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Abstract Background The mutations of oncogenic epidermal growth factor receptor (EGFR) is an important cause of lung adenocarcinoma (LUAD) malignance. It has been knowm that metabolic reprogramming is an important hallmark of malignant tumors, and purine metabolism is a key metabolic pathway for tumor progression and drug resistance, but its relationship with the EGFR-mutant LUAD is unclear. Methods Metabolic reprogramming was studied through capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolic profiling analysis. Cell proliferation in vitro was evaluated by EdU staining and cell cycle assay. Tumorigenicity in vivo was tested by subcutaneous tumor formation experiment in nude mice. The binding of hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was detected by DNA pull‑down assay and Chromatin immunoprecipitation (ChIP) assays. HIF-1α, HPRT1, DNA damage and cell apoptosis related genes were examined by western blot. In addition, RNA sequencing, mass spectrometry and bioinformatics analysis were performed. Results We found that mutated EGFR (muEGFR) upregulates HPRT1 to promote purine metabolism and tumorigenesis of EGFR-mutant LUAD. Mechanistically, muEGFR increases HIF-1α expression through protein stability. Meanwhile, up-regulated HIF-1α bound to the promoter of HPRT1 and transcriptionally activates HPRT1 expression, enhancing purine metabolism to maintain rapid tumor cell proliferation in EGFR-mutant LUAD. Further, gefitinib inhibited the synthesis of purine nucleotides, and HPRT1 inhibition increased the sensitivity of gefitinib to EGFR-mutant LUAD. Conclusions Our study reveals that muEGFR-HIF-1α-HPRT1 axis plays a key role in EGFR-mutant LUAD and provides a new strategy-inhibiting purine metabolism for treating EGFR-mutant LUAD.

Abstract Background Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant cause of cancer-related mortality, with drug resistance posing a substantial obstacle to effective therapy. LncRNAs have emerged as pivotal regulators of NSCLC progression, suggesting potential targets for cancer diagnosis and treatment. Therefore, identifying new lncRNAs as therapeutic targets and comprehending their underlying regulatory mechanisms are crucial for treating NSCLC. Materials and methods RNA-sequencing data from 149 lung adenocarcinoma (LUAD) patients, including 130 responders and 19 nonresponders to primary treatment, were analyzed to identify the most effective lncRNAs. The effects and regulatory pathways of the selected lncRNAs on NSCLC and cisplatin resistance were investigated. Results Glioblastoma-downregulated RNA (GLIDR) was the most effective lncRNA in nonresponsive NSCLC patients undergoing primary treatment, and it was highly expressed in NSCLC patients and those with cisplatin-resistant NSCLC. Reducing GLIDR expression enhanced cisplatin sensitivity in resistant NSCLC and decreased the malignant characteristics of NSCLC. Moreover, bioinformatic analysis and luciferase assays revealed that microRNA-342-5p (miR-342-5p) directly targets GLIDR. MiR-342-5p overexpression inhibited NSCLC cell proliferation, migration, and invasion, whereas miR-342-5p inhibition promoted NSCLC malignancy, which was rescued by suppressing GLIDR. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) was identified as a downstream target of miR-342-5p. PPARGC1A inhibition increased cisplatin sensitivity in resistant NSCLC. Moreover, PPARGC1A inhibition suppresses NSCLC malignancy, whereas PPARGC1A overexpression promoted it. Furthermore, GLIDR overexpression was found to counteract the inhibitory effects of miR-342-5p on PPARGC1A, and increased PPARGC1A expression reversed the inhibition of NSCLC malignancies caused by decreased GLIDR. Conclusions GLIDR is a prognostic marker for cisplatin treatment in NSCLC and a therapeutic target in cisplatin-resistant NSCLC. GLIDR promotes NSCLC progression by sponging miR-342-5p to regulate PPARGC1A expression and regulates cisplatin resistance through the miR-342-5p/PPARGC1A axis, underscoring its potential as a therapeutic target in cisplatin-resistant NSCLC.

