Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Analysis of health risk factors for older adults living alone in China and establishment and evaluation of a nomogram prediction model.

Objective: To understand the health status of older adults living alone in China and analyze the influencing factors, so as to provide reference for improving the health status of older adults living alone. Methods: Based on CGSS data from China General Social Survey (2017), the influencing factors of health status of older adults living alone were analyzed by unconditional Logistic regression, and the R software was used to develop a nomogram for predicting the risk of self-assessed unhealthy adverse outcomes. Results: Gender, annual income, mandarin listening level and participation in medical insurance were the influencing factors of self-rated health of older adults living alone. Age and annual income are the influencing factors of physiological health. Annual income and Internet use were influential factors for mental health. C-Statistic of nomogram prediction model was 0.645. The calibration curve showed that goodness of fit test (χ2 = 58.09, p < 0.001), and the overall prediction ability of the model was good. Conclusion: The health status of older adults living alone in the home-based older adults care is worrying, and it is affected by various factors. We should pay more attention to older adults living alone, improve the ability of listening and distinguishing mandarin and the use of health information platforms for older adults living alone, and further implement medical insurance policies and health services. Announcing the solution to promote healthy home-based care for older adults living alone.

IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.

Asp-tRNAAsn/Glu-tRNAGln amidotransferase A subunit-like amidase mediates the degradation of insecticide flonicamid by Variovorax boronicumulans CGMCC 4969.

The main metabolic product of the pyridinecarboxamide insecticide flonicamid, N-(4-trifluoromethylnicotinyl)glycinamide (TFNG-AM), has been shown to have very high mobility in soil, leading to its accumulation in the environment. Catabolic pathways of flonicamid have been widely reported, but few studies have focused on the metabolism of TFNG-AM. Here, the rapid transformation of TFNG-AM and production of the corresponding acid product N-(4-trifluoromethylnicotinoyl) glycine (TFNG) by the plant growth-promoting bacterium Variovorax boronicumulans CGMCC 4969 were investigated. With TFNG-AM at an initial concentration of 0.86 mmol/L, 90.70 % was transformed by V. boronicumulans CGMCC 4969 resting cells within 20 d, with a degradation half-life of 4.82 d. A novel amidase that potentially mediated this transformation process, called AmiD, was identified by bioinformatic analyses. The gene encoding amiD was cloned and expressed recombinantly in Escherichia coli, and the enzyme AmiD was characterized. Key amino acid residue Val154, which is associated with the catalytic activity and substrate specificity of signature family amidases, was identified for the first time by homology modeling, structural alignment, and site-directed mutagenesis analyses. When compared to wild-type recombinant AmiD, the mutant AmiD V154G demonstrated a 3.08-fold increase in activity toward TFNG-AM. The activity of AmiD V154G was greatly increased toward aromatic L-phenylalanine amides, heterocyclic TFNG-AM and IAM, and aliphatic asparagine, whereas it was dramatically lowered toward benzamide, phenylacetamide, nicotinamide, acetamide, acrylamide, and hexanamid. Quantitative PCR analysis revealed that AmiD may be a substrate-inducible enzyme in V. boronicumulans CGMCC 4969. The mechanism of transcriptional regulation of AmiD by a member of the AraC family of regulators encoded upstream of the amiD gene was preliminarily investigated. This study deepens our understanding of the mechanisms of metabolism of toxic amides in the environment, providing new ideas for microbial bioremediation.

Single-cell transcriptome analysis profiling lymphatic invasion-related TME in colorectal cancer.

Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI- based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.

Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS.

Whole Genome Sequencing Highlights the Pathogenic Profile in Nocardia Keratitis.

