Optimizing prediction models for pancreatic fistula after pancreatectomy:Current status and future perspectives

Postoperative pancreatic fistula(POPF)is a frequent complication after pancre-atectomy,leading to increased morbidity and mortality.Optimizing prediction models for POPF has emerged as a critical focus in surgical research.Although over sixty models following pancreaticoduodenectomy,predominantly reliant on a variety of clinical,surgical,and radiological parameters,have been documented,their predictive accuracy remains suboptimal in external validation and across diverse populations.As models after distal pancreatectomy continue to be pro-gressively reported,their external validation is eagerly anticipated.Conversely,POPF prediction after central pancreatectomy is in its nascent stage,warranting urgent need for further development and validation.The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance.Moreover,there is potential for the development of personalized prediction models based on patient-or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF.In the future,prospective multicenter studies and the integration of novel imaging technologies,such as artificial intelligence-based radiomics,may further refine predictive models.Addressing these issues is anticipated to revolutionize risk stratification,clinical decision-making,and postoperative management in patients undergoing pancre-atectomy.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Pediatric GNAO1 encephalopathies:from molecular etiology of the disease to drug discovery

Gao is the major G protein in neurons,where it transduces signals from numerous G proteincoupled receptors(GPCRs)such as D2 dopamine,μ-opioid,M2 muscarinic,or α2-adrenergic receptors.In 2013,the first mutations in GNAO1,the gene encoding Gao,were described in pediatric patients with encephalopathies(Nakamura et al.,2013),suffering from movementdisorders,epileptic seizures。

Transitions of care across hospital settings in patients with inflammatory bowel disease

BACKGROUND Inflammatory bowel disease(IBD) is a chronic, inflammatory disorder characterised by both intestinal and extra-intestinal pathology. Patients may receive both emergency and elective care from several providers, often in different hospital settings. Poorly managed transitions of care between providers can lead to inefficiencies in care and patient safety issues. To ensure that the sharing of patient information between providers is appropriate, timely, accurate and secure, effective data-sharing infrastructure needs to be developed. To optimise inter-hospital data-sharing for IBD patients, we need to better understand patterns of hospital encounters in this group.AIM To determine the type and location of hospital services accessed by IBD patients in England.METHODSThis was a retrospective observational study using Hospital Episode Statistics, a large administrative patient data set from the National Health Service in England.Adult patients with a diagnosis of IBD following admission to hospital were followed over a 2-year period to determine the proportion of care accessed at the same hospital providing their outpatient IBD care, defined as their ‘home provider'. Secondary outcome measures included the geographic distribution of patient-sharing, regional and age-related differences in accessing services, and type and frequency of outpatient encounters.RESULTS95055 patients accessed hospital services on 1760156 occasions over a 2-year follow-up period. The proportion of these encounters with their identified IBD‘home provider' was 73.3%, 87.8% and 83.1% for accident and emergency,inpatient and outpatient encounters respectively. Patients living in metropolitan centres and younger patients were less likely to attend their ‘home provider' for hospital services. The most commonly attended specialty services were gastroenterology, general surgery and ophthalmology.CONCLUSION Transitions of care between secondary care settings are common for patients with IBD. Effective systems of data-sharing and care integration are essential to providing safe and effective care for patients. Geographic and age-related patterns of care transitions identified in this study may be used to guide interventions aimed at improving continuity of care.

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface healing.Extensive clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive protocol.Therefore,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical management.Throughout the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to diabe-tes.We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenviron-ment.promote larizationand.ultimatel accelerateskin healing in diabetic mice.The results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic conditions.This novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

Cyclodextrin Based Host-Guest Inclusion Complex, an Approach to Enhancing the Physicochemical and Biopharmaceutical Application of Poorly Water-soluble Drugs

Host-guest inclusion complexes have been extensively studied for drug delivery applications.The host molecule,typically cyclodextrin,creates a cavity,in which the guest molecule,such as a drug,can be encapsulated.This encapsulation can protect the drug from degradation,improve its solubility and stability,and enhance its bioavailability.Moreover,host-guest inclusion complexes can facilitate targeted drug delivery by selectively releasing drugs at the site of action.Various techniques,such as covalent bonding,non-covalent interactions,and self-assembly have been used to form these complexes.Host-guest inclusion complexes have shown great potential for improving the efficacy and safety of drug delivery systems.This mini review summarizes the application and recent progress of the cyclodextrin-based host-guest inclusion complex,highlighting the enhanced physicochemical and biopharmaceutical application of pharmaceutical drugs via formulation of its inclusion complex.

