Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Monte Carlo method for evaluation of surface emission rate measurement uncertainty

The aim of this study is to evaluate the uncertainty of 2πα and 2πβ surface emission rates using the windowless multiwire proportional counter method.This study used the Monte Carlo method (MCM) to validate the conventional Guide to the Expression of Uncertainty in Measurement (GUM) method.A dead time measurement model for the two-source method was established based on the characteristics of a single-channel measurement system,and the voltage threshold correction factor measurement function was indirectly obtained by fitting the threshold correction curve.The uncertainty in the surface emission rate was calculated using the GUM method and the law of propagation of uncertainty.The MCM provided clear definitions for each input quantity and its uncertainty distribution,and the simulation training was realized with a complete and complex mathematical model.The results of the surface emission rate uncertainty evaluation for four radioactive plane sources using both methods showed the uncertainty’s consistency E_(n)<0.070 for the comparison of each source,and the uncertainty results of the GUM were all lower than those of the MCM.However,the MCM has a more objective evaluation process and can serve as a validation tool for GUM results.

Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma:A case report

BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching

BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.

Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury

AIM:To investigate the protective effects,antioxidant potential,and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-Daspartate(NMDA)-induced retinal ganglion cell(RGC)injury in a mouse model of glaucoma.METHODS:The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining.Intracellular reactive oxygen species(ROS)production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry.The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina.The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatographymass spectroscopy(LC-MS)and untargeted metabolomics analyses.RESULTS:Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro.Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model.Untargeted metabolomics analyses showed that eicosane increased multiple metabolites,including L-arginine and L-carnitine,in the retina.CONCLUSION:Eicosane has protective effects,antioxidant potential,and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma

BACKGROUND Traumatic brain injury(TBI)imposes a substantial societal and familial burden due to its high disability and fatality rates,rendering it a serious public health problem.Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium(POD),which affects their quality of life.Anxiety has been linked to increased POD incidence in some studies,while others have found no correlation.AIM To investigate the correlation of POD risk factors,preoperative inflammatory factors,and mood disorders in patients with TBI.METHODS We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023.Patients were grouped as POD and non-POD,according to their POD status,and the general data of the two groups were compared.Inflammatory factor levels were detected preoperatively,and the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to investigate the risk factors associated with POD in these patients.Logistic regression was used to identify the independent risk factors.RESULTS Twenty-one patients(26.25%)developed POD,including 7,10,and 4 cases of the excitatory,inhibitory,and mixed types,respectively.There were 59 cases(73.75%)in the non-POD group.Compared with the non-POD group,the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale(GCS)scores before admission,unilateral mydriasis,preoperative hemorrhagic shock,intraventricular hemorrhage(IVH),and postoperative hyperglycemic hyperosmolar disease(P<0.05).In the POD group,interleukin-6(IL-6),human tumor necrosis factor-α(TNF-α),myeloperoxidase levels,HAMA,and HAMD scores were higher than those in the non-POD group(all P<0.05).Logistic multivariate analysis showed that GCS score at admission,IVH,IL-6,TNF-α,HAMA,and HAMD were independent risk factors for POD in patients with TBI(P<0.05).CONCLUSION Low GCS score at admission,IVH,elevated IL-6 and TNF-α,other inflammatory indicators,anxiety,and depression,can increase the risk of POD in patients with TBI after surgery.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Prolonged course of Paxlovid administration in a centenarian with COVID-19:A case report

BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019(COVID-19)infection.CASE SUMMARY A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days.During treatment,the patient was complicated with lung infection and heart failure,and nucleic acid remained positive.After expert consultation,a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days.Meanwhile,anti-heart failure and antibiotics were administered;the heart failure and pulmonary infection were improved.Finally,on the 33^(th) day of admission,nucleic acid turned negative,body temperature returned to normal,cough and sputum,fatigue,poor appetite and other symptoms basically improved.The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function,diarrhea,nausea and vomiting,myalgia,chest tightness and other side effects,and was discharged from hospital with good recovery.CONCLUSION This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