Abstract Background This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. Methods This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. Results A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P

Abstract Objective To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). Methods PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. Results Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P

Abstract Objective This study aimed to explore the feasibility and advantages of a modified chest tube suture-fixation technique in uniportal video-assisted thoracic surgery for pulmonary resection. Methods A retrospective analysis was conducted on 116 patients who underwent uniportal video-assisted thoracic surgery (U-VATS) for lung diseases in Zhengzhou People’s Hospital between October 2019 and October 2021. Patients were stratified into two groups based on the applied suture-fixation methods, i.e., 72 patients in the active group and 44 patients in the control group. The two groups were subsequently compared in the terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, chest tube removal time, wound healing grade, length of hospital stay, incision healing grade, and patient satisfaction. Results There was no significant difference between the two groups in terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, and length of hospital stay (P = 0.167, 0.185, 0.085, 0.051, 0.927, and 0.362, respectively). However, the chest tube removal time, incision healing grade, and incision scar satisfaction in the active group were significantly better compared with those of the control group (P =

Abstract Background As the preoperative examination of esophageal cancer has improved, the likelihood of finding diseases in other organs that require surgical treatment has also increased. The purpose of this study was to explore the feasibility of combined surgery for esophageal cancer by analyzing the occurrence of postoperative complications in patients with esophageal cancer. Methods The clinical characteristics of 1566 patients with esophageal cancer who underwent thoracic surgery in our hospital between January 2017 and September 2022 were analyzed retrospectively. The feasibility of combined surgery for esophageal cancer was analyzed by comparing postoperative complications in patients who underwent simple esophageal cancer surgery (SEC) with those in patients who underwent combined surgery for esophageal cancer (COEC). The tendency scores of patients in the COEC and SEC groups (1:2) were matched to balance the confounding clinical factors, and the difference in postoperative complications was further analyzed. Moreover, we performed a subgroup analysis of esophagectomy combined with lung resection (ECL). In addition, the independent risk factors for postoperative Clavien–Dindo ≥ grade III complications of esophageal cancer were analyzed by multivariate logistic regression. Results A total of 1566 patients (1147 (73.2%) males and 419 (26.8%) females), with an average age of 64.2 years, were analyzed. There was no significant difference in postoperative complications between the SEC and COEC groups according to the Clavien-Dindo classification (P=0.713). An analysis of the complications revealed that those in the COEC group had a higher incidence of lung consolidation than those in the SEC group (P=0.007). However, when we performed propensity score matching (PSM) on the SEC and COEC groups, there was still no significant difference in complications according to the Clavien–Dindo classification (P=0.346); furthermore, when a detailed analysis of complications was performed, there was no significant difference between the two. In subgroup analysis, after we performed PSM in ECL patients and SEC patients, we also found no significant difference in postoperative complications between patients with ECL and patients with SEC. In addition, we found that a history of diabetes (OR=1.604, P=0.029, 95% CI=1.049–2.454), a history of coronary heart disease (OR=1.592, P=0.046, 95% CI=1.008–2.515), diffusing capacity of the lungs for carbon monoxide (DLCO) (OR=0.916, P=0.024, 95% CI=0.849–0.988), and ALB level (OR=0.955, P=0.007, 95% CI=0.924–0.987) were independent factors that influenced postoperative complications in esophageal cancer patients with grade III or higher complications. Conclusion Combined surgery for esophageal cancer does not increase the incidence of postoperative complications. In addition, a history of diabetes mellitus or coronary heart disease, carbon monoxide dispersion, and preoperative ALB level are independent risk factors for grade III or higher postoperative complications of esophageal cancer.

Abstract Objective To discuss the application of bilateral simultaneous sequential single-incision video-assisted thoracic surgery in multiple nodules in both lungs. Methods A retrospective analysis of 10 patients in Zhengzhou People’s Hospital who underwent single-incision thoracoscopic surgery to treat multiple nodules in both lungs at the same time from September 2019 to January 2021, and analyze the perioperative indicators (general condition, smoking history, family history, follow-up time of pulmonary nodules, size, location, height and weight, pulmonary function, intraoperative blood loss, operation time, color and volume of drainage fluid, catheterization time, perioperative complications, length of stay, pathology, patient satisfaction, etc.). Results All 10 patients used single-incision thoracoscopy to complete bilateral simultaneous sequential operations, aged 32 to 70 years, 8 female patients, 2 male patients, preoperative follow-up time ranging from 1 day to 2 years, a total of 23 lung nodules were removed except for the benign lesions in one nodule in the 2 patients, the other nodules were tumorous lesions (91.3%). The average total hospital stay was 10.5 days (8–14 days), and the average operation time was 194.5 min (145–292 min). The blood loss ranged from 10 to 280 ml, all patients had no serious complications during the perioperative period, and they recovered well and were discharged smoothly, and the satisfaction reached 100%. Conclusion Single-incision bilateral simultaneous sequential thoracoscopy have certain advantages in the treatment of patients with multiple nodules in both lungs, conforms to the concept of rapid recovery, and is a feasible choice in the shared decision making of doctors and patients.

