing the formation of harmful by-product nitrogen dioxide(NO2) to below 3.5 ppb. This study provides a feasible strategy for designing high-efficiency O2 activation photocatalysts for NO oxidation.

Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis.

BACKGROUND: Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. METHODS: The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. RESULTS: ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e-6). CONCLUSIONS: Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9.

An automatic measurement method for the response of Caenorhabditis elegans to chemicals.

BACKGROUND: Caenorhabditis elegans is a widely used model animal. Chemotaxis assay is one of the experiments that study the effects of different chemicals on nematodes. It is mainly used to study the effects of different chemicals on the perception behavior of nematodes. By conducting this experiment, not only can the neurotoxicity of chemicals be reflected, but also the impact of chemicals on physiological functions regulated by the nervous system, such as nematode feeding behavior and basic motor ability. OBJECTIVE: The experiment of detecting the response of nematode to chemicals is also a common method of chemical toxicity testing based on nematode models. In the analysis of worm tendency behavior, manual operations are generally used. Manually processing a large number of worms under a microscope is very time-consuming and labor-intensive. The current quantitative methods for nematode chemotaxis experiments are not only time-consuming and labor-intensive, but also biased in experimental results due to differences in judgment standards among experimenters. The automatic and efficient quantification method for nematode chemotaxis experiments is a very important technical difficulty in the field of nematode experiments. METHODS: Here, we have designed an automatic quantification method for nematode chemotaxis experiments by incorporating image acquisition and processing techniques into the nematode experiment. RESULTS: The experimental results show that the Pearson correlation coefficient between manual and automatic counting results is 0.978. CONCLUSION: This proves the effectiveness of our method. Applying the automatic measurement method to replace manual counting by the experimenter can improve work efficiency, and reduce errors in human counting operations.

Traditional Chinese Medicine JianPiHuaTan formula improving quality of life and survival in patients with colorectal cancer through RAS/RAF downstream signaling pathways.

Objective: JianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth. Methods: 300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF. Results: JPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration. Conclusion: These findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration.

Impact of pretreatment body mass index on the survival of head and neck cancer patients.

BACKGROUND: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. METHODS: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. RESULTS: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. CONCLUSIONS: This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Efficacy and feasibility of self-made negative pressure reflux system combined with rigid ureteroscope in the treatment of upper ureteral calculi in exercise-minded patients

Objective: To explore the efficacy and feasibility of self-made negative pressure reflux system combined with rigid ureteroscopy in the treatment of upper ureteral calculi.Methods: The clinical data of 379 Exercise-minded patients with upper ureteral calculi treated in our hospital from January 2018 to August 2022 were analyzed retrospectively. F8.0/9.8STORZ ureteroscope was used to explore the ureteral opening on the affected side, and then the 200μm wavelength holmium laser fiber and F4 ureteral catheter were inserted into the stone incarceration site through the rigid ureteroscope, and the residual stone fragments which were clinically meaningless (the maximum diameter of the stone < 2mm) were completely sucked out by negative pressure reflux system.Results: A total of 379 Exercise-minded patients were included in this study, with a one-time success rate of 97.1% (368/379), aged 26 to 76 years, with an average of (47.5) years. Most of the Exercise-minded patients (63.2%) had low back pain and hematuria before operation. The average diameter of stone was 0.8cm~2.8cm, the mean diameter of the stone was 1.8±1.0 cm.The operation time ranged from 18min to 52min, with an average of (37.86±25.64)min.The average length of hospital stay was (2.7±1.7) days (range, 1-8 days). On the first day after operation, the stone clearance rate was 84.43% (320/379), and the stone clearance rate was 90.77% (344/379) 3 months after operation. Among them, 4 Exercise-minded patients developed fever and 6 Exercise-minded patients had mild urinary fistula or renal pelvis perforation. Stone composition analysis was mainly ammonium phosphate stones and calcium oxalate stones.Conclusion: The treatment of upper ureteral calculi with self-made negative pressure reflux system combined with hard ureteroscope has the advantages of high stone clearance rate, low complications and greatly reducing the utilization rate of soft lens，and had high clinical promotion value. (AU)

Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer / Factores clinicopatológicos predictivos de metástasis ganglionares cervicales en el cáncer de tiroides diferenciado

BACKGROUND: Cervical lymph node metastasis (LNM) has been proven to be a predictor for locoregional recurrence in differentiated thyroid carcinoma (DTC). Clinicopathological features could be effective predictive factors for central and lateral LNM of DTC, and provide references to surgeons for cervical neck dissection. METHODS: Retrospective analysis of clinicopathological data was performed on 420 patients who underwent initial surgery from 2010 to 2015. RESULTS: The incidence of central and lateral LNM was calculated. Of 420 patients, 247 (58.8%) exhibited central LNM, and 185 (44.1%) exhibited lateral LNM. There were 29 (6.9%) cases confirmed to have skip metastasis. Univariate and multivariate analysis revealed that tumour location, tumour size, multifocality, capsular invasion, affected lobes, and age were independent predictors of central LNM. Tumour location, capsular invasion, affected lobes, and tumour size were independent predictors of lateral LNM. CONCLUSIONS: Our findings suggest that tumour location, affected lobes, capsular invasion, age, tumour size and multifocality may be taken as predictive factors for cervical LNM of DTC. Meticulous perioperative evaluation of cervical LNM and prophylactic cervical lymph node dissection that aims to remove the occult lymph nodes may be an option for DTC with risk factors

ANTECEDENTES: Las metástasis ganglionares cervicales (LNM) han demostrado ser un factor predictivo de recidiva locorregional en el cáncer de tiroides diferenciado (DTC). Las características clinicopatológicas podrían ser factores predictivos efectivos para LNM central y lateral en el DTC, y aportar referencias a los cirujanos de cara a la disección de los ganglios del cuello. MÉTODOS: Análisis retrospectivo de datos clinicopatológicos realizado en 420 pacientes sometidos a cirugía inicial desde 2010 a 2015. RESULTADOS: Se calculó la incidencia de las LNM centrales y laterales. De los 420 pacientes, 247 (58,8%) reflejaron LNM central y 185 (44,1%) LNM lateral. Se produjeron 29 (6,9%) casos confirmados de metástasis discontinuas. El análisis univariante y multivariante reveló que la localización, el tamaño del tumor, la multifocalidad, la invasión capsular, los lóbulos afectados y la edad eran factores predictivos independientes de la LNM central. La localización tumoral, la invasión capsular, los lóbulos afectados y el tamaño del tumor eran factores predictivos independientes de la LNM lateral. CONCLUSIONES: Nuestros hallazgos indican que la localización tumoral, los lóbulos afectados, la invasión capsular, la edad, el tamaño del tumor y la multifocalidad pueden considerarse factores predictivos para la LNM cervical de DTC. La evaluación meticulosa perioperativa de la LNM cervical y la disección profiláctica de los ganglios cervicales, cuyo objetivo es extirpar los ganglios ocultos, puede ser una opción para el DTC con factores de riesgo