TRP channel-related LncRNAs, AC092535.4 and LINC01637, as novel prognostic biomarkers for uveal melanoma.

Introduction: Transient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood. Methods: We employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay. Results: The risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The in vitro experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown. Discussion: Two TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets.

Pre-packaged cold-chain ready-to-eat food as a source of sporadic listeriosis in Beijing, China.

OBJECTIVES: Using a sporadic case of listeriosis suspected to have been caused by consuming a pre-packaged cold-chain ready-to-eat (RTE) food in Beijing, China in 2021 as an exemplar, this study demonstrated the importance of thoroughly investigating the source of listeriosis up to the production point for mitigating infection risk during routine monitoring of Listeria in food facilities and national surveillance program using whole-genome sequencing (WGS). METHODS: Epidemiological, laboratory, traceback, and plant investigations were used to identify the source of infection. RESULTS: WGS showed the isolate from the patient was genetically indistinguishable from that of the implicated food. During a plant investigation, L. monocytogenes was detected in 26% (9/35) of the environmental samples and one of two raw material samples, confirming the source. CONCLUSION: To our knowledge, this is the first investigation in China linking a case of L. monocytogenes infection to a suspected food and its production environment. This report highlights the risk of L. monocytogenes contamination of RTE food and demonstrates the role of food safety risk monitoring in identifying potential sources of infection. Reinforcing control programs in RTE processing plants, intensified surveillance of microorganisms in food products and targeted health education is required to mitigate the infection risk.

Temporal trends and correlates in multiple hospitalizations among older adults: findings from a nationally representative sample in China.

OBJECTIVE: This study aims to examine the trends and correlates in multiple hospitalizations among older adults in China. METHODS: The data were from the China Health and Retirement Longitudinal Study (CHARLS), and generalized ordered logit model (GOLM) was used to identify the correlates of multiple hospitalizations among older adults aged≥60 years old. RESULTS: Between 2011 and 2018, the proportion of older adults having multiple hospitalizations in the past year showed an increasing trend in the total sample (p value for trend = 0.014). Being older, male, illiterate, living in the middle/western region, having higher annual per capita household expenditure, health insurance, multimorbidity, and being depressed were associated with increased odds of multiple hospitalizations. CONCLUSIONS: Our findings indicated that older adults with multiple hospitalizations may expect an increasing burden on healthcare system. More efforts are needed to improve health insurance and primary healthcare to reduce avoidable hospitalizations.

Pathogenic Surveillance of Foodborne Illness-Related Diarrhea - Beijing Municipality, China, 2013-2023.

What is already known about this topic?: Foodborne diseases present a significant public health concern, particularly in China, where they represent a significant food safety challenge. Currently, there is a need for a thorough and systematic analysis of the extended epidemiological patterns of foodborne diseases in Beijing Municipality. What is added by this report?: Monitoring results show that Norovirus and diarrheagenic Escherichia coli (DEC) are the most commonly identified foodborne diarrheal pathogens. Individuals aged 19-30 are at a higher risk of foodborne diarrhea in Beijing, with Salmonella infection being associated with fever symptoms. What are the implications for public health practice?: This study analyzes 11 years of consecutive monitoring data to enhance understanding of the epidemiological and clinical features of foodborne diarrhea in Beijing. It aims to identify high-risk populations, assist in clinical pathogen identification and treatment, and support the development of tailored preventive strategies.

Community Incidence Estimates of Five Pathogens Based on Foodborne Diseases Active Surveillance - China, 2023.

What is already known about this topic?: Foodborne diseases, representing significant food safety and public health challenges globally, are not well-documented in terms of incidence, particularly for cases characterized by acute gastroenteritis (AGI) in China. What is added by this report?: This study developed a pyramid model to estimate the incidence of five pathogens, stratified by gender and age. The estimated incidences per 100,000 people with 95% uncertainty intervals (UI) are as follows: Norovirus, 3,188.28 (95% UI: 2,518.03, 7,296.96); Salmonella spp., 1,295.59 (95% UI: 1,002.62, 1,573.11); diarrheagenic E. coli (DEC), 782.62 (95% UI: 651.19, 932.05); Vibrio parahaemolyticus, 404.06 (95% UI: 342.19, 468.93); and Shigella spp., 26.73 (95% UI: 21.05, 33.46). What are the implications for public health practice?: This study elucidates the incidence rates across various gender and age groups, thereby identifying priority populations for targeted preventive interventions aimed at reducing disease burden. These insights are crucial for the development of public health policies and management of food safety risks.

