CDYL1 fosters double-strand break-induced transcription silencing and promotes homology-directed repair

Cells have evolved DNA damage response （DDR） to repair DNA lesions and thus preserving genomic stability and impeding carcinogenesis. DNA damage induction is accompanied by transient transcription repression. Here, we describe a previously unrecognized role of chromodomain Y-like （CDYL1） protein in fortifying double-strand break （DSB）-induced transcription repression and repair. We showed that CDYL1 is rapidly recruited to damaged euchromatic regions in a poly （ADP-ribose） polymerase 1 （PARP1）-dependent, but ataxia telangiectasia mutated （ATM）-independent, manner. While the C-terminal region, containing the enoyl-CoA hydratase like （ECH） domain, of CDYL1 binds to poly （ADP-ribose） （PAR） moieties and mediates CDYL1 accumulation at DNA damage sites, the chromodomain and histone H3 trimethylated on lysine 9 （H3K9me3） mark are dispensable for its recruitment. Furthermore, CDYL1 promotes the recruitment of enhancer of zeste homolog 2 （EZH2）, stimulates local increase of the repressive methyl mark H3K27me3, and promotes transcription silencing at DSB sites. In addition, following DNA damage induction, CDYL1 depletion causes persistent G2/M arrest and alters H2AX and replication protein A （RPA2） phosphorylation. Remarkably, the ‘traffic-light reporter’ system revealed that CDYL1 mainly promotes homology-directed repair （HDR） of DSBs in vivo. Consequently, CDYL1-knockout cells display synthetic lethality with the chemotherapeutic agent, cisplatin. Altogether, our findings identify CDYL1 as a new component of the DDR and suggest that the HDR-defective ‘BRCAness’ phenotype of CDYL1-deficient cells could be exploited for eradicating cancer cells harboring CDYL1 mutations.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Neural membrane repair at the core of regeneration

Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.

Modeling Expected Failure Considering Repair Time and Degradation: A Rail System Case Study

The repeated failures of any equipment or systems are modeled as a renewal process. The management needs an assessment of the number of future failures to allocate the resources needed for fast repairs. Based on the idea of expectation by conditioning, special Volterra-type integral equations are derived for general types of repairs, considering the length of repair and reduced degradation of the idle object. In addition to minimal repair and failure replacement, partial repairs are also discussed when the repair results in reduction of the number of future failures or decreases the effective age of the object. Numerical integration-based algorithm and simulation study are performed to solve the resulting integral equation. Since the geometry degradation in different dimensions of a rail track and controlling and maintaining defects are of importance, a numerical example using the rail industry data is conducted. Expected number of failures of different failure type modes in rail track is calculated within a two-year interval. Results show that within a two-year period, anticipated occurrences of cross level failures, surface failures, and DPI failures are 2.4, 3.8, and 5.8, respectively.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

Spent graphite regeneration:Exploring diverse repairing manners with impurities-catalyzing effect towards high performance and low energy consumption

Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.

LncRNA HOTAIR promotes DNA damage repair and radioresistance by targeting ATR in colorectal cancer

Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.

Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

The DNA damage repair complex MoMMS21-MoSMC5 is required for infection-related development and pathogenicity of Magnaporthe oryzae

The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.

Experimental Study on Engineering Behavior of Solidified Soil for Scour Repair and Protection

A new scour countermeasure using solidified slurry for offshore foundation has been proposed recently.Fluidized solidified slurry is pumped to seabed area around foundation for scour protection or pumped into the developed scour holes for scour repair as the fluidized material solidifies gradually.In the pumping operation and solidification,the engineering behaviors of solidified slurry require to be considered synthetically for the reliable application in scour repair and protection of ocean engineering such as the pumpability related flow value,flow diffusion behavior related rheological property,anti-scour performance related retention rate in solidification and bearing capacity related strength property after solidification.In this study,a series of laboratory tests are conducted to investigate the effects of mix proportion(initial water content and binder content)on the flow value,rheological properties,density,retention rate of solidified slurry and unconfined compressive strength(UCS).The results reveal that the flow value increases with the water content and decreases with the binder amount.All the solidified slurry exhibits Bingham plastic behavior when the shear rate is larger than 5 s^(-1).The Bingham model has been employed to fit the rheology test results,and empirical formulas for obtaining the density,yield stress and viscosity are established,providing scientific support for the numerical assessment of flow and diffusion of solidified slurry.Retention rate of solidified slurry decreases with the water flow velocity and flow value,which means the pumpability of solidified slurry is contrary to anti-scour performance.The unconfined compressive strength after solidification reduces as the water content increases and binder content decreases.A design and application procedure of solidified soil for scour repair and protection is also proposed for engineering reference.