Aptamer-functionalized nanoplatforms overcoming temozolomide resistance in synergistic chemo/photothermal therapy through alleviating tumor hypoxia

Tumor hypoxia is intimately associated with gliomas,which represents a significant threat to human health and are resistant to the first-line chemotherapeutic drug temozolomide(TMZ)due to hypoxia.In this work,to overcome TMZ resistance in orthotopic gliomas,aptamer-functionalized liposomes are manufactured to encapsulate TMZ and photothermal agent IR780,and can cross the blood-brain barrier and actively target gliomas.It is possible to employ liposomes for both fluorescence and photoacoustic imaging simultaneously due to their stability and excellent photothermal conversion capabilities.This chemo/photothermal synergistic therapeutic effect of liposomes on gliomas is demonstrated by their abilities to target orthotopic gliomas,alleviate tumor hypoxia and consequently reverse resistance of glioma cells to TMZ,thereby extending the survival time of tumor-bearing mice,making the nanoplatforms and their synergistic chemo/photothermal therapy as a potential clinical treatment for gliomas.

Prognostic value of the RNA editing enzyme: ADAR1, and its association with immune cells infiltration in pancreatic adenocarcinoma

The adenosine deaminase acting on RNA(ADAR)protein family was well characterized as RNA editing enzymes converting adenosines to inosines(A-to-l)in dsRNA structures.They share a homologous structure including the dsRNA-binding domain and the deaminase domain.ADAR1 function as the primary editing enzyme for A-to-l mutation because of its higher and ubiquitous expression compared to ADAR2 and ADAR3 in eukaryotes.

Machine learning improves prediction of severity and outcomes of acute pancreatitis:a prospective multi-center cohort study

Dear Editor,Acute pancreatitis(AP)is a common acute pancreatic disease of variable severity and outcomes(Mederos et al.,2021).According to systemic and local complications,patients can be classified into severe,moderately severe,and mild AP(Banks et al.,2013).About 20%of AP patients develop severe acute pancreatitis(SAP,with persistent organ failures)of whom 20%–50%die.

Corrigendum to“Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone”[Bioact.Mater.10C(April 2022)32-47]

The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).

Corrigendum to‘Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation’[Bioactive Materials,Volume 9(March 2022)Page 491-507]

The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).

Reduction of pancreatic β-cell dedifferentiation after gastric bypass surgery in diabetic rats

Dear Editor, Type 2 diabetes mellitus （T2DM） develops only in insulin-resistant subjects when pancreatic β-cell compensation fails （Matveyenko and Butler, 2006）. Decreased insulin secretory function and reduced cell mass are traditionally viewed as major contributing factors in β-cell insufficiency. A recent study using a diabetic rodent model suggests that progressive β-cell de- differentiation is an important underlying mechanism in β-cell failure （Talchai et al., 2012）. β-cell dedifferentiation in diabetes refers to the loss by healthy β-cells of key components characteristic of the differen- tiated state （Dor and Glaser, 2013）, including insulin （for its secretory product）, Glut2 （for glucose intake）, and PDX-1 （for critical insulin transcription factor）, β-cell dedifferentiation may be largely respon- sible for not only β-cell secretory dysfunction but also impaired β-cell identity. In view of findings that bariatric surgery in a rodent T2DM model led to increased β-cell mass and improved islet morphology （Strader et al., 2009）, we investigated the effects of gastric bypass surgery on dedifferentiated β-cells.

