Objective To investigate the therapeutic effects and mechanisms of kinsenoside in amyotrophic lateral sclerosis(ALS)using an induced pluripotent stem cell(iPSC)-derived motor neuron model.Methods Motor neurons differentiated from SOD1^D90A mutant iPSCs were used as the ALS model.Isogenic motor neurons corrected to wild-type SOD1(SOD1^D90D)via TALEN technology served as controls.The safe concentration range and optimal treatment concentration of kinsenoside in the ALS cell model were determined.Morphological assessments were then conducted to evaluate its ameliorative effects on axonal degeneration phenotypes,and changes in cellular energy metabolism were measured.Expression levels of KEAP1/Nrf2,key molecules in the oxidative stress pathway,were determined by molecular biology techniques,and potential downstream targets were investigated.Results In the ALS cell model treated with kinseoside,pathological phenotypes were significantly ameliorated,as evidenced by reduced axonal swelling and increased axonal length.Meanwhile,abnormal mitochondrial aggregation within swollen axons was markedly alleviated,intracellular ATP levels were significantly elevated,and lactate content in the culture supernatant was reduced.Mechanistic studies revealed that after kinseoside treatment,KEAP1 protein levels decreased while Nrf2 protein levels increased in ALS model cells.TheqRT-PCR results confirmed that kinseoside reversed the mRNA transcription levels of mitochondrial fusion-related genes MFN2 and OPA1,as well as the mitophagy-related gene PINK1.Conclusion Kinsenoside may ameliorate the pathological damage of ALS motor neuron model by regulating the KEAP1/Nrf2 oxidative stress pathway and the expression of genes related to mitochondrial fusion and mitophagy.

Objective To explore the pathological mechanism underlying the exacerbation of ischemic stroke(IS)injury by ovarian aging(OVA),and to elucidate the therapeutic mechanism of curcumin screened based on pathological targets against OVA-aggravated IS injury.Methods Datasets of OVA(GSE81579)and IS(GSE16561)were retrieved from the Gene Expression Omnibus(GEO)database.Core intersecting genes were screened through differential expression analysis,Gene Set Enrichment Analysis(GSEA),and Venn analysis.The Database for Annotation,Visualization and Integrated Discovery(David)was used for Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses.Potential traditional Chinese medicines(TCMs)were screened via the Coremine Medicine database,and their active ingredients were further identified through literature review.A middle cerebral artery occlusion/reperfusion(MCAO/R)model was established in female Sprague-Dawley(SD)rats.The rats were randomly divided into five groups:the sham operation(Sham)group,MCAO/R model group,ovariectomy combined with MCAO/R(M&OVA)group,ovariectomy+MCAO/R+curcumin treatment(M&OVA&Cur)group,and ovariectomy+MCAO/R+curcumin+nicotinamide intervention(M&OVA&Cur&Nico)group.Multiple detection methods including neurological function scoring,2,3,5-triphenyltetrazolium chloride(TTC)staining,hematoxylin-eosin(H&E)staining,immunofluorescence assay,transmission electron microscopy(TEM),and Western blot were adopted to verify the protective effect and mechanism of curcumin.Results A total of 80 core intersecting genes were identified between OVA and IS,which were mainly enriched in the inflammatory response,C-X3-C chemokine binding,and NOD-like receptor signaling pathways.Curcuma longa and its active ingredient curcumin were finally screened as the targeted therapeutic agent.In vivo animal experiments demonstrated that rats in the M&OVA group exhibited significantly aggravated cerebral injury compared with those in the sole MCAO/R group.Treatment with curcumin at the dose of 200 mg/kg per day remarkably alleviated neurological deficits,reduced cerebral infarct volume,and inhibited the activation of NLRP3 inflammasome in M&OVA rats.Moreover,the neuroprotective effects of curcumin were markedly abrogated after intervention with nicotinamide,a specific SIRT1 inhibitor.Conclusion Ovarian aging aggravates ischemic stroke injury by activating inflammatory responses.Curcumin can attenuate OVA-aggravated cerebral ischemic injury via regulating the SIRT1-NLRP3 signaling axis,which provides a reliable theoretical basis for the clinical treatment of OVA-complicated ischemic stroke.

