Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores.

Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown. Here, we report crystal structures of human MIS12C associated with a fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of this interaction. The structure of MIS12:CENP-C complements previously determined high-resolution structures of functional regions of NDC80C and KNL1C and allows us to build a near-complete structural model of the KMN assembly. Our work illuminates the structural organization of essential chromosome segregation machinery that is conserved in most eukaryotes.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

A 3,3'-Difluoro-2,2'-Bithiophene Based Donor Polymer Realizing High Efficiency (>17%) Single Junction Binary Organic Solar Cells.

In this study, two novel donor-acceptor (D-A) copolymers are designed and synthesized, DTBT-2T and DTBT-2T2F with 2,2'-bithiophene or 3,3'-difluoro-2,2'-bithiophene as the donor unit and dithienobenzothiadiazole as the acceptor unit, and used them as donor materials in non-fullerene organic solar cells (OSCs). Due to enhanced planarity of polymer chains resulted by the intramolecular F···S noncovalent interactions, the incorporation of 3,3'-difluoro-2,2'-bithiophene unit instead of 2,2'-bithiophene into the polymers can enhance their molecular packing, crystallinity and hole mobility. The DTBT-2T:L8-BO based binary OSCs deliver a power conversion efficiency (PCE) of only 9.71% with a Voc of 0.78 V, a Jsc of 20.69 mA cm-2 , and an FF of 59.67%. Moreover, the introduction of fluoro atoms can lower the highest occupied molecular orbital levels. As a result, DTBT-2T2F:L8-BO based single-junction binary OSCs exhibited less recombination loss, more balanced charge mobility, and more favorable morphology, resulting in an impressive PCE of 17.03% with a higher Voc of 0.89 V, a Jsc of 25.40 mA cm-2, and an FF of 75.74%. These results indicate that 3,3'-difluoro-2,2'-bithiophene unit can be used as an effective building block to synthesize high performance polymer donor materials. This work greatly expands the selection range of donor units for constructing high-performance polymers.

Organic Electrolyte Additive: Dual Functions Toward Fast Sulfur Conversion and Stable Li Deposition for Advanced Li-S Batteries.

Lithium-sulfur (Li-S) battery is of great potential for the next generation energy storage device due to the high specific capacity energy density. However, the sluggish kinetics of S redox and the dendrite Li growth are the main challenges to hinder its commercial application. Herein, an organic electrolyte additive, i.e., benzyl chloride (BzCl), is applied as the remedy to address the two issues. In detail, BzCl can split into Bz· radical to react with the polysulfides, forming a Bz-S-Bz intermediate, which changes the conversion path of S and improves the kinetics by accelerating the S splitting. Meanwhile, a tight and robust solid electrolyte interphase (SEI) rich in inorganic ingredients namely LiCl, LiF, and Li2 O, is formed on the surface of Li metal, accelerating the ion conductivity and blocking the decomposition of the solvent and lithium polysulfides. Therefore, the Li-S battery with BzCl as the additive remains high capacity of 693.2 mAh g-1 after 220 cycles at 0.5 C with a low decay rate of 0.11%. This work provides a novel strategy to boost the electrochemical performances in both cathode and anode and gives a guide on the electrolyte design toward high-performance Li-S batteries.

Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.