Purpose: Nocardia keratitis is a serious and sight-threatening condition. This study aims to reveal the virulence and antimicrobial resistance gene profile of Nocardia strains using whole genome sequencing. Methods: Whole-genome sequencing was performed on 23 cornea-derived Nocardia strains. Together with genomic data from the respiratory tract and the environment, 141 genomes were then utilized for phylogenetic and pan-genome analyses, followed by virulence and antibiotic resistance analysis. The correlations between virulence genes and pathogenicity were experimentally validated, including the characteristics of Nocardia colonies and clinical and histopathological evaluations of Nocardia keratitis mice models. Results: Whole-genome sequencing of 141 Nocardia strains revealed a mean of 220 virulence genes contributed to bacterial pathogenesis. The mce gene family analysis led to the categorization of strains from the cornea into groups A, B, and C. The colonies of group C had the largest diameter, height, and fastest growth rate. The size of corneal ulcers and the clinical scores showed a significant increase in mouse models induced by group C. The relative expression levels of pro-inflammatory cytokines (CD4, IFN-γ, IL-6Rα, and TNF-α) in the lesion area exhibited an increasing trend from group A to group C. Antibiotic resistance genes (ARGs) spanned nine distinct drug classes, four resistance mechanisms, and seven primary antimicrobial resistance gene families. Conclusions: Whole genome sequencing highlights the pathogenic role of mce gene family in Nocardia keratitis. Its distribution pattern may contribute to the distinct characteristics of the growth of Nocardia colonies and the clinical severity of the mice models.

Thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of EGF to inhibit cervical cancer recurrence.

Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.

Long-term fasting induced basal thermogenesis flexibility in female Japanese quails.

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Effects of sintering additives and sintering methods on the mechanical, antimicrobial and optical properties of Si3N4 bioceramics.

Si3N4 bioceramics were fabricated using GPS and SPS method with MgO-RE2O3 (RE = La, Nd, Gd, Ho and Lu) sintering additives. The effect of sintering methods and sintering additives on the grain growth, mechanical, antimicrobial properties and color of Si3N4 bioceramics were studied. Samples sintered with GPS are composed of ß-Si3N4 and samples sintered with SPS are composed of α-Si3N4 and ß-Si3N4. The growth of ß-Si3N4 grains in samples sintered with GPS are more adequate. Samples sintered with GPS exhibit a S. aureus inactivation rate up to 98% and a bright color appearance with a hardness of about 13 GPa and a fracture toughness up to 7.5 MPa m1/2, suitable for dental implants. And samples sintered with SPS exhibit a hardness of about 17 GPa and a fracture toughness about 6 MPa m1/2.

Determinants of health poverty vulnerability in rural areas of Western China in the post-poverty relief era: an analysis based on the Anderson behavioral model.

BACKGROUND: Although China has eliminated absolute poverty, the effects of sickness still pose a threat to the prospect of returning to poverty in western rural areas. However, poverty governance extends beyond solving absolute poverty, and should enhance the family's ability to resist risks, proactively identify the existence of risks, and facilitate preventive measures to reduce the probability of falling into poverty again. This study aimed to assess the health poverty vulnerability of rural households in western China and decompose its determinants. METHODS: Based on survey data from 2022, the three-stage feasible generalized least squares method was used to calculate the health poverty vulnerability index. Then, Anderson's health behavior theory model was extended to analyse various influencing factors using binary logistic regression, and the contribution of each influencing factor was decomposed using the Shapley index. Finally, Tobit regression and the censored least absolute deviations estimation (clad) method were used to test the model's robustness. RESULTS: A total of 5455 families in the rural Ningxia region of western China were included in the study. The health poverty vulnerability index of the sample population in 2022 was 0.3000 ± 0.2223, and families with vulnerability ≥0.5 accounted for 16.9% of the sample population. From the Anderson behavioral model, the three models including propensity, enabling, and demand factors had the best fit, and the AIC and BIC values were the smallest. The Shapley decomposition showed that the dimensions of the propensity factor, number of residents, age and educational level of the household head, and dependency ratio were the most important factors influencing vulnerability to health poverty. Tobit regression and the clad method proved the reliability of the constructed model through a robustness test. CONCLUSION: Rural areas still face the risk of becoming poor or falling into poverty owing to residents' health problems. Health poverty alleviation should gradually change from a focus on treatment to prevention, and formulate a set of accurate and efficient intervention policies from a forward-looking perspective to consolidate the results of health poverty alleviation and prevent widescale poverty return.

Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway.

