A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification.

Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3' UTR of TAPBP, was further validated in a case-control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13-1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC.

Investigation on the effectiveness of ventilation dilution on mitigating COVID-19 patients' secondary airway damage due to exposure to disinfectants.

Chlorine-containing disinfectants are widely used in hospitals to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection. Meanwhile, ventilation is a simple but effective means to maintain clean air. It is essential to explore the exposure level and health effects of coronavirus disease 2019 patients' inhalation exposure to by-products of chloride-containing disinfectants under frequent surface disinfection and understand the role of ventilation in mitigating subsequent airway damage. We determined ventilation dilution performance and indoor air quality of two intensive care unit wards of the largest temporary hospital constructed in China, Leishenshan Hospital. The chloride inhalation exposure levels, and health risks indicated by interleukin-6 and D-dimer test results of 32 patients were analysed. The mean ± standard deviation values of the outdoor air change rate in the two intensive care unit wards were 8.8 ± 1.5 h-1 (Intensive care unit 1) and 4.1 ± 1.4 h-1 (Intensive care unit 2). The median carbon dioxide and fine particulate matter concentrations were 480 ppm and 19 µg/m3 for intensive care unit 1, and 567 ppm and 21 µg/m3 for intensive care unit 2, all of which were around the average levels of those in permanent hospitals (579 ppm and 21 µg/m3). Of these patients, the median (lower quartile, upper quartile) chloride exposure time and calculated dose were 26.66 (2.89, 57.21) h and 0.357 (0.008, 1.317) mg, respectively. A statistically significant positive correlation was observed between interleukin-6 and D-dimer concentrations. To conclude, ventilation helped maintain ward air cleanliness and health risks were not observed.

Indoor dryness and humidification-induced arsenic inhalation exposure above 4200 m in Ngari, China.

Ngari Prefecture, Tibet, China, features its ultrahigh altitude above 4200 m, very little annual precipitation and extremely low relative humidity. Residents who have migrated to Tibet from the plains use indoor humidification to reduce the respiratory discomfort caused by prolonged exposure to dry indoor air. In this study, field investigations and analysis of residential indoor environments and humidification methods in Ngari Prefecture revealed that ninety-eight percent of humidifier consumers in the prefecture used low-cost ultrasonic humidifiers filled with indoor tap water. The results revealed that the arsenic (As) concentration of the tap water was 41.6 µg/L, over four times China's standards for drinking water quality (10 µg/L). The source As concentration in the air humidified by the tap water-filled ultrasonic humidifier is (619.8 ± 59.1) (ng/m3 ·air), while no As was detected in the air humidified by the evaporative humidifier. For ultrasonic humidifier with tap water-filled, the inhalation dose of a healthy adult was 45.4 ng/d. The minute ventilation volume of migrated residents who had been in Ngari for less than two years (12.5 ± 4.3 L/min) was greater than those of the long-term residents (10.0 ± 4.5 L/min), which may exacerbate the short-term inhalation exposure risk for migrated residents. To reduce the health risks associated with As exposure, evaporative humidifiers are recommended for households using domestic water. If ultrasonic humidifiers are used, the tap water must be purified with terminal filters.

Affordable measures to monitor and alarm nosocomial SARS-CoV-2 infection due to poor ventilation.

