Association of prenatal exposure to perfluorinated and polyfluoroalkyl substances with childhood neurodevelopment: A systematic review and meta-analysis.

BACKGROUND: Although previous studies have shown an association between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children, the results have been inconsistent. We summarize studies on the association between prenatal PFAS exposure and neurodevelopment in children in order to better understand the relationship. OBJECTIVE: We conducted a meta-analysis of prenatal PFAS exposure and developmental outcomes associated with intellectual, executive function and behavioral difficulty in children to explore the relationship between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children. METHODS: We searched for articles published up to August 3, 2023, included and quantified original studies on PFAS and child Intelligence Quotient (IQ), executive function and behavioral difficulty during pregnancy, and systematically summarized articles that could not be quantified. CONCLUSION: There is evidence of sex-specific relationship between PFAS exposure and children's PIQ. We found that PFOS [ß = -1.56, 95% CI = -2.96, - 0.07; exposure = per 1 ln (ng/ml) increase], PFOA [ß = -1.87, 95% CI = -3.29, - 0.46; exposure = per 1 ln (ng/ml) increase], PFHxS [ß = -2.02, 95% CI = -3.23, - 0.81; exposure = per 1 ln (ng/ml) increase] decreased performance IQ in boys, but PFOS [ß = 1.56, 95% CI = 0.06, 3.06; exposure = per 1 ln (ng/ml) increase] increased performance IQ in girls. PFAS are associated with executive function impairments in children, but not related to behavioral difficulty in children.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

1,25-Dihydroxvitamin D3 attenuates the damage of human immortalised keratinocytes caused by Ultraviolet-B.

OBJECTIVE: Ultraviolet-B (UVB) radiation is an important factor in causing skin damage. The study is to explore whether 1,25-Dihydroxvitamin D3(1,25(OH)2D3) will attenuate the damage of human immortalised keratinocytes (HaCaT) cells caused by UVB and relevant underlying mechanisms. METHODS: CCK-8 was employed to determine the UVB irradiation intensity and 1,25(OH)2D3 concentration. Western blot was used to detect the expression of NF-κB, Caspase9, Caspase3, Bax, Bcl2, FADD, CytC, Beclin-1; Flowcytometry was applied to measure the production of ROS. RESULTS: The concentration of 1,25(OH)2D3 used in the study was 100 nM and the UVB irradiation intensity was 20 mJ/cm2. Compared with the HaCaT cells irradiated with UVB, the HaCaT cells that were pre-treated with 1,25(OH)2D3 had lower production of ROS, lower expression of NF-κB, Caspase9, Caspase3, Bax, FADD, CytC and Beclin-1(P < 0.05). CONCLUSION: 1,25(OH)2D3 could inhibit the development of oxidative stress and apoptosis in HaCaTs triggered by UVB. This inhibition might be achieved through the suppression of mitochondria-modulated apoptosis and autophagy. Vitamin D may be a potential UVB protective component.

Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma.

OBJECTIVE: Histology grade, subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival. The aim of the study was to investigate the relationship between chromosomal instability, morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma (LNMA). METHODS: We developed a whole genome copy number variation (WGCNV) scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples. RESULTS: Higher histological grades, aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score, particularly in CNV regions enriched for tumor suppressor genes and oncogenes. In addition, we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types (<100 cells) isolated by sample laser capture microdissection. CONCLUSIONS: Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.

Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for advanced primary hepatic angiosarcoma: a case report.

BACKGROUND: Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid tumor, with high rates of local recurrence and distant metastasis, and poor prognosis. There are no established treatment guidelines for PHA. CASE PRESENTATION: A 78-year-old asymptomatic man with PHA that was successfully treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells (RAK cells). After one month of treatment, there was a clear reduction in the size and number of the liver metastases; and after nearly 15 months, most of the lesions were stable, no new lesions had developed, and the side effect of treatment was minor. CONCLUSION: Pazopanib, PD-1 inhibitor and RAK cells could serve as a potential option for the treatment of advanced PHA.

ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma.