BACKGROUND: Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, the mechanism of TIM3-mediated CD8+TILs exhaustion in DLBCL remains poorly understood. Therefore, we aimed to clarify the potential pathway involved in TIM3-mediated CD8+TILs exhaustion and its significance in DLBCL. METHODS: The expression of TIM3 and its correlation with CD8+TILs exhaustion, the key ligand of TIM3, and the potential pathway of TIM3-mediated CD8+TILs exhaustion in DLBCL were analyzed using single-cell RNA sequencing and validated by RNA sequencing. The biological significance of TIM3-related pathway in DLBCL was investigated based on RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction data. Finally, the possible regulatory mechanism of TIM3-related pathway in DLBCL was explored using single-cell RNA sequencing and RNA sequencing. RESULTS: Our results demonstrated that CD8+TILs, especially the terminally exhausted state, were the major clusters that expressed TIM3 in DLBCL. Galectin-9, mainly expressed in M2 macrophages, is the key ligand of TIM3 and can induce the exhaustion of CD8+TILs through TIM3/Galectin-9 pathway. Meanwhile, high TIM3/Galectin-9 enrichment is related to immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, and poor response to CHOP-based chemotherapy, and can predict the clinical efficacy of immune checkpoint blockade therapy in DLBCL. Furthermore, the TIM3/Galectin-9 enrichment in DLBCL may be regulated by the IFN-γ signaling pathway. CONCLUSIONS: Our study highlights that TIM3/Galectin-9 pathway plays a crucial role in CD8+TILs exhaustion and the immune escape of DLBCL, which facilitates further functional studies and could provide a theoretical basis for the development of novel immunotherapy in DLBCL.

The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis.

Previous studies have focused on the impact of individual RNA modifications on tumor development. This study comprehensively investigated the effects of multiple RNA modifications, including m6A, alternative polyadenylation, pseudouridine, adenosine-to-inosine editing, and uridylation, on gastric cancer (GC). By analyzing 1,946 GC samples from eleven independent cohorts, we identified distinct clusters of RNA modification genes with varying survival rates and immunological characteristics. We assessed the chromatin activity of these RNA modification clusters through regulon enrichment analysis. A prognostic model was developed using Stepwise Regression and Random Survival Forest algorithms and validated in ten independent datasets. Notably, the low-risk group showed a more favorable prognosis and positive response to immune checkpoint blockade therapy. Single-cell RNA sequencing confirmed the abundant expression of signature genes in B cells and plasma cells. Overall, our findings shed light on the potential significance of multiple RNA modifications in GC prognosis, stemness development, and chemotherapy resistance.

Language model enables end-to-end accurate detection of cancer from cell-free DNA.

We present a language model Affordable Cancer Interception and Diagnostics (ACID) that can achieve high classification performance in the diagnosis of cancer exclusively from using raw cfDNA sequencing reads. We formulate ACID as an autoregressive language model. ACID is pretrained with language sentences that are obtained from concatenation of raw sequencing reads and diagnostic labels. We benchmark ACID against three methods. On testing set subjected to whole-genome sequencing, ACID significantly outperforms the best benchmarked method in diagnosis of cancer [Area Under the Receiver Operating Curve (AUROC), 0.924 versus 0.853; P < 0.001] and detection of hepatocellular carcinoma (AUROC, 0.981 versus 0.917; P < 0.001). ACID can achieve high accuracy with just 10 000 reads per sample. Meanwhile, ACID achieves the best performance on testing sets that were subjected to bisulfite sequencing compared with benchmarked methods. In summary, we present an affordable, simple yet efficient end-to-end paradigm for cancer detection using raw cfDNA sequencing reads.

The effect of childhood trauma on depression in college students: A moderated mediation model.

OBJECTIVE: Childhood trauma is considered as a critical risk factor for depression. Although many studies have investigated the pathway of Childhood trauma to depression, especially the mediating or moderating effects of cognitive emotion regulation strategies or neuroticism or stress perception, the results were inconsistent and the underlying psychological mechanisms of depression remain unclear. This study aims to explore the influence and mechanism of childhood trauma on depression in college students, and establish a full model among these interactive factors. METHODS: 1272 college students were surveyed using the childhood trauma questionnaire (CTQ), short version of center for epidemiologic studies depression scale (CES-D), Chinese perceived stress scale (CPSS), neuroticism extraversion openness five-factor inventory (NEO-FFI), and the Cognitive Emotion Regulation Questionnaire (CERQ). RESULTS: (1) Childhood trauma, neuroticism, stress perception, and maladaptive cognitive emotion regulation strategies were all significantly and positively correlated with depression among college students; (2) Stress perception and neuroticism act as a chain mediator between childhood trauma and depression in college students. (3) Maladaptive cognitive emotion regulation strategies play a moderating role in "childhood trauma-neuroticism-depression". CONCLUSION: Childhood trauma increases the risk of depression in college students by affecting neuroticism and stress perception, and high levels of maladaptive cognitive emotion regulation strategies link neuroticism and enhance the effect of childhood trauma on depression in college students.