Since the coronavirus disease 2019 (COVID-19) outbreak, the nosocomial infection rate worldwide has been reported high. It is urgent to figure out an affordable way to monitor and alarm nosocomial infection. Carbon dioxide (CO2 ) concentration can reflect the ventilation performance and crowdedness, so CO2 sensors were placed in Beijing Tsinghua Changgung Hospital's fever clinic and emergency department where the nosocomial infection risk was high. Patients' medical records were extracted to figure out their timelines and whereabouts. Based on these, site-specific CO2 concentration thresholds were calculated by the dilution equation and sites' risk ratios were determined to evaluate ventilation performance. CO2 concentration successfully revealed that the expiratory tracer was poorly diluted in the mechanically ventilated inner spaces, compared to naturally ventilated outer spaces, among all of the monitoring sites that COVID-19 patients visited. Sufficient ventilation, personal protection, and disinfection measures led to no nosocomial infection in this hospital. The actual outdoor airflow rate per person (Qc ) during the COVID-19 patients' presence was estimated for reference using equilibrium analysis. During the stay of single COVID-19 patient wearing a mask, the minimum Qc value was 15-18 L/(s·person). When the patient was given throat swab sampling, the minimum Qc value was 21 L/(s·person). The Qc value reached 36-42 L/(s·person) thanks to window-inducted natural ventilation, when two COVID-19 patients wearing masks shared the same space with other patients or healthcare workers. The CO2 concentration monitoring system proved to be effective in assessing nosocomial infection risk by reflecting real-time dilution of patients' exhalation.

[Implementation and application of the new information system of air pollution and health impact monitoring].

OBJECTIVE: To establish a new information system of air pollution and health effects surveillance including of data collection, data management, data quality control and statistics and visual display. METHODS: To integrate the limits of authority, process management, quality control into the whole process of data collecting, data processing, data auditing and statistics through B/S framework according to the design concept of separating the professional applications from permissions management, and the data centralized management. RESULTS: The key functions of the information system including data collection, three level auditing, statistics, visual display and system management have been implemented. The system has been applied in the national project of 31 provinces, 65 cities and 126 monitoring points. Up to now there is more than 16 million business records stored in the system and the amount of the data has reached more than 10 G. CONCLUSION: The new information system has run well since it is online. It has not only met the monitoring requirements but also provided the foundational support for the research and policy making.

[Application of classified protection of information security in the information system of air pollution and health impact monitoring].

OBJECTIVE: To study the application of classified protection of information security in the information system of air pollution and health impact monitoring, so as to solve the possible safety risk of the information system. METHODS: According to the relevant national standards and requirements for the information system security classified protection, and the professional characteristics of the information system, to design and implement the security architecture of information system, also to determine the protection level of information system. RESULTS: Basic security measures for the information system were developed in the technical safety and management safety aspects according to the protection levels, which effectively prevented the security risk of the information system. CONCLUSION: The information system established relatively complete information security protection measures, to enhanced the security of professional information and system service, and to ensure the safety of air pollution and health impact monitoring project carried out smoothly.

[Designing and implementation of the data quality control in the information system of air pollution and health impact monitoring].

OBJECTIVE: To implement the data quality control in the information system of air pollution and health impact monitoring, and improve the data quality. METHODS: Building the rule database recognized by the computer through summarizing and refining data quality verification rules to control the data quality through off-line quality control and on-line quality control. RESULTS: The data quality control in the whole process is realized, which includes data collection, toolkit verification, document verification, data checking and data auditing. CONCLUSION: The information system of air pollution and health impact monitoring has realized the automatic data quality control, which can provide the experience and demonstration for the other surveillance and scientific research.

[Design and implementation of online statistical analysis function in information system of air pollution and health impact monitoring].

OBJECTIVE: To implement the online statistical analysis function in information system of air pollution and health impact monitoring, and obtain the data analysis information real-time. METHODS: Using the descriptive statistical method as well as time-series analysis and multivariate regression analysis, SQL language and visual tools to implement online statistical analysis based on database software. RESULTS: Generate basic statistical tables and summary tables of air pollution exposure and health impact data online; Generate tendency charts of each data part online and proceed interaction connecting to database; Generate butting sheets which can lead to R, SAS and SPSS directly online. CONCLUSION: The information system air pollution and health impact monitoring implements the statistical analysis function online, which can provide real-time analysis result to its users.

Direct Growth of MoS2 Microspheres on Ni Foam as a Hybrid Nanocomposite Efficient for Oxygen Evolution Reaction.