OBJECTIVE: The relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. METHODS: Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded. RESULTS: Of the 313 MPE samples, 27 (8.6%) were confirmed as ALK expression-positive, and the Ventana IHC ALK (D5F3)-positive rate was 17.3% (27/156) in wild-type epidermal growth factor receptor (EGFR) MPE samples. Twenty-three of the 27 IHC ALK (D5F3)-positive samples were positive by FISH. Of the 11 Ventana IHC ALK (D5F3)-positive patients who received crizotinib therapy, 2 patients had complete response (CR), 5 had partial response (PR) and 3 had stable disease (SD). CONCLUSIONS: The ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.

[A standardized protocol for detection of ALK protein expression and gene fusion in lung adenocarcinoma cytologic specimens].

OBJECTIVE: The aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens. METHODS: Lung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens. RESULTS: Among the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance. CONCLUSIONS: The standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion.

[Expression of Girdin in brain tissues of Alzheimer's disease].

OBJECTIVE: To investigate the expression of Girdin and its significance in Alzheimer's disease (AD). METHODS: Fifty-nine autopsy cases from Department of Pathology, Beijing Hospital from January 1988 to December 2013, including 35 AD cases and 24 non-AD cases as control. Girdin and amyloid ß-protein (Aß) expression was evaluated immunohistochemically by EnVision method. The correlation between Girdin and Aß was analyzed. RESULTS: Girdin expression was localized in the nucleus and/or cytoplasm. The expression rates of Girdin were 20.0% (7/35) in the AD group and 83.3% (20/24) in the non-AD group, respectively. The difference was significant (Yates's correction for continuity χ(2)=20.527, P<0.05). Girdin expression and Aß deposition also correlated significantly (P<0.05). CONCLUSIONS: Girdin shows reduced expression in AD, and is correlated positively with Aß deposition. This suggests that Girdin may play an important role in the occurrence and development of AD.

[Clinicopathological characteristics of aortic aneurysm in elderly patients].

OBJECTIVE: To explore the prevalence and clinicopathological features of aortic aneurysm (AA) in elderly inpatients at autopsy. METHODS: All the AA cases were retrospectively analyzed in 909 autopsy cases aged 60-100 years in our hospital. The pathological changes, comorbidities and death reasons were evaluated. RESULTS: AA was diagnosed pathologically in 59 patients (6.5%), clinical diagnosis was not made in 37(62.7%) cases. The AA prevalence in patients aged ≥ 80 years was significantly higher than patients <80 years (10.2% vs. 2.9%, χ(2)=19.97, P<0.01). Abdominal AA was more common (91.5%) and the prevalence of multiple AA was 20.3%. Coronary artery disease (CAD) was diagnosed in 44 AA patients (74.6%) including 21(35.6%) with severe coronary artery stenosis and 7(11.9%) with three-vessel disease, 31 patients (52.5%) died of cardiac-cerebral diseases, including 7(11.9%) with ruptured AA. CONCLUSIONS: The prevalence of AA was high in elderly inpatients aged ≥80 years with a relatively high missed diagnosis rate. AA was often complicated with CAD. The main cause of death of AA patients was cardiac-cerebral diseases. The screening, evaluation and treatment of AA should be enhanced in elderly patients, especially in patients aged 80 years and over.

[Pathological characteristics of coronary artery disease in elderly patients aged 80 years and over].

OBJECTIVE: To define the pathological changes of coronary artery and compare the clinical diagnosis and pathological diagnosis differences in elderly patients aged 80 and over. METHODS: A total of 909 autopsy cases aged 60-100 years in our hospital from April 1st 1969 to October 31th 2013 were analyzed. The prevalence and pathological features of coronary artery disease (CAD) in cases aged 80 years and over were compared with those aged 60-79 years old. The misdiagnosis and missed diagnosis rate were calculated. RESULTS: The prevalence of CAD by autopsy (63.8% (289/453) vs. 39.9% (182/456), P<0.01), old myocardial infarction (OMI) by autopsy (63.0% (182/289) vs. 51.6% (94/182), P<0.05) and chronic myocardial ischemia by autopsy (22.5% (65/289) vs. 7.1% (13/182), P<0.01) were significantly higher while the prevalence of acute myocardial infarction (AMI) by autopsy was significantly lower (22.1% (64/289) vs. 42.9% (78/182), P<0.01) in aged 80 and over group compared to 60-79 years old group. The misdiagnosis rate of CAD was 65.2% (107/164), the missed diagnosis rate of OMI was 62.1% (113/182) and the missed diagnosis rate of AMI was 37.5% (24/64) in the aged 80 and over group. CONCLUSIONS: The prevalence of CAD and misdiagnosis and missed diagnosis rate are high in dead inpatients aged 80 years and over. OMI is more common but often missed in this group. Thus, the diagnosis and evaluation of CAD should be enhanced in this patient group.

Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling.

BACKGROUND: Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms. RESULTS: The effects of rapamycin in vivo were evaluated by modified deep vein thrombosis animal model. The platelets were from healthy volunteers and the platelet-endothelium (purchased from ATCC) adhesion in cultured endothelial cells was assessed. Membrane rufflings in endothelial cells were examined by confocal and electron microscope. Thrombus formation increased in rats that were injected with rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin-treated endothelium in rats. Rapamycin enhanced membrane ruffling in human umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs. The platelet-HUVECs adhesion was attenuated when cells were treated with cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion. CONCLUSIONS: In conclusion, we found that endothelial membrane remodeling induced by rapamycin is crucial for the adhesion of platelets to endothelial cells and thereby for thrombosis in vivo, and that the endothelial membrane remodeling is autophagy dependent.

[A standard protocol for detection of EGFR mutations in cytologic specimens].

OBJECTIVE: The aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens. METHODS: 287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides. RESULTS: Tumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⁺ group and 2 months in the ARMS⁻ group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⁺ group and 7 months in the ARMS⁻ group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⁺ and Seq⁻ groups (P = 0.227, P = 0.510, respectively), and Seq⁺/ARMS⁺ and Seq⁻/ARMS⁺ groups (P = 0.354, P = 0.334, respectively). CONCLUSIONS: The detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.

[Clinicopathological diagnosis of IgG4-related disease: report of eight cases].

OBJECTIVE: To evaluate the clinical and pathological features of IgG4-related disease (IgG4RD). METHODS: The clinical data, laboratory profiles, radiological, pathological and therapeutic features of eight cases of IgG4RD were analyzed. This cohort included two cases of common bile duct and partial hepatectomy specimens, two of submandibular gland excision specimens, one from lung biopsy specimen, one from open lung biopsy specimen, one from renal biopsy specimen, and one from renal excision specimen. In all cases, adequate lesion tissues were obtained. They were paraffin embedded, HE stained, and additional special stains and immunohistochemistry performed (MaxVision method). RESULTS: This series consisted of five males and three females, with a mean age of onset of 60 years. Five cases were suspected to be malignant pre-operatively, including two cases suspected of common bile duct carcinoma, two suspected of salivary gland tumor, and one suspected of renal pelvic carcinoma. Elevated serum levels of IgG4 and IgE were detected in five cases and eosinophilia in four cases. Multi-organ involvement was noted in four cases. The major histopathological features associated with IgG4-RD were: dense lymphoplasmacytic infiltrate, with lymphoid follicle formation. Extensive eosinophilic infiltrate (> 10/HPF) was seen in four cases; fibrosis that was arranged at least focally in a storiform pattern was also noted. The numbers of IgG4 positive plasma cells were > 20-50/HPF, while the IgG4 to IgG ratio was more than 40%. Obliterative phlebitis was present in four cases. Other pathological changes such as necrotizing vasculitis or lymphoma were not found. Five patients responded well to glucocorticoids. CONCLUSIONS: IgG4RD has relatively specific histopathological features; accurate evaluation of the absolute and relative number of IgG4 positive plasma cells in lesional tissue, combining with clinical examination and exclusion of other causes of elevated IgG4, allows the diagnosis of IgG4RD. IgG4RD has complicated clinical manifestation, and glucocorticoids therapy is efficacious.

Preservation of cfRNA in cytological supernatants for cfDNA & cfRNA double detection in non-small cell lung cancer patients.