Acanthamoeba Keratitis in China: Genotypic and Clinical Correlations.

Purpose: To investigate the relationship between Acanthamoeba genotypes, clinical manifestations, and outcomes in Acanthamoeba keratitis (AK) patients. Methods: This retrospective study included 159 culture-confirmed AK patients. Patients' data were collected, including demographics, initial diagnosis, treatments, and clinical features. The genotype of Acanthamoeba was identified through sequencing the Diagnostic Fragment 3 (DF3) region in the small ribosomal subunit RNA genes. The phylogenetic tree was constructed using the ClustalW model and maximum likelihood method. Cases with "poor outcome" were defined based on specific clinical criteria, including corneal perforation, keratoplasty, other eye surgery, duration of anti-amoebic therapy ≥8.0 months, and final visual acuity ≤20/80. "Better outcome" cases were the remainder. The correlation between T4 subtypes, clinical phenotypes, and clinical prognosis were further analyzed. Results: In this study, AK was primarily attributed to the T4A genotype, with a positive correlation between geographical and genetic distances. The primary clinical associated with T4 subtypes was deep stromal infiltration. Results was also showed a significant association between T4 subtypes and clinical outcomes (P = 0.021). Further analysis revealed that T4C was closely associated with a better prognosis (P = 0.040) and T4D with worse outcomes (P = 0.013). Conclusions: In China, AK was predominantly caused by the T4A subtype. Geographical distance positively correlated with genetic distance. Clinical prognosis varied among different subtypes, notably in T4C and T4D. Translational Relevance: This study demonstrated the association between T4 subtypes and clinical phenotypes, as well as the effects of T4 subtypes on clinical prognosis.

Fine-scale mapping of chromosome 9q22.33 identifies candidate causal variant in ovarian cancer.

Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10-7; rs1889268, P = 3.71 × 10-2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.

Surgical approach to and morphology of visually significant persistent pupillary membranes.

PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: A prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: Thirty-one eyes from 19 patients were included with the mean age of 7.2 years. Three morphological variants of PPMs were observed: Type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); Type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; Type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The best corrected visual acuity was significantly improved from 0.34±0.18 logMAR preoperatively to 0.17±0.09 logMAR postoperatively (P <.001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSION: PPMs were categorized into three types according to their different morphologies, which helped to determine the best surgical strategy.

Relationship between the health poverty vulnerability and multimorbidity patterns identified with latent class analysis aged 45 years or more adults in Northwestern China: A cross-section study.

This study aims to identify multimorbidity patterns and examine whether health poverty vulnerability (HPV) varies among adults aged 45 years or more. Data from 4338 participants were extracted from a Chinese cross-sectional study. Latent class analysis was used to identify multimorbidity patterns based on 11 self-reported chronic diseases. A 3-stage feasible generalized least-squares method was used to measure the HPV. The associations and influencing factors were analyzed using the Tobit model. The mean HPV values were 0.105 ±â€…0.225 and 0.329 ±â€…0.357, based on extreme poverty and those of low- and middle-income countries' poverty line, respectively. Four latent multimorbidity patterns were identified, comprising hypertension (57.33%), cardiovascular diseases (19.94%), the musculoskeletal system (13.09%), and spine (9.64%). The HPV value from hypertension (coefficient [Coef] =0.03, 95% confidence interval (CI) = 0.00-0.05) was significantly higher than that of the musculoskeletal system based on extreme poverty. In addition, the HPV values for hypertension (Coef =0.08, 95% CI = 0.05-0.11), spine (Coef =0.06, 95% CI = 0.02-0.11), and cardiovascular diseases (Coef =0.07, 95% CI = 0.03-0.11) were significantly high based on low- and middle-income countries' poverty line. Age ≥75 years, registered poor households, catastrophic medical expenditure, and toilet style were major risk factors. Although the multimorbidity pattern-induced HPV has been significant improved on extreme poverty, it still poses a very serious challenge with regard to low- to middle-income countries' poverty line. The sensitivity analysis proved the robustness of the results. Policymakers should focus on adults with 3 multimorbidity patterns, namely, registered poor households, age ≥75 years, and catastrophic health expenditure, to adopt targeted interventions to prevent and eliminate HPV.