Objective To investigate the effects of canagliflozin on nicotine-induced arterial stiffness,and its possible mechanisms of action.Methods An animal model of nicotine-induced arterial stiffness was established by subcutaneously implanting osmotic microinfusion pumps into C57BL/6 mice to deliver a continuous infusion of nicotine;the model animals were then treated with canagliflozin to explore the effect of canagliflozin on arterial stiffness in these animals.In the in vivo experiments,ultrasound technology was employed to measure the aortic pulse wave velocity(PWV)in mice;aortic histopathology and vascular remodeling were examined using hematoxylin-eosin(HE)staining,Masson's trichrome staining,and Verhoeff's van Gieson(EVG)staining.Additionally,Western blot and immunofluorescence techniques were employed to detect the expression levels of matrix metalloproteinase-2(MMP-2),MMP-9,collagen Ⅰ,and fibronectin.Nicotine-treated murine aortic smooth muscle cells(Movas)were treated with canagliflozin in vitro,and Western blot analysis was used to detect changes in the expression of key proteins in the transforming growth factor-β1(TGF-β1)signaling pathway.Results Compared with mice in the control group,canagliflozin significantly suppressed the nicotine-induced increase in PWV in mice,also significantly reduced collagen fibre deposition and elastic fibre degradation.Furthermore,canagliflozin significantly downregulated the nicotine-induced expression of Collagen Ⅰ,fibronectin,MMP2 and MMP9 at the protein level,whilst also significantly inhibiting the nicotine-mediated increase in CollagenⅠ and MMP2 mRNA levels.In vitro experiments revealed that nicotine significantly up-regulated the expression of TGF-β1 and Smad2/Smad3 in mouse aortic smooth muscle cells,whereas canagliflozin significantly reversed the nicotine-induced up-regulation of these molecules.Conclusion Canagliflozin markedly suppressed nicotine-induced arterial stiffness in mice,potentially through its significant inhibition of nicotine-induced collagen fibre deposition and elastic fiber degradation.This effect may involve canagliflozin-mediated suppression of TGF-β1/Smad signaling pathway in mouse aortic smooth muscle cells.

Objective To explore the improvement effect of curcumin on systemic lupus erythematosus(SLE)in mice and analyze its mechanism.Methods Ten MRL/MpJ mice were used as the control group,while 40 MRL/lpr mice were randomly divided into four groups:the model group,the low-dose group,the high-dose group,and the combination group,with 10 mice in each group.The low-dose and high-dose groups were administered curcumin at doses of 250 mg/kg and 500 mg/kg,respectively,via oral gavage.The combination group received 500 mg/kg of curcumin via oral gavage along with an intravenous injection of 20 mg/kg of the phosphatidylinositol-3-kinase(PI3K)activator 740Y-P.After 8 weeks of continuous intervention,24-hour urinary protein,serum creatinine(Scr),and blood urea nitrogen(BUN)levels were measured.Serum levels of inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ)]and autoantibodies[anti-small nuclear ribonucleoprotein(snRNP/Sm)and anti-doublestranded DNA(dsDNA)antibodies]were detected by using ELISA.Renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Immunofluorescence was used to detect immune complex and complement deposition.Western blot was performed to assess the expression levels of CD4,CD19,CD20,PI3K,phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),mammalian target of rapamycin(mTOR),and phosphorylated mTOR(p-mTOR).Results Compared with the control group,the 24-hour urine protein,serum Scr and BUN levels,serum inflammatory factors(IL-6,TNF-α,IFN-γ),autoantibodies(anti-dsDNA,anti-snRNP/Sm),renal IgG and C3 deposition levels,and CD4,CD19,CD20,p-PI3K,p-Akt,p-mTOR protein expressions in the model group were significantly increased(all P<0.05).The above indicators in low and high dose groups were significantly lower,and the effect was more significant in the high-dose group.The indexs were significantly lower than that in the model group,and the effect in the high-dose group was more significant(all P<0.05).The above indexes in the combined group were higher than those in the high dose group(P<0.05).HE staining showed that the pathological changes of renal tissue in low and high dose groups were obviously improved,especially in high dose group,and the damage of renal tissue in combined group was more serious than that in high dose group.Conclusion Curcumin can ameliorate immune dysregulation and renal injury in SLE mice,potentially through the regulation of the PI3K/Akt/mTOR signaling pathway.

Objective To investigate the mechanism by which indoxyl sulfate(IS)induces pyroptosis in MC3T3-E1 pre-osteoblasts and inhibits osteogenic differentiation through the Caspase-8/GSDME pathway.Methods MC3T3-E1 cells were treated with IS at various concentrations(0,25,50,and 100 μmol/L)for 24,48,and 72 h.Cell proliferative activity was assessed using the CCK-8 assay,and apoptosis was detected by Annexin Ⅴ-FITC/PI flowcytometry.After the optimal concentration and exposure time were selected based on preliminary experiments,the cells were divided into the control group,IS group,and IS combined with the Caspase-8-specific inhibitor Z-IETD-FMK group.Lactate dehydrogenase(LDH)release,Caspase-8/GSDME-related protein expression(Western blot),alkaline phosphatase(ALP)activity,osteogenesis-related protein expression,and calcium nodule formation(ARS staining)were detected in the three groups.Results IS showed dose-dependent cytotoxicity after 48 h of treatment,with the strongest inhibitory effect at 100 μmol/L,significantly reducing cell viability(P<0.01).Western blot analysis showed that IS upregulated the expression of Caspase-8,cleaved Caspase-8,gasdermin E(GSDME),and its cleaved product GSDME-N(all P<0.01),and promoted LDH release(P<0.01).These changes were partially reversed after Z-IETD-FMK intervention(all P<0.05).Regarding osteogenic function,IS significantly inhibited ALP activity on days 3 and 5(both P<0.01),downregulated the mRNA and protein expression levels of osteopontin(OPN),osteocalcin(OCN),and bone sialoprotein(BSP)(P<0.01),and reduced ARS-stained calcium nodule formation(P<0.01).After blockade of the pyroptosis pathway,osteogenesis-related indicators recovered to varying degrees(all P<0.05).Conclusion IS induces pyroptosis in MC3T3-E1 cells by activating the Caspase-8/GSDME pathway,causing cell membrane rupture and functional impairment,thereby inhibiting early and late osteogenic differentiation.This pathway may represent a key molecular mechanism underlying the osteotoxic effects of IS.

