Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Snap-through behaviors and nonlinear vibrations of a bistable composite laminated cantilever shell:an experimental and numerical study

The snap-through behaviors and nonlinear vibrations are investigated for a bistable composite laminated cantilever shell subjected to transversal foundation excitation based on experimental and theoretical approaches.An improved experimental specimen is designed in order to satisfy the cantilever support boundary condition,which is composed of an asymmetric region and a symmetric region.The symmetric region of the experimental specimen is entirely clamped,which is rigidly connected to an electromagnetic shaker,while the asymmetric region remains free of constraint.Different motion paths are realized for the bistable cantilever shell by changing the input signal levels of the electromagnetic shaker,and the displacement responses of the shell are collected by the laser displacement sensors.The numerical simulation is conducted based on the established theoretical model of the bistable composite laminated cantilever shell,and an off-axis three-dimensional dynamic snap-through domain is obtained.The numerical solutions are in good agreement with the experimental results.The nonlinear stiffness characteristics,dynamic snap-through domain,and chaos and bifurcation behaviors of the shell are quantitatively analyzed.Due to the asymmetry of the boundary condition and the shell,the upper stable-state of the shell exhibits an obvious soft spring stiffness characteristic,and the lower stable-state shows a linear stiffness characteristic of the shell.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

Ultra-Robust and High-Performance Rotational Triboelectric Nanogenerator by Bearing Charge Pumping

As an emerging technology to convert environmental high-entropy energy into electrical energy,triboelectric nanogenerator(TENG)has great demands for further enhancing the service lifetime and output performance in practical applications.Here,an ultra-robust and high-performance rotational triboelectric nanogenerator(R-TENG)by bearing charge pumping is proposed.The R-TENG composes of a pumping TENG(P-TENG),an output TENG(O-TENG),a voltage-multiplying circuit(VMC),and a buffer capacitor.The P-TENG is designed with freestanding mode based on a rolling ball bearing,which can also act as the rotating mechanical energy harvester.The output low charge from the P-TENG is accumulated and pumped to the non-contact O-TENG,which can simultaneously realize ultralow mechanical wear and high output performance.The matched instantaneous power of R-TENG is increased by 32 times under 300 r/min.Furthermore,the transferring charge of R-TENG can remain 95%during 15 days(6.4×10^(6)cycles)continuous operation.This work presents a realizable method to further enhance the durability of TENG,which would facilitate the practical applications of high-performance TENG in harvesting distributed ambient micro mechanical energy.

Effect of comprehensive nursing on the quality of life and swallowing function in individuals diagnosed with ischemic stroke

BACKGROUND Ischemic stroke(IS)is a widely recognized disease characterized by high preva-lence,mortality,morbidity,disability,and recurrence rates.It ranks prominently in terms of mortality,constituting 60%-80%of stroke cases.AIM To explore the impact of comprehensive nursing care on the quality of life and swallowing function in individuals diagnosed with IS.METHODS This study comprised 172 patients with IS admitted to our hospital between February 2018 to March 2021.The participants were divided into two groups,namely the control group(n=80)receiving routine care and the research group(n=92)receiving comprehensive care.Various assessment scales,including the standard swallowing function assessment scale(SSA),National Institutes of Health Stroke scale(NIHSS),European stroke scale(ESS),self-rating anxiety scale(SAS),self-rating depression scale(SDS),Barthel index(BI),and the motor func-tion assessment scale(MAS),were employed to evaluate the improvement in swallowing function,neurological deficits,clinical outcomes,anxiety,depression,daily living activities,and motor function before and after care.Furthermore,the study compared the occurrence of adverse reactions during the nursing period,life quality before and after the intervention,rehabilitation compliance,and nursing satisfaction between the two groups.RESULTS After the nursing intervention,the research group exhibited significantly improved SSA and NIHSS scores compared to the control group(P<0.05).Moreover,both groups demonstrated significant reductions in SAS and SDS scores(P<0.05),with the research group showing more obvious advantages(P<0.05).Compared to the control group,the research group displayed significantly better ESS,BI,and MAS scores(P<0.05),coupled with a lower incidence of adverse reactions(P<0.05).Additionally,the research group demonstrated markedly higher levels of life quality,rehabilitation compliance,and nursing satisfaction compared to the control group(P<0.05).CONCLUSION Comprehensive nursing effectively improved swallowing function,quality of life,and patient satisfaction,high-lighting its clinical significance.