Effects of β-Glucan Supplementation on Repairing of Phenol-Induced Vaginal Mucosal Epithelium Damage in Rats

Objective: To investigate the effects of different concentrations of β-glucan on the repair of damaged vaginal mucosa, the expression of vascular endothelial growth factor (VEGF), and the inflammatory factor-6 (IL-6) in vaginal tissues. Methods: Thirty-six adult female specific pathogen free (SPF)-grade Wistar rats were randomly divided into 3 phase groups with 12 rats each. Vaginal inflammation rat models were established by injecting phenol gel into the vagina of each rat at a dose of 0.1 ml/100g body weight. After modeling, rats were divided into 4 groups based on different concentrations of the test agent. The control group was injected with 0.5 ml of saline, experimental group A was injected with 0.375 ml saline 0.125 ml β-glucan, experimental group B was injected with 0.25 ml saline 0.25 ml β-glucan, and experimental group C was injected with 0.50 ml β-glucan. The injection sites were selected at the 3 o’clock and 9 o’clock positions of the vagina. Rats were sacrificed at 7-, 14-, and 28-days post-injection, and tissue samples were collected from the injection sites and prepared for histological analysis. New blood vessels and fibroblast numbers in the tissues were observed after Hematoxylin-eosin (HE) staining. The expression levels of VEGF and IL-6 in the tissues were measured using quantificational reverse transcription polymerase chain reaction (qRT-PCR). Results: Histological examination of vaginal tissue specimens at 7-, 14-, and 28-days post-injection showed that on day 7, there were no significant changes in the experimental groups compared to the control group. However, on days 14 and 28, the experimental groups showed more new blood vessels, macrophages, and fibroblasts with increased activity compared to the control group. The expression levels of VEGF in vaginal tissues were elevated on days 14 and 28 in the experimental groups. The comparison of IL-6 levels in vaginal tissues on day 28 showed that serum IL-6 levels returned to normal, and there was no statistically significant difference between the experimental and control groups. Conclusion: In the 3 experimental phases, the increase in VEGF levels in vaginal tissues on day 14 post-injection was more pronounced with higher concentrations of β-glucan, and IL-6 levels returned to normal on day 28. β-Glucan can enhance VEGF levels in damaged vaginal tissues, promote the repair of damaged vaginal tissues, and higher concentrations of β-glucan have a better effect.

Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Preheating-assisted solid-state friction stir repair of Al-Mg-Si alloy plate at different rotational speeds

Additive friction stir deposition(AFSD)is a novel structural repair and manufacturing technology has become a research hotspot at home and abroad in the past five years.In this work,the microstructural evolution and mechanical performance of the Al-Mg-Si alloy plate repaired by the preheating-assisted AFSD process were investigated.To evaluate the tool rotation speed and substrate preheating for repair quality,the AFSD technique was used to additively repair 5 mm depth blind holes on 6061 aluminum alloy substrates.The results showed that preheat-assisted AFSD repair significantly improved joint bonding and joint strength compared to the control non-preheat substrate condition.Moreover,increasing rotation speed was also beneficial to improve the metallurgical bonding of the interface and avoid volume defects.Under preheating conditions,the UTS and elongation were positively correlated with rotation speed.Under the process parameters of preheated substrate and tool rotation speed of 1000 r/min,defect-free specimens could be obtained accompanied by tensile fracture occurring in the substrate rather than the repaired zone.The UTS and elongation reached the maximum values of 164.2MPa and 13.4%,which are equivalent to 99.4%and 140%of the heated substrate,respectively.