Objective To investigate the effects of CTCF on self-renewal and immune escape of liver cancer stem cells through the SALL3/DNMT3A axis.Methods HCCLM3 cells and liver cancer stem cells(LCSCs)were assigned to the HCCLM3 group and LCSC group,respectively.LCSCs transfected with sh-CTCF delivered by tLyP-1-modified extracellular vesicles were defined as the tLyP-1-EV-sh-CTCF-LCSC group.LCSCs treated with the WZB117 inhibitor were defined as the WZB117 inhibitor-LCSC group.Quantitative reverse transcription PCR(qRT-PCR)was used to detect CTCF mRNA expression in the HCCLM3 and LCSC groups,as well as the mRNA expression levels of glycolysis-related markers(HK2 and PFKM)and stemness-related markers(FBP1 and PCK1)in the LCSC,tLyP-1-EV-sh-CTCF-LCSC,and WZB117 inhibitor-LCSC groups.Cell migration and colony formation assays were performed to evaluate the effects of CTCF knockdown and glycolysis inhibition on LCSC stemness.qRT-PCR was further used to assess the effects of CTCF knockdown on SALL3 and DNMT3A expression and the effect of SALL3 overexpression on DNMT3A expression.Results Compared with the untreated control group,cells transfected with tLyP-1-EV-sh-CTCF showed significantly reduced CTCF mRNA and protein expression levels(both P<0.05).Compared with the LCSC group,the tLyP-1-EV-sh-CTCF-LCSC group showed decreased mRNA expression of PFKM and PCK1(both P<0.05),while HK2 and FBP1 showed downward trends without statistical significance(both P>0.05).After WZB117 treatment,the mRNA expression levels of PFKM and PCK1 were also reduced(both P<0.05),whereas HK2 and FBP1 showed decreasing trends without statistical significance(both P>0.05).SALL3 overexpression inhibited PD-L1 expression,promoted MHC-I expression,suppressed LCSC self-renewal,and reduced immune escape-related molecular phenotypes,accompanied by downregulation of glycolysis-related molecules(all P<0.05).Transfection with tLyP-1-EV-sh-CTCF upregulated SALL3 expression and downregulated DNMT3A expression,accompanied by decreased expression of glycolysis-related molecules(all P<0.05).Conclusion CTCF knockdown is associated with downregulation of glycolysis-related markers through modulation of the SALL3/DNMT3A axis,accompanied by attenuated self-renewal and immune escape-related molecular phenotypes in liver cancer stem cells.

Objective To explore the effect of α1-antitrypsin deficiency(AAT)on fetal growth restriction(FGR)induced by pyroptosis of placental trophoblast scorch through NLRP3/caspase-1 pathway.Methods An FGR model was established by inducing HTR-8/SVneo cells with hypoxia/reoxygenation(H/R)in vitro.The cells were divided into the control(Con)group,Con+AAT group,H/R group,H/R+AAT group,and an additional AMPK activator(AICAR)intervention group to validate the underlying pathway.Pyroptosis was detected by flow cytometry,and the expression of related proteins were measured by Western blotting.In vivo,an FGR mouse model was induced by maternal hypoxia(10.5% O₂).The mice were divided into the normal group,FGR group,and FGR+AAT group.The weights of fetuses and placentas were measured,and immunohistochemistry was performed to analyze the expression of AAT,AMP-activated protein kinase(AMPK),and Caspase-1 in placental tissues.Results In vitro,H/R exposure significantly reduced AAT expression,elevated the p-AMPK/AMPK ratio,and increased the protein levels of NLRP3,Caspase-1,and apoptosis-associated speck-like protein containing a CARD(ASC),along with an increased pyroptosis rate.These effects were reversed by AAT supplementation,whereas AICAR blocked the protective effects of AAT.In vivo,FGR mice exhibited reduced fetal and placental weights,decreased placental efficiency,diminished placental AAT expression,elevated p-AMPK/AMPK ratio,and upregulated NLRP3 pathway-related proteins.AAT intervention improved pregnancy outcomes and downregulated the expression of these proteins.Conclusion AAT attenuates hypoxia-induced FGR by inhibiting trophoblast pyroptosis mediated through the AMPK/NLRP3/ASC/Caspase-1 signaling axis,suggesting a potential therapeutic target for FGR.