MoS2 microspheres are directly grown on the conductive Ni foam and the as-obtained MoS2 -Ni electrodes exhibit highly efficient electrocatalytic performances for oxygen evolution in 1.0 m NaOH, displaying a rather low overpotential of 0.310 V at 20.0 mA cm(-2) , a high current density, good cyclic stability, and excellent flexibility.

[Effect of Interaction between PLIN Gene Polymorphisms and Open Lifestyle Intervention on Weight-loss in Chinese Han Adults].

OBJECTIVE: To explore the effect of the interaction between PLIN gene polymorphisms and open lifestyle intervention on weight-loss in Chinese Han adults. METHODS: Totally 109 overweight or obese subjects were assigned by random number table to the intervention group (n=56) or control group (n=53),and subjects in the intervention group received 22-week open lifestyle intervention. Anthropometric and metabolic indicators were measured for all subjects before and after intervention,and the PLIN1,PLIN4,and PLIN6 genotypes were amplified by polymerase chain reaction and sequenced through the first-generation sequencing technologies. RESULTS: Among all these subjects,the rare allele C was dominant at PLIN1 (0.619),the common allele G was dominant at PLIN4 (0.606),and the common allele A was dominant at PLIN6 (0.564),in which PLIN1 and PLIN4 as well as PLIN4 and PLIN6 were in strong linkage disequilibrium (D'>0.9). After intervention,the body mass index,waist circumference,and body fat percent of female subjects were significantly decreased in intervention group and were lower than in control group;in male subjects,however,only the waist circumference showed significant difference with the control group (P<0.05). Subjects carrying rare allele homozygote of PLIN6 got less weight/fat loss than those carrying common alleles in intervention group,while subjects carrying rare allele of PLIN1 had more weight/fat increase than those with common allele homozygote in control group (P<0.05). Females in intervention group carrying any one of rare allele homozygotes of PLIN1,PLIN4 and PLIN6 got less weight/fat loss than those with common alleles,and female subjects carrying the rare allele homozygote haplotype of PLIN1/PLIN4 or PLIN4/PLIN6 got less weight/fat loss than those with other haplotypes (P<0.05). CONCLUSION: The interaction between open lifestyle intervention and PLIN gene polymorphisms can directly influence weight-loss in Chinese Han overweight and obese adults.

Increased peripheral proinflammatory T helper subsets contribute to cardiovascular complications in diabetic patients.

BACKGROUND: Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. METHODS: The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). RESULTS: Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. CONCLUSIONS: Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

Altitude-associated trends in bacterial communities in ultrahigh-altitude residences.

BACKGROUND: Indoor bacterial communities may change with altitude because their major contributors, outdoor bacterial communities, vary with altitude. People's health effects from bacteria inhalation exposure can also vary with altitude because human respiratory physiology changes with oxygen content in air. Accordingly, adjusting indoor bacterial communities may help to acclimate newcomers from low-altitude environments to ultrahigh-altitude environments. To lay the groundwork for further research, we aimed to first elucidate the bacterial communities in ultrahigh-altitude residences and the effects of altitude on these communities. We collected 187 environmental samples from residential communities at ultrahigh altitudes of 3811-4651 m in Ngari, China and sequenced bacterial 16S rRNA genes. RESULTS: On one hand, when abundant genera in ultrahigh-altitude residences and those reported by previous studies on low-altitude residences were compared, nine genera were shared, whereas other five genera were abundant only at ultrahigh altitudes. On the other hand, when the bacterial communities of residences at different ultrahigh altitudes were further compared, the bacterial composition in indoor surface samples varied significantly with altitude. The relative abundance of five bacterial genera in indoor air samples and 10 genera and three phyla in indoor surface samples varied monotonically with altitude. CONCLUSIONS: Altitude may be a long-neglected factor that shapes residential bacterial communities and thus warrants attention.