Epidemiological Insights into Foodborne Pathogens Through qPCR Exploration of Prevalence - Beijing Municipality, China, January 2022-April 2023.

What is already known on this topic?: Foodborne diseases present a substantial global health risk. Traditional diagnostic methods have constraints, but advancements in molecular techniques, like quantitative polymerase chain reaction (qPCR), provide a hopeful solution. What is added by this report?: We examined 1,011 stool samples from individuals suspected of foodborne illnesses. Our analysis indicated a significant presence of Clostridium perfringens, Salmonella enterica, enterotoxigenic Escherichia coli (ETEC), and adenovirus. Notably, co-infections were identified in 71.22% of the samples. What are the implications for public health practice?: The data emphasize a notable prevalence of co-infections, highlighting the complexity of foodborne illnesses. This study underscores the significance of utilizing contemporary diagnostic methods in densely populated urban areas such as Beijing Municipality.

The Influence of Drug-Eluting Beads Transarterial Chemoembolization on Serum Levels of Soluble Programmed Cell Death Protein-1 in Advanced Hepatocellular Carcinoma Patients.

Aim: This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs). Materials and Methods: A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed. Results: The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE. Conclusion: The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.

Risk factors associated with food consumption and food-handling habits for sporadic listeriosis: a case-control study in China from 2013 to 2022.

The prevalence of listeriosis in China has been increasing in recent years. Listeriosis primarily spreads through contaminated food. However, the resilient causative organism, Listeria monocytogenes, and its extended incubation period pose challenges in identifying risk factors associated with food consumption and food-handling habits. This study aimed to identify the risk factors associated with food consumption and food-handling habits for listeriosis in China. A matched case-control study (1:1 ratio) was conducted, which enrolled all eligible cases of listeriosis between 1 January 2013 and 31 December 2022 in China. Basic information and possible risk factors associated with food consumption and food-handling habits were collected. Overall, 359 patients were enrolled, including 208 perinatal and 151 non-perinatal cases. Univariate and multivariable logistic analyzes were performed for the perinatal group. For the perinatal and non-perinatal groups, ice cream and Chinese cold dishes were the high-risk foods for listeriosis (odds ratio (OR) 2.09 95% confidence interval (CI): 1.23-3.55; OR 3.17 95% CI: 1.29-7.81), respectively; consumption of leftovers and pet ownership were the high-risk food-handling habits (OR 1.92 95% CI: 1.03-3.59; OR 3.00 95% CI: 1.11-8.11), respectively. In both groups, separation of raw and cooked foods was a protective factor (OR 0.27 95% CI: 0.14-0.51; OR 0.35 95% CI: 0.14-0.89), while refrigerator cleaning reduced the infection risk by 64.94-70.41% only in the perinatal group. The identification of high-risk foods and food-handling habits for listeriosis is important for improving food safety guidelines for vulnerable populations.

Inhibition of PCSK9 prevents and alleviates cholesterol gallstones through PPARα-mediated CYP7A1 activation.