Objective To investigate the regulatory effect of Lycium barbarum polysaccharide(LBP)on the anabolic and catabolic balance of nucleus pulposus(NP)cells during intervertebral disc degeneration(IVDD),and to elucidate its underlying mechanism.Methods In the in vivo experiment,a rat lumbar IVDD model was established by surgical puncture using SD rats.The rats were randomly divided into sham operation group,model group,and low-,medium-,and high-dose LBP groups.After intervention,morphological changes of intervertebral disc tissues were observed by Safranin O-fast green staining and hematoxylin-eosin(HE)staining.NP cell apoptosis was detected by TUNEL staining.The protein expression levels of anabolic markers(typeⅡcollagen,COL2;aggrecan,ACAN)and catabolic markers(matrix metalloproteinase-13,MMP-13;a disintegrin and metalloproteinase with thrombospondin motifs 5,ADAMTS-5)in NP tissues were detected by Western blotting.In the in vitro experiment,Rat NP cells were isolated and cultured,and an IVDD cell model was established using interleukin-1β(IL-1β).The cells were divided into control group,model group,LBP group,and LBP+PI3K inhibitor group.Cell proliferation and apoptosis were assessed by CCK-8 assay and flow cytometry,respectively.The mRNA levels of anabolic markers(COL2,ACAN)and catabolic markers(MMP-13,ADAMTS-5)were detected by qPCR.The phosphorylation levels of key proteins of the PI3K/Akt/mTOR pathway(p-PI3K,p-Akt,p-mTOR)were measured by Western blotting.Results Compared with the model group,each LBP treatment group(especially the medium-and high-dose groups)exhibited significantly alleviated intervertebral disc degeneration in vivo.Intact NP structure and increased Safranin O-fast green staining intensity were observed in histological staining,indicating reduced proteoglycan loss.A marked decrease in NP cell apoptosis rate was revealed by TUNEL staining.After LBP treatment,the expression of COL2 and ACAN were up-regulated in a dose-dependent manner,while the expression of MMP-13 and ADAMTS-5 were down-regulated(all P<0.05).The viability of IL-1β-induced degenerative NP cells was significantly enhanced and cell apoptosis was effectively inhibited in vitro.The phosphorylation of key proteins of the PI3K/Akt/mTOR pathway(p-PI3K,p-Akt,p-mTOR)was promoted,and a metabolic balance-regulating effect was exhibited by promoting COL2 and ACAN expression and inhibiting MMP-13 and ADAMTS-5 expression.These protective effects of LBP were significantly blocked by the addition of a PI3K inhibitor(all P<0.05).Conclusion LBP effectively delays the progression of intervertebral disc degeneration both in vivo and in vitro.Its mechanism may involve activation of the PI3K/Akt/mTOR signaling pathway,thereby positively regulating the anabolic and catabolic balance of nucleus pulposus cells.

Objective To investigate the effect and underlying mechanism of cryptochrome 2(Cry2)gene overexpression on the proliferation and apoptosis of hepatocellular carcinoma(HCC)cells.Methods The expression levels of Cry2 mRNA and protein in human immortalized hepatocytes(THLE-3)and HCC cell lines(HepG2,HuH-7,SNU-398,and MHCC97-H)were determined using qRT-PCR and Western blot.Cry2 overexpression plasmid(OE-Cry2),c-Myc overexpression plasmid(OE-c-Myc),and their respective negative controls(Vector)were transfected into HuH-7 cells.Cells were treated with either 10 μmol/L proteasome inhibitor(MG132)or 100 μg/mL cycloheximide(CHX).The mRNA expression levels of Cry2 and c-Myc were assessed by qRT-PCR,while Western blot was used to evaluate the protein expression levels of Cry2,c-Myc,and cleaved Caspase-3.Cell proliferation was measured using CCK-8 assay,and the apoptosis rate was determined by flow cytometry.Additionally,the ubiquitination level of the c-Myc protein following Cry2 overexpression was analyzed using an immunoprecipitation(IP)assay.Results Compared with THLE-3 cells,the expression levels of Cry2 mRNA and protein in all HCC cell lines were significantly reduced(all P<0.05).Cry2 overexpression reduced the proliferation rate,induced apoptosis,upregulated cleaved Caspase-3 expression,and promoted ubiquitin-mediated degradation of c-Myc in HuH-7 cells.However,c-Myc overexpression reversed the effects of Cry2 overexpression on both cell proliferation and apoptosis in HuH-7 cells.Conclusion Overexpression of Cry2 may inhibit the proliferation and induce apoptosis of HCC cells.Its mechanism of action may be related to mediating c-Myc ubiquitination and degradation.