Impact of altitude on the dosage of indoor particulates entering an individual's small airways.

The complexity of indoor particulate exposure intensifies at higher altitudes owing to the increased lung capacity that residents develop to meet the higher oxygen demands. Altitude variations impact atmospheric pressure and alter particulate dynamics in ambient air and the human respiratory tract, complicating particulate inhalation. This study assessed the fraction of PM2.5 and PM10 entering small airways. This assessment covered an altitude range from 400 m above sea level to 3650 m, and an in vitro respiratory tract model was used. The experimental results confirmed that with increasing altitude, the penetration fractions of PM2.5 and PM10 significantly increased from 0.133 ± 0.031 and 0.141 ± 0.045 to 0.404 ± 0.159 and 0.353 ± 0.132, respectively. Additionally, the computational fluid dynamics simulation results revealed that among particles with sizes of 0.1 to 10 µm, the 7.5-µm particles exhibited the most substantial reduction in deposition in the upper airway, displaying a decrease of 6.27%. Our findings underscore the health risks faced by low-altitude residents during acclimatization to higher altitudes, as they experience heightened exposure to particulate matter sources.

Long-term 4-nonylphenol exposure drives cervical cell malignancy through MAPK-mediated ferroptosis inhibition.

4-NP (4-nonylphenol), a prevalent environmental endocrine disruptor with estrogenic properties, is commonly detected in drinking water and food sources. It poses a significant risk of endocrine disruption, thereby influencing the onset and progression of diverse diseases, including tumorigenesis. However, its specific impact on cervical cancer remains to be fully elucidated. Our study focused on the biological effects of sustained exposure to low-dose 4-NP on human normal cervical epithelial cells (HcerEpic). After a continuous 30-week exposure to 4-NP, the treated cells exhibited a significant malignant transformation, whereas the solvent control group showed limited malignant phenotypes. Subsequent analyses of the metabolomic profiles of the transformed cells unveiled marked irregularities in glutathione metabolism and unsaturated fatty acid metabolism. Analyses of transcriptomic profiles revealed significant activation of the MAPK signaling pathway and suppression of ferroptosis processes in these cells. Furthermore, the expression of MT2A was significantly upregulated following 4-NP exposure. Knockdown of MT2A restored the aberrant activation of the MAPK signaling pathway, elevated antioxidant capacity, ferroptosis inhibition, and ultimately the development of malignant phenotypes that induced by 4-NP in the transformed cells. Mechanistically, MT2A increased cellular antioxidant capabilities and facilitated the removal of toxic iron ions by enhancing the phosphorylation of ERK1/2 and JNK MAPK pathways. The administration of activators and inhibitors of the MAPK pathway confirmed that the MAPK pathway mediated the 4-NP-induced suppression of ferroptosis and, ultimately, the malignant transformation of cervical epithelial cells. Overall, our findings elucidated a dynamic molecular transformation induced by prolonged exposure to 4-NP, and delineated comprehensive biological perspectives underlying 4-NP-induced cervical carcinogenesis. This offers novel theoretical underpinnings for the assessment of the carcinogenic risks associated with 4-NP.

Effects of Polymer Properties on Solid-State Shear Pulverization: Thermoplastic Processability and Nanofiller Dispersibility.