BACKGROUND: Resistance to targeted therapies represents a significant hurdle to successfully treating hepatocellular carcinoma (HCC). While epigenetic abnormalities are critical determinants of HCC relapse and therapeutic resistance, the underlying mechanisms are poorly understood. We aimed to address whether and how dysregulated epigenetic regulators have regulatory and functional communications in establishing and maintaining drug resistance. METHODS: HCC-resistant cells were characterized by CCK-8, IncuCyte Live-Cell analysis, flow cytometry and wound-healing assays. Target expression was assessed by qPCR and Western blotting. Global and promoter DNA methylation was measured by dotblotting, methylated-DNA immunoprecipitation and enzymatic digestion. Protein interaction and promoter binding of DNMT3a-TET2 were investigated by co-immunoprecipitation, ChIP-qPCR. The regulatory and functional roles of DNMT3a and TET2 were studied by lentivirus infection and puromycin selection. The association of DNMT and TET expression with drug response and survival of HCC patients was assessed by public datasets, spearman correlation coefficients and online tools. RESULTS: We identified the coordination of DNMT3a and TET2 as an actionable mechanism of drug resistance in HCC. The faster growth and migration of resistant HCC cells were attributed to DNMT3a and TET2 upregulation followed by increased 5mC and 5hmC production. HCC patients with higher DNMT3a and TET2 had a shorter survival time with a less favorable response to sorafenib therapy than those with lower expression. Cancer stem cell-like cells (CSCs) displayed DNMT3a and TET2 overexpression, which were insensitive to sorafenib. Either genetic or pharmacological suppression of DNMT3a or/and TET2 impaired resistant cell growth and oncosphere formation, and restored sorafenib sensitivity. Mechanistically, DNMT3a did not establish a regulatory circuit with TET2, but formed a complex with TET2 and HDAC2. This complex bound the promoters of oncogenes (i.e., CDK1, CCNA2, RASEF), and upregulated them without involving promoter DNA methylation. In contrast, DNMT3a-TET2 crosstalk silences tumor suppressors (i.e., P15, SOCS2) through a corepressor complex with HDAC2 along with increased promoter DNA methylation. CONCLUSIONS: We demonstrate that DNMT3a and TET2 act coordinately to regulate HCC cell fate in DNA methylation-dependent and -independent manners, representing strong predictors for drug resistance and poor prognosis, and thus are promising therapeutic targets for refractory HCC.

AnWRKY29 and AnHSP90 synergistically modulate trehalose levels in a desert shrub leaves during osmotic stress.

Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.

Screening and Evaluation of Children's Sensitively Toxic Chemicals in New Mosquito Repellent Products Based on a Nationwide Investigation.

New mosquito repellent products (NMRPs) are emerging popular repellents among children. There are increasing reports on children's sensitization reactions caused by NMRPs, while regulations on their productions, sales, or usage are still lacking. One of the reasons could be the missing comprehensive risk assessment. We first conducted a nationwide investigation on children's NMRP usage preferences. Then, we high-throughput screened volatile or semivolatile organic chemicals (VOCs/SVOCs) in five representative NMRPs by the headspace gas chromatography-orbitrap high-resolution mass spectrometry analytical method. After that, toxic compounds were recognized based on the toxicity forecaster (ToxCast) database. A total of 277 VOCs/SVOCs were recognized, and 70 of them were identified as toxic compounds. In a combination of concentrations, toxicities, absorption, distribution, metabolism, and excretion characteristics in the body, 28 chemicals were finally proposed as priority-controlled compounds in NMRPs. Exposure risks of recognized toxic chemicals through NMRPs by inhalation and dermal intake for children across the country were also assessed. Average daily intakes were in the range of 0.20-7.31 mg/kg/day for children in different provinces, and the children in southeastern coastal provinces were found to face higher exposure risks. By controlling the high-priority chemicals, the risks were expected to be reduced by about 46.8% on average. Results of this study are therefore believed to evaluate exposure risks, encourage safe production, and promote reasonable management of NMRPs.

Reliable biological and multi-omics research through biometrology.

Metrology is the science of measurement and its applications, whereas biometrology is the science of biological measurement and its applications. Biometrology aims to achieve accuracy and consistency of biological measurements by focusing on the development of metrological traceability, biological reference measurement procedures, and reference materials. Irreproducibility of biological and multi-omics research results from different laboratories, platforms, and analysis methods is hampering the translation of research into clinical uses and can often be attributed to the lack of biologists' attention to the general principles of metrology. In this paper, the progresses of biometrology including metrology on nucleic acid, protein, and cell measurements and its impacts on the improvement of reliability and comparability in biological research are reviewed. Challenges in obtaining more reliable biological and multi-omics measurements due to the lack of primary reference measurement procedures and new standards for biological reference materials faced by biometrology are discussed. In the future, in addition to establishing reliable reference measurement procedures, developing reference materials from single or multiple parameters to multi-omics scale should be emphasized. Thinking in way of biometrology is warranted for facilitating the translation of high-throughput omics research into clinical practices.

Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster.