Objective To investigate the role of abnormal methylation of the neuronal pentraxin 2(NPTX2)promoter region in cognitive impairment after acute cerebral infarction(ACI),and to analyze its relationship with the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods A rat model of middle cerebral artery occlusion/reperfusion(MCAO/R)was established using a modified suture method.Experimental animals were randomly divided into sham operation group,model group,demethylation intervention group,NPTX2 overexpression group,and NPTX2 overexpression+PI3K inhibitor group.Neurological function was assessed by modified neurological severity score(mNSS).Learning and memory abilities were evaluated by Morris water maze.Methylation status of the NPTX2 promoter region in hippocampal tissue was detected by methylation-specific PCR.The transcription and translation levels of NPTX2 were measured by qPCR and Western blotting,respectively.Neuronal apoptosis was analyzed by TUNEL staining.The phosphorylation level of key proteins of the PI3K/Akt pathway and the expression of apoptosis-related factors Bcl-2,Bax and Caspase-3 were detected by Western blotting.Results Compared with the sham operation group,rats in the model group showed significant cognitive decline and a marked increase in mNSS score.Meanwhile,the positive rate of NPTX2 promoter methylation in the hippocampus was significantly increased,NPTX2 mRNA and protein expressions were suppressed,the p-Akt/Akt ratio was decreased,and the number of apoptotic neurons was increased(all P<0.05).After different drug interventions,rats in the demethylation group and the NPTX2 overexpression group showed improved cognitive function,significantly decreased mNSS score,increased NPTX2 expression,increased p-Akt/Akt ratio,increased Bcl-2 protein expression,and decreased Bax and Caspase-3 protein expressions(all P<0.05).However,combined application of the PI3K inhibitor LY294002 significantly attenuated the neuroprotective effects induced by NPTX2 overexpression.Conclusion After acute cerebral infarction,hypermethylation of the NPTX2 gene promoter in the rat hippocampus leads to inhibition of its expression.This process may promote neuronal apoptosis by downregulation of the PI3K/Akt signaling pathway,thereby exacerbating the progression of cognitive dysfunction.

Objective To investigate the effects of sesamin on learning,memory and neuroinflammation in Alzheimer's disease(AD)rats based on RIP1/RIP3/MLKL pathway.Methods AD rats models were established by injecting amyloid beta 1-42(Aβ1-42)solution.The rats were randomly divided into AD group,low-dose sesamin(sesamin-low,80 mg/kg)group,high-dose sesamin(sesamin-high,160 mg/kg)group,piracetam(500 mg/kg)group,and sesamin-high+rRIP1(8 μg/kg)group.Ten rats injected with normal saline served as the blank group.After intervention,behavioral tests were conducted to evaluate spatial learning and memory abilities in the rats.ELISA was used to detect the levels of Aβ1-42,interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and IL-6.Tissue sections were prepared to examine pathological morphology,neuronal apoptosis,and glial fibrillary acidic protein(GFAP)expression.Western blot was performed to detect the expression of proteins realted to the RIP1/RIP3/MLKL pathway.Results Compared with blank group,AD group showed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,and upregulated expression of RIP1,RIP3,and MLKL,along with reduced platform crossing frequency(all P<0.05).Compared with AD group,sesamin-low group,sesamin-high group,and piracetam group exhibited decreased escape latency,reduced levels of Aβ1-42,IL-1β,TNF-α,and IL-6,decreased neuronal apoptosis,diminished GFAP expression,downregulated expression of RIP1,RIP3,and MLKL,and increased platform crossing frequency(all P<0.05).Compared with sesamin-high group,sesamin-high+rRIP1 group shouwed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,upregulated expression of RIP1,RIP3,and MLKL,and reduced platform crossing frequency(all P<0.05).Conclusion Sesamin alleviates neuroinflammation and improves learning and memory abilities in AD rats by inhibiting the RIP1/RIP3/MLKL pathway.