Changes in visual performance after implantation of different intraocular lenses

AIM:To evaluate the trending visual performance of different intraocular lenses(IOLs)over time after implantation.METHODS:Ninety-one patients received cataract surgery with implantations of monofocal(Mon)IOLs,segmental refractive(SegRef)IOLs,diffractive(Dif)IOLs,and extendeddepth-of-focus(EDoF)IOLs were included.The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared.RESULTS:Most of the visual parameters improved over the postoperative 6mo.The postoperative visual acuity(POVA)of the Mon IOL,SegRef IOL,and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group.Nevertheless,the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo.The optical quality initially improved in the EDoF IOL group,then in the Mon IOL,SegRef IOL,and Dif IOL groups.POVA and objective visual performance of the Mon IOL and EDoF IOL groups,as well as POVA and visual quality of the Dif IOL group,improved in the postoperative 1mo and stabilized.Within the postoperative 6mo,gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group,as well as in the postoperative optical quality of the Dif IOL group.CONCLUSION:The visual performance is different among eyes implanted with different IOLs.The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

Functional connectivity of paired default mode network subregions in patients with eye trauma

AIM:To study functional brain abnormalities in patients with eye trauma(ET)and to discuss the pathophysiological mechanisms of ET.METHODS:Totally 31 ET patients and 31 healthy controls(HCs)were recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the functional connectivity(FC)method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Pearson’s correlation analysis was used to explore the relationship between FC values in specific brain regions and clinical behaviors in patients with ET.RESULTS:Significantly increased FC between several regions was identified including the medial prefrontal cortex(MPFC)and left hippocampus formations(HF),the MPFC and left inferior parietal lobule(IPL),the left IPL and left medial temporal lobe(MTL),the left IPL and right MTL,and the right IPL and left MTL.No decreased region-to-region connectivity was detected in default mode network(DMN)sub-regions in patients with ET.Compared with HCs,ET patients exhibited significantly increased FC between several paired DMN regions,as follows:posterior cingulate cortex(PCC)and right HF(HF.R,t=2.196,P=0.032),right inferior parietal cortices(IPC.R)and left MTL(MTL.L,t=2.243,P=0.029),and right MTL(MTL.R)and HF.R(t=2.236,P=0.029).CONCLUSION:FC values in multiple brain regions of ET patients are abnormal,suggesting that these brain regions in ET patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of ET.

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).

Aspects of the Molecular Markers of Hemostatic Mechanism in Qinical Medicine

Thrombosis is the pathological process resulting from the inappropriate and propagation of the hemostatic response. The principle determinants of thrombosis can be categorized in contemporary terms according to Virchow' s paradigm: abnormalities in endothelial function ( vessel function ), rheotogy ( blood flow ), or blood component,either alone or in combination, can promote thrombus formation.

Effect of continuous nursing combined with respiratory exercise nursing on pulmonary function of postoperative patients with lung cancer

BACKGROUND Lung cancer is a malignant tumor with high morbidity and mortality among cancers.Surgery is currently one of the primary methods of treating lung cancer.Although it can slow down the progression of the disease by removing the lesion,this invasive surgery inevitably damages the integrity of the patient’s chest.Moreover,the patient’s pulmonary function may have a low compensatory capacity after surgery,causing various respiratory diseases such as atelectasis,respiratory function decline,and even serious cardiovascular disease.All of these have great negative impacts on the surgical effect and the prognosis of patients.With the continuous exploration and development of nursing,continuous nursing and respiratory exercise nursing have been gradually applied in the nursing of patients after lung cancer surgery,and have achieved good nursing results.AIM To investigate the effect of continuous nursing combined with respiratory exercise nursing on the pulmonary function of postoperative patients with lung cancer.METHODS A total of 80 patients with lung cancer who underwent surgery in our hospital from January 2021 to December 2021 were selected as the study subjects.All subjects were randomly divided into the control group(n=40 cases)and the experimental group(n=40 cases).Patients with lung cancer in the control group were given conventional nursing after surgery,while the experimental group was given continuous nursing combined with respiratory exercise nursing based on conventional nursing.The recovery of pulmonary function and respiratory symptoms was observed before and after 3 mo of intervention in both groups.The pulmonary function parameters,blood gas analysis,MD Anderson Symptom Inventory-lung cancer module(MDASI-LC)scores,incidence of pulmonary complications,and Morisky compliance scores were compared between the two groups before and after 3 mo of intervention.RESULTS There was no significant difference in pulmonary function and blood gas analysis between the two groups before intervention(P>0.05).3 mo after the intervention,the pulmonary function parameters in the experimental group(SpO2,VC,MVV,FEV1,FEV1%pred,and FEV1/FVC)were higher than those in the control group,and the differences were statistically significant(P<0.05).There was no significant difference in blood gas analysis between the two groups before intervention(P>0.05).PaO2 in the experimental group was significantly higher than that in the control group,and PaCO_(2) was significantly lower than that in the control group 3 mo after the intervention.The difference had statistical significance(P<0.05).3 mo after the intervention,the MDASI score of respiratory symptoms in the experimental group was significantly lower than that in the control group(P<0.05),and the incidence of pulmonary complications was lower than that in the control group(P<0.05).In addition,the treatment compliance and nursing satisfaction of patients in the experimental group were higher than those in the control group,and the differences were statistically significant(P<0.05).CONCLUSION Continuous nursing combined with respiratory exercise nursing can significantly accelerate the recovery of respiratory function in postoperative lung cancer patients,reduce the incidence of postoperative complications of lung cancer as well as improve the treatment compliance of patients.