Pyrethrum extract from dry flowers of Tanacetum cinerariifolium (formally Chrysanthemum cinerariifolium) has been used globally as a popular insect repellent against arthropod pests for thousands of years. However, the mechanistic basis of pyrethrum repellency remains unknown. In this study, we found that pyrethrum spatially repels and activates olfactory responses in Drosophila melanogaster, a genetically tractable model insect, and the closely-related D. suzukii which is a serious invasive fruit crop pest. The discovery of spatial pyrethrum repellency and olfactory response to pyrethrum in D. melanogaster facilitated our identification of four odorant receptors, Or7a, Or42b, Or59b and Or98a that are responsive to pyrethrum. Further analysis showed that the first three Ors are activated by pyrethrins, the major insecticidal components in pyrethrum, whereas Or98a is activated by (E)-ß-farnesene (EBF), a sesquiterpene and a minor component in pyrethrum. Importantly, knockout of Or7a, Or59b or Or98a individually abolished fly avoidance to pyrethrum, while knockout of Or42b had no effect, demonstrating that simultaneous activation of Or7a, Or59b and Or98a is required for pyrethrum repellency in D. melanogaster. Our study provides insights into the molecular basis of repellency of one of the most ancient and globally used insect repellents. Identification of pyrethrum-responsive Ors opens the door to develop new synthetic insect repellent mixtures that are highly effective and broad-spectrum.

Designing A-D-A Type Fused-Ring Electron Acceptors with a Bulky 3D Substituent at the Central Donor Core to Minimize Non-Radiative Losses and Enhance Organic Solar Cell Efficiency.

Designing and synthesizing narrow band gap acceptors that exhibit high photoluminescence quantum yield (PLQY) and strong crystallinity is a highly effective, yet challenging, approach to reducing non-radiative energy losses (▵Enr) and boosting the performance of organic solar cells (OSCs). We have successfully designed and synthesized an A-D-A type fused-ring electron acceptor, named DM-F, which features a planar molecular backbone adorned with bulky three-dimensional camphane side groups at its central core. These bulky substituents effectively hinder the formation of H-aggregates of the acceptors, promoting the formation of more J-aggregates and notably elevating the PLQY of the acceptor in the film. As anticipated, DM-F showcases pronounced near-infrared absorption coupled with impressive crystallinity. Organic solar cells (OSCs) leveraging DM-F exhibit a high EQEEL value and remarkably low ▵Enr of 0.14 eV-currently the most minimal reported value for OSCs. Moreover, the power conversion efficiency (PCE) of binary and ternary OSCs utilizing DM-F has reached 16.16 % and 20.09 %, respectively, marking a new apex in reported efficiency within the OSCs field. In conclusion, our study reveals that designing narrow band gap acceptors with high PLQY is an effective way to reduce ▵Enr and improve the PCE of OSCs.

From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

Triglyceride-glucose index as a marker of adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of cardiovascular diseases (CVDs). However, its prognostic value in patients with coronary heart disease (CHD) and hypertension remains unclear. METHODS: A total of 1467 hospitalized patients with CHD and hypertension from January 2021 to December 2021 were included in this prospective and observational clinical study. The TyG index was calculated as Ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoint was a compound endpoint, defined as the first occurrence of all-cause mortality or total nonfatal CVDs events within one-year follow up. The secondary endpoint was atherosclerotic CVD (ASCVD) events, including non-fatal stroke/transient ischemic attack (TIA) and recurrent CHD events. We used restricted cubic spline analysis and multivariate adjusted Cox proportional hazard models to investigate the associations of the TyG index with primary endpoint events. RESULTS: During the one-year follow-up period, 154 (10.5%) primary endpoint events were recorded, including 129 (8.8%) ASCVD events. After adjusting for confounding variables, for per standard deviation (SD) increase in the TyG index, the risk of incident primary endpoint events increased by 28% [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04-1.59]. Compared with subjects in the lowest tertile (T1), the fully adjusted HR for primary endpoint events was 1.43 (95% CI 0.90-2.26) in the middle (T2) and 1.73 (95% CI 1.06-2.82) in highest tertile (T3) (P for trend = 0.018). Similar results were observed in ASCVD events. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoint events increased as TyG index increased. CONCLUSIONS: The elevated TyG index was a potential marker of adverse prognosis in patients with CHD and hypertension.

Cereal polyphenols inhibition mechanisms on advanced glycation end products and regulation on type 2 diabetes.