Objective To evaluate the efficacy of using the disappearance of cricoarytenoid joint mobility as an indicator for guiding the timing of gastroscope insertion during sedated gastroscopy.Methods A total of 60 patients undergoing sedated gastroscopy at Wuhan Fourth Hospital were enrolled,including both genders,aged 18-79 years,with a body mass index(BMI)of 18-30 kg/m²,and American Society of Anesthesiologists(ASA)physical statusⅠ-Ⅲ.Patients were randomly divided into an observation group(n=30)and a control group(n=30)using random number table method.Anesthesia was conducted in both groups with intravenous sufentanil 0.1 μg/kg,followed by intravenous propofol 1-2 mg/kg 2 min later.Insertion indicators were assessed 2 min after the initial loading dose in both groups.In the observation group,gastroscope insertion was performed after disappearance of cricoarytenoid joint mobility.Whereas in the control group,insertion was performed after disappearance of eyelash reflex.Additional propofol(0.5 mg/kg)would be administered if intubating conditions were suboptimal.Intraoperative maintenance was achieved with a propofol infusion at 4-10 mg/(kg·h).The number of patients in optimal intubating conditions was recorded in both groups.Incidences of coughing,body movement,groaning,respiratory depression,and rescue anesthesia during insertion were documented.Intraoperative anesthetic consumption,anesthesia duration,and endoscopic procedure time were recorded.Respiratory depression during the procedure and heart rate(HR)and blood pressure(BP)at four time points were recorded:before anesthesia(T0),after the initial propofol loading dose(T1),at endoscope insertion(T2),and 5 min after insertion(T3).Postoperative adverse reactions were also documented.Results Two minutes after the initial loading dose,24 patients in the observation group exhibited disappearance of cricoarytenoid joint motion,whereas eyelash reflex disappeared in all patients in the control group,with a statistically significant difference between the two groups(P<0.05).During the insertion phase,the control group showed 6 cases of coughing/movement,3 of hiccups,2 of groaning,and 2 of decreased SpO₂;6 patients required a supplemental dose of propofol.No adverse events occurred in the observation group.Statistically significant differences were observed between the two groups in the incidence of coughing,body movement,and the number of patients requiring supplemental anesthesia during the insertion phase(all P<0.05).No significant difference was found between the two groups in anesthetic consumption,anesthesia duration,or procedure time(all P>0.05).HR and BP remained stable in the observation group,whereas the control group showed sinus tachycardia and elevated BP at T2(all P<0.05).No postoperative agitation,delirium,or delayed emergence was observed in either group.Conclusion Disappearance of cricoarytenoid joint mobility is a reliable guiding indicator for gastroscope insertion timing during sedated gastroscopy,and is associated with fewer insertion-related adverse events,including coughing,body movements,and hemodynamic fluctuations.

Objective To evaluate the clinical efficacy of Compound Sophora Decoction enema combined with conventional western medicine for the treatment of radiation enteritis.Methods A retrospective analysis was performed on 95 patients with radiation enteritis treated at the Department of Traditional Chinese Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,between January 2020 and December 2024.Patients were divided into control group(n=47,receiving conventional western medicine:dexamethasone and montmorillonite powder)and treatment group(n=48,receiving conventional treatment plus Compound Sophora Decoction enema once daily for one week).Traditional Chinese medicine(TCM)syndrome scores,serum inflammatory markers,and Karnofsky Performance Status(KPS)scores were compared between the two groups post-treatment.Results The overall symptom remission rate was significantly higher in the treatment group than in the control group(93.75%vs.78.72%,P<0.01).Following the treatment,both groups demonstrated significant improvements in TCM syndrome scores,serum inflammatory markers,and KPS scores(all P<0.05).Furthermore,the treatment group exhibited significantly greater improvements in these parameters compared with the control group(all P<0.05).Conclusion Compound Sophora Decoction enema combined with conventional western medicine significantly alleviates clinical symptoms,reduces systemic inflammation,and improves performance status in patients with radiation enteritis,offering a superior therapeutic outcome compared to conventional western medicine alone.

Objective To explore the characteristics of gut microbiota in patients with early-onset colorectal cancer(EOCRC)and its correlation with circulating inflammatory factor profiles.Methods A total of 326 EOCRC patients admitted to the Second Affiliated Hospital of Hunan University of Chinese Medicine from December 2021 to December 2024 were selected as the observation group,and 300 cases of late-onset colorectal cancer(LOCRC)were enrolled as the control group.The levels of high-mobility group box 1(HMGB1),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were compared between the two groups.Differences in intestinal bacterial counts and and inflammatory factor levels among EOCRC patients with different clinical stages and pathological characteristics(differentiation degree,tumor size,lymphovascular invasion)were analyzed.Pearson correlation analysis was used to examine the correlation between specific gut bacteria and inflammatory cytokines in EOCRC patients.Results Serum levels of HMGB1,IL-6,and TNF-α in the observation group were significantly higher than those in the control group(all P<0.01).The counts of Escherichia coli(E.coli)and Enterococcus faecalis (E.faecalis),as well as the Simpson index,were higher in the observation group,while the counts of Bifidobacterium,Lactobacillus,and Bacteroides,and the Shannon index were lower than those in the control group(all P<0.01).Significant differences in gut microbiota and inflammatory factor levels were observed among EOCRC patients with different clinical stages,differentiation degrees,tumor sizes,and neural/vascular invasion status(all P<0.05).Specifically,EOCRC patients with stage Ⅲ,poor differentiation,tumor diameter >5 cm,and neurovascular invasion exhibited higher counts of E.coli and E.faecalis and higher levels of HMGB1,IL-6,and TNF-α,along with lower counts of Bifidobacterium,Lactobacillus,and Bacteroides(all P<0.05).Pearson correlation analysis showed that E.coli and E.faecalis were positively correlated with serum HMGB1,IL-6,and TNF-α in EOCRC patients,while Bifidobacterium,Lactobacillus,and Bacteroides were negatively correlated with these inflammatory factors(all P<0.01).Conclusion EOCRC patients have significant alterations in gut microbiota structure,and the abundance of specific bacterial is closely related to the spectrum of circulating inflammatory factors.The "microbiota-inflammation" axis is closely related to the clinicopathological characteristics of EOCRC,which can be used as a potential indicator to evaluate the severity of EOCRC and provide a new basis for its individualized treatment.