Effect of wood dust type on mechanical properties, wear behavior, biodegradability, and resistance to natural weathering of wood-plastic composites

The present work reports the inclusion of different proportions of Mango/Sheesham/Mahogany/Babool dust to polypropylene for improving mechanical,wear behavior and biodegradability of wood-plastic composite(WPC).The wood dust(10%,15%,20%by weight)was mixed with polypropylene granules and WPCs were prepared using an injection molding technique.The mechanical,wear,and morphological characterizations of fabricated WPCs were carried out using standard ASTM methods,pin on disk apparatus,and scanning electron microscopy(SEM),respectively.Further,the biodegradability and resistance to natural weathering of WPCs were evaluated following ASTM D5338-11 and ASTM D1435-99,respectively.The WPCs consisting ofBabool and Sheesham dust were having superior mechanical properties whereas the WPCs consisting of Mango and Mahogany were more wear resistant.It was found that increasing wood powder proportion results in higher Young's modulus,lesser wear rate,and decreased stress at break.The WPCs made of Sheesham dust were least biodegradable.It was noticed that the biodegradability corresponds with resistance to natural weathering;more biodegradable WPCs were having the lesser resistance to natural weathering.

Antioxidant-enriched autologous biogel promoted diabetic wound healing by remodeling inherent posttraumatic inflammatory patterning and restoring compromised microenvironment homeostasis

Successful wound healing depends on the reconstruction of proper tissue homeostasis,particularly in the posttraumatic inflammatory tissue microenvironment.Diabetes jeopardizes tissues’immune homeostasis in cutaneous wounds,causing persistent chronic inflammation and cytokine dysfunction.Previously,we developed an autologous regeneration factor(ARF)technology to extract the cytokine composite from autologous tissue to restore immune homeostasis and promote wound healing.However,treatment efficacy was significantly compromised in diabetic conditions.Therefore,we proposed that a combination of melatonin and ARF,which is beneficial for proper immune homeostasis reconstruction,could be an effective treatment for diabetic wounds.Our research showed that the utilization of melatonin-mediated ARF biogel(AM gel)promoted diabetic wound regeneration at a more rapid healing rate.RNA-Seq analysis showed that AM gel treatment could restore more favorable immune tissue homeostasis with unique inflammatory patterning as a result of the diminished intensity of acute and chronic inflammation.Currently,AM gel could be a novel and promising therapeutic strategy for diabetic wounds in clinical practice through favorable immune homeostatic reconstructions in the tissue microenvironment and proper posttraumatic inflammation patterning.

Bisphosphonate-based nanocomposite hydrogels for biomedical applications

Nanocomposite hydrogels consist of polymeric network embedded with functional nanoparticles or nanostructures,which not only contribute to the enhanced mechanical properties but also exhibit the bioactivities for regulating cell behavior.Bisphosphonates(BPs)are capable of coordinating with various metal ions and modulating bone homeostasis.Thanks to the inherent dynamic properties of metal–ligand coordination bonds,BPbased nanocomposite hydrogels possess tunable mechanical properties,highly dynamic structures,and the capability to mediate controlled release of encapsulated therapeutic agents,thereby making them highly versatile for various biomedical applications.This review presents the comprehensive overview of recent developments in BP-based nanocomposite hydrogels with an emphasis on the properties of embedded nanoparticles(NPs)and interactions between hydrogel network and NPs.Furthermore,various challenges in the biomedical applications of these hydrogels are discussed to provide an outlook of potential clinical translation.

Proteome-wide prediction of protein-protein interactions from high-throughput data

In this paper,we present a brief review of the existing computational methods for predicting proteome-wide protein-protein interaction networks from high-throughput data.The availability of various types of omics data provides great opportunity and also un-precedented challenge to infer the interactome in cells.Reconstructing the interactome or interaction network is a crucial step for studying the functional relationship among proteins and the involved biological processes.The protein interaction network will provide valuable resources and alternatives to decipher the mechanisms of these functionally interacting elements as well as the running system of cellular operations.In this paper,we describe the main steps of predicting protein-protein interaction networks and categorize the available ap-proaches to couple the physical and functional linkages.The future topics and the analyses beyond prediction are also discussed and concluded.

Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.

Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration.In this work,we assembled a biomimetic hyaluronic acid nanocomposite hydrogel(HA-BP hydrogel)by coordination bonds with bisphosphonates(BPs),which are antiosteoclastic drugs.The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment.Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP.Furthermore,the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts,which are considered essential during bone regeneration,whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP.The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone.Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.

侵入性操作的安全标准警惕执行鸿沟

英格兰国家健康体系（NHS）最近发布了一系列推荐，旨在保证接受侵人性操作患者的医疗更安全。这些推荐部分基于对未遂事件、严重事故和所谓“绝不该发生的事件”进行的国家和地方性分析得出的教训，展现为一种总体性文件框架。