Due to medical waste’s infection and hazard, it can cause potential environmental and public health risks, so medical waste management is of great importance especially in developing countries. The objective of the s...Due to medical waste’s infection and hazard, it can cause potential environmental and public health risks, so medical waste management is of great importance especially in developing countries. The objective of the study was to analyze and assess current status of medical waste management in the light of semi-structured interview in medical institutions and the medical waste disposal centre. As a medium-sized city of China and its respective nature, Xinxiang was selected as the case study. In order to significantly improve eco-efficiency of medical waste management (MWM) and minimize the environmental risks, this paper identified key factors determining the implementation of MWM on the basis of the local realities and situations of medical waste, and then an integrated MWM system was developed. Such the regulations should be improved;MWM database platform should be strengthened;unified coordination ability of the MWM should be developed;and a suitable rural recycling network should be set up.展开更多
Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor ...Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor education for college and university students is an urgent need of the high-quality development of the society and the internal requirement of promoting the all-round development of individuals.This study analyzes the importance of strengthening labor education for college and university students in the new era and proposes four practical pathways which draw on labor courses and campus activities,social practices,scientific research projects,and internships.After implementing these pathways,a survey of 967 students showed that students’understanding and awareness of labor was deepened,their hands-on skills and interests in science and labor practices were improved,and they became more cordially respectful to the working class.Taken together,the exploration and practice of these pathways helps college and university students to recognize their abilities,strengths,and interests,and guides them to form good labor habits that permeate all aspects of their studies and lives.展开更多
Chronic pharyngitis(CP)is a prevalent medical condition in the field of otorhinolaryngology characterized by persistent inflammation of the pharyngeal mucosa,submucosa,and lymphoid tissue.The etiology of CP is multifa...Chronic pharyngitis(CP)is a prevalent medical condition in the field of otorhinolaryngology characterized by persistent inflammation of the pharyngeal mucosa,submucosa,and lymphoid tissue.The etiology of CP is multifactorial,with noninfectious factors such as personal habits(e.g.,smoking and drinking).展开更多
Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially pre...Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.展开更多
Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ...Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.展开更多
Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal ...Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the discontinuation of ICIs.展开更多
Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinom...Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.展开更多
BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple ...BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.展开更多
Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disabili...Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disability and death.A study by Zhao et al.using magnetic resonance imaging on 49 gas explosion survivors revealed significant damage to brain regions like the hippocampus and cerebral cortex.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes ...BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.展开更多
BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact.Chemotherapy alone often yields suboptimal outcomes in both the short and long term,characterized by high rates of local recurrence ...BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact.Chemotherapy alone often yields suboptimal outcomes in both the short and long term,characterized by high rates of local recurrence and distant metastasis,leading to a poor long-term prognosis.AIM To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization(DEB-TACE)combined with targeted therapy for the treatment of unresectable liver cancer.METHODS We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020.Based on the different treatment regimens administered,patients were divided into the control(36 patients receiving sorafenib alone)and joint(38 patients receiving small particle DEB-TACE combined with sorafenib)groups.We compared liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB)]and serum tumor markers[alpha fetoprotein(AFP)]before and after treatment in both groups.Short-term efficacy measures[complete response(CR),partial response,progression disease,stable disease,objective response rate(ORR),and disease control rate(DCR)]were assessed post-treatment.Long-term follow-up evaluated median overall survival(OS),progression-free survival(PFS),and adverse reaction rates between the two groups.RESULTS One month post-treatment,the joint group demonstrated significantly higher rates of CR,ORR,and DCR compared to the control group(P<0.05).Three days after treatment,the joint group showed elevated levels of ALT,AST,and TBIL but reduced levels of ALB and AFP compared to the control group(P<0.05).The median OS was 18 months for the control group and 25 months for the joint group,while the median PFS was 15 months for the control group and 22 months for the joint group,with significant differences observed(log-rank:χ2=7.824,6.861,respectively;P=0.005,0.009,respectively).The incidence of adverse reactions was not significantly different between the groups(P>0.05).CONCLUSION The combination of small particle DEB-TACE and sorafenib significantly improves both short-and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.展开更多
BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of...BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura,which was not taken seriously enough.As the disease progressed,pleural effusion gradually appeared,and after systematic diagnosis and treatment,she was diagnosed with“primary light chain amyloidosis”.She achieved rapid hematological remission after treatment with a daratumumab+bortezomib+cyclophosphamide+dexamethasone regimen.CONCLUSION Periorbital purpura can be the only initial symptom of primary light chain amyloidosis;we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.展开更多
BACKGROUND There is an increasingly strong demand for appearance and physical beauty in social life,marriage,and other aspects with the development of society and the improvement of material living standards.An increa...BACKGROUND There is an increasingly strong demand for appearance and physical beauty in social life,marriage,and other aspects with the development of society and the improvement of material living standards.An increasing number of people have improved their appearance and physical shape through aesthetic plastic surgery.The female breast plays a significant role in physical beauty,and droopy or atrophied breasts can frequently lead to psychological inferiority and lack of confidence in women.This,in turn,can affect their mental health and quality of life.AIM To analyze preoperative and postoperative self-image pressure-level changes of autologous fat breast augmentation patients and their impact on social adaptability.METHODS We selected 160 patients who underwent autologous fat breast augmentation at the First Affiliated Hospital of Xinxiang Medical University from January 2020 to December 2022 using random sampling method.The general information,selfimage pressure level,and social adaptability of the patients were investigated using a basic information survey,body image self-assessment scale,and social adaptability scale.The self-image pressure-level changes and their effects on the social adaptability of patients before and after autologous fat breast augmentation were analyzed.RESULTS We collected 142 valid questionnaires.The single-factor analysis results showed no statistically significant difference in the self-image pressure level and social adaptability score of patients with different ages,marital status,and monthly income.However,there were significant differences in social adaptability among patients with different education levels and employment statuses.The correlation analysis results revealed a significant correlation between the self-image pressure level and social adaptability score before and after surgery.Multiple factors analysis results showed that the degree of concern caused by appearance in selfimage pressure,the degree of possible behavioral intervention,the related distress caused by body image,and the influence of body image on social life influenced the social adaptability of autologous fat breast augmentation patients.CONCLUSION The self-image pressure on autologous fat breast augmentation patients is inversely proportional to their social adaptability.展开更多
Scarlet fever(SF)is a common infectious disease caused by group A streptococcus(GAS)[1].During the 18th and 19th centuries,SF was a significant cause of mortality in children aged 5-15 years worldwide[2].The incidence...Scarlet fever(SF)is a common infectious disease caused by group A streptococcus(GAS)[1].During the 18th and 19th centuries,SF was a significant cause of mortality in children aged 5-15 years worldwide[2].The incidence and fatality rates of SF have decreased remarkably due to the widespread use of effective antibiotics and improvements in diet and sanitation[3].However,the recent resurgence of SF has sparked significant interest in infectious diseases[1,3].Given the insufficient understanding of the triggers that cause SF outbreaks and the absence of available vaccines to prevent GAS infection to date[1],effective prevention and control programs are needed to manage the ongoing spread of SF.展开更多
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvatio...Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.展开更多
Background:Neuro-inflammation is regarded as one of the critical pathogenesis in neurodegenerative diseases,which is characterized by the activated microglial cells.Pectolinarin(Pec),a natural flavonoid that exists in...Background:Neuro-inflammation is regarded as one of the critical pathogenesis in neurodegenerative diseases,which is characterized by the activated microglial cells.Pectolinarin(Pec),a natural flavonoid that exists in many Chinese herbal medicines,has been reported to have various biological activities.However,the effects and mechanisms on neuro-inflammation are not clear.Methods:In this study,the inhibitory effects and mechanisms of Pec on neuro-inflammation were investigated in the LPS-stimulated microglial BV_(2) cells.BV_(2) microglial cells were treated with Pec or vehicle,followed by LPS.Enzyme-linked immunosorbent assay,real-time quantitative PCR,nitric oxide and reactive oxygen species assay,and western blot were performed to examine the effects of Pec on neuro-inflammatory responses.Results:We showed that Pec significantly inhibited the expression of tumor necrosis factorαand interleukin 6 in mRNA and protein levels induced by LPS.Moreover,the production of nitric oxide,iNOS,reactive oxygen species,and COX-2 were suppressed by Pec in LPS-stimulated microglial BV_(2) cells.In addition,Pec inhibited LPS-induced inflammation via nuclear factor kappa B signaling pathway,as evidenced by the reduction of the phosphorylation of inhibitor of nuclear factor kappa-B kinase,the degradation of IκBα,and the nuclear translocation of p65.Conclusion:Taken together,Pec exhibited anti-inflammatory effects in LPS-stimulated microglial BV_(2) cells via nuclear factor kappa B signaling pathway,which might provide therapeutic potential for neuro-inflammation and neurodegenerative diseases.展开更多
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to creat...Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.展开更多
Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20%of the total cases.Currently,trastuzumab+chemotherapy is the...Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20%of the total cases.Currently,trastuzumab+chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer,and the combination has exhibited definite efficacy in HER2-targeted therapy.However,the emergence of drug resistance during treatment considerably reduces its effectiveness;thus,it is imperative to investigate the potential mechanisms underlying resistance.In the present review article,we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases,aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.展开更多
Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments.After a period of dormancy,organisms often exhibit exceptional resilience.This period is typically divided into ...Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments.After a period of dormancy,organisms often exhibit exceptional resilience.This period is typically divided into hibernation and aestivation based on seasonal patterns.However,the mechanisms by which organisms adapt to their environments during dormancy,as well as the potential relationships between different states of dormancy,deserve further exploration.Here,we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation,respectively.Based on histological and transcriptomic analysis of multiple organs,we discovered that dormancy involved a coordinated functional response across organs.Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures.Notably,similarities in gene expression patterns pertaining to energy metabolism,neural activity,and biosynthesis were noted during hibernation,suggesting a potential correlation between hibernation and aestivation.To further explore the relationship between these two phenomena,we analyzed other dormancy-capable species using data from publicly available databases.This comparative analysis revealed that most orthologous genes involved in metabolism,cell proliferation,and neural function exhibited consistent expression patterns during dormancy,indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution.In conclusion,this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.展开更多
BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic a...BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.展开更多
文摘Due to medical waste’s infection and hazard, it can cause potential environmental and public health risks, so medical waste management is of great importance especially in developing countries. The objective of the study was to analyze and assess current status of medical waste management in the light of semi-structured interview in medical institutions and the medical waste disposal centre. As a medium-sized city of China and its respective nature, Xinxiang was selected as the case study. In order to significantly improve eco-efficiency of medical waste management (MWM) and minimize the environmental risks, this paper identified key factors determining the implementation of MWM on the basis of the local realities and situations of medical waste, and then an integrated MWM system was developed. Such the regulations should be improved;MWM database platform should be strengthened;unified coordination ability of the MWM should be developed;and a suitable rural recycling network should be set up.
基金supported by Research Project of Henan Provincial Social Science Circles Federation(SKL-2023-1059)Higher Education Research Project of Henan Association of Higher Education(2021SXHLX175)Research Projects from Xinxiang Municipal Social Science Circles Federation(SKL-2023-126 and SKL-2023-136).
文摘Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor education for college and university students is an urgent need of the high-quality development of the society and the internal requirement of promoting the all-round development of individuals.This study analyzes the importance of strengthening labor education for college and university students in the new era and proposes four practical pathways which draw on labor courses and campus activities,social practices,scientific research projects,and internships.After implementing these pathways,a survey of 967 students showed that students’understanding and awareness of labor was deepened,their hands-on skills and interests in science and labor practices were improved,and they became more cordially respectful to the working class.Taken together,the exploration and practice of these pathways helps college and university students to recognize their abilities,strengths,and interests,and guides them to form good labor habits that permeate all aspects of their studies and lives.
基金supported by the Key Scientific and Technological Research Projects of Henan Province[222102310600]the Key Scientific Research Projects in Universities of Henan Province[23A330006]Science and Technology Key Project of Xinxiang[No.GG2020059]
文摘Chronic pharyngitis(CP)is a prevalent medical condition in the field of otorhinolaryngology characterized by persistent inflammation of the pharyngeal mucosa,submucosa,and lymphoid tissue.The etiology of CP is multifactorial,with noninfectious factors such as personal habits(e.g.,smoking and drinking).
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.
基金supported by Open Project of the Key Laboratory of Trauma and Orthopedics Research Medicine in Henan Province,No.HZKFKT20220504(to YZ)the National Natural Science Foundation of China,No.32000877(to YZ)and Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZ)。
文摘Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.
基金Supported by the National Natural Science Foundation of China,No.81671226Natural Science Foundation of Henan Province,No.232300421047+1 种基金Science and Technology Innovation Talents in Universities of Henan Province,No.24HASTIT067Henan Province Young and Middle-aged Health Science and Technology Innovation Talent Project,No.JQRC2023001.
文摘Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the discontinuation of ICIs.
文摘Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.
基金Supported by the Key Medical Scientific and Technological Project of Henan Province,No.SBGJ202102188Henan Provincial Medical Science and Technology Project,No.LHGJ20221012the Key Project of Science and Technology of Xinxiang,No.GG2020027.
