Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Multiple founding paternal lineages inferred from the newly-developed 639-plex Y-SNP panel suggested the complex admixture and migration history of Chinese people.

BACKGROUND: Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. RESULTS: Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. CONCLUSIONS: Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.

Shape-Selective Alkylation of Toluene with Ethanol over a Twin Intergrowth Structured ZSM-5: Modulation of Acidity and Diffusivity via Interface Engineering.

ZSM-5 zeolites with modified acidity and diffusivity are employed as catalysts for the shape-selective alkylation of toluene with ethanol to para-ethyltoluene (p-ET). To avoid pore blocking and loss of active sites caused by traditional methods of enhancing para-selectivity using modifiers, here, we constructed twin intergrowth structured ZSM-5 (Z5-T), achieving modulation of the inherent acidity and diffusivity through interface engineering. The characterization results demonstrate that due to the intergrowth interface, the Z5-T catalyst forms more inherent Lewis acid sites and also renders more sinusoidal channels opened to the surface. Z5-T with an appropriate acidity and enhanced shape-selectivity inhibits side reactions such as isomerization and coke formation, demonstrating improved p-ET selectivity (>90%) and catalytic stability (>200 h) in the alkylation of toluene with ethanol.

Structure, Properties, Preparation, and Application of Layered Titanates.

As a typical cation-exchangeable layered compound, layered titanate has a unique open layered structure. Its excellent physical and chemical properties allow its wide use in the energy, environmental protection, electronics, biology, and other fields. This paper reviews the recent progress in the research on the structure, synthesis, properties, and application of layered titanates. Various reactivities, as well as the advantages and disadvantages, of different synthetic methods are discussed. The reaction mechanism and influencing factors of the ion exchange reaction, intercalation reaction, and exfoliation reaction are analyzed. The latest research progress on layered titanates and their modified products in the fields of photocatalysis, adsorption, electrochemistry, and other applications is summarized. Finally, the future development of layered titanate and its exfoliated product two-dimensional nanosheets is proposed.

Assessing the Feasibility of Simplifying the Scanning Protocol for Spinal Metastases With Vertebral Compression Fractures Using Only the Dixon T2-Weighted Sequence.

OBJECTIVE: Conventional imaging protocols, including sagittal T1-weighted imaging (T1WI) and water-only T2-weighted imaging (T2WI), are time consuming when screening for spinal metastases with vertebral compression fractures (VCFs). In this study, we aimed to assess the accuracy of using only the Dixon T2-weighted sequence in the diagnosis of spinal metastases with VCFs to determine its suitability as a simplified protocol for this task. METHODS: This retrospective study included 27 patients diagnosed with spinal metastases and VCFs. Qualitative analysis was performed separately by two musculoskeletal radiologists, who independently performed diagnostic evaluations of each vertebra using both conventional and simplified protocols. McNemar's test was then used to compare the differences in diagnostic results, and Cohen's kappa coefficient was used to assess interobserver and interprotocol agreement. Diagnostic performance values for both protocols, including sensitivity, specificity, and area under the curve, were then determined based on the reference standard. Quantitative image analysis was performed randomly for 30 metastases on T1WI and fat-only T2WI to measure the signal intensity, signal-to-noise ratio, and contrast-to-noise ratio. RESULTS: The diagnosis of VCFs by both radiologists was in full agreement with the reference standard. The classification of spinal metastases and diagnostic performance values determined by both radiologists were not significantly different between the two protocols (all P > 0.05), and the consistency between observers and protocols was excellent (κ = 0.973-0.991). The contrast-to-noise ratio of fat-only T2WI was significantly higher than that of T1WI (P < 0.001). CONCLUSIONS: The Dixon T2-weighted sequence alone performed well in diagnosing spinal metastases with VCFs, performing no worse than the conventional protocol (T1WI and water-only T2WI). This suggests that the Dixon T2-weighted sequence alone can serve as a simplified protocol for the diagnosis of spinal metastases with VCFs, thereby avoiding the need for more intricate scanning procedures.

Developmental validation of a high-resolution panel genotyping 639 Y-chromosome SNP and InDel markers and its evolutionary features in Chinese populations.

Uniparental-inherited haploid genetic marker of Y-chromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741×. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/µL tannic acid, 20 ng/µL humic acid, or 37.5 µM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.

A Novel Estrone Degradation Gene Cluster and Catabolic Mechanism in Microbacterium oxydans ML-6.