Solid-state shear pulverization (SSSP) is an alternative polymer processing technique based on twin-screw extrusion with a continuous cooling system. In SSSP, low-temperature mechanochemistry modifies the macromolecular architecture and morphology, which in turn leads to physical property changes in the material. While a wide range of homopolymers, polymer blends, and polymer (nano)composites have been previously developed with SSSP, a fundamental understanding of how mechanochemistry affects polymer chain architecture and structure, and in turn, material properties, has not been elucidated. This paper conducts a systematic processing-structure-property relationship investigation of 10 thermoplastic polymers with varying properties, as they are subjected to consistent SSSP mechanochemical pulverization and nanocomposite compounding. Structural, mechanical, and thermal characteristics of the neat polymers are correlated to their response to SSSP by way of process covariants. Further, we investigate how SSSP processing parameters cause structural changes such as molecular weight reduction and filler dispersion level, which in turn dictate system properties like melt viscosity and thermal stability. Mechanochemical engagement with a high degree of physical contact during pulverization and compounding, characterized by the SSSP covariants exhibiting specific mechanical energy values above 4 kJ/g and an average screw temperature above 20 °C, is ensured when polymers have a glass transition temperature below the processing temperature (<50 °C) and high toughness (>40 MPa). Crystallinity and low thermal diffusivity (<0.2 mm2/s) are additional factors for engaged SSSP processing. Chain scission is an unavoidable outcome of SSSP, though the associated molecular weight reduction was <10% for 7 out of 10 polymers. The elucidated processing-structure-property relationships would allow the SSSP process for a given polymer system to be tailored to the specific needs for molecular structure alterations and performance improvements.

Protective effect of Cordyceps sinensis against diabetic kidney disease through promoting proliferation and inhibiting apoptosis of renal proximal tubular cells.

BACKGROUND: Diabetic kidney disease (DKD) has mainly been considered as a glomerular disease. Our previous study showed that the progression of DKD was highly correlated with the dysfunction of renal proximal tubular cells. Fermented Cordyceps sinensis (CS), a substitute for natural CS, is a prominent herb widely used in China, and has exhibited excellent efficacy on DKD. However, the underlying mechanisms remain poorly understood. METHODS: The database analysis was used to identify the main therapeutic targets and pathways of CS involved in DKD treatment. Next, the protective effects of fermented CS on high glucose (HG, 30 mM) induced HK-2 cell injury was validated through cell proliferation and apoptosis assay, including CCK-8, EdU and TUNEL. Finally, quantitative real­time PCR (qRT-PCR) and western blotting were used to verify key target genes. RESULTS: Our results revealed that 9 main targets (RELA, JNK1, PTEN, VEGFA, EGF, ERK2, CASP3, AKT1, MMP9) were recognized as key therapeutic targets with excellent binding affinity screened by database analysis and molecular docking. The biological processes were identified by Gene Ontology (GO) enrichment, which appeared mainly involved in the positive regulation of cell proliferation as well as the negative regulation of apoptosis. The verification experiments in vitro revealed that fermented CS significantly attenuated the HG-induced cytotoxicity and apoptosis, and promoted the proliferation of HK-2 cells. Moreover, fermented CS significantly downregulated the expressions of Bax, Caspase-3, VEGFA, P-AKT and P-ERK, and upregulated the expression of PTEN compared with that of HG group. CONCLUSION: Our results demonstrate that the fermented CS has nephroprotective effects significantly, which functions via promoting proliferation and inhibiting apoptosis of renal proximal tubular cells, likely by targeting Caspase-3, Bax, VEGFA and PTEN. Furthermore, AKT and ERK signaling pathway may be the critical mechanisms underlying the efficacy of fermented CS in DKD treatment.

Downregulation of BUBR1 regulates the proliferation and cell cycle of breast cancer cells and increases the sensitivity of cells to cisplatin.