Recent Construction Technology Innovations and Practices for Large-Span Arch Bridges in China

Arch bridges provide significant technical and economic benefits under suitable conditions.In particular,concrete-filled steel tubular(CFST)arch bridges and steel-reinforced concrete(SRC)arch bridges are two types of arch bridges that have gained great economic competitiveness and span growth potential due to advancements in construction technology,engineering materials,and construction equipment over the past 30 years.Under the leadership of the author,two record-breaking arch bridges—that is,the Pingnan Third Bridge(a CFST arch bridge),with a span of 560 m,and the Tian’e Longtan Bridge(an SRC arch bridge),with a span of 600 m—have been built in the past five years,embodying great technological breakthroughs in the construction of these two types of arch bridges.This paper takes these two arch bridges as examples to systematically summarize the latest technological innovations and practices in the construction of CFST arch bridges and SRC arch bridges in China.The technological innovations of CFST arch bridges include cable-stayed fastening-hanging cantilevered assembly methods,new in-tube concrete materials,in-tube concrete pouring techniques,a novel thrust abutment foundation for nonrocky terrain,and measures to reduce the quantity of temporary facilities.The technological innovations of SRC arch bridges involve arch skeleton stiffness selection,the development of encasing concrete materials,encasing concrete pouring,arch rib stress mitigation,and longitudinal reinforcement optimization.To conclude,future research focuses and development directions for these two types of arch bridges are proposed.

Green synthesis of ZSM-5 using silica fume and catalytic co-cracking of lignin and plastics for production of monocyclic aromatics

ZSM-5 with hierarchical pore structure was synthesized by a simple two-step hydrothermal crystallization from silica fume without using any organic ammonium templates.The synthesized ZSM-5 were oval shaped particles with a particle size about 2.0 μm and weak acid-dominated with proper Brønsted(B)and Lewis(L)acid sites.The ZSM-5 was used for catalytic co-cracking of n-octane and guaiacol,lowdensity polyethylene(LDPE)and alkali lignin(AL)to enhance the production of benzene,toluene,ethylbenzene and xylene(BTEX).The most significant synergistic effect occurred at n-octane/guaiacol at 1:1 and LDPE/AL at 1:3,under the condition,the achieved BTEX selectivity were 24%and 33%(mass)higher than the calculated values(weighted average).The highest BTEX selectivity reached 88.5%,which was 3.7%and 54.2%higher than those from individual cracking LDPE and AL.The synthesized ZSM-5 exhibited superior catalytic performance compared to the commercial ZSM-5,indicating potential application prospect.

Coral records of Mid-Holocene sea-level highstands and climate responses in the northern South China Sea

High-resolution sea-level data and high-precision dating of corals in the northern South China Sea(SCS)during the Holocene provide a reference and historical background for current and future sea-level changes and a basis for scientific assessment of the evolutionary trend of coral reefs in the SCS.Although sporadic studies have been performed around Hainan Island in the northern SCS,the reconstructed sea level presents different values or is controversial because the indicative meaning of the sea-level indicators were neither quantified nor uniform criteria.Here,we determined the quantitative relationship between modern living coral and sea level by measuring the top surfaces of 27 live Porites corals from the inner reef flat along the east coast of Hainan Island and assessed the accuracy of results obtained using coral as sea-level indicators.Additionally,three in situ fossil Porites corals were analyzed based on elevation measurements,digital X-ray radiography,and U-Th dating.The survey results showed that the indicative meanings for the modern live Porites corals is(146.09±8.35)cm below the mean tide level(MTL).It suggested that their upward growth limit is constrained by the sea level,and the lowest low water is the highest level of survival for the modern live Porites corals.Based on the newly defined indicative meanings,6 new sea-level index points(SLIPs)were obtained and 19 published SLIPs were recalculated.Those SLIPs indicated a relative sea level fluctuation between(227.7±9.8)cm to(154.88±9.8)cm MTL between(5393±25)cal a BP and(3390±12)cal a BP,providing evidences of the Mid-Holocene sea-level highstand in the northern SCS.Besides that,our analysis demonstrated that different sea-level histories may be produced based on different indicative meanings or criteria.The dataset of 276 coral U-Th ages indicates that coral reef development in the northern SCS comprised the initial development,boom growth,decline,and flourishing development again.A comparison with regional records indicated that synergistic effects of climatic and environmental factors were involved in the development of coral reefs in the northern SCS.Thus,the cessation of coral reef development during the Holocene in the northern SCS was probably associated with the dry and cold climate in South China,as reflected in the synchronous weakening of the ENSO and East Asian summer monsoon induced by the reduction of the 65°N summer insolation,which forced the migration of the Intertropical Convergence Zone.