Global-scale estrone (E1) contamination of soil and aquatic environments results from the widespread use of animal manure as fertilizer, threatening both human health and environmental security. A detailed understanding of the degradation of E1 by microorganisms and the associated catabolic mechanism remains a key challenge for the bioremediation of E1-contaminated soil. Here, Microbacterium oxydans ML-6, isolated from estrogen-contaminated soil, was shown to efficiently degrade E1. A complete catabolic pathway for E1 was proposed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR). In particular, a novel gene cluster (moc) associated with E1 catabolism was predicted. The combination of heterologous expression, gene knockout, and complementation experiments demonstrated that the 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) encoded by the mocA gene was responsible for the initial hydroxylation of E1. Furthermore, to demonstrate the detoxification of E1 by strain ML-6, phytotoxicity tests were performed. Overall, our findings provide new insight into the molecular mechanism underlying the diversity of E1 catabolism in microorganisms and suggest that M. oxydans ML-6 and its enzymes have potential applications in E1 bioremediation to reduce or eliminate E1-related environmental pollution. IMPORTANCE Steroidal estrogens (SEs) are mainly produced by animals, while bacteria are major consumers of SEs in the biosphere. However, the understanding of the gene clusters that participate in E1 degradation is still limited, and the enzymes involved in the biodegradation of E1 have not been well characterized. The present study reports that M. oxydans ML-6 has effective SE degradation capacity, which facilitates the development of strain ML-6 as a broad-spectrum biocatalyst for the production of certain desired compounds. A novel gene cluster (moc) associated with E1 catabolism was predicted. The 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) identified in the moc cluster was found to be necessary and specific for the initial hydroxylation of E1 to generate 4-OHE1, providing new insight into the biological role of flavoprotein monooxygenase.

Predicting pathological complete response of neoadjuvant radiotherapy and targeted therapy for soft tissue sarcoma by whole-tumor texture analysis of multisequence MRI imaging.

OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined_Model with features at multiple time points showed the best performance.

Oriented Plate-like KNbO3 Polycrystals: Topochemical Mesocrystal Conversion and Piezoelectric and Photocatalytic Responses.

KNbO3 (KN) with a perovskite structure is an outstanding representative of lead-free piezoelectric materials, and its mesocrystals have broad application prospects in the fields of catalysis, energy storage, and conversion. However, the formation conditions of KN mesocrystals reported so far are difficult owing to their high aspect ratio and excellent preferred orientation. In this study, the solvothermal process was used successfully to prepare the flake-like potassium salt of Lindquist hexaniobate (K8Nb6O19·10H2O). Subsequently, the precursor niobate was calcined to prepare two-dimensional (2D) plate-like KN mesocrystals. The formation mechanism of the plate-like KN mesocrystals is further revealed from a paired topochemical mesocrystal conversion of K8Nb6O19·10H2O niobate. Finally, the microscopic piezoelectric and photocatalytic responses of the obtained plate-like KN mesocrystals were investigated. The high piezoelectric coefficient of plate-like KN mesocrystals implies that excellent charge separation promotes the photocatalytic performance of rhodamine B (RhB). This study provides a strategy for the efficient application of 2D oriented materials in the field of piezoelectricity and photocatalysis.

The trend of unintentional injury-related mortality among children aged under-five years in China, 2010-2020: a retrospective analysis from a national surveillance system.

