ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

In this work,a tetrahedral DNA nanostructure(TDN)functionalized rotational paper-based analytical device(RPAD)was constructed for rapid and highly sensitive detection of aflatoxin B1(AFB1)using exonucleaseⅠ(ExoⅠ)and G-quadruplex(G4)dimer.Herein,a single-stranded DNA,containing both of the G4 dimer sequence and AFB1 recognition sequence,was used as the recognition probe(G4 dimer probe).TDN was used to precisely regulate the orientation and distribution density of G4 dimer probe to improve the recognition efficiency of the system.ExoⅠas a single stranded DNA specific nuclease was introduced for effective amplification of the detection signal.G4 dimer was employed to enhance the fluorescence signal of thioflavin T(ThT).In the absence of AFB1,the G4 dimer structure of G4 dimer probe could specifically bind with ThT to generate dramatic fluorescence enhancement.However,in the presence of AFB1,AFB1 could specifically bind with G4 dimer probe,resulting in the dissociation of G4 dimer probe from TDN and further be digested by ExoⅠ.At the same time,the released AFB1 could bind to G4 dimer probe on the TDN again by this way to generate signal amplification.After this cycle,the amount of aptamer on the TDN was decreased,accompanied by the reduction of G4 dimer on TDN.In this case,the fluorescence intensity of the system was reduced.The designed RPAD showed a good linear response in AFB1 concentration range of 0.0001-500 ng/mL and the limit of detection was 0.1 pg/mL.Moreover,the proposed strategy was successfully applied to detection of AFB1 in peanut and wine.The developed TDN/G4 dimer/ExoⅠstrategy improved the specificity and sensitivity of the system significantly.

Objective:To explore the relationship between psychological resilience,professional identity and employment pressure of nursing students with different educational levels,and analyze its influencing factors.Methods:A total of 208 nursing students with different educational levels were investigated by using the general information questionnaire,the employment pressure questionnaire of nursing students,the psychological resilience scale and the professional identity questionnaire.The correlation among psychological resilience,professional identity and employment stress was analyzed by Pearson correlation analysis.Results:The total score of professional identity,psychological resilience,and employment stress was(54.46±12.34),(57.62±18.66),and(98.30±20.25),respectively.There was no significant difference in professional identity score and psychological resilience score among nursing students with different educational levels(P＞0.05).There was no significant difference in the employment stress scores between nursing students upgrading from a junior college and undergraduate and junior college nursing students(P＞0.05),while the employment stress score of junior college nursing students were significantly higher than that of undergraduate nursing students(P＜0.05).Pearson correlation analysis showed that the total score of employment stress was positively correlated with the total score of psychological resilience(r=0.252),and the total score of professional identity(r=0.312)(P＜0.01).Conclusions:The psychological resilience of nursing students is at the average level,professional identity is low,and the employment pressure of junior college nursing students is higher than that of undergraduates.Targeted interventions should be developed to improve the psychological resilience and professional identity of nursing students,and reduce the employment pressure level of junior college nursing students.

Disharmony between nutritive qi(ying)and defensive qi(wei)is the core pathogenesis of insomnia.The normal function of ying-wei in the generation,dispersion,divergence and aggregation is the precondition for the realization of the coordination between ying and wei.The disordered function of ying-wei in the generation,dispersion,divergence and aggregation will cause the disharmony between ying and wei,and then the insomnia occurs.For the treatment of insomnia caused by the disordered function of ying-wei in the generation,Guizhi Decoction associated prescriptions are used for strengthening middle energizer and nourishing ying and wei.For the treatment of insomnia caused by the disordered function of ying-wei in the dispersion,Mahuang Decoction associated prescriptions are used to relieve the exterior and eliminate the pathogen for insomnia patients with the manifestations of the attack of exopathogens,and Xiao Chaihu Decoction associated prescriptions are used to dredge the triple energizer for insomnia patients with the dysfunction of the triple energizer.For the treatment of insomnia caused by the disordered function of ying-wei in the divergence,Rhei Radix et Rhizoma associated bitter-cold prescriptions are used to purge the interior heat for insomnia patients with abundant interior heat syndrome,Gypsum Fibrosum associated pungent-cold prescriptions are used to release muscles and clear heat for insomnia patients with the interior heat complicated by exterior syndrome,Natrii Sulfas Exsiccatus associated salty-cold prescriptions are used to clear heat,moisten dryness and dissipate the masses for insomnia patients with interior heat complicated by dryness syndrome,sour-cold medicines are used to clear heat and remove retained water,supplement deficiency and relieve exterior for insomnia patients with interior heat complicated by water-retention syndrome,deficiency syndrome and exterior syndrome,and Ophiopogonis Radix associated prescriptions and Lillli Bulbus associated prescriptions are used to clear heat and nourish ying for insomnia patients with the consumption of ying and yin.For the treatment of insomnia caused by the disordered function of ying-wei in the aggregation,the compatibility of Poria and Cinnamomi Ramulus is used for warming yang and resolving fluid retention in patients with fluid retention,Taohong Siwu Decoction associated prescriptions are used to activate blood and remove stasis in patients with predominance of blood stasis syndrome,the compatibility of Poria and Paeoniae Radix Alba are used to treat retained water and blood stasis in patients with water-blood co-morbidity.Treating insomnia caused by disharmony between ying and wei from the perspective of the function of ying-wei in the generation,dispersion,divergence and aggregation is aimed at the core pathogenesis of insomnia,which makes the treatment easy to be carried out,and can provide reference for clinical differentiation and treatment of insomnia.