BACKGROUD: Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. METHODS: A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. RESULTS: Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. CONCLUSION: These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.

Surface Acoustic Wave-Enhanced Multi-View Acoustofluidic Rotation Cytometry (MARC) for Pre-Cytopathological Screening.

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave-enhanced multi-view acoustofluidic rotation cytometry (MARC) technique is developed for pre-cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi-angle observations and amplifies subtle cell differences, particularly in the nuclear-to-cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC-screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening.

A Familial Case of Multiple Endocrine Neoplasia 2A: From Morphology to Genetic Alterations Penetration in Three Generations of a Family.

This paper illustrates a rare syndrome of multiple endocrine neoplasia type 2A (MEN2A) in a family of three generations. In our case, the father, son and one daughter developed phaeochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) over a period of 35 years. Because of the metachronous onset of the disease and lack of digital medical records in the past, the syndrome was not found until a recent fine needle aspiration of an MTC-metastasized lymph node from the son. All resected tumors from the family members were then reviewed and supplemented with immunohistochemical studies, previously wrong diagnoses were then corrected. Further molecular study of targeted sequencing also revealed a RET germline mutation (C634G) in the family tree including the three members with onset of the disease and one granddaughter who had no disease at the time of testing. Despite the syndrome being well-known, it may still be misdiagnosed because of its rarity and long disease onset. A few lessons can be learned from this unique case. Successful diagnosis requires high suspicion and surveillance and a tri-level methodology including a careful review of family history, pathology and genetic counselling.

Perfluorooctanoic acid (PFOA) exposure in relation to the kidneys: A review of current available literature.

Perfluorooctanoic acid is an artificial and non-degradable chemical. It is widely used due to its stable nature. It can enter the human body through food, drinking water, inhalation of household dust and contact with products containing perfluorooctanoic acid. It accumulates in the human body, causing potential harmful effects on human health. Based on the biodegradability and bioaccumulation of perfluorooctanoic acid in the human body, there are increasing concerns about the adverse effects of perfluorooctanoic acid exposure on kidneys. Research shows that kidney is the main accumulation organ of Perfluorooctanoic acid, and Perfluorooctanoic acid can cause nephrotoxicity and produce adverse effects on kidney function, but the exact mechanism is still unknown. In this review, we summarize the relationship between Perfluorooctanoic acid exposure and kidney health, evaluate risks more clearly, and provide a theoretical basis for subsequent research.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

Sputum cell-free DNA for detection of alterations of multiple driver genes in lung adenocarcinoma.

BACKGROUND: Sputum cell-free DNA (cfDNA) has been confirmed to be a valued surrogate sample for detection of EGFR mutations in patients with lung adenocarcinoma (LAC). Whether it is suitable for detection of mutations of multiple driver genes has not been reported. METHODS: A total of 83 patients with LAC were enrolled and their sputum and paired tumor samples were collected. A next-generation sequencing (NGS)-based 10-gene panel was used to test sputum supernatant-derived cfDNA and paired tumor DNA. The sputum sediments were used for cytological evaluation. RESULTS: The total positive rates of hotspot mutations of the 10 driver genes in sputum cfDNA and matched tissue samples were 65.1% and 77.1%, respectively. The overall detection sensitivity of variants in sputum cfDNA was 81.3% (95% confidence interval [CI], 69.2%, 89.5%) and the specificity was 100% (95% CI, 79.1%, 100%). The sensitivities of testing sputum cfDNA from patients with stage IIIB-IV was 87.0% (95% CI, 74.5%, 94.1%); the sensitivities of testing sputum cfDNA from patients with malignant sputum was 92.3% (95% CI, 78.0%, 98.0%); and the sensitivity of testing sputum cfDNA from patients with malignant sputum in stage IIIB-IV were 94.1% (95% CI, 78.9%, 99.0%). CONCLUSIONS: This study demonstrated that sputum cfDNA were successfully used for the detection of multiple driver genes by NGS. Sputum cfDNA could be a valuable surrogate clinical sample for all-in-one test of mutations to guide target therapies, especially for patients with advanced LAC and malignant sputum.