Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.

Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

COVID-19 exacerbates psoriasis progression through inducing IFN-αexpression

As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cytokines[1],and microbial infection is a predisposing factor in up to 45%of patients[2].Infection with SARS-CoV-2 may trigger the aggravation of psoriasis.Thus,we conducted a survey to explore the proportion of psoriasis patients who experienced exacerbation and relapse after SARS-CoV-2 infection and also performed a preliminary investigation into the mechanisms involved.One hundred and twenty-four psoriasis patients(79 males and 45 females)who contracted COVID-19 were followed up and provided detailed information.

Impact of comorbid subthreshold depressive symptoms on cancerrelated fatigue and complications in adults with leukemia

BACKGROUND Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain.Therefore,these patients do not have high quality of life.According to the World Health Organization,the incidence of leukemia in China in 2020 was 5.1/100000,the mortality rate was 3.3/100000,and the prevalence rate was 16.7/100000.Therefore,it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients.AIM To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients,thereby providing a basis for early diagnosis and treatment in clinical practice.METHODS A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an,Shaanxi Province,China,from August 2022 to December 2023.Patients with a score>16 on the Chinese Classification of Mental Disorders(CCMD-3)and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group(n=95),while 100 leukemia patients admitted during the same period were classified as the control group.Data were collected using Epidata 3.1 software,and comparisons were made between the two groups regarding general clinical data,the Piper Fatigue Scale(PFS),the Pittsburgh Sleep Quality Index(PSQI),the Numeric Rating Scale for pain assessment,laboratory indicators,and the occurrence of complications.RESULTS In this survey,120 leukemia patients with depression were preliminarily screened,95 patients with subthreshold depression were ultimately selected as the subthreshold depression group,and 100 leukemia patients admitted during the same period were enrolled as the normal group.Comparison of basic clinical data between the two groups revealed no significant differences in age,sex,body mass index,cognitive function,or comorbidity with other chronic diseases.However,there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups(P<0.05).Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups,but there were statistically significant differences in pain scores,PSQI scores,PFS scores,hemoglobin levels,and C-reactive protein levels(P<0.05).Spearman’s correlation analysis indicated that cancer-related fatigue was correlated with age,hemoglobin levels,C-reactive protein levels,pain,and regular exercise among leukemia patients with subthreshold depression.Multivariate regression analysis revealed that advanced age,combined radiotherapy,pain,and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression,while regular exercise was a protective factor against cancer-related fatigue.Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group(4%)than in the depressive group(24.21%;P<0.001).CONCLUSION Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications.These findings may be related to advanced age,combined radiotherapy,pain,and low hemoglobin levels,while regular exercise may effectively alleviate symptoms.

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

Advances in regional nodal management of early-stage breast cancer

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis

Objective:To evaluate the anti-allergic effect of boeravinone B against ovalbumin-induced allergic rhinitis in mice and explore its possible mechanism.Methods:For the induction of allergic rhinitis,mice were intraperitoneally sensitized and intranasally challenged with ovalbumin,as well as orally received various concentrations of boeravinone B.Nasal mucosal inflammation,and the levels of nitric oxide,β-hexosaminidase,IFN-γ,LTC-4,myeloperoxidase,Nrf2,HO-1,GATA-3,ROR-γ,T-bet,antioxidant parameters,and allergen-specific cytokines were assessed.Results:Boeravinone B markedly reduced ovalbumin-induced increase in the number of episodes of nasal sneezing,rubbing,and discharge,as well as the levels of IgE,IgG1,andβ-hexosaminidase(P<0.05).It also significantly reduced differential cell count,myeloperoxidase,oxide-nitrosative stress,and the levels of IL-1β,IL-4,IL-5,IL-6,IL-13,IL-17,tumor necrosis factor-α,GATA-3,and ROR-γwhile enhancing the level of T-bet.Conclusions:Boeravinone B is a potential therapeutic agent for allergic rhinitis by modulating various inflammatory mediators and immune responses.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells

BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy

AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among the glaucoma patients,54 were treated with medication,while 25 remained untreated.Central corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation coefficient.RESULTS:The CNFD was reduced in glaucoma groups compared to healthy subjects(P<0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients.As the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P<0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P<0.001).In the absence of medication,CNFD in males was lower than that in females(P<0.05).Among patients under medication therapy,CNFD remained consistent between males and females.CONCLUSION:Antiglaucoma eye drops affect the microstructure of corneal nerves.IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Changes in posterior corneal elevation after small incision lenticule extraction for different myopic diopters

●AIM:To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction(SMILE)with different myopic diopters.●METHODS:Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study.Patients were allocated into three groups based on the preoperative spherical equivalent(SE):low myopia(SE≥-3.00 D),moderate myopia(-3.00 D>SE>-6.00 D)and high myopia(SE≤-6.00 D).Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times(1wk,1,3,6mo,and 1y).Posterior mean elevation(PME)at 25 predetermined points of 3 concentric circles(2-,4-,and 6-mm diameter)above the best fit sphere was analyzed.●RESULTS:All surgeries were completed uneventfully and no ectasia was found through the observation.The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively(1mo:P=0.017;3mo:P=0.018).The effect of time onΔPME was statistically significant(2-mm ring:P=0.001;4-mm ring:P<0.001;6-mm ring:P<0.001).The effect of different corneal locations onΔPME was significant except 1wk postoperatively(1mo:P=0.000;3mo:P=0.000;6mo:P=0.001;1y:P=0.001).Posterior corneal stability was linearly correlated with SE,central corneal thickness,ablation depth,residual bed thickness,percent ablation depth and percent stromal bed thickness.●CONCLUSION:The posterior corneal surface changes dynamically after SMILE.No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery.SMILE has good stability,accuracy,safety and predictability.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy:Familial aggregation of obesity

BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been elucidated.AIM To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO.METHODS A total of 193 patients with obesity who underwent SG were selected.Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between groups.RESULTS We defined FAO as the presence of two or more first-degree relatives with obesity.Patients with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO preoperatively.However,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.

Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps

BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases

The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

A surgical alternative of fusiform penetrating keratoplasty for the management of severe infectious keratitis

AIM:To describe the surgical procedure of fusiform penetrating keratoplasty(FPK)using multiple trephines of different sizes for treating patients with severe infectious keratitis.METHODS:Fourteen eyes underwent FPK,and 15 eyes received conventional penetrating keratoplasty(PK)were included in the study.The best-corrected visual acuity(BCVA),refractive outcomes,endothelial cell density,and postoperative complications were recorded.RESULTS:The FPK group was followed for an average of 15.3±2.1mo,whereas the PK group was followed for 16.1±1.9mo.The corneal ulcers were elliptical-shaped in all 14 eyes in the FPK group.The mean BCVA(logMAR,0.26±0.13)showed no statistically significant differences from that in the PK group(logMAR,0.21±0.12,P>0.05)at 1y after surgery.But the mean curvature,mean astigmatism,and mean spherical equivalent in the FPK group were lower than those in the PK group(P<0.05).Peripheral anterior synechia was observed in one patient in the FPK group,whereas 6 patients in the PK group.Suture loosening and neovascularization were observed in 4 and 5 eyes in the PK group,respectively.No graft immune rejection or elevation of intraocular pressure was observed in the two groups.CONCLUSION:For patients with elliptical-shaped corneas or corneal ulcers,FPK can avoid disrupting of corneal limbus,reduce the risk of postoperative complications,and can result in satisfactory visual quality.

Pleural effusion,ascites,colon ulcers and hematochezia:What we can learn from the diagnostic process of a patient with plasma cell myeloma:A case report

BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with PCM.CASE SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody stools.Computed tomography revealed pleural effusion and ascites.Pleural effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were negative.Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis.Echocardiography revealed enlarged atria and reduced left ventricular systolic function.The diagnosis remained unclear.Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels.Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type.Smear cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested PCM.Flow cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and CD117.Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal abnormalities.Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining.The patient was finally diagnosed with PCM.CONCLUSION A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.