Advanced glycation end products (AGEs), the products of non-enzymatic browning reactions between the active carbonyl groups of reducing sugars and the free amines of amino acids, are largely considered oxidative derivatives resulting from diabetic hyperglycemia, which are further recognized as a potential risk for insulin resistance (IR) and type 2 diabetes (T2D). The accumulation of AGEs can trigger numerous negative effects such as oxidative stress, carbonyl stress, inflammation, autophagy dysfunction and imbalance of gut microbiota. Recently, studies have shown that cereal polyphenols have the ability to inhibit the formation of AGEs, thereby preventing and alleviating T2D. In the meanwhile, phenolics compounds could produce different biological effects due to the quantitative structure activity-relationship. This review highlights the effects of cereal polyphenols as a nonpharmacologic intervention in anti-AGEs and alleviating T2D based on the effects of oxidative stress, carbonyl stress, inflammation, autophagy, and gut microbiota, which also provides a new perspective on the etiology and treatment of diabetes.

Research advance of non-thermal processing technologies on ovalbumin properties: The gelation, foaming, emulsification, allergenicity, immunoregulation and its delivery system application.

Ovalbumin (OVA) is the most abundant protein in egg white, with excellent functional properties (e.g., gelling, foaming, emulsifying properties). Nevertheless, OVA has strong allergenicity, which is usually mediated by specific IgE thus results in gut microbiota dysbiosis and causes atopic dermatitis, asthma, and other inflammation actions. Processing technologies and the interactions with other active ingredients can influence the functional properties and allergic epitopes of OVA. This review focuses on the non-thermal processing technologies effects on the functional properties and allergenicity of OVA. Moreover, the research advance about immunomodulatory mechanisms of OVA-mediated food allergy and the role of gut microbiota in OVA allergy was summarized. Finally, the interactions between OVA and active ingredients (such as polyphenols and polysaccharides) and OVA-based delivery systems construction are summarized. Compared with traditional thermal processing technologies, novel non-thermal processing techniques have less damage to OVA nutritional value, which also improve OVA properties. OVA can interact with various active ingredients by covalent and non-covalent interactions during processing, which can alter the structure or allergic epitopes to affect OVA/active components properties. The interactions can promote OVA-based delivery systems construction, such as emulsions, hydrogels, microencapsulation, nanoparticles to encapsulate bioactive components and monitor freshness for improving foods quality and safety.

Research advances in citrus polyphenols: green extraction technologies, gut homeostasis regulation, and nano-targeted delivery system application.

Citrus polyphenols can modulate gut microbiota and such bi-directional interaction that can yield metabolites such as short-chain fatty acids (SCFAs) to aid in gut homeostasis. Such interaction provides citrus polyphenols with powerful prebiotic potential, contributing to guts' health status and metabolic regulation. Citrus polyphenols encompass unique polymethoxy flavonoids imparting non-polar nature that improve their bioactivities and ability to penetrate the blood-brain barrier. Green extraction technology targeting recovery of these polyphenols has received increasing attention due to its advantages of high extraction yield, short extraction time, low solvent consumption, and environmental friendliness. However, the low bioavailability of citrus polyphenols limits their applications in extraction from citrus by-products. Meanwhile, nano-encapsulation technology may serve as a promising approach to improve citrus polyphenols' bioavailability. As citrus polyphenols encompass multiple hydroxyl groups, they are potential to interact with bio-macromolecules such as proteins and polysaccharides in nano-encapsulated systems that can improve their bioavailability. This multifaceted review provides a research basis for the green and efficient extraction techniques of citrus polyphenols, as well as integrated mechanisms for its anti-inflammation, alleviating metabolic syndrome, and regulating gut homeostasis, which is more capitalized upon using nano-delivery systems as discussed in that review to maximize their health and food applications.

Multi-omics profiling of primary hepatic stellate cells from advanced liver fibrosis patients reveals distinctive molecular signatures.

BACKGROUND AND AIM: Hepatic fibrosis is a common pathogenic outcome of almost all chronic liver diseases and a growing public health problem globally. However, the key genes or proteins driving liver fibrosis and cirrhosis are not well understood. We aimed to identify novel hepatic fibrosis genes of human primary hepatic stellate cells (HSCs). METHODS: Human primary HSCs were isolated from surgically resected advanced fibrosis liver tissues (n = 6) and surgical resection of normal liver tissue around hemangioma (n = 5). Differences in the expression levels of mRNA and proteins from HSCs in advanced fibrosis group and the control group were analyzed using RNA sequencing and mass spectrometry as transcriptomic and proteomic approaches. The obtained biomarkers were further validated through real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and Western blot. RESULTS: A total of 2156 transcripts and 711 proteins were found to be differently expressed between the advanced fibrosis group and the control group patients. The Venn diagram shows that a total of 96 upregulated molecules are overlapped in both the transcriptomic and proteomic datasets. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis indicated that those overlapped genes were mainly involved in wound healing, cell adhesion regulation, and actin binding, which reflects the major biological conversions in liver cirrhosis process. Pyruvate kinase M2 and EH domain-containing 2 were identified as potential new markers for advanced liver cirrhosis, which have been validated in primary human HSCs and in vitro cellular hepatic fibrosis model Lieming Xu-2 (LX-2) cells. CONCLUSIONS: Our results revealed the major transcriptomic and proteomic changes during liver cirrhosis process and identified new biomarkers and potential therapeutic targets for advanced liver fibrosis.