文摘BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer types.The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue.Therefore,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)stress.METHODS Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined.Subsequently,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays.In vivo experiments were performed using murine xenograft model.To elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine.RESULTS The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues.Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent manner.In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice.Additionally,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT.Moreover,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein.The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis,EMT,and autophagy.Furthermore,blocking autophagy increases the ratio of apoptosis and migration.CONCLUSION Collectively,we demonstrate for the first time that amlodipine promotes apoptosis,induces autophagy,and inhibits migration through ER stress,thereby exerting anti-tumor effects in EC.
基金supported by the National Natural Science Foundation of China[U2004102]the Science and Technology Project of Henan Province[232102311071]the Natural Science Foundation of Henan Province[202300410312]。
文摘Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disability and death.A study by Zhao et al.using magnetic resonance imaging on 49 gas explosion survivors revealed significant damage to brain regions like the hippocampus and cerebral cortex.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.
文摘BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact.Chemotherapy alone often yields suboptimal outcomes in both the short and long term,characterized by high rates of local recurrence and distant metastasis,leading to a poor long-term prognosis.AIM To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization(DEB-TACE)combined with targeted therapy for the treatment of unresectable liver cancer.METHODS We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020.Based on the different treatment regimens administered,patients were divided into the control(36 patients receiving sorafenib alone)and joint(38 patients receiving small particle DEB-TACE combined with sorafenib)groups.We compared liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB)]and serum tumor markers[alpha fetoprotein(AFP)]before and after treatment in both groups.Short-term efficacy measures[complete response(CR),partial response,progression disease,stable disease,objective response rate(ORR),and disease control rate(DCR)]were assessed post-treatment.Long-term follow-up evaluated median overall survival(OS),progression-free survival(PFS),and adverse reaction rates between the two groups.RESULTS One month post-treatment,the joint group demonstrated significantly higher rates of CR,ORR,and DCR compared to the control group(P<0.05).Three days after treatment,the joint group showed elevated levels of ALT,AST,and TBIL but reduced levels of ALB and AFP compared to the control group(P<0.05).The median OS was 18 months for the control group and 25 months for the joint group,while the median PFS was 15 months for the control group and 22 months for the joint group,with significant differences observed(log-rank:χ2=7.824,6.861,respectively;P=0.005,0.009,respectively).The incidence of adverse reactions was not significantly different between the groups(P>0.05).CONCLUSION The combination of small particle DEB-TACE and sorafenib significantly improves both short-and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.
基金Supported by the Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20210533Xinxiang Science and Technology Research Project,No.GG2020029.
文摘BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura,which was not taken seriously enough.As the disease progressed,pleural effusion gradually appeared,and after systematic diagnosis and treatment,she was diagnosed with“primary light chain amyloidosis”.She achieved rapid hematological remission after treatment with a daratumumab+bortezomib+cyclophosphamide+dexamethasone regimen.CONCLUSION Periorbital purpura can be the only initial symptom of primary light chain amyloidosis;we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.
文摘BACKGROUND There is an increasingly strong demand for appearance and physical beauty in social life,marriage,and other aspects with the development of society and the improvement of material living standards.An increasing number of people have improved their appearance and physical shape through aesthetic plastic surgery.The female breast plays a significant role in physical beauty,and droopy or atrophied breasts can frequently lead to psychological inferiority and lack of confidence in women.This,in turn,can affect their mental health and quality of life.AIM To analyze preoperative and postoperative self-image pressure-level changes of autologous fat breast augmentation patients and their impact on social adaptability.METHODS We selected 160 patients who underwent autologous fat breast augmentation at the First Affiliated Hospital of Xinxiang Medical University from January 2020 to December 2022 using random sampling method.The general information,selfimage pressure level,and social adaptability of the patients were investigated using a basic information survey,body image self-assessment scale,and social adaptability scale.The self-image pressure-level changes and their effects on the social adaptability of patients before and after autologous fat breast augmentation were analyzed.RESULTS We collected 142 valid questionnaires.The single-factor analysis results showed no statistically significant difference in the self-image pressure level and social adaptability score of patients with different ages,marital status,and monthly income.However,there were significant differences in social adaptability among patients with different education levels and employment statuses.The correlation analysis results revealed a significant correlation between the self-image pressure level and social adaptability score before and after surgery.Multiple factors analysis results showed that the degree of concern caused by appearance in selfimage pressure,the degree of possible behavioral intervention,the related distress caused by body image,and the influence of body image on social life influenced the social adaptability of autologous fat breast augmentation patients.CONCLUSION The self-image pressure on autologous fat breast augmentation patients is inversely proportional to their social adaptability.
