BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective To investigate the clinical diagnostic value of plasma RAS association domain family 1A(RASSF1A)gene methylation combined with tumor marker detection in non-small cell lung cancer(NSCLC).Methods A total of 98 NSCLC patients admitted to Qinhuangdao First Hospital from June 2023 to March 2024 were selected as the NSCLC group,and 95 patients who under-went pulmonary examinations during the same period but were not diagnosed with NSCLC were selected as the disease control group.Their general clinical data were collected.The correlations among plasma RASSF1A gene methylation,tumor markers,and clinicopatho-logical features were analyzed.The effects of RASSF1A gene methylation and tumor markers on the diagnosis of NSCLC were analyzed by the multivariate Logistic regression.A predictive model was constructed,and its effectiveness was evaluated by the receiver operating characteristics(ROC)curve and goodness of fit test.Results There were significant differences(P＜0.05)in smoking history,neu-ron specific enolase(NSE),carcinoembryonic antigen(CEA),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and RASSF1A methylation levels between the NSCLC group and non-NSCLC group.There were also significant differences(P＜0.05)in RASSF1A methylation levels,NSE,CEA,and CYFR21-1 levels among NSCLC patients with different clinical characteristics such as tumor diam-eter,differentiation degree,and growth type.The results of multivariate Logistic analysis showed that RASSF1A methylation levels(OR=1.071,95％CI:1.042-1.100),NSE(OR=1.168,95％CI:1.132-1.204),CEA(OR=1.154,95％CI:1.121-1.187),and CYFR21-1(OR=1.089,95％CI:1.023-1.195)were all independent risk factors for the diagnosis of NSCLC.A model predicting the occurrence of NSCLC was constructed using the principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),and the ROC curve analysis results showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the prediction model for the RASSF1A methylation level combined with NSE,CEA,and CYFR21-1 were 0.922(95％CI:0.896-0.948),0.897,and 0.851,respectively,which were higher than those of the RASSF1A methylation level,NSE,CEA,and CYFR21-1 alone.Conclusion The prediction model of plasma RASSF1A gene methylation level combined with tumor markers has high diagnostic value for NSCLC and can be used for the clinical diagnosis of NSCLC.

Objective:To conduct a scoping review of the related research on the maternal-fetal attachment in pregnant women after assisted reproductive technology (ART), summarize the research status of maternal-fetal attachment, and provide reference for future research prospects.Methods:A search was conducted for studies published in PubMed, Embase, EBSCO, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese Medical Journal Full-text Database, from the date of database construction to January 24, 2024. The results of the literature were screened, extracted, and summarized.Results:A total of 15 studies were included. Among them, 14 observational studies reported that the overall status of maternal-fetal attachment of ART pregnant women was in good condition, but the data sources of domestic research were insufficient. Three evaluation tools were used in 15 articles. The related factors were summarized as demographic factors (age and personality traits), pregnancy-related factors (such as conception method, gestational age, history of infertility, history of miscarriage, etc), and psychosocial factors (such as anxiety, depression, conflicts, attitudes towards childbirth, acceptance of pregnancy, social support, marital satisfaction, etc). Four studies put forward suggestions or conducted intervention studies on improving maternal-fetal attachment of ART pregnant women.Conclusions:There is a lack of attention to the maternal-fetal attachment of ART pregnant women in China. Due to the complexity and diversity of its influencing factors, we should deeply explore the characteristics of maternal-fetal attachment development of ART pregnant women at all stages of pregnancy, and carry out more high-quality research. At the same time, we should pay attention to and carry out early screening of maternal-fetal attachment disorders, formulate targeted interventions, so as to promote the establishment of high-quality maternal-fetal attachment, and lay a solid foundation for future maternal-infant relationships.

Objective:To retrieve, screen, evaluate and integrate the relevant evidence of nursing management for patent foramen ovale detected by contrast transesophageal echocardiography (cTEE) to provide a basis for clinical practice.Methods:A systematic search was conducted in relevant Chinese and English databases, guideline websites, and professional association websites such as China National Knowledge Infrastructure, Wanfang database, PubMed, and MedLink, etc. Relevant literatures on the detection of patent foramen ovale by cTEE were included, including guidelines, expert conconsensus, clinical decisions, evidence summaries, and systematic reviews. The search period was from the establishment of the database to July 31, 2024. Two evidence-based nursing researchers evaluated the quality of the literature and extracted relevant evidence in combination with clinical situations.Results:A total of 15 literatures were included. Among them, there were 3 guidelines, 6 expert consensuses, 3 clinical decisions, 2 quasi-experiments, and 1 systematic review. Thirty pieces of evidence were summarized from five aspects: assessment, education and publicity, preparation before examination, detection during examination, care after examination.Conclusions:The best evidence for the nursing management of patent foramen ovale detected by cTEE is of high quality and strong authority, which can provide evidence-based basis for standardizing clinical practice and accurately and efficiently detecting patent foramen ovale.