The short- and long-term outcomes of laparoscopic pancreaticoduodenectomy combining with different type of mesentericoportal vein resection and reconstruction for pancreatic head adenocarcinoma: a Chinese multicenter retrospective cohort study.

BACKGROUND: The results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs. METHODS: Patients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared. RESULTS: In total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS. CONCLUSIONS: In LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.

Association of milk consumption with the incidence of cholelithiasis disease in the US adult population.

BACKGROUND: Cholelithiasis is a common digestive system disease that imposes major burden on patients and society. Investigating the relationship between dietary factors and cholelithiasis risk can provide a basis for disease prevention. Previous studies on milk intake and cholelithiasis incidence have been limited.Therefore, the aim of our study was to assess the association between milk consumption and the incidence of cholelithiasis in males and females. METHODS: We selected 14,722 adults (≥ 18 years old) from National Center for Health Statistics (NHANSE) 2017-2020, and collected general characteristics of patients in the database, such as age, gender, race and body mass index (BMI), as well as dietary information (milk consumption). The occurrence of cholelithiasis was used as the outcome event, and the group was divided into cholelithiasis and non-cholelithiasis groups according to the outcome event. We used logistic regression models in generalized linear model (GLM) functions, controlling for demographic, lifestyle, and dietary factors, to estimate the association between milk intake and the incidence of cholelithiasis in males and females. RESULTS: A total of 14,722 adults were included. In the present study, the overall weighted prevalence of cholelithiasis was 10.96%, with 15.18% and 6.48% prevalence in females and males, respectively. Compared to infrequent milk intake, frequent milk intake (once a week or more) in females was associated with reduced cholelithiasis risk (OR 0.74, 95% CI 0.61-0.90). Daily milk intake in males was also related to lower cholelithiasis risk (OR 0.69-0.82). As adjusted variables increased in the models, predictive performance was improved (AUC 0.711 in females, 0.730 in males). CONCLUSIONS: Appropriate milk intake may correlate with decreased cholelithiasis risk. Our study provides a basis for dietary interventions against gallstones, but prospective studies are needed to verify the results.

Machine learning-based models for the prediction of breast cancer recurrence risk.

Breast cancer is the most common malignancy diagnosed in women worldwide. The prevalence and incidence of breast cancer is increasing every year; therefore, early diagnosis along with suitable relapse detection is an important strategy for prognosis improvement. This study aimed to compare different machine algorithms to select the best model for predicting breast cancer recurrence. The prediction model was developed by using eleven different machine learning (ML) algorithms, including logistic regression (LR), random forest (RF), support vector classification (SVC), extreme gradient boosting (XGBoost), gradient boosting decision tree (GBDT), decision tree, multilayer perceptron (MLP), linear discriminant analysis (LDA), adaptive boosting (AdaBoost), Gaussian naive Bayes (GaussianNB), and light gradient boosting machine (LightGBM), to predict breast cancer recurrence. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score were used to evaluate the performance of the prognostic model. Based on performance, the optimal ML was selected, and feature importance was ranked by Shapley Additive Explanation (SHAP) values. Compared to the other 10 algorithms, the results showed that the AdaBoost algorithm had the best prediction performance for successfully predicting breast cancer recurrence and was adopted in the establishment of the prediction model. Moreover, CA125, CEA, Fbg, and tumor diameter were found to be the most important features in our dataset to predict breast cancer recurrence. More importantly, our study is the first to use the SHAP method to improve the interpretability of clinicians to predict the recurrence model of breast cancer based on the AdaBoost algorithm. The AdaBoost algorithm offers a clinical decision support model and successfully identifies the recurrence of breast cancer.