基金supported by the Key Scientific Research Project of Universities in Henan(21A330004)Supported by the Open Project Program of the First Hospital of Xinxiang Medical University(XZZX2022002).
文摘Scarlet fever(SF)is a common infectious disease caused by group A streptococcus(GAS)[1].During the 18th and 19th centuries,SF was a significant cause of mortality in children aged 5-15 years worldwide[2].The incidence and fatality rates of SF have decreased remarkably due to the widespread use of effective antibiotics and improvements in diet and sanitation[3].However,the recent resurgence of SF has sparked significant interest in infectious diseases[1,3].Given the insufficient understanding of the triggers that cause SF outbreaks and the absence of available vaccines to prevent GAS infection to date[1],effective prevention and control programs are needed to manage the ongoing spread of SF.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
基金supported by the grants from the Training Program for Young Backbone Teachers in Colleges and Universities of Henan Province(2021GGJS103)the Program for Science and Technology Innovation Team in Universities of Henan Province(22IRTSTHN030)the Henan Neural Development Engineering Research Center for Children Foundation(SG201909).
文摘Background:Neuro-inflammation is regarded as one of the critical pathogenesis in neurodegenerative diseases,which is characterized by the activated microglial cells.Pectolinarin(Pec),a natural flavonoid that exists in many Chinese herbal medicines,has been reported to have various biological activities.However,the effects and mechanisms on neuro-inflammation are not clear.Methods:In this study,the inhibitory effects and mechanisms of Pec on neuro-inflammation were investigated in the LPS-stimulated microglial BV_(2) cells.BV_(2) microglial cells were treated with Pec or vehicle,followed by LPS.Enzyme-linked immunosorbent assay,real-time quantitative PCR,nitric oxide and reactive oxygen species assay,and western blot were performed to examine the effects of Pec on neuro-inflammatory responses.Results:We showed that Pec significantly inhibited the expression of tumor necrosis factorαand interleukin 6 in mRNA and protein levels induced by LPS.Moreover,the production of nitric oxide,iNOS,reactive oxygen species,and COX-2 were suppressed by Pec in LPS-stimulated microglial BV_(2) cells.In addition,Pec inhibited LPS-induced inflammation via nuclear factor kappa B signaling pathway,as evidenced by the reduction of the phosphorylation of inhibitor of nuclear factor kappa-B kinase,the degradation of IκBα,and the nuclear translocation of p65.Conclusion:Taken together,Pec exhibited anti-inflammatory effects in LPS-stimulated microglial BV_(2) cells via nuclear factor kappa B signaling pathway,which might provide therapeutic potential for neuro-inflammation and neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China[No.U21A20334,82373544]Hebei Provincial Department of Science and Technology Centrally Guided Local Development Fund Project[236Z7705G]Occupational health risk assessment and the formulation of national occupational health standards[102393220020090000020].
文摘Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.
基金supported by the Project of Henan Provincial Medical Science and Technology Research Plan(No.SBGJ202301004 and No.LHGJ20210186)the Key Science Fund project of Henan Provincial Natural Science Foundation(No.232300421119).
文摘Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20%of the total cases.Currently,trastuzumab+chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer,and the combination has exhibited definite efficacy in HER2-targeted therapy.However,the emergence of drug resistance during treatment considerably reduces its effectiveness;thus,it is imperative to investigate the potential mechanisms underlying resistance.In the present review article,we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases,aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.
基金supported by the National Natural Science Foundation of China (32170480,31972866)Youth Innovation Promotion Association,Chinese Academy of Sciences (http://www.yicas.cn)+1 种基金Young Top-notch Talent Cultivation Program of Hubei ProvinceWuhan Branch,Supercomputing Center,Chinese Academy of Sciences,China。
文摘Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments.After a period of dormancy,organisms often exhibit exceptional resilience.This period is typically divided into hibernation and aestivation based on seasonal patterns.However,the mechanisms by which organisms adapt to their environments during dormancy,as well as the potential relationships between different states of dormancy,deserve further exploration.Here,we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation,respectively.Based on histological and transcriptomic analysis of multiple organs,we discovered that dormancy involved a coordinated functional response across organs.Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures.Notably,similarities in gene expression patterns pertaining to energy metabolism,neural activity,and biosynthesis were noted during hibernation,suggesting a potential correlation between hibernation and aestivation.To further explore the relationship between these two phenomena,we analyzed other dormancy-capable species using data from publicly available databases.This comparative analysis revealed that most orthologous genes involved in metabolism,cell proliferation,and neural function exhibited consistent expression patterns during dormancy,indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution.In conclusion,this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.
文摘BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.