Objective To explore the role of sulodexide(SDX)in neointimal hyperplasia of arteriovenous fistulas(AVFs)in chronic kidney disease(CKD)rats and its possible mechanism.Methods A total of 18 male rats(weighing 300±50 g)were randomly and equally divided into AVF group,CKD+AVF group(CKD induction followed by AVF surgery and then gavaged with normal saline for 2 months),and CKD+AVF+SDX group[treated as in the CKD+AVF group but with 8 mg/(kg·d)SDX gavage].HE staining was used to observe the degree of neointimal hyperplasia.The expression of Hippo pathway related molecules,Yes-associated protein(YAP),pYAP and connective tissue growth factor(CTGF,YAP downstream target protein,one of mesenchymal marker)was detected by immunofluorescence assay.After human umbilical vein cell fusion EAHy926 cells were treated with 0,2.5,5,10,20 or 40 μg/mL SDX for 24 h,and with 2.5 μg/mL SDXfor24,48 or 72 h,respectively,CCK-8 assay was used to measure cell survival rate.Moreover,the serum sample from CKD rat was used to treat EAHy926 cells,and then the cells were treated with SDX or YAP inhibitor verteporfin.The expression levels of YAP,pYAP,CTGF and endothelial cell marker CD31 were detected by Western blotting.Results HE staining and immunofluorescence assay showed that CKD rats had serious neointimal hyperplasia in AVFs(P＜0.05),and slightly lower expression of pYAP and enhanced expression of CTGF(P＜0.05)when compared with the rats of the AVF group.While,SDX treatment alleviated the neointimal hyperplasia of AVFs,enhanced the expression of pYAP and reduced the expression of CTGF(P＜0.05).CCK-8 assay showed that cell survival rate was decreased significantly in a dose-and time-dependent manner after SDX treatment(P＜0.05).Western blotting revealed that SDX increased the expression of pYAP and CD31 while inhibited the expression of CTGF in EAHy926 cells(P＜0.05),which was consistent with the effect of verteporfin treatment.Conclusion SDX can block YAP activation caused by CKD and attenuate neointimal hyperplasia in AVFs.

Objective To explore the clinical value of anti-Müllerian hormone(AMH)to optimize endocrine therapy for peri-menopausal early breast cancer.Methods Two hundred and four patients of pre-menopausal breast cancer aged 45-55 years old between 2020 and 2023 were enrolled,and AMH≤0.1 ng/mL was considered as cut-off value for menopause.Switching from selective estrogen receptor modulator(SERM)to aromatase inhibitor aromatase inhibitor(AI)and initial endocrine therapy regimens were based on AMH,follicle-stimulating hormone(FSH)and estradiol(E2).Results Pre-chemotherapy AMH level was significantly negatively correlated with FSH level(P<0.001).Among 100 cases who were amenorrhea for one year during SERM treatment,42 cases did not have AMH testing.Fourteen out of the 42 cases switched to AI within one year,and ovarian function recovery(OFR)occurred in 2 cases after AI switching.Fifteen cases with AMH>0.1 ng/mL did not switch to AI within one year.Forty among 43 cases with AMH≤0.1 ng/mL switched to AI,after a significantly shorter median SERM treatment duration(3.15 months vs.8.14 months,P<0.001)and a significantly lower OFR rate(0 vs.12.5%,P=0.023)compared with those who did not test AMH but switched to AI.AMH≤0.1 ng/mL was an independent risk factor of transition to menopause shortly in peri-menopausal patients(OR=35.857,P<0.001).Among 104 cases with AMH tested before adjuvant chemotherapy,69 cases had AMH>0.1 ng/mL.Thirty-one out of the 69 cases were treated with ovarian function suppression(OFS)initially and 38 with SERM initially.Thirty-five cases with AMH≤0.1 ng/mL were all treated with SERM initially,with a higher rate of switching to AI(71.4%vs.23.7%,P<0.001)and a shorter SERM treatment duration(6.52 months vs.13.56 months,P=0.016)compared with the 38 cases(AMH>0.1 ng/mL)treated initially with SERM.After a median 30-month follow-up,no recurrence was observed in these thirty-five cases treated with SERM initially and AMH≤0.1 ng/mL,just like in OFS group.And they had a tendency of improved survival outcome compared with those treated with SERM initially and AMH>0.1 ng/mL(Log Rank P=0.076).Conclusion AMH could evaluate and predict menopause accurately,resulting in optimizing endocrine therapy for peri-menopausal patients effectively and safely.