BACKGROUND: In this study, we estimated the trend of unintentional injury mortality among children aged under-five years in China during 2010-2020. METHODS: Data were obtained from China's Under 5 Child Mortality Surveillance System (U5CMSS). The total unintentional injury mortality and all specific-causes unintentional injury mortality was calculated, annual numbers of deaths and live births were adjusted by a 3-year moving average under-reporting rate. The Poisson regression model and the Cochran-Mantel-Haenszel method were used to calculate the average annual decline rate (AADR) and the adjusted relative risk (aRR) of the unintentional injury mortality. RESULTS: In 2010-2020, a total of 7,925 unintentional injury-related deaths were reported in U5CMSS, accounting for 18.7% of all reported deaths. The overall proportion of unintentional injury-related deaths to total under-five children deaths has increased from 15.2% to 2010 to 23.8% in 2020 (χ2 = 227.0, p < 0.001), the unintentional injury mortality significantly decreased from 249.3 deaths per 100,000 live births in 2010 to 178.8 deaths per 100,000 live births in 2020, with an AADR 3.7% (95%CI 3.1-4.4). The unintentional injury mortality rate decreased from 2010 to 2020 in both urban (from 68.1 to 59.7 per 100,000 live births) and rural (from 323.1 to 230.0 per 100,000 live births) areas (urban: χ2 = 3.1, p < 0.08; rural: χ2 = 113.5, p < 0.001). The annual rates of decline in rural areas and urban areas were 4.2% (95%CI 3.4-4.9) and 1.5% (95%CI 0.1-3.3), respectively. The leading causes of unintentional injury mortality were suffocation (2,611, 32.9%), drowning (2,398, 30.3%), and traffic injury (1,428, 12.8%) in 2010-2020. The cause-specific of unintentional injury mortality rates decreased with varying AADRs in 2010-2020, except for traffic injury. The composition of unintentional injury-related deaths also varied by age group. Suffocation was the leading cause in infants, drowning and traffic injury were the leading causes in children aged 1-4 years. Suffocation and poisoning has high incidence in October to March and drowning has high in June to August. CONCLUSION: The unintentional injury mortality rate of children aged under-five years decreased significantly from 2010 to 2020 in China, but great inequity exists in unintentional injury mortality in urban and rural areas. Unintentional injuries are still an important public health problem affecting the health of Chinese children. Effective strategies should be strengthened to reduce unintentional injury in children and these policies and programmes should be targeted to more specific populations, such as rural areas and males.

Association between GPC2 polymorphisms and neuroblastoma risk in Chinese children.

BACKGROUND: The cell surface glycoprotein glypican 2 (GPC2) has been shown to increase susceptibility to neuroblastoma, which is the most common malignancy in children. However, associations between single nucleotide polymorphism(s) of GPC2 and neuroblastoma risk remain unclarified. METHODS: We conducted a case-control study to investigate two GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) in 473 healthy controls and 402 pediatric patients with neuroblastoma. Single nucleotide polymorphism (SNP) genotyping was conducted on the samples by the TaqMan technique, and the data were subsequently analyzed by the t test, chi-squared test, and logistic regression model. In addition, we further performed stratification analysis by age, sex, tumor site of origin, or clinical stage to control confounding factors. RESULTS: According to the data of dominant models (GA/AA vs. GG: adjusted OR = 0.99, 95% CI = 0.76-1.29, p = 0.943; CT/TT vs. CC: adjusted OR = 0.91, 95% CI = 0.70-1.19, p = 0.498) or other comparisons, as well as the conjoint analysis (adjusted OR = 1.22, 95% CI = 0.93-1.59, p = 0.152), we unfortunately proved that the analysis of single or multiple loci did not support any significant association of GPC2 polymorphisms with susceptibility to neuroblastoma. CONCLUSION: GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) are unable to statistically affect neuroblastoma risk in Chinese children. Therefore, more samples, especially from patients of various ethnic backgrounds, are required to increase the sample size and verify the effect of GPC2 polymorphisms on neuroblastoma risk in the presence of ethnic factor.

Structurally Diverse Sesquiterpenoids with NO Production and α-Glucosidase Inhibitory Activities from the Fruits of Schisandra chinensis.

Chemical fractionation of the AcOEt partition, generated from the EtOH extract of the fruits of Schisandra chinensis, afforded a series of sesquiterpenyl constituents including two new cadinanes, a new eudesmane, two new widdranes (a handling artefact and a new natural product), a new bisabolane and two new natural cuparane enantiomers, along with 15 known structurally related analogs. Structures of the new compounds were unambiguously characterized by interpretation of detailed spectroscopic data including ESI-MS and 1D/2D NMR, with their absolute configurations being established by electronic circular dichroism (ECD) calculation and induced ECD experiment. The inhibitory effects of all the isolates against α-glucosidase and lipopolysaccharide (LPS) induced nitric oxide (NO) production in murine RAW264.7 macrophages, as well as their antibacterial and cytotoxic potential, were evaluated, with selective compounds showing moderate α-glucosidase and NO inhibitory activity. Notably, canangaterpene III exhibited the most significant NO inhibitory effect with an IC50 value of 31.50±1.49 µM.

[Analysis of epigenetic modification gene mutations among patients with acute myeloid leukemia].

