Interpretable CT radiomics model for invasiveness prediction in patients with ground-glass nodules.

AIM: To evaluate the performance of an interpretable computed tomography (CT) radiomic model in predicting the invasiveness of ground-glass nodules (GGNs). MATERIALS AND METHODS: The study was conducted retrospectively from 1 August 2017 to 1 August 2022, at three different centres. Two hundred and thirty patients with GGNs were enrolled at centre I as a training cohort. Centres II (n=157) and III (n=156) formed two external validation cohorts. Radiomics features extracted based on CT were reduced by a coarse-fine feature screening strategy. A radiomic model was developed through the use of the LASSO (least absolute shrinkage and selection operator) and XGBoost algorithms. Then, a radiological model was established through multivariate logistic regression analysis. Finally, the interpretability of the model was explored using SHapley Additive exPlanations (SHAP). RESULTS: The radiomic XGBoost model outperformed the radiomic logistic model and radiological model in assessing the invasiveness of GGNs. The area under the curve (AUC) values for the radiomic XGBoost model were 0.885 (95% confidence interval [CI] 0.836-0.923), 0.853 (95% CI 0.790-0.906), and 0.838 (95% CI 0.773-0.902) in the training and the two external validation cohorts, respectively. The SHAP method allowed for both a quantitative and visual representation of how decisions were made using a given model for each individual patient. This can provide a deeper understanding of the decision-making mechanisms within the model and the factors that contribute to its prediction effectiveness. CONCLUSIONS: The present interpretable CT radiomics model has the potential to preoperatively evaluate the invasiveness of GGNs. Furthermore, it can provide personalised, image-based clinical-decision support.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

[Distribution and reference intervals of daytime intraocular pressure in the eye health screening population of Handan].

Objective: To describe the distribution and establish reference intervals (RI) of daytime intraocular pressure (IOP) in the eye health screening population of Handan. Methods: This cross-sectional study included subjects who participated in eye health screening at the Physical Examination Center of Handan First Hospital from May 2021 to June 2022. A complete general and ocular examination was performed, including measurements of visual acuity and IOP (using Goldmann tonometry), slit lamp microscopy, fundus photography, and anterior and posterior segment optical coherence tomography. Subjects with factors that could cause significant changes in IOP or affect the accuracy of IOP measurement, or with an inability to measure IOP were excluded. Simple random sampling was used to select participants, who were grouped by gender and age (18 to <30, 30 to <40, 40 to <50, 50 to <60, 60 to <70, and ≥70 years). Central corneal thickness and IOP at 8 to 11 o'clock in one eye of each participant were recorded. The independent sample t test and ANOVA were used for statistical analysis, and the RI of IOP values was calculated by x¯±1.96s. Results: A total of 9 310 subjects had their IOP measured, and 3 491 participants (3 491 eyes) were randomly selected from 7 886 healthy subjects. The age of the participants was (47.74±14.47) years old, ranging from 18 to 90 years old. There were 1 694 males and 1 797 females. The central corneal thickness of all participants was (525.56±49.39) µm. The daytime IOP of all participants was (15.40±2.54) mmHg (1 mmHg=0.133 kPa), and the RI was 10.42 to 20.39 mmHg. The IOP was (15.49±2.58) mmHg for males and (15.29±2.49) mmHg for females, and the gender difference was statistically significant (P<0.05). The RI of daytime IOP values was 10.43 to 20.54 mmHg for males and 10.41 to 20.18 mmHg for females. There were significant differences in daytime IOP [(15.13±2.58), (15.33±2.53), (15.49±2.50), (15.53±2.55), (15.39±2.62), and (15.28±2.52) mmHg] among 6 age groups (P<0.05). Conclusions: The distribution of daytime IOP in different gender and age groups in the eye health screening population of Handan and the RIs derived from the distribution were roughly the same as the international normal IOP RI (10 to 21 mmHg). It is recommended to refer to the RI of daytime IOP values of different genders and ages for clinical decision.

Genetic diversity of wild soybean populations in Dongying, China, by simple sequence repeat analysis.

Annual wild soybean (Glycine soja Sieb. et Zucc.), the ancestor of cultivated soybean (G. max), is believed to be a potential gene source for further improvement of soybean to cope with environmental stress. In this study, 10 simple sequence repeat (SSR) markers were used to evaluate the genetic diversity and population genetic structure in five wild soybean populations using 195 accessions collected from Dongying, China. Ten SSR markers yielded 90 bands, with an average of nine bands per marker. The percentage of polymorphic loci (P) was 97.78%, the distribution of expected heterozygosity (HE) was 0.1994-0.4460 with an average of 0.3262, and the distribution from Shannon's information index (I) was 0.3595-0.6506 with an average of 0.5386. The results showed that wild soybean had a high degree of genetic diversity at the species level. Nei's differentiation coefficient (FST) was 0.1533, and gene flow (Nm) was 1.3805, which indicated that genetic variation mainly existed within populations and that there was a certain level of gene exchange between populations. Some genetic differentiation occurred among populations, although this was not significant. Cluster analysis indicated that there was no significant correlation between the genetic structure of wild soybean populations and their geographic distribution, and the clustering results may be relatively consistent with the habitats of the accessions. In the present study, the genetic diversity of wild soybeans showed a broad genetic base and enables suggestions for the conservation of this plant to be made.

Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel.