Objective To explore the association of the TSLP gene polymorphisms at rs3806932,rs11466741 and rs2289278 loci with childhood asthma and serum TSLP levels,and to analyze the effects of gene-environment interactions on asthma risk in children.Methods A total of 145 children with asthma and 108 healthy controls were included.Genotyping was performed using KASP and MassARRAY SNP technologies,and serum TSLP levels were measured by ELISA.Differences in allele and genotype frequencies between the two groups were analyzed,along with the impact of genetic models on asthma risk.Differences in serum TSLP levels across groups were compared.Linkage disequilibrium and haplotype analysis were performed using Haploview 4.2,and GMDR 0.9 software was used to assess gene-environment interactions.Results No significant differences were found in the allele and genotype frequencies of the three TSLP gene loci between the two groups(P＞0.05).Under the co-dominant model,children with the AG genotype at the rs3806932 locus had 1.750 times the risk of developing asthma compared to those with the AA genotype(95％CI:1.018-3.010,P=0.043).Under co-dominant and overdominant models,children with the CT genotype at the rs11466741 locus had 1.705 times the asthma risk compared to those with the CC genotype(95％CI:1.006-2.891,P=0.048),and 1.698 times the risk compared to those with the CC-TT genotype(95％CI:1.019-2.827,P=0.041).Serum TSLP levels were significantly higher in asthma patients with the CT genotype than those with the CC genotype at the rs11466741 locus(P=0.032).Serum TSLP levels were higher in the asthma group with allergic rhinitis(AR)compared to the group without AR(P＜0.01).No significant differences were observed in the distribution of haplotypes frequencies(AC,GT,GC)between the two groups(P＞0.05).GMDR analysis showed that the highest asthma risk was observed in children with heterozygous genotypes(CT,AG)at both rs11466741 and rs2289278,or those with the CT genotype at rs11466741,a history of passive smoking,and a cesarean section delivery(P＜0.05).Conclusion Polymorphisms in the TSLP gene at rs3806932 and rs11466741 are associated with an increased risk of childhood asthma.Variants at the rs11466741 locus affect serum TSLP levels in children with asthma.Asthma combined with AR leads to elevation of serum TSLP levels.The interaction between rs11466741 and rs2289278,along with environmental factors(passive smoking and cesarean section),contributes to the increase of asthma risk in children.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

OBJECTIVE To explore the clinical value of metagenomic next generation sequencing(mNGS)in detec-tion of pathogens from the patients with pulmonary infection.METHODS The clinical data were collected from 103 patients with pulmonary infection who were treated in respiratory and critical care medicine department of Gansu Province People's Hospital from Jun.2021 to Jun.2023.The pathogens were detected from all of the patients with the use of mNGS for bronchoalveolar lavage fluid(BALF)and traditional cultures(including sputum culture and BALF culture).The positive rates,consistency,distribution,efficacy and curative effects were observed and sys-tematically compared between the two detection methods.RESULTS Totally 122 strains of bacteria,47 strains of fungi,94 strains of viruses,3 strains of Mycoplasma and 2 strains of Chlamydia were detected from the 103 pa-tients by mNGS,as compared with only 45 strains of bacteria and 20 strains of fungi that were detected by the tra-ditional culture method.The positive rate of detection of pathogens was 89.32％by mNGS,higher than 38.83％of the traditional culture method(P＜0.001).There was certain difference in the distribution of pathogens be-tween the two detection method,the two detection method showed the poor consistency of detection efficacy,and the effect of targeted drug therapy based on the mNGS-detected pathogens was higher than that of the mNGS-negative empirical therapy(P＜0.001).In addition,some of drug resistance genes could be detected by mNGS.CONCLUSIONS The mNGS shows remarkable higher efficacy in detection of the pathogens causing pul-monary infections than the traditional culture method and can detect various types of pathogens.The effect of the targeted drug therapy based on the pathogens detected by mNGS is remarkable.It plays an imorptant role in guid-ing the clinical diagnosis and treatment of the patients with pulmonary infections.

Objective:To investigate the difference between routine pulmonary ventilation function test (PFT) and impulse oscillometry (IOS) in children with bronchial asthma (BA) control and children without BA control.Methods:A total of 165 BA children admitted to the Shenzhen Longhua District People′s Hospital from January to December 2023 were selected. 73 children with asthma control test score ≥23 were selected as the control group, and 92 children with asthma control test score <23 were selected as the control group. The difference of indexes between the two groups were statistically compared in terms of PFT [forced expiratory volume in one second (FEV 1), ratio of FEV 1 to forced vital capacity (FVC) (FEV 1/FVC), instantaneous forced expiratory flow at 50% of forced vital capacity (FEF 50), instantaneous forced expiratory flow at 75% of forced vital capacity (FEF 75), maximum mid expiratory flow (MMEF), peak expiratory flow (PEF)], and IOS metrics [respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), difference between R5 and R20 (R5-R20), reactance at 5 Hz (X5), total respiratory impedance at 5 Hz (Z5), resonance frequency (Fres), reactance area (AX)]. The predictive value of PFT and IOS indexes to BA was analyzed. Results:The levels of FEV 1, FEV 1/FVC, FEF 50, FEF 75, PEF and MMEF in PFT index of the control group were significantly higher than those in the non-control group, and the levels of Z5, R5, R20, R5-R20, X5, AX and Fres in IOS index were significantly lower than those in the non-control group. There was statistical significance between the two groups (all P<0.05). The area under the curve (AUC) predicted by PFT indexes was less than 0.7, and the AUC of FEF 50 and MMEF (all 0.633) was the largest. Among the IOS indexes, Z5, R5, R5-R20, X5, AX and Fres predicted the AUC of BA uncontrolled to be >0.7, while AX had the largest predictive value for BA uncontrolled (AUC=0.786, 95% CI: 0.736-0.836), sensitivity was 78.26%, specificity was 64.13%. Conclusions:All indexes of PFT and IOS have good sensitivity in evaluating the degree of BA control in children, and IOS has better clinical value in predicting uncontrolled BA, among which AX has the greatest predictive value for uncontrolled BA.

Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P＜0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P＜0.001),lymph node metastasis(P=0.015),and T staging(P＜0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95％CI:2.73-9.02);HR=2.33(95％CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.