Objective To explore the high-risk factors of postpartum urinary retention in primiparas and evaluate the efficacy of low-frequency pulsed electrical stimulation combined with WAFF exercise for this condition.Methods A total of 160 primiparous women with postpartum urinary retention who were admitted to the First Hospital of Hebei Medical University,Baoding Maternal and Child Health Hospital,and Shijiazhuang Huayao Hospital,North China Medical and Health Group from March 2022 to June 2025 were selected as the research subjects and assigned to the postpartum urinary retention group(n=160).Meanwhile,160 primiparas without postpartum urinary retention during the same period were randomly selected at a 1∶1 ratio and assigned to the non-urinary retention group(n=160).Additionally,the primiparas in the urinary retention group were divided into the control group(n=80)and the observation group(n=80)according to different treatment methods.The clinical data of all patients were recorded,and the influencing factors were analyzed using the Logistic regression model.A nomogram prediction model was constructed based on the characteristic variables and evaluated.The clinical efficacy,clinical indicators,urodynamics,and pelvic floor function were compared between the two groups of primiparas with urinary retention.Results The multivariate analysis results showed that neonatal weight(OR=5.834),second stage of labor duration(OR=1.143),forceps-assisted delivery(OR=3.744),oxytocin use(OR=2.489),and episiotomy(OR=2.102)were independent risk factors for postpartum urinary retention in primiparas(all P<0.05).A nomogram model was constructed based on the results of Logistic regression analysis,with an area under the curve(AUC)of 0.863(95%CI:0.824—0.903).The calibration curve suggested that the model had good predictive performance.After treatment,the total effective rate of the observation group was significantly higher than that of the control group(95.00% vs.78.75%,P<0.01).The first voiding time,first voided volume,and post-void residual urine volume in the observation group were significantly better than those in the control group(all P<0.01).The maximum urinary flow rate,maximum urethral closure pressure,and detrusor pressure in the observation group were significantly higher than those in the control group(all P<0.01).Additionally,the vaginal systolic pressure,resting pressure,and systolic duration in the observation group were significantly higher than those in the control group(all P<0.01).Conclusion Neonatal macrosomia(excessive birth weight),prolonged second stage of labor,forceps-assisted delivery,oxytocin use,and episiotomy are independent risk factors for postpartum urinary retention in primiparas.The nomogram model constructed based on these factors has good predictive value.Low-frequency pulsed electrical stimulation combined with WAFF exercise can effectively alleviate the symptoms of postpartum urinary retention in primiparas,promote the recovery of bladder function and pelvic floor muscle function.As a safe and effective intervention method,it is worthy of clinical promotion and application.

With the aging population and the increasing prevalence of fracture-related diseases,timely and accurate diagnosis of spinal fractures has become increasingly important.Although traditional imaging modalities,including X-ray,computed tomography(CT),and magnetic resonance imaging(MRI),remain the gold standards for diagnosis,they are challenged by complex spinal anatomy and the similarity between adjacent vertebrae,which frequently lead to a certain proportion of missed diagnoses.In recent years,deep learning has demonstrated substantial potential in medical imaging,particularly in the diagnosis of spinal fractures,where it has improved detection rates and diagnostic accuracy.This review summarizes recent advances in deep learning-based imaging diagnosis of spinal fractures,covering key applications such as automated detection,image segmentation,fracture classification,and preoperative planning.In addition,current challenges are discussed,including issues related to data quality,limited model interpretability,barriers to clinical translation,and technical limitations.To facilitate the clinical implementation of artificial intelligence technologies,future research directions are proposed,including innovative technologies such as few-shot learning,federated learning,and multimodal data fusion.Ultimately,the continued advancement of deep learning techniques is expected to enhance personalized and precise diagnostic capabilities as well as prognostic management for patients with spinal fractures.