Outcome of meniscal repairs in paediatric population:A tertiary centre experience

BACKGROUND Meniscal sparing surgery is a widely utilised treatment option for unstable meniscal tears with the aim of minimising the risk of progression towards osteoarthritis.However,there is limited data in the literature on meniscal repair outcomes in skeletally immature patients.AIM To evaluate the re-operation rate and functional outcomes of meniscal repairs in children and adolescents.METHODS We performed a retrospective review of all patients who underwent arthroscopic meniscal repair surgery between January 2007 and January 2018.All patients were under the age of 18 at the time of surgery.Procedures were all performed by a single surgeon.Information was gathered from our hospital Electronic Patient Records system.The primary outcome measure was re-operation rate(need for further surgery on the same meniscus).Secondary outcome measures were surgical complications and patient reported outcome measures that were International Knee Documentation Committee(IKDC),Tegner and Lysholm scores.RESULTS We identified 59 patients who underwent 66 All-inside meniscal repairs(32 medial meniscus and 34 Lateral meniscus).Meniscal repairs were performed utilizing FasT-Fix(Smith and Nephew)implants.There were 37 males and 22 females with an average age of 14 years(range 6-16).The average follow-up time was 53 months(range 26-140).Six patients had concomitant anterior cruciate ligament reconstruction surgery along with the meniscal repair.There were no requiring further meniscal repairs and 9 patients underwent partial meniscectomies.The mean postoperative IKDC score was 88(44-100),Tegner score was 7(2-10)and Lysholm score was 94(57-100).CONCLUSION Our results showed that arthroscopic repair of meniscal tears in the paediatric population is an effective treatment option that has a low failure rate and good postoperative clinical with the advantage of preserving meniscal tissues.

Analysis of the Cicatricial Acceleration Method (MAC®) in Skin Repair in Wistar Rattus norvegicus with Induced Chemical Burns

Introduction: The cicatricial acceleration method (MAC®) promotes photobiological effects of an anti-inflammatory and healing nature. Its therapeutic radiation is emitted, producing photobiostimulant effects that result in rapid tissue repair and better tissue quality. The treatment of burns has always been a challenge, which involves both performing surgery and controlling and guiding scar regeneration, avoiding possible morbidities. Objective: To evaluate the effects of applying the MAC methodology with an AlGa (aluminum, gallium arsenide) laser on the time and quality of tissue repair in the skin of rats after induced chemical burns. Method: 22 adult male rats were subjected to a second-degree chemical burn on the back using 50% trichloroacetic acid. After the burns, the animals were randomly separated into 2 groups: control and experimental. The control group (G1) received placebo laser therapy and the laser group (G2) underwent laser irradiation with an energy density of 100 J/cm2. Histological analysis and macroscopic evaluation were carried out by means of the paper template method. Results: Group G1 showed (53%) of the necrosis area and group G2 showed (11%) necrosis area. Conclusion: The cicatricial acceleration method (MAC®) favored the repair of wounds caused by a 2nd-degree chemical burn, optimizing time and improving quality.

Repair of Second-Generation Recycled Fine Aggregate of Waste Concrete from Freeze-Thaw Environment by Carbonation Treatment

The reuse of waste recycled concrete from harsh environments has become a research hotspot in the field of construction.This study investigated the repair effect of carbonation treatment on second-generation recycled fine aggregate(SRFA)obtained from recycled fine aggregate concrete(RFAC)subjected to freeze-thaw(FT)cycles.Before and after carbonation,the properties of SRFA were evaluated.Carbonated second-generation recycled fine aggregate(CSRFA)at five substitution rates(0%,25%,50%,75%,100%)to replace SRFA was used to prepare carbonated second-generation recycled fine aggregate concrete(CSRFAC).The water absorption,porosity and mechanical properties of CSRFAC were tested,and its frost-resisting durability was evaluated.The results showed after carbonation treatment,the physical properties of SRFA was improved and met the requirements of II aggregate.The micro-hardness of the interfacial transition zone and attached mortar in CSRFA was 50.5%and 31.2%higher than that in SRFA,respectively.With the increase of CSRFA replacement rate,the water absorption and porosity of CSRFAC gradually decreased,and the mechanical properties and frost resistance of CSRFAC were gradually improved.Carbonation treatment effectively repairs the damage of SRFA caused by FT cycles and improves its application potential.