This study aimed to investigate the effects of RhoGDIα knockdown on apoptosis and the chemosensitivity of lung cancer cells to paclitaxel. The signaling proteins involved were also assessed. RhoGDIα expression was assessed by RT-PCR, Western blotting and immunohistochemistry. Apoptosis was determined by flow cytometric assessment, and cell viability was measured with the MTT assay. Phosphorylation levels of signaling proteins, ERK, JNK, Akt, Bad and IκBα were tested by Western blotting and immunohistochemistry. Positivity for RhoGDIα in lung cancer tissues was significantly higher than in paracancerous tissues. Downregulation of RhoGDIα was associated with significantly increased apoptosis and repressed cell viability. This effect could be due to the consequent upregulation of p-JNK, as well as decreased levels of p-ERK, p-Bad and p-IκBα. Knockdown of RhoGDIα strengthened the effect on apoptosis and inhibition of cell viability induced by paclitaxel treatment. This chemosensitization effect could be a result of the intensification of pro-apoptotic JNK activation, and repression of anti-apoptotic p-ERK, p-Bad and p-IκBα expression stimulated by paclitaxel. In summary, our study indicated that RhoGDIα could be a promising therapeutic target, and the combination of RhoGDIα siRNA and paclitaxel might be a valuable potential therapy for lung cancer treatment.

Sources of formaldehyde and their contributions to photochemical O3 formation at an urban site in the Pearl River Delta, southern China.

Two models (the Positive Matrix Factorization (PMF) model and a photochemical box model with Master Chemical Mechanism (PBM-MCM)) were applied to analyze the formaldehyde (HCHO) data collected in July 2006 at an urban site (GPEMC) in the Pearl River Delta (PRD), southern China. Three major HCHO sources (secondary formation, vehicular exhaust, and solvent usage) were identified and they were found to contribute in average 53%, 31% and 16% respectively to the total HCHO loading at GPEMC. Alkenes was the most important group contributing to the secondary formation of HCHO, followed by aromatics and alkanes. Among them, trans-2-butene had the largest contribution to secondary HCHO formation, with the average percentage of 16 ± 4%, followed by i-butene, cis-2-butene, propene, isoprene and m,p-xylene. Secondary HCHO and HCHO emitted from vehicular emissions contributed comparably to ground-based measured O3 and HOx radical at GPEMC, higher than that from solvent usage (1.3 ± 0.1 ppbv and (4.1 ± 0.3) × 106 molecule/cm3 for O3 and HOx radical). Our results highlight the importance of secondary HCHO formation for both photochemical formation of ozone and the oxidative capacity of the atmosphere in this region. It is hence critical for policy makers to propose strategies for controlling VOCs from vehicular emissions in order to reduce secondary HCHO formation. Our results also have important implication for improving the understanding of the source apportionments of HCHO and their contributions to photochemical pollution in the PRD region in China.

PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer.

Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell's responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention.

[Analyses of chromosomal karyotypes and cytogenetic variations of animal cell lines].

After the master cell stock(mcs) and working cell bank of more than 30 different strains of 7 animal kidney cell lines (F-81 or CRFK cell line, MDCK cell line, Vero or Vero-2 cell line, MA-104 cell line and BHK-21 cell line) were established in China, the chromosomal number variations and structural aberrations of the above lines, primary feline or canine kidney cell (FKC or CKC) and HeLa cell line were investigated and their karyotypes of routine or Giemsa chromosomal bands were analyzed. The carcinogenesis or tumorigenicity testing of these cells in about 700 nude mice and for colony formation in soft agar (SA) and for agglutination under different concentration of plant lectins was carried out. Both tumorigenicity-negative strains of F-81, CRFK, Vero or Vero-2 lines and very-low-tumorigenicity strains of MDCK line were successfully selected and evaluated for the production of canine or feline combination viral vaccines, which are free of infectious agents, and described with respect to cytogenetic characteristics and tumorigenicity. Rate of modal chromosome number represents the ratio of cell number having modal chromosome number to all the split cell number analyzed at random. Rate of difference represents the ratio of difference of the rate of modal chromosome number between mcs (master cell stock) + n and mcs passages. The chromosomal analysis results showed that the ratio of difference of the rate of modal chromosome number between mcs + n and mcs passages was not more than 5%-15% and the structure aberrations was generally 0%-3%, not more than 5%-10%, thus the hereditary character of cell lines is comparatively stable without significant difference between different passages. The genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species specific. Experimental models were established for the researches on the prevention and prophylaxis of malignant tumors or cancers and their genetically biological characteristics. Tests showed that there was correlation among cell line chromosome number variations, anchorage independence in soft agar, agglutination under plant lectins and tumor-forming ability in nude mice. Since testing in vitro is more economic, simpler, faster, and is thought to be reliable, we recommend plant lectins followed by SA or analysis of karyotypes as the initial means for monitoring tumorigenicity of animal cell line in nude mice.

BRCA1 is differentially expressed in human tumor cells.

Mutations of the human breast cancer susceptibility gene 1 (BRCA1) confers a risk for breast, ovarian and prostate cancers and BRCA1 exerts multiple biological functions. Using Western blot and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays, we have determined the expression of endogenous BRCA1 protein and mRNA in forty-three human tumor cell lines established from eleven types of human tumor tissues. BRCA1 was differentially expressed in tumor cell lines. No significant association was found between BRCA1 expression and the p53 gene status of cell lines. The disruption of wild-type p53 by either the human papillomavirus E6 oncogene or the mutant p53 gene (143Ala-->Val) did not cause any significant alteration in basal level of BRCA1 expression, while the knockout of p21 (-/-) by homologous recombination assay and Blocking Gadd45 expression by constitutive antisense expression slightly increased BRCA1 protein expression. Therefore, although the functional significance of the differential expression in human tumor cells is currently unknown, the present data provide a valuable background for further study of BRCA1 in tumor cell lines.