Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype.

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling. SIGNIFICANCE: The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy-based longitudinal monitoring of patient tumor transcriptomes.

Discrete element simulation of vibration compaction of slag subgrade.

In this study, to improve the compaction quality and parameters of slag, discrete element models of irregular rock particles (10-60 mm) and circular soil particles (5 mm) were established based on on-site slag screening results. The motion of the vibratory roller was captured by coupling the roadbed model with the roller model in a simulation in which the roller vibrated and compacted the slag subgrade. The results indicated that (1) the best compaction was achieved when the small particle content was 40%, the medium particle content was 20%, and the large particle content was 40%. (2) When the slag was dominated by small rock particles, the optimum compaction frequency was 28 Hz, and when large rock particles dominated, the optimum compaction frequency was 33 Hz. (3) Rock particles were the primary particles that experienced stress in the vibration compaction, and the compressive force and displacement depended on the particle size. (4) The longitudinal and vertical displacements and rotation angles of the soil and rock particles were examined. The results of this study are conducive for advancing the understanding of slag compaction and improving the working efficiency and compaction quality of rollers.

Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway.

Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway's role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.

Study of the mechanism of action of sand therapy on atherosclerosis based on the two-phase flow-Casson model.

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis.

Study on the Effect of Liuwei Dihuang Pills on Regulating the Antigen Cross-Presenting Ability of Dendritic Cells by Interfering with Gap Junctional Communication Function / 广州中医药大学学报

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Clinical characteristics and influencing factors of chronic obstructive pulmonary disease in patients with non-small cell lung cancer in Hubei province / 公共卫生与预防医学

Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.

Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy With Immunotherapy Result in Different Tumor Shrinkage Patterns in TripleNegative Breast Cancer / 한국유방암학회지

Purpose@#This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. @*Methods@#This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change.Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. @*Results@#Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. @*Conclusion@#Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

The effect of robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty for ureteral stricture / 中华泌尿外科杂志

Objective:To investigate the clinical safety and efficacy of robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty for ureteral stricture.Methods:The clinical data of 6 patients with ureteral stricture admitted to the Guizhou Provincial People's Hospital from December 2020 to August 2022 were retrospectively analyzed. There were 3 males and 3 females, with an average age of (40.2±11.5) years old. The status of ureteral stricture and hydronephrosis was measured by ultrasonography, CT urography and ureteral retrograde angiography. There were 2 cases of left ureteral stricture and 4 cases of right ureteral stricture, including 4 cases of upper segment stricture and 2 cases of middle segment stricture. The separation of the renal pelvis on the affected side was 3.2 (2.1, 4.2) cm. The length of ureteral stricture was 3.8 (2.5, 4.3) (1.0-5.0) cm, and the preoperative blood creatinine was 90(71, 97)μmol/L. Robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty was performed in all cases under general anesthesia. The strictured ureter segment was separated and longitudinally cut during the operation. The lingual mucosal grafts 2.5-5.0 cm in length and 1.0-1.5 cm in width was cut according to the stricture. Then the lingual mucosal grafts were harvested and placed in the strictured ureter as a ventral onlay. One double J tube was placed in the affected side in all cases during operation. The perioperative outcomes and complications were analyzed. The blood creatinine and renal pelvis separation on the affected side after surgery were compared with the preoperation.Results:All the surgeries were successfully completed. The average operative time was (190.8 ± 59.0) min, median blood loss was 40 (20, 63) ml, postoperative indwelling time of the drainage tube was 6 (4, 6) days, gastrointestinal function recovery time was 3 (2, 3) days, postoperative hospital stay was 6 (6, 7) days. The patients had clear pronunciation and lingual incision recovered 1 week post-operatively. The urine tube was removed 2 weeks after surgery, and the double J tube was removed 8 (6, 10) weeks post-operatively. Radiological examination revealed significant difference in hydronephrosis on the affected side 3 months post-operatively compared with the preoperation, and the separation of the renal pelvis on the affected side was 1.2 (1.2, 1.4) cm after surgery. The blood creatinine was 79(71, 104)μmol/L at 3 month after surgery, which was also improved compared with preoperative.Conclusions:Robot-assisted laparoscopic ventral onlay lingual mucosal graft ureteroplasty is a feasible and safe option for the treatment of ureteral stricture with less trauma, rapid recovery, and less complications.

Application of electronic inhaler monitoring for adherence of inhalational drug administration in patients with chronic respiratory diseases / 中华全科医师杂志

The adherence of inhalational drug administration is closely related the treatment effectiveness for patients with chronic respiratory diseases; on the other hand, poor adherence may increase healthcare costs or even lead to the death of patients. Electronic inhaler monitoring, currently considered the gold standard for assessing adherence, can provide clinicians with objectively accurate medication data, thereby assisting in clinical decision-making. This article provides a review of the significance of inhalation administration, the newly concept of medication adherence, the challenges faced in chronic respiratory diseases, and the current status of the application and value of electronic inhaler monitoring in improving adherence of inhalational drug administration for respiratory disease patients.

Mechanism underlying exosomal lncRNA H19 derived from umbilical cord mesenchymal stem cells promotes cartilage injury repair / 中国组织工程研究

BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Effects of endoscopic foraminoplasty and laminoplasty on biomechanical properties of intervertebral disc and isthmus / 中国组织工程研究

BACKGROUND:Endoscopic treatment of lumbar disc herniation has obvious advantages over traditional open surgery.Endoscopic surgery involves the implantation of a working cannula,which requires only partial bone removal,and there are no studies on the effects of two types of intraoperative foraminoplasty and laminoplasty on the mechanical properties of the local structure of the lumbar spine. OBJECTIVE:To compare the effect of foraminoplasty and laminoplasty on the biomechanical properties of disc and isthmus of the responsible segment. METHODS:The lumbosacral CT images of a healthy male volunteer were taken,and a finite element model M0 of the L3 to sacral vertebrae was established,on which the primary and secondary foraminoplasty models M1 and M2 of the L5/S1 and the laminoplasty model M3 were built.The same load was applied to compare the intervertebral motion range,disc Von Mises stress and equivalent stress characteristics of L5 vertebral isthmus with each model. RESULTS AND CONCLUSION:(1)Compared with M