OBJECTIVE: To investigate the carrier rate and clinical characteristics of epigenetic modification gene mutations (EMMs) among patients with acute myeloid leukemia (AML). METHODS: One hundred seventy two patients who were initially diagnosed with AML at the First People's Hospital of Lianyungang from May 2011 to February 2021 were selected as the study subjects. Next-generation sequencing was carried out to detect variants of 42 myeloid genes among these patients. Clinical and molecular characteristics of patients with EMMs and the effect of demethylation drugs (HMAs) on their survival were analyzed. RESULTS: Among the 172 AML patients, 71 (41.28%) were found to harbor the EMMs, and carrier rates were TET2 (14.53%, 25/172), DNMT3A (11.63%, 20/172), ASXL1 (9.30%, 16/172), IDH2 (9.30%, 16/172), IDH1 (8.14%, 14/172), EZH2 (0.58%, 1/172). Patients with EMMs (+) had lower peripheral hemoglobin compared with those with EMMs(-) (72 g/L vs. 88 g/L, Z = -1.985, P = 0.041). The proportion of EMMs(+) among elderly AML patients was significantly higher than that of young AML patients[71.11% (32/45) vs. 30.70% (39/127), χ² = 22.38, P < 0.001]. EMMs(+) were significantly correlated with NPM1 gene variants (r = 0.413, P < 0.001), while negatively correlated with CEPBA double variants (r = -0.219, P < 0.05). Compared with conventional chemotherapy regimens, HMAs-containing chemotherapy regimens have improved the median progression-free survival (PFS) and median overall survival (OS) among intermediate-risk AML patients with EMMs(+) (PFS: 11.5 months vs. 25.5 months, P < 0.05; 12.5 months vs. 27 months, P < 0.05). Similarly, Compared with conventional chemotherapy regimens, chemotherapy with HMAs had increased median PFS and median OS in elderly AML patients with EMMs(+) (4 months vs. 18.5 months, P < 0.05; 7 months vs. 23.5 months, P < 0.05). CONCLUSION: Patients with AML have a high rate of EMMs carriage, and HMAs-containing chemotherapy regimens can prolong the survival of elderly patients with AML with poor prognosis, which may provide a reference for individualized treatment.

Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression.

Objective: AlkB homolog 5 (ALKBH5) has been proven to be closely related to tumors. However, the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported. Methods: The potential functional single-nucleotide polymorphisms (SNPs) in ALKBH5 were identified by National Center for Biotechnology Information (NCBI) dbSNP screening and SNPinfo software. TaqMan probes were used for genotyping. A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma. The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry (IHC). Cell counting kit-8 (CCK-8), plate colony formation and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to compare cell migration and invasion. Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism. RNA sequencing, N6-methyladenosine (m6A) sequencing, m6A methylated RNA immunoprecipitation (MeRIP) and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1. Results: ALKBH5 was highly expressed in neuroblastoma. Knocking down ALKBH5 inhibited the proliferation, migration and invasion of cancer cells. miR-186-3p negatively regulates the expression of ALKBH5, and this ability is affected by the rs8400 polymorphism. When the G nucleotide was mutated to A, the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased, resulting in upregulation of ALKBH5. SPP1 is the downstream target gene of the ALKBH5 oncogene. Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma. Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma. Conclusions: We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms. The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.

Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells.

BACKGROUND: Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital-based cohort cases. METHODS: We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan-Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. RESULTS: We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P < 0.05). Furthermore, patients with a low amount of immune cells exhibited poor prognosis (P = 0.046). The expression of PSPH significantly increased in activated memory CD4 T cells, resting NK cells and M0 macrophages (P = 0.037, < 0.001, and 0.005, respectively). CONCLUSIONS: This study highlighted that PSPH influences the prognosis of patients with gastric cancer, and this is associated with the infiltration of tumour immune cells, indicating that PSPH may be a new immune-related target for treating gastric cancer.

Prediction of the therapeutic efficacy of epirubicin combined with ifosfamide in patients with lung metastases from soft tissue sarcoma based on contrast-enhanced CT radiomics features.