Myasthenia gravis(MG)is an autoimmune disorder mediated by autoantibodies that primarily affect the postsynaptic membrane of the neuromuscular junction,with the core clinical features being fluctuating weakness and easy fatigability of skeletal muscles.Among these,fluctuating ptosis and diplopia often present as the initial symptoms.Objective,accurate,and quantitative assessment of extraocular muscle function is of critical significance in the diagnosis establishment,disease monitoring,treatment efficacy evaluation,and prognosis prediction of ocular myasthenia gravis.Traditional clinical assessment methods largely rely on subjective judgment and suffer from insufficient sensitivity.In recent years,with the rapid advancement of digital technology,imaging modalities,and artificial intelligence,substantial progress has been achieved in the quantitative evaluation of extraocular muscle function.This article systematically reviews the current technological advances in quantitative assessment of extraocular muscles in MG patients,compares and analyzes the advantages and limitations of various methods,and provides perspectives on future directions in this field.

The treatment of chronic arthritic pain has long been confronted with clinical challenges,such as insufficient efficacy of traditional analgesic drugs and significant adverse reactions.As a non-destructive neuromodulation technique,pulsed radiofrequency(PRF)shows unique potential by targeting the transient receptor potential(TRP)channel family(TRPV1,TRPA1,and TRPM3).This review systematically explores the interaction mechanism between PRF and TRP channels in arthritic pain:As a key hub for pain perception,TRP channels are continuously activated in the arthritic microenvironment(characterized by acidification,oxidative stress,and inflammatory factors),which promotes the progression from peripheral sensitization to central sensitization.PRF regulates the function of TRP via non-thermal biological effects,including modulating neuronal membrane potential and calcium oscillation,improving mitochondrial function and neuroglial interaction,as well as regulating endogenous opioid peptide and γ-aminobutyric acid(GABA)systems to inhibit the activity of the TRP channel family.This study establishes the regulatory axis of "PRF-TRP-arthritic pain",proposes that TRP expression profiles can serve as predictive biomarkers for PRF efficacy,and elucidates the TRP-dependent mechanisms underlying differential responses to PRF among various arthritis subtypes.This article constructs a "PRF-TRP-arthritic pain" regulatory axis,proposes that the TRP expression profile may serve as a predictive marker for PRF efficacy,and elaborates on the TRP-dependent mechanism underlying the differential PRF responses among different arthritis subtypes.PRF has evolved from a simple analgesic tool to a regulator of neural plasticity.By integrating neuro-immune-ion channel functions through TRP channels,PRF promotes the transformation of arthritis treatment from an anti-inflammatory model to neural homeostasis reconstruction,thereby providing a new approach for chronic pain management.

As a prevalent malignant neoplasm among the elderly,colorectal cancer(CRC)poses a severe threat to public health.Many elderly CRC patients are intolerant to the side effects of chemoradiotherapy,anesthetic hazards and postoperative rehabilitation complications,underscoring the urgent clinical need for well-tolerated and gentle treatment options.Given the close pathophysiological correlation between gut microbiota and colorectal cancer,this paper reviews existing literature to systematically elaborate the mechanisms whereby distinct gut microbial species mediate CRC initiation and progression.Current evidence indicates that targeted gut microbiota modulation can serve as an interventional strategy against CRC.Such interventions include stabilizing the abundance and homeostasis of beneficial intestinal bacteria while suppressing the pathogenic damage induced by harmful strains,as well as sustaining physiological equilibrium of the gut microbiome to preserve its regular secretory function and production of health-promoting metabolites for intestinal protection.These findings suggest that harnessing the physiological properties of gut microbiota may facilitate the development of a gentle anti-cancer therapy tailored specifically for elderly patients with colorectal cancer.

The protein encoded by Coronin 1B(CORO1B)gene is an actin-binding protein,the serine-2 residue of which can be phosphorylated by protein kinase C(PKC)to regulate the polymerization and depolymerization of actin,thereby participating in many important pathological and physiological processes,like cytoskeletal reorganization,cell motility,migration,and metastasis.Numerous studies have also found that the CORO1B gene is associated with the occurrence and development of various types of tumors.This article reviews the research progress on the relationship between the CORO1B gene and tumors.

Brain metastases are a common and clinically challenging manifestation of solid tumors and are generally associated with poor prognosis and limited systemic treatment options.Effective intracranial drug delivery remains difficult because of the blood-brain barrier,the blood-tumor barrier,and the distinct immune microenvironment of brain metastases.Antibody-drug conjugates(ADCs),consisting of a monoclonal antibody,a chemical linker,and a cytotoxic payload,have shown substantial clinical value in multiple solid tumors.Accumulating evidence of intracranial activity in patients with brain metastases from breast cancer,lung cancer,and other solid tumors suggests that ADCs may provide new opportunities for systemic treatment in this setting.This review summarizes the potential mechanisms of action,clinical evidence,safety considerations,and future research directions of ADCs for brain metastases from solid tumors,aiming to inform optimization of therapeutic strategies for this patient population.