Abstract Background RNA preparations contaminated with genomic DNA (gDNA) are frequently disregarded by RNA-seq studies. Such contamination may generate false results; however, their effect on the outcomes of RNA-seq analyses is unknown. To address this gap in our knowledge, here we added different concentrations of gDNA to total RNA preparations and subjected them to RNA-seq analysis. Results We found that the contaminating gDNA altered the quantification of transcripts at relatively high concentrations. Differentially expressed genes (DEGs) resulting from gDNA contamination may therefore contribute to higher rates of false enrichment of pathways compared with analogous samples lacking numerous DEGs. A strategy was developed to correct gene expression levels in gDNA-contaminated RNA samples, which assessed the magnitude of contamination to improve the reliability of the results. Conclusions Our study indicates that caution must be exercised when interpreting results associated with low-abundance transcripts. The data provided here will likely serve as a valuable resource to evaluate the influence of gDNA contamination on RNA-seq analysis, particularly related to the detection of putative novel gene elements.

Abstract Background Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. Methods First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. Results First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. Conclusions Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

Abstract We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.

Abstract Background Enchondromas originating in the epiphyses of long bones are rare and epiphyseal osteoid osteomas are also uncommon. Diagnosis can become elusive when enchondromas or osteoid osteomas occur in atypical locations and present with nonspecific clinical and imaging characteristics. Case presentation We report a case of epiphyseal enchondroma of the left proximal femur in a 15-year-old girl with a 2-month history of left lower extremity pain. Preoperative CT displayed thickened cortex in the anterior surface of the left proximal femur with specks of calcification and inhomogeneity of the adjacent bone marrow cavity. She was diagnosed with osteoid osteoma. Postoperative pathological examination of surgically excised specimens revealed a diagnosis of enchondromas. Conclusions Our case highlights that enchondroma should be considered in lesions of the epiphysis.

Abstract Background Chronic allograft injury (CAI) is a significant reason for which many grafts were lost. The study was conducted to assess the usefulness of diffusional kurtosis imaging (DKI) technology in the non-invasive assessment of CAI. Methods Between February 2019 and October 2019, 110 renal allograft recipients were included to analyze relevant DKI parameters. According to estimated glomerular filtration rate (eGFR) (mL/min/ 1.73 m2) level, they were divided to 3 groups: group 1, eGFR ≥ 60 (n = 10); group 2, eGFR 30–60 (n = 69); group 3, eGFR

Abstract Background The 100-pod fresh weight (PFW), 100-seed fresh weight (SFW), 100-seed dry weight (SDW) and moisture content of fresh seeds (MCFS) at the R6 stage are crucial factors for vegetable soybean yield. However, the genetic basis of yield at the R6 stage remains largely ambiguous in soybean. Results To better understand the molecular mechanism underlying yield, we investigated four yield-related traits of 133 soybean landraces in two consecutive years and conducted a genome-wide association study (GWAS) using 82,187 single nucleotide polymorphisms (SNPs). The GWAS results revealed a total of 14, 15, 63 and 48 SNPs for PFW, SFW, SDW and MCFS, respectively. Among these markers, 35 SNPs were repeatedly identified in all evaluated environments (2015, 2016, and the average across the two years), and most co-localized with yield-related QTLs identified in previous studies. AX-90496773 and AX-90460290 were large-effect markers for PFW and MCFS, respectively. The two markers were stably identified in all environments and tagged to linkage disequilibrium (LD) blocks. Six potential candidate genes were predicted in LD blocks; five of them showed significantly different expression levels between the extreme materials with large PFW or MCFS variation at the seed development stage. Therefore, the five genes Glyma.16g018200, Glyma.16g018300, Glyma.05g243400, Glyma.05g244100 and Glyma.05g245300 were regarded as candidate genes associated with PFW and MCFS. Conclusion These results provide useful information for the development of functional markers and exploration of candidate genes in vegetable soybean high-yield breeding programs.