OBJECTIVE: To investigate the value of contrast-enhanced computed tomography (CECT) radiomics features in predicting the efficacy of epirubicin combined with ifosfamide in patients with pulmonary metastases from soft tissue sarcoma. METHODS: A retrospective analysis of 51 patients with pulmonary metastases from soft tissue sarcoma who received the chemotherapy regimen of epirubicin combined with ifosfamide was performed, and efficacy was evaluated by Recist1.1. ROIs (1 or 2) were selected for each patient. Lung metastases were used as target lesions (86 target lesions total), and the patients were divided into a progression group (n = 29) and a non-progressive group (n = 57); the latter included a stable group (n = 34) and a partial response group (n = 23). Information on lung metastases was extracted from CECT images before chemotherapy, and all lesions were delineated by ITK-SNAP software manually or semiautomatically. The decision tree classifier had a better performance in all radiomics models. A receiver operating characteristic curve was plotted to evaluate the predictive performance of the radiomics model. RESULTS: In total, 851 CECT radiomics features were extracted for each target lesion and finally reduced to 2 radiomics features, which were then used to construct a radiomics model. Areas under the curves of the model for predicting lesion progression were 0.917 and 0.856 in training and testing groups, respectively. CONCLUSION: The model established based on the radiomics features of CECT before treatment has certain predictive value for assessing the efficacy of chemotherapy for patients with soft tissue sarcoma lung metastases.

Geographical disparities in infant mortality in the rural areas of China: a descriptive study, 2010-2018.

BACKGROUND: The infant mortality rate (IMR) is considered a basic measure of public health for countries around the world. The specific aim of our study was to provide an updated description of infant mortality rate among different regions in rural China, and assess the trends and causes of the IMR geographical disparities. METHODS: Data were collected from China's Under-5 Child Mortality Surveillance System(U5CMSS). The annual number of deaths and causes of death were adjusted using a 3-year moving average underreporting rate based on annual national data quality control results. The average annual decline rate (AADR) and the relative risk (RR) of the IMR and cause-specific infant mortality were calculated by Poisson regression and the Cochran-Mantel-Haenszel method. Data analysis was completed by SAS software. RESULTS: There was an apparent decrease in infant mortality in rural China from 2010 to 2018, at the AADR of 11.0% (95%CI 9.6-12.4), 11.2% (95%CI 10.3-12.1) and 6.6% (95%CI 6.0-7.3) in the eastern, central and western rural areas, respectively. The IMR was highest in the western rural area, followed by the central and eastern rural areas. Compared with the eastern rural area, the RR of infant mortality in the central rural area remained at 1.4-1.6 and increased from 2.4 (95%CI 2.3-2.6) in 2010-2012 to 3.1 (95% CI 2.9-3.4) in 2016-2018 in the western rural area. Pneumonia, preterm birth /LBW and birth asphyxia were the leading causes of infant deaths in the western rural area. Mortality rates of these three causes fell significantly in 2010-2018 but contributed to a higher proportion of deaths in the western rural area than in the central and western rural ares. CONCLUSIONS: Our study indicated that the infant mortality rate dropped significantly from 2010 to 2018, however, geographical disparities of IMR in rural China are still persist. Therefore, there is an urgent need for public health programmes and policy interventions for infants in western rural China.

Bis-Iridoids from Pterocephalus hookeri and Evaluation of Their Anti-Inflammatory Activity.

Four new secoiridoid-iridoid heterodimers, pterocenoids E-H (1-4), together with a known analog (5), were separated from the whole plants of Pterocephalus hookeri. Their structures were characterized by detailed spectroscopic analyses and NMR comparison with reported data for known analogs. Pterocenoid E (1) represents the first bis-iridoid example incorporating a rare trans-fused monomeric unit, and the C(8) configuration in 5 was corrected to be reversed to the original assignment. Among all the isolates, compound 5 not only showed moderate inhibition against the nitric oxide production (IC50 =36.0±4.3 µM) but also dose-dependently suppressed the secretion of an important pro-inflammatory cytokine TNF-α, in lipopolysaccharide-induced RAW264.7 cells.

Isolation, Structure Characterization, Total Synthesis and Biological Evaluation of Cinnamic Acid Derivatives from Tinospora sagittata.

Thirteen cinnamic acid derivatives (1-13), including six formerly unreported hybrids incorporating different short-chain fatty acid esters (1-6), have been obtained and structurally elucidated from an ethnological herb Tinospora sagittata. The structures of them have been established by spectroscopic data analyses and NMR comparison with known analogs, while those of 1, 2, 4 and 6 have been further supported by total synthesis, and it is the first report of this type of metabolites from the title species. All the isolates have been assessed in an array of bioassays encompassing cytotoxic, antibacterial, anti-inflammatory, antioxidant, as well as α-glucosidase and HDAC1 inhibitory models. Compound 7 showed significant inhibitory activity against α-glucosidase, and half of the isolates also displayed moderate antiradical effect.

mRNA vaccine for cancer immunotherapy.

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.