Dark Matter Search in Dwarf Irregular Galaxies with Ten Years of Data from the Ice Cube Neutrino Observatory

Dwarf irregular galaxies(dIrrs),as rotationally supported systems,have more reliable J-factor measurements than dwarf spheroidal galaxies and have received attention as targets for dark matter detection in recent years.In this paper,we use 10 yr of IceCube muon-track data and an unbinned maximum-likelihood-ratio method to search for neutrino signals beyond the background from the directions of seven dIrrs,aiming to detect neutrinos produced by heavy annihilation dark matter.We do not detect any significant signal.Based on such null results,we calculate the upper limits on the velocity-averaged annihilation cross section for 1 TeV–10 PeV dark matter.Our limits,although weaker than the strictest constraints in the literature in this mass range,are also a good complement to the existing results considering the more reliable J-factor measurements of dIrrs.

GLOBAL CONVERGENCE OF A CAUTIOUS PROJECTION BFGS ALGORITHM FOR NONCONVEX PROBLEMS WITHOUT GRADIENT LIPSCHITZ CONTINUITY

A cautious projection BFGS method is proposed for solving nonconvex unconstrained optimization problems.The global convergence of this method as well as a stronger general convergence result can be proven without a gradient Lipschitz continuity assumption,which is more in line with the actual problems than the existing modified BFGS methods and the traditional BFGS method.Under some additional conditions,the method presented has a superlinear convergence rate,which can be regarded as an extension and supplement of BFGS-type methods with the projection technique.Finally,the effectiveness and application prospects of the proposed method are verified by numerical experiments.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling

BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Constraining the Earth-mass Primordial Black Hole Mergers Model of the Non-repeating FRBs Using the First CHIME/FRB Catalog

In this paper,we upgrade the constraints for the Earth-mass primordial black hole mergers model based on the first Canadian Hydrogen Intensity Mapping Experiment(CHIME)/fast radio burst(FRB)catalog.Assuming the null hypothesis that the observed non-repeating FRBs originate from Earth-mass primordial black hole mergers,we find that how the charges were distributed in the primordial black hole population is well described by a double powerlaw function with typical charge value of law function with typical charge value of q_(c)/10^(-5)=1.60_(-0.28)^(+0.28),where the power-law index α_(1)=2.33_(-0.18)^(+0.15) for q<q_(c) and α_(2)=4.56_(-0.26)^(+0.30)for q≥q_(c).Here,q represents the charge of the black hole in units of√GM,where M is the mass of the black hole.Furthermore,we infer the local event rate of the bursts is 8.8_(-2.1)^(+5.7)×10^(4)Gpc^(-3) yr^(-1),which indicates that an abundance of the primordial black hole population f■10^(-4) is needed to account for the observed FRBs by CHIME.The results of this paper lay the basis for further research on the electromagnetic radiation background generated by the merger of primordial black hole mergers.

U-Pb zircon geochronology of basaltic pyroclastic rocks from the basement beneath the Xisha Islands in the northwestern South China Sea and its geological significance

As one of the micro-blocks dispersed in the South China Sea(SCS), the basement of the Xisha Islands has rarely been drilled because of the thick overlying Cenozoic sediments, which has led to a confused understanding of the pre-Cenozoic basement of the Xisha Islands. Well CK-1, a kilometer-scale major scientific drill in the Xisha Islands in the northwestern SCS, penetrated thick reefal limestone(0–888.4 m) and the underlying basement rocks(888.4–901.4 m). In this study, we present the zircon U-Pb ages of basement basaltic pyroclastic rocks from Well CK-1 in the Xisha Islands of the northwestern SCS to investigate the basement nature of the Xisha microblock. The basement of Well CK-1 consists of basaltic pyroclastic rocks on the seamount. The zircon grains yielded apparent ages ranging from ca. 2 138.9 Ma to ca. 36 Ma. The old group of zircon grains from Well CK-1 was considered to be inherited zircons. Two Cenozoic zircons gave a weighted mean 206Pb/238U age of(36.3 ± 1.1) Ma,Mean Squared Weighted Deviations(MSWD) = 1.2, which may represent the maximum age of the volcano eruption. The Yanshanian inherited zircons(116.9–105.7 Ma and 146.1–130.2 Ma) from Well CK-1 are consistent with the zircons from Well XK-1, indicating that the basement of Chenhang Island may be similar to that of Well XK-1. We propose that the Xisha micro-block may have developed on a uniform Late Jurassic metamorphic crystalline basement, intruded by Cretaceous granitic magma.

Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of mice.Methods We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 days.Fecal samples from the colon were analyzed using 16S rRNA sequencing.Results Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or BPF.This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus.Additionally,pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic pathways.Considering the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient:A case report

BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent years.Mycobacterium canariasense(M.canariasense)was first reported as an opportunistic pathogen in 2004,but there have been very few case reports since then.Nocardia is a genus of aerobic and Gram-positive bacilli,and these species are also opportunistic pathogens and in the Mycobacteriales order.Conventional methods for diagnosis of NTM are inefficient.Metagenomic next-generation sequencing(mNGS)can rapidly detect many pathogenic microorganisms,even rare species.Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms.There are no previous reports of infection by M.canariasense and Nocardia farcinica(N.farcinica),especially in immunocompetent patients.This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M.canariasense,N.farcinica,and Candida parapsilosis(C.parapsilosis)based on mNGS.CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk,and recurrent episodes of moderate-grade fever for 1 wk.She received antibiotics for 1 wk at a local hospital,and experienced defervescence,but the productive cough and chest pain persisted.We collected samples of a lung lesion and alveolar lavage fluid for mNGS.The lung tissue was positive for M.canariasense,N.farcinica,and C.parapsilosis,and the alveolar lavage fluid was positive for M.canariasense.The diagnosis was pneumonia,and application of appropriate antibiotic therapy cured the patient.CONCLUSION Etiological diagnosis is critical for patients with infectious diseases.mNGS can identify rare and novel pathogens,and does not require a priori knowledge.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students

AIM:To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.METHODS:Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University.Their data were used to identify the different types of accommodation and nonstrabismic binocular vision dysfunction and to determine their frequency.Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities.RESULTS:The results showed that 36.71%of the subjects had accommodation and non-strabismic binocular vision issues,with 8.86%being attributed to accommodation dysfunction and 27.85%to binocular abnormalities.Convergence insufficiency(CI)was the most common abnormality,accounting for 13.29%.Those with these abnormalities experienced higher levels of eyestrain(χ2=69.518,P<0.001).The linear correlations were observed between the difference of binocular spherical equivalent(SE)and the index of horizontal esotropia at a distance(r=0.231,P=0.004)and the asthenopia survey scale(ASS)score(r=0.346,P<0.001).Furthermore,the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range(r=-0.321,P<0.001),the convergence of negative fusion images at close range(r=-0.294,P<0.001),the vergence facility(VF;r=-0.234,P=0.003),and the set of negative fusion images at far range(r=-0.237,P=0.003).Logistic regression analysis indicated that gender,age,and the difference in right and binocular SE did not influence the emergence of these abnormalities.CONCLUSION:Binocular vision abnormalities are more prevalent than accommodation dysfunction,with CI being the most frequent type.Greater binocular refractive disparity leads to more severe eyestrain symptoms.

Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a major health challenge with high incidence and poor survival rates in China.Systemic therapies,particularly tyrosine kinase inhibitors(TKIs),are the first-line treatment for advanced HCC,but resistance is common.The Rho GTPase family member Rho GTPase activating protein 12(ARHGAP12),which regulates cell adhesion and invasion,is a potential therapeutic target for overcoming TKI resistance in HCC.However,no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported.AIM To unveil the expression of ARHGAP12 in HCC,its role in TKI resistance and its potential associated pathways.METHODS This study used single-cell RNA sequencing(scRNA-seq)to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis.CellChat was used to investigate focal adhesion(FA)pathway regulation.We integrated bulk RNA data(RNA-seq and microarray),immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels,correlating with clinical outcomes.We assessed ARHGAP12 expression in TKI-resistant HCC,integrated conventional HCC to explore its mechanism,identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy.RESULTS ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA.In malignant hepatocytes in high-score FA groups,MDK-[integrin alpha 6(ITGA6)+integrinβ-1(ITGB1)]showed specificity in ligand-receptor interactions.ARHGAP12 mRNA and protein were upregulated in bulk RNA,immunohistochemistry and proteomics,and higher expression was associated with a worse prognosis.ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway.ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA.High expression of ARHGAP12 was associated with adverse reactions to sorafenib,cabozantinib and regorafenib,but not to immunotherapy.CONCLUSION ARHGAP12 expression is elevated in HCC and TKI-resistant HCC,and its regulatory role in FA may underlie the TKI-resistant phenotype.