BACKGROUND & AIMS: Dysregulated cholesterol metabolism is the major factor responsible for cholesterol gallstones (CGS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol homeostasis and its inhibitors secure approval for treating various cholesterol metabolic disorders such as hypercholesterolemia and cardiovascular diseases, but its role in CGS remains unclear. Our study aims to clarify mechanisms by which PCSK9 promotes CGS formation and explore the application of the PCSK9 inhibitor, alirocumab, in preventing and treating CGS. APPROACH & RESULTS: The expressions of PCSK9 were notably increased in CGS patients' serum, bile, and liver tissues compared to those without gallstones. Moreover, among CGS patients, hepatic PCSK9 was positively correlated with hepatic cholesterol and negatively correlated with hepatic bile acids (BAs), suggesting PCSK9 was involved in disrupted hepatic cholesterol metabolism related to CGS. Mechanistically, in vitro experiments demonstrated that inhibition of PCSK9 enhanced nuclear expression of PPARα by diminishing its lysosomal degradation and subsequently activated CYP7A1 transcription. Finally, inhibition of PCSK9 prevented CGS formation and dissolved the existing stones in CGS mice by elevating the conversion of cholesterol into BAs through PPARα-mediated CYP7A1 activation. Additionally, serum PCSK9 level may function as a prognostic signature to evaluate the therapeutic efficacy of PCSK9 inhibitors. CONCLUSIONS: Inhibition of PCSK9 exerts preventive and therapeutic effects on CGS by activating PPARα-mediated CYP7A1 expression and facilitating the conversion of cholesterol into BAs, which highlights the potential of PCSK9 inhibition as a promising candidate for preventing and treating CGS in clinical applications. IMPACT AND IMPLICATIONS: PCSK9 plays a pivotal role in cholesterol metabolism and its inhibitors are approved for clinical use in cardiovascular diseases. Our study observes inhibition of PCSK9 prevents and dissolves CGS by activating PPARα-mediated CYP7A1 expression and facilitating the conversion of cholesterol into BAs. Mechanistically, PCSK9 inhibition enhanced the nuclear expression of PPARα by diminishing its lysosomal degradation and subsequently activated CYP7A1 transcription. Our study sheds light on the new function and mechanism of PCSK9 in CGS, providing a novel preventive and therapeutic target with potential clinical applications.

Barriers to uptake of cataract surgery among elderly patients in rural China: a cross-sectional study.

OBJECTIVE: To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered. DESIGN: We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery. SETTING: Rural communities in Handan, China. PARTICIPANTS: Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract. RESULTS: Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p<0.01), self-reported better physical capacity (p<0.001) and having had a recent physical examination (p=0.01) were significantly associated with acceptance of vision screening. The only variable significantly associated with acceptance of surgery was presenting visual acuity, with better vision inversely associated with acceptance of surgery (p<0.05) models. CONCLUSION: Our results suggest that refusal of basic eye examinations may be at least as important a determinant of low surgical rates in rural China as lack of acceptance of surgery itself.

Exploring the Preferences of Parents of Children with Myopia in Rural China for Eye Care Services Under Privatization Policy: Evidence from a Discrete Choice Experiment.

OBJECTIVES: This study aims to measure the preferences and valuations of parents of students with myopia parents for eye care service attributes in rural China, and to quantify the potential welfare impacts of privatization policy on children's eye care services. METHODS: A discrete choice experiment was designed and implemented among a sample of parents of children with myopia in rural China. We randomly selected 350 participants from the list of subjects obtained from local town schools and family doctors using a random number table method. The participants were asked to choose between two hypothetical scenarios defined by five attributes: provider type, distance, price, lenses type, and refractionists' professional competencies. We estimate conditional logit and mixed logit models to approximate individual preferences for these attributes and estimate the welfare effects by calculating willingness to pay. RESULTS: Respondents (n = 336) showed a significant preference for public providers of refractive error services, myopia control lenses, and professional refractionists (P < 0.01 for each). Consumer welfare losses due to a prohibition of the public provision of refractive error services could be compensated by improving the quality of products and services delivered by private providers. Lastly, both parent and child demographics and previous experience of eye care service consumption are important predictors of willingness to pay for refractive error services. CONCLUSIONS: The privatization policy on children's eye care services would not cater to the preferences of rural consumers, inevitably leading to welfare losses. However, reduced consumer welfare could be compensated by improving the quality of products and service delivery from private providers. These results could help inform strategies to improve and reduce inequities in access to high-quality eye care services in rural China.

A Novel TGF-ß-Related Signature for Predicting Prognosis, Tumor Microenvironment, and Therapeutic Response in Colorectal Cancer.

