Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Zika virus(ZIKV)is a mosquito-borne flavivirus associated with neurological complications such as Limbari syndrome in adults and microcephaly in newborns.As there are no drugs or preventive vaccines available to specifically treat ZIKV infection,there is an urgent need to take comprehensive measures to prevent and control ZIKV infection and stop its spread.In this paper,we reviewed the structure and function of ZIKV gene and protein,and summarized the progress in the development of virus-targeting anti-ZIKV drug candidates through high-throughput screening and drug relocation,and summarized the mechanism of action of virus and host cell targeting drug candidates.The research and development trend of small molecule antiviral drugs in the future is prospected,which provides reference for promoting the research and development of new anti-ZIKV drugs.

Objective To investigate the levels and clinical significance of serum secreted frizzled related protein 5(SFRP5),soluble cell adhesion molecule-1(sICAM-1),and Fetuin-B in patients with type 2 diabetes mellitus(T2DM)complicated with metabolic syndrome(MS).Methods A total of 142 T2DM patients ad-mitted in the Jiamusi Hospital of Infectious Diseases from April 2021 to April 2023 were selected as the study subjects.T2DM patients were grouped into MS group(n=75)and non MS group(n=67)based on whether they had MS.Enzyme linked immunosorbent assay(ELISA)was applied to determine the expression levels of serum SFRP5,sICAM-1,and Fetuin-B.Logistic regression was applied to analyze and determine the influen-cing factors of complicated MS in T2DM patients.The diagnostic efficacy of SFRP5,sICAM-1,and Fetuin-B in T2DM patients with MS was analyzed by establishing receiver operating characteristic(ROC)curve.Results There were statistically significant differences in HDL-C and HOMA-IR between the MS group and the non MS group(P＜0.05).Compared with the non MS group,the serum SFRP5 level in the MS group de-creased(P＜0.05),while the sICAM-1 and Fetuin-B levels increased(P＜0.05).Logistic regression analysis showed that SFRP5 and HDL-C were protective factors for the development of MS in T2DM patients(P＜0.05),while sICAM-1,Fetuin-B,and HOMA-IR were risk factors for the development of MS in T2DM pa-tients(P＜0.05).The combination of serum SFRP5,sICAM-1 and Fetuin-B had the largest area under the curve in diagnosing MS in T2DM patients,and its evaluation efficacy was obviously better than that of the in-dividual diagnosis of serum SFRP5,sICAM-1,and Fetuin-B(Zcombination-SFRP5=2.466,P=0.014,Zcombination-SICAM-1=3.550,P＜0.001,Zcombination-Fetuin-B=3.697,P＜0.001).Conclusion The serum SFRP5 level in patients with T2DM complicated with MS decreases,while sICAM-1 and Fetuin-B levels increase.The combination of the three has a good effect in diagnosing complicated MS in T2DM patients.

OBJECTIVE: To compare the biomechanical properties of personalized Y-shaped plates with horizontal plates, vertical plates, and traditional Y-shaped plates in the treatment of distal humeral intra-articular fractures through finite element analysis, and to evaluate their potential for clinical application. METHODS: The study selected a 38-year-old male volunteer and obtained a three-dimensional model of the humerus by scanning his upper limbs using a 64-slice spiral CT. Four types of fracture-internal fixation models were constructed using Mimics 19.0, Geomagic Wrap 2017, Creo 6.0, and other software: horizontal plates, vertical plates, traditional Y-shaped plate, and personalized Y-shaped plate. The models were then meshed using Hypermesh 14.0 software, and material properties and boundary conditions were defined in Abaqus 6.14 software. AnyBody 7.3 software was used to simulate elbow flexion and extension movements, calculate muscle strength, joint forces, and load torques, and compare the peak stress and maximum displacement of the four fixation methods at different motion angles (10°, 30°, 50°, 70°, 90°, 110°, 130°, 150°) during elbow flexion and extension. RESULTS: Under dynamic loading during elbow flexion and extension, the personalized Y-shaped plate exhibits significant biomechanical advantages. During elbow flexion, the peak internal fixation stress of the personalized Y-shaped plate was (28.8±0.9) MPa, which was significantly lower than that of the horizontal plates, vertical plates, and traditional Y-shaped plate ( P<0.05). During elbow extension, the peak internal fixation stress of the personalized Y-shaped plate was (18.1±1.6) MPa, which was lower than those of the other three models, with significant differences when compared with horizontal plates and vertical plates ( P<0.05). Regarding the peak humeral stress, the personalized Y-shaped plate model showed mean values of (10.9±0.8) and (13.1±1.4) MPa during elbow flexion and extension, respectively, which were significantly lower than those of the other three models ( P<0.05). Displacement analysis showed that the maximum displacement of the humerus with the personalized Y-shaped plate during elbow flexion was (2.03±0.08) mm, slightly higher than that of the horizontal plates, but significantly lower than that of the vertical plates, showing significant differences ( P<0.05). During elbow extension, the maximum displacement of the humerus with the personalized Y-shaped plate was (1.93±0.13) mm, which was lower than that of the other three models, with significant differences when compared with vertical plates and traditional Y-shaped plates ( P<0.05). Stress contour analysis showed that the stress of the personalized Y-shaped plate was primarily concentrated at the bifurcation of the Y-shaped structure. Displacement contour analysis showed that the personalized Y-shaped plate effectively controlled the displacement of the distal humerus during both flexion and extension, demonstrating excellent stability. CONCLUSION The personalized Y-shaped plate demonstrates excellent biomechanical performance in the treatment of distal humeral intra-articular fractures, with lower stress and displacement, providing more stable fixation effects.
Humans ; Male ; Adult ; Healthy Volunteers ; Finite Element Analysis ; Tomography, Spiral Computed ; Models, Anatomic ; Biomechanical Phenomena ; Humeral Fractures, Distal/surgery* ; Fracture Fixation, Internal/instrumentation* ; Bone Plates ; Computer Simulation ; Precision Medicine/methods* ; Elbow Joint/surgery* ; Elbow/surgery* ; Humerus/surgery* ; Torque ; Stress, Mechanical ; Intra-Articular Fractures/surgery* ; Prosthesis Design/methods* ; Imaging, Three-Dimensional ; Range of Motion, Articular