Abstract Background The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known. Methods In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences. A total of 1991 volunteers were recruited from local villages and Plasmodium subclinical infections were estimated by light microscopy (LM), rapid diagnostic tests (RDTs) and nested PCR. The nested PCR analysis was performed with a modified pooling strategy that was optimized based on an initial estimate the infection prevalence. Results The overall malaria infection prevalence based on all methods was 13.9% (277/1991) and it differed drastically among the townships, with Paletwa in the western border having the highest infection rate (22.9%) and Thabeikkyin in central Myanmar having the lowest (3.9%). As expected, nested PCR was the most sensitive and identified 226 (11.4%) individuals with parasite infections. Among the parasite species, Plasmodium vivax was the most prevalent in all locations, while Plasmodium falciparum also accounted for 32% of infections in the western township Paletwa. Two RDTs based on the detection of the hrp2 antigen detected a total of 103 P. falciparum infections, and the ultrasensitive RDT detected 20% more P. falciparum infections than the conventional RDT. In contrast, LM missed the majority of the subclinical infections and only identified 14 Plasmodium infections. Conclusions Cross-sectional surveys identified considerable levels of asymptomatic Plasmodium infections in endemic populations of Myanmar with P. vivax becoming the predominant parasite species. Geographical heterogeneity of subclinical infections calls for active surveillance of parasite infections in endemic areas. The pooling scheme designed for nested PCR analysis offers a more practical strategy for large-scale epidemiological studies of parasite prevalence. Such information is important for decision-makers to put forward a more realistic action plan for malaria elimination.

Abstract Background Porcine circovirus type 3 (PCV3) is an emerging circovirus species, that has been reported in major pig-raising countries including the United States, China, South Korea, Brazil, Spain, and Poland. Results A real-time loop-mediated isothermal amplification (LAMP) assay was developed for rapid detection of porcine circovirus 3 (PCV3). The method had a detection limit of 1 × 101 copies/μL with no cross-reactions with classical swine fever virus (CSFV) C strain, foot-and-mouth disease virus (FMDV), porcine circovirus 2 (PCV2) LG vaccine strain, porcine epidemic diarrhoea virus (PEDV), porcine respiratory and reproductive syndrome virus (PRRSV), or pseudorabies virus (PRV). The PCV3 positive detection rate of 203 clinical samples for the real-time LAMP assay was 89.66% (182/203). Conclusions The real-time LAMP assay is highly sensitive, and specific for use in epidemiological investigations of PCV3.

Abstract Background Chicken anemia virus (CAV), avian reovirus (ARV), infectious bursal disease virus (IBDV), Marek’s disease virus (MDV) and reticuloendotheliosis virus (REV) all cause immunosuppressive disease in birds through vertical or horizontal transmission. Mixed infections with these immunosuppressive pathogens lead to atypical clinical signs and obstruct accurate diagnoses and epidemiological investigations. Therefore, it is essential to develop a high-throughput assay for the simultaneous detection of these immunosuppressive viruses with high specificity and sensitivity. The aim of this study was to establish a novel method using a RT-PCR assay combined with fluorescence labeled polystyrene bead microarray (multiplex xTAG assay) to detect single or mixed viral infections. Results The results showed that the established xTAG assay had no nonspecific reactions with avian influenza virus (AIV), infectious bronchitis virus (IBV), newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS). The limit of detection was 1.0 × 103 copies/μL for IBDV and 1.0 × 102copies/μL for the other four viruses. Ninety field samples were tested and the results were confirmed using conventional RT-PCR methods. The detection results of these two methods were 100% consistent. The established multiplex xTAG assay allows a high throughput and simultaneous detection of five chicken immunosuppressive viruses. Conclusion The multiplex xTAG assay has been showed to be an additional tool for molecular epidemiology studies of five chicken immunosuppressive viruses in the poultry industry.