Resilience-Oriented Load Restoration Method and Repair Strategies for Regional Integrated Electricity-Natural Gas System

The rising frequency of extreme disaster events seriously threatens the safe and secure operation of the regional integrated electricity-natural gas system(RIENGS).With the growing level of coupling between electric and natural gas systems,it is critical to enhance the load restoration capability of both systems.This paper proposes a coordinated optimization strategy for resilience-enhanced RIENGS load restoration and repair scheduling and transforms it into a mixed integer second-order cone programming(MISOCP)model.The proposed model considers the distribution network reconfiguration and the coordinated repair strategy between the two systems,minimizing the total system load loss cost and repair time.In addition,a bi-directional gas flow model is used to describe the natural gas system,which can provide the RIENGS with more flexibility for load restoration during natural gas system failure.Finally,the effectiveness of the proposed approach is verified by conducting case studies on the test systems RIENGS E13-G7 and RIENGS E123-G20.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Single-incision laparoscopic transabdominal preperitoneal repair in the treatment of adult female patients with inguinal hernia

BACKGROUND Women have a 3%lifetime chance of developing an inguinal hernia,which is not as common in men.Due to its cosmetic benefits,single-incision laparoscopic transabdominal preperitoneal(SIL-TAPP)inguinal hernia repair is becoming in-creasingly popular in the management of inguinal hernia in women.However,there are no studies comparing the safety and applicability of SIL-TAPP repair with conventional laparoscopic transabdominal preperitoneal(CL-TAPP)inguinal hernia repair for the treatment of inguinal hernia in women.AIM To compare the outcomes of SIL-TAPP and CL-TAPP repair in adult female patients with inguinal hernia and to estimate the safety and applicability of SIL-TAPP repair in adult female inguinal hernia patients.METHODS We retrospectively compared the clinical information and follow-up data of fe-male inguinal hernia patients who underwent SIL-TAPP inguinal hernia repair and those who underwent CL-TAPP inguinal hernia repair at the Affiliated Hos-pital of Nantong University from February 2018 to December 2020 and assessed the long-term and short-term outcomes of both cohorts.RESULTS This study included 123 patients,with 71 undergoing SIL-TAPP repair and 52 un-dergoing CL-TAPP repair.The two cohorts of patients and inguinal hernia charac-teristics were similar,with no statistically meaningful difference.The rate of intraoperative inferior epigastric vessel injury was lower in patients in the SIL-TAPP cohort(0,0%)than in patients in the CL-TAPP cohort(4,7.7%)and was significantly different(P<0.05).In addition,the median[interquartile range(IQR)]total hospitalization costs were significantly lower in patients in the SIL-TAPP cohort[$3287(3218-3325)]than in patients in the CL-TAPP cohort[$3511(3491-3599)].Postoperatively,the occurrence rate of trocar site hernia was lower in the SIL-TAPP cohort(0,0%)than in the CL-TAPP cohort(4,7.7%),and the median(IQR)cosmetic score was significantly higher in the SIL-TAPP cohort[10(10-10)]than in the CL-TAPP cohort[9(9-10)].CONCLUSION SIL-TAPP repair did not increase the incidence of intraoperative and postoperative complications in female in-guinal hernia patients.Moreover,female inguinal hernia patients who underwent SIL-TAPP repair had a lower probability of trocar site hernia and inferior epigastric vessel injury than female inguinal hernia patients who un-derwent CL-TAPP repair.In addition,female inguinal hernia patients who underwent SIL-TAPP repair reported a more aesthetically pleasing postoperative abdominal incision.Therefore,SIL-TAPP repair is a better option for the treatment of inguinal hernias in women.