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To observe the value of machine learning(ML)models based on brain functional network features combining clinical indicators for predicting postoperative outcomes of patients with drug-resistant mesial temporal lobe epilepsy(DR-mTLE).Methods Totally 84 patients with unilateral DR-mTLE who underwent surgery were retrospectively enrolled and classified into seizure free(SF)group(n=55)and non-seizure free(NSF)group(n=29)according to one-year postoperative follow-up.Clinical data were analyzed to screen independent predictors of postoperative outcomes.Based on brain preoperative resting-state functional MRI,brain functional networks were constructed using graph theory analysis,and 587 features were extracted.Five-fold cross validation was used to divide the data into training set and test set,then the optimal brain functional network features related to postoperative outcomes of DR-mTLE patients were selected.Combining with clinically relevant independent predictors,ML models were constructed using classifiers including Gaussian process(GP),logistic regression(LR),support vector machine(SVM)and quadratic discriminant analysis(QDA),respectively,and the prediction efficacy,calibration and clinical value of each ML model were evaluated.Results Both course of disease and lesion location were clinically relevant independent predictors of postoperative outcome of DR-mTLE patients(OR=0.928,5.710,P=0.010,0.016).Four optimal brain function network features were selected,including betweenness centrality of the third zone of cerebellar vermis,degree centrality of right globus pallidus,nodal efficiency of temporal left inferior temporal gyrus and nodal clustering coefficient of left inferior parietal lobule.The average area under the curve(AUC)of GP,LR,SVM and QDA models in test set was 0.868,0.864,0.875 and 0.870,respectively.Calibration curves and decision curve analysis indicated that each ML model had good calibration and high clinical net benefit.Conclusion ML models based on brain functional network features combining with clinical indicators could be used to effectively predict postoperative outcomes in DR-mTLE patients.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To investigate the current situation of kinesiophobia in patients with in vitro fertilization and embryo transfer and to analyse its influencing factors, so as to provide a reference for the intervention research on kinesiophobia in patients with embryo transfer.Methods:Patients in the first trimester of pregnancy after in vitro fertilization and embryo transfer in the Women's Hospital, School of Medicine, Zhejiang University from August to October 2024 were selected by convenience sampling method, and the general information questionnaire, Tampa Scale of Kine-siophobia (TSK), General Perceived Self-Efficacy Scale (GSES), the Brief Illness Perception Questionnaire (BIPQ) and Social Support Rating Sca1e (SSRS) were used as research tools for cross-sectional investigation, and the influencing factors were analysed by univariate and multiple linear regression.Results:A total of 318 pregnant women in the early stage were finally included, with an average age of (33.11 ± 4.55) years old. The TSK score was (40.40 ± 4.22) points, the GSES score was (25.64 ± 5.25) points, the BIPQ score was (34.30 ± 9.97) points, the SSRS score was (37.98 ± 5.65) points, among which 79.25%(252/318) cases had kinesiophobia. Multiple linear regression analysis showed that age, educational level, exercise frequency before transplantation, self-efficacy, and disease perception were important influencing factors of kinesiophobia in the early pregnancy of in vitro fertilization-embryo transfer patients ( t values were -3.39 to 3.11, all P<0.05). Conclusions:The incidence of kinesiophobia in embryo transfer patients is at a medium to high level, and nursing staff should pay attention to patients with young age, low education level and low daily exercise, and at the same time improve patients′self-efficacy and control of disease perception, reduce the occurrence of kinesitophobia in early pregnancy, improve mental state during pregnancy and promote their health.

Objective:To investigate the current situation of kinesiophobia in patients with in vitro fertilization and embryo transfer and to analyse its influencing factors, so as to provide a reference for the intervention research on kinesiophobia in patients with embryo transfer.Methods:Patients in the first trimester of pregnancy after in vitro fertilization and embryo transfer in the Women's Hospital, School of Medicine, Zhejiang University from August to October 2024 were selected by convenience sampling method, and the general information questionnaire, Tampa Scale of Kine-siophobia (TSK), General Perceived Self-Efficacy Scale (GSES), the Brief Illness Perception Questionnaire (BIPQ) and Social Support Rating Sca1e (SSRS) were used as research tools for cross-sectional investigation, and the influencing factors were analysed by univariate and multiple linear regression.Results:A total of 318 pregnant women in the early stage were finally included, with an average age of (33.11 ± 4.55) years old. The TSK score was (40.40 ± 4.22) points, the GSES score was (25.64 ± 5.25) points, the BIPQ score was (34.30 ± 9.97) points, the SSRS score was (37.98 ± 5.65) points, among which 79.25%(252/318) cases had kinesiophobia. Multiple linear regression analysis showed that age, educational level, exercise frequency before transplantation, self-efficacy, and disease perception were important influencing factors of kinesiophobia in the early pregnancy of in vitro fertilization-embryo transfer patients ( t values were -3.39 to 3.11, all P<0.05). Conclusions:The incidence of kinesiophobia in embryo transfer patients is at a medium to high level, and nursing staff should pay attention to patients with young age, low education level and low daily exercise, and at the same time improve patients′self-efficacy and control of disease perception, reduce the occurrence of kinesitophobia in early pregnancy, improve mental state during pregnancy and promote their health.