Therapeutic role of growth factors in treating diabetic wound

Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

Comparison of efficacy of conbercept,aflibercept,and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion:a Meta-analysis

AIM:To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor(VEGF)drugs in the treatment of macular edema(ME)due to retinal vein occlusion(RVO)based on the evidence pooled from current clinical trials and observational studies.METHODS:A systematic literature search was conducted on nine online databases from inception until April 30,2022.The main endpoints were best corrected visual acuity(BCVA),central macular thickness(CMT),and adverse events(AEs).Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs.The retrieved data were analyzed using Stata software(version 12.0).RESULTS:A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis.It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo[weight mean difference(WMD)=-0.03,P=0.001;WMD=-0.05,P=0.019],but the effects were not different from that of ranibizumab at 6mo.Moreover,there was not statistically significant dif ference in the propor tion of patients gaining≥15 letters at 12-24mo between aflibercept and ranibizumab[odds ratio(OR)=1.16,P=0.427].Conbercept had higher mean CMT change effects at 1mo(WMD=-14.43,P=0.014)and 6mo(WMD=-35.63,P≤0.001)compared with ranibizumab.Meanwhile,the mean CMT change effects at 1mo(WMD=-10.14,P=0.170),6mo(WMD=-26.98,P=0.140)and 12-24mo(WMD=-12.34,P=0.071)were comparable among the groups.Similarly,AEs were not significantly different among the treatments(OR=0.75,P=0.305;OR=1.04,P=0.89).The stability of effect size of mean BCVA and CMT improved with the increase in sample size.Aflibercept and conbercept required fewer injections compared with ranibizumab.CONCLUSION:This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept,ranibizumab,and aflibercept in the treatment of RVOME.Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab.Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.

Effect of a disposable endoscope precleaning kit in the cleaning procedure of gastrointestinal endoscope:A multi-center observational study

BACKGROUND Precleaning is a key step in endoscopic reprocessing.AIM To develop an effective and economic endoscope cleaning method by using a disposable endoscope bedside precleaning kit.METHODS Altogether,228 used gastrointestinal endoscopes were selected from five high-volume endoscopy units and precleaned by a traditional precleaning bucket(group T)or a disposable endoscope bedside precleaning kit(group D).Each group was further subdivided based on the replacement frequency of the cleaning solution,which was replaced every time in subgroups T1 and D1 and every several times in subgroups Ts and Ds.The adenosine triphosphate(ATP)level and residual proteins were measured three times:Before and after precleaning and after manual cleaning.RESULTS After precleaning,the precleaning kit significantly reduced the ATP levels(P=0.034)and has a more stable ATP clearance rate than the traditional precleaning bucket.The precleaning kit also saved a quarter of the cost of enzymatic detergent used during the precleaning process.After manual cleaning,the ATP levels were also significantly lower in the precleaning kit group than in the traditional precleaning bucket group(P<0.05).Meanwhile,the number of uses of the cleaning solution(up to four times)has no significant impact on the cleaning effect(P>0.05).CONCLUSION Considering its economic cost and cleaning effect,the use of a disposable endoscope bedside precleaning kit can be an optimal option in the precleaning stage with the cleaning solution being replaced several times in the manual cleaning stage.