Breast cancer (BC) is a significant tissue for women's health worldwide. The spindle assembly checkpoint protein family includes BUBR1 (Bub1-related kinase or MAD3/Bub1b). High expression of BUBR1 promotes cell cycle disorders, leading to cell carcinogenesis and cancer progression. However, the underlying molecular mechanism and the role of BUBR1 in BC progression are unclear. The published dataset was analyzed to evaluate the clinical relevance of BUBR1. BUBR1 was knocked down in BC cells using shRNA. The CCK-8 assay was used to measure the cell viability, and mRNA and protein expression levels were detected by RT-qPCR and Western blot (WB). Cell apoptosis and cell cycle were detected by flow cytometry. Subcutaneous xenograft model was used to assess in vivo tumor growth. BUBR1 was found to be highly expressed in BC. The high expression of BUBR1 was associated with poor prognosis of BC patients. Upon BUBR1 knockdown using shRNA, the proliferation and metastatic ability of cells were decreased. Moreover, the cells with BUBR1 knockdown underwent cell cycle arrest. And the results showed that BUBR1 loss inhibited the phosphorylation of TAK1/JNK. In vitro and in vivo studies indicated the knockdown of BUBR1 rendered the BC cells more sensitive to cisplatin. In summary, BUBR1 may be a potential therapeutic target for BC and targeting BUBR1 may help overcome cisplatin resistance in BC patients.

Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma.

PURPOSE: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis. METHODS: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. RESULTS: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26-131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan-Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85-403.15) days vs 164 (95% CI 77.76-250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74-268.26) days vs 74 (95% CI 41.23-106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136-0.848), p = 0.021). CONCLUSION: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. TRIAL REGISTRATION: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.

BRAFV600E genetic testing should be recommended for Bethesda III or V thyroid nodules based on fine-needle aspiration.

The preoperative diagnosis of thyroid nodules now routinely includes BRAFV600E genetic testing in most provincial and municipal hospitals in China. This study identified the most suitable patients of thyroid nodule for BRAFV600E genetic testing. We retrospectively collected data of patients from the Hospital Information System that had undergone fine needle aspiration biopsy (FNAB) from May 2019 to December 2021. Data of FNAB, BRAFV600E genetic testing, and post-surgical pathological diagnosis were collected. A total of 12,392 patients were included in this study. Among them, 7,010 patients underwent solely FNAB, while 5,382 patients had both FNAB and BRAFV600E genetic testing. In the FNAB group, 2,065 thyroid nodules were surgically removed, with a 93.12% malignancy rate. In the FNAB + BRAF group, 2,005 nodules were dissected, and the malignancy rate was 98.20%. However, it was evident that in the subgroups, the combination of FNAB and BRAFV600E genetic testing only benefited Bethesda III (p < 0.001) and V (p = 0.001) nodules. Overall, the combination of FNAB with BRAFV600E genetic testing significantly improved the malignancy rate of surgical thyroid nodes at our hospital when compared to FNAB alone. The subgroup analysis showed that BRAFV600E genetic testing only benefited Bethesda III and V nodules. These findings provide a clinical reference for rationally selecting the most suitable population for BRAFV600E genetic testing.

Flotillin-1 promotes progression and dampens chemosensitivity to cisplatin in gastric cancer via ERK and AKT signaling pathways.

BACKGROUND: Several past studies have reported the overexpression of Flotillin-1 in a variety of cancer types. Cisplatin is a chemotherapeutic drug commonly used for cancer treatment. The present study investigated the role of Flotillin-1 in the progression of GC and assessed whether it assists in the chemical sensitization of GC cells toward cisplatin. METHOD: The expression of Flotillin-1 was detected both in human gastric mucosal cells and GC cells. Next, siRNA and shRNA were used to construct a stable cell line expressing low levels of Flotillin-1. Furthermore, the Cell Counting Kit 8 (CCK-8), flow cytometry, and transwell assays were employed to detect the impact of Flotillin-1 on GC cells. In addition, a nude mouse model of human GC was used to verify the knockdown of Flotillin-1 to increase the sensitivity of GC cells to cisplatin. RESULTS: Flotillin-1 was overexpressed in GC cells when compared to that in human gastric mucosal cells. The results for in vitro and vivo assays revealed that the knockdown of Flotillin-1 could significantly inhibit the proliferation of GC cells and increased the sensitivity of GC cells to cisplatin via the regulation of the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathway. CONCLUSION: Flotillin-1 might be used as a molecular marker for GC diagnosis and could be explored as a potential new target for the treatment of GC.