The transforming growth factor beta (TGF-ß) signaling plays a critical role in immune evasion and tumor progression. However, its modulatory influences on prognosis, tumor microenvironment (TME), and therapeutic efficacy remain unknown in colorectal cancer (CRC). We summarized TGF-ß-related genes and comprehensively estimated their expression pattern in 2142 CRC samples from 9 datasets. Two distinct cluster patterns were divided and biological characteristics of each pattern were further analyzed. Then, to quantify the TGF-ß cluster pattern of individual CRC patient, we generated the TGF-ß score (TGFBscore) model based on TGF-ß cluster pattern-relevant differentially expressed genes (DEGs). Subsequently, we conducted correlation analysis for TGFBscore and clinical prognosis, consensus molecular subtypes (CMSs), TME characteristics, liver metastasis, drug response, and immunotherapeutic efficacy in CRC. We illustrated transcriptional and genetic alterations of TGF-ß-relevant genes, which were closely linked with carcinogenic pathways. We identified two different TGF-ß cluster patterns, characterized by a high and a low TGFBscore. The TGFBscore-high group was significantly linked with worse patient survival, epithelial-mesenchymal transition (EMT) activation, liver metastasis tendency, and the infiltration of immunosuppressive cells (regulatory T cells [Tregs], M2 macrophages, cancer-associated fibroblasts [CAFs], and myeloid-derived suppressor cells [MDSCs]), while the TGFBscore-low group was linked with a survival advantage, epithelial phenotype, early CRC staging, and the infiltration of immune-activated cells (B cell, CD4 T cell, natural killer T [NKT] cell, and T helper 1 [Th1] cell). In terms of predicting drug response, TGFBscore negatively correlated (sensitive to TGFBscore-high group) with drugs targeting PI3K/mTOR, JNK and p38, RTK signaling pathways, and positively correlated (sensitive to TGFBscore-low group) with drugs targeting EGFR signaling pathway. Also, TGFBscore could predict the efficacy of different anti-tumor therapies. TGFBscore-low patients might benefit more from anti-PDL1 immunotherapy, adjuvant chemotherapy (ACT), and ERBB targeted therapy, whereas TGFBscore-high patients might benefit more from antiangiogenic targeted therapy. Our study constructed a novel TGF-ß scoring model that could predict prognosis, liver metastasis tendency, and TME characteristics for CRC patients. More importantly, this work emphasizes the potential clinical utility of TGFBscore in evaluating the efficacy of chemotherapy, targeted therapy, and immunotherapy, guiding individualized precision treatment in CRC.

Visual genetic typing of glioma using proximity-anchored in situ spectral coding amplification.

Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity-anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA mutations, enabling visual typing of brain gliomas with different pathological grades at the single-cell and tissue levels. The ligation-based padlock probe can discriminate one-nucleotide variations, and the design of proximity primers enables the anchoring of amplicons on target RNA, thus improving localization accuracy. The DNA module-based spectral coding strategy can dramatically improve the multiplexing capacity for imaging RNA mutations through one-time labelling, with low cost and simple operation. One-target-one-amplicon amplification confers ProxISCA the ability to quantify RNA mutation copy number with single-molecule resolution. Based on this approach, it is found that gliomas with higher malignant grades express more genes with high correlation at the cellular and tissue levels and show greater cellular heterogeneity. ProxISCA provides a tool for glioma research and precise diagnosis, which can reveal the relationship between cellular heterogeneity and glioma occurrence or development and assist in pathological prognosis.

Mean platelet volume and the association with all-cause mortality and cardiovascular mortality among incident peritoneal dialysis patients.

BACKGROUND: While mean platelet volume (MPV) is linked to severity and all-cause mortality in patients with sepsis, its association with all-cause mortality and cardiovascular mortality in patients treated with peritoneal dialysis (PD) remains unknown. OBJECTIVES: The purpose of this study was to estimate the relationship between MPV and all-cause mortality and cardiovascular mortality among patients treated with PD. METHOD: We retrospectively collected 1322 patients treated with PD from November 1, 2005 to August 31, 2019. All-cause mortality and cardiovascular mortality was identified as the primary outcome. MPV was classified into three categories by means of X-tile software. The correlation between MPV and all-cause mortality was assessed by Cox model. Survival curves were performed by Kaplan-Meier method. RESULTS: The median follow-up period was 50 months (30-80 months), and a total of 360 deaths were recorded. With respect to all-cause mortality, patients in MVP ≥ 10.2 fL had considerably higher risk of all-cause mortality among three models (HR 0.68, 95%CI 0.56-0.84; HR 0.70, 95%CI 0.56-0.87; HR 0.73, 95%CI 0.59-0.91; respectively). Moreover, patients treated with PD, whose MVP ≥ 10.2 fL, also suffered from significantly higher risk of cardiovascular mortality in model 1, 2, and 3 (HR 0.63, 95%CI 0.46-0.85; HR 0.66, 95%CI 0.48-0.91; HR 0.69, 95%CI 0.50-0.95; respectively). CONCLUSIONS: This study indicates that MPV is independently correlated with both all-cause mortality and cardiovascular mortality in PD.

One-Base-Gap Circular Probe-Mediated Dual Amplification for Isothermal Detection of N6-Methyladenosine Modifications.

N6-Methyladenosine (m6A) stands out as the predominant internal modification in mammalian RNA, exerting crucial regulatory functions in the metabolism of mRNA. Currently available methods have been limited by an inability to quantify m6A modification at precise sites. In this work, we screened a Bst 2.0 warm start DNA polymerase with the capability of discriminating m6A from adenosine (A) and developed a robust m6A RNA detection method that enables isothermal and ultrasensitive quantification of m6A RNA at single-base resolution. The detection limit of the assay could reach about 0.02 amol, and the quantitative accuracy of the assay was verified in real cell samples. Furthermore, we applied this assay to single-cell analysis and found that the coefficients of variation of the MALAT1 m6A 2611 site in glioblastoma U251 cells showed over 20% higher than in oligodendrocytes MO3.13 cells. This method provides a highly sensitive analytical tool for site-specific m6A detection and quantification, which is expected to provide a basis for precise disease diagnosis and epigenetic transcriptional regulation.

Structural insights into the oligomeric effects on catalytic activity of a decameric feruloyl esterase and its application in ferulic acid production.

Oligomeric feruloyl esterase (FAE) has great application prospect in industry due to its potentially high stability and fine-tuned activity. However, the relationship between catalytic capability and oligomeric structure remains undetermined. Here we identified and characterized a novel, cold-adapted FAE (BtFae) derived from Bacteroides thetaiotaomicron. Structural studies unraveled that BtFae adopts a barrel-like decameric architecture unique in esterase families. By disrupting the interface, the monomeric variant exhibited significantly reduced catalytic activity and stability toward methyl ferulate, potentially due to its impact on the flexibility of the catalytic triad. Additionally, our results also showed that the monomerization of BtFae severely decreased the ferulic acid release from de-starched wheat bran and insoluble wheat arabinoxylan by 75 % and 80 %, respectively. Collectively, this study revealed novel connections between oligomerization and FAE catalytic function, which will benefit for further protein engineering of FAEs at the quaternary structure level for improved industrial applications.

Sweroside functionalized with Mesenchymal Stem cells derived exosomes attenuates sepsis-induced myocardial injury by modulating oxidative stress and apoptosis in rats.

Sepsis is a life-threatening problem by organ dysfunction influenced by negative inflammatory responses and stimulated oxidative stress, which most of sepsis patients about 40-60% are accompanied with myocardial injury. Recently, stem cells derived exosomes could effectively apply in the numerous diseases by combined with natural therapeutic agents. In the present investigation, Sweroside functionalized with exosomes to control inflammatory responses by sepsis and significantly proved the function of depreciated myocardial injury-induced by LPS. The sweroside could have effectively delivered to cardiomyocytes cells via exosome carriers. The induced-SMI rats exhibited severe myocardial injury and apoptosis by in vivo experiments and treatment of sweroside-functionalized exosomes (SWO/EX) reassured the phenotypes. Importantly, SWO/EX significantly downregulated the ROS generation in the SMI rat models. The SOD and GSH activity were also suppressed in SMI rat models, and treated models with SWO/EXO could have effective liberating activity in the Rats. Meanwhile, SWO/EXO treated LPS-induced cardiomyocytes displayed that significant reduction of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) levels and also increasing cell survival and prevented apoptosis. Thus, we demonstrate that MS-cells derived exosome with sweroside could have effectively impede sepsis-induced myocardial injury. SWO/EX formulations might be applied as a potent therapeutic agent for SMI therapy.

Lenvatinib plus sintilimab with or without transarterial chemoembolization for intermediate or advanced stage hepatocellular carcinoma: a propensity score-matching cohort study.

In this retrospective study, we compared the efficacy and safety of lenvatinib plus sintilimab, with or without transarterial chemoembolization (TLS vs. LS), in patients with intermediate or advanced stage hepatocellular carcinoma (HCC). Eligible patients who received combination therapy with TLS or LS at Tianjin Medical University Cancer Institute & Hospital from December 2018 to October 2020 were propensity score matched (PSM) to correct for potential confounding biases between the two groups. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS), overall response rate (ORR) and treatment-related adverse events (TRAEs). Cox proportional hazards models were used to identify prognostic factors. The study included 152 patients (LS group, n=54, TLS group, n=98). After PSM, patients in the TLS group had significantly longer PFS (11.1 versus 5.1 months, P=0.033), OS (not reached versus 14.0 months, P=0.0039) and ORR (modified Response Evaluation Criteria in Solid Tumors: 44.0% versus 23.1%; P=0.028) than those in the LS group. In the multivariate Cox regression analysis, the treatment regimen (TLS versus LS) was an independent predictor for both PFS (HR=0.551; 95% CI: 0.334-0.912; P=0.020) and OS (HR=0.349; 95% CI: 0.176-0.692; P=0.003) and CA19-9 level was an independent predictor for OS (HR=1.005; 95% CI: 1.002-1.008; P=0.000). No significant differences in the incidence of grade ≥3 TRAEs were reported between the two treatment groups. In conclusion, triple combination therapy with TLS improved survival with an acceptable safety profile compared with LS in patients with intermediate or advanced stage HCC.

Combination of RCA and DNAzyme for Dual-Signal Isothermal Amplification of Exosome RNA.

The RNA contained in exosomes plays a crucial role in information transfer between cells in various life activities. The accurate detection of low-abundance exosome RNA (exRNA) is of great significance for cell function studies and the early diagnosis of diseases. However, their intrinsic properties, such as their short length and high sequence homology, represent great challenges for exRNA detection. In this paper, we developed a dual-signal isothermal amplification method based on rolling circle amplification (RCA) coupled with DNAzyme (RCA-DNAzyme). The sensitive detection of low-abundance exRNA, the specific recognition of their targets and the amplification of the detection signal were studied and explored. By designing padlock probes to specifically bind to the target exRNA, while relying on the ligation reaction to enhance recognition, the precise targeting of exosome RNA was realized. The combination of RCA and DNAzyme could achieve a twice-as-large isothermal amplification of the signal compared to RCA alone. This RCA-DNAzyme assay could sensitively detect a target exRNA at a concentration as low as 527 fM and could effectively distinguish the target from other miRNA sequences. In addition, this technology was successfully proven to be effective for the quantitative detection of miR-21 by spike recovery, providing a new research approach for the accurate detection of low-abundance exRNA and the exploration of unknown exRNA functions.

Attribution Analysis of Household Foodborne Disease Outbreaks in China, 2010-2020.

Foodborne diseases have become a serious public health problem worldwide, and foodborne disease outbreaks have placed a heavy disease burden on China. Foodborne disease outbreaks occur most frequently among families in China. The objectives of this study were to analyze the cause of household foodborne disease outbreaks in China from 2010 to 2020 and to identify where preventive measures could be targeted. All data were obtained from the China Foodborne Disease Surveillance System Report. A total of 17,985 outbreaks, which resulted in 73,252 illnesses, 38,829 hospitalizations, and 1269 deaths, were reported in this period. Most household outbreaks of foodborne diseases occurred in May-October, and the highest number occurred in July (3620 outbreaks, 20%). The province with the highest number of outbreaks was Yunnan Province (4829 outbreaks), followed by Hunan Province (2264 outbreaks). The attribution analysis revealed that fungi (mainly poisonous mushrooms) were the most implicated food category, with 8873 (49.3%) cases. The second was poisonous plants and their products, with 1552 (8.6%) cases. Fungi were the primary etiologic agent, with 31,125 illnesses, accounting for 42.5% of the incidents. Inedibility and misuse (9423 outbreaks), unknown origin (2505 outbreaks), and improper processing (2365 outbreaks) were the main contributing factors causing outbreaks of foodborne diseases. The results show that southwest China was a high-risk area for household foodborne diseases. Therefore, public health institutions should strengthen supervision and food safety education of residents to reduce the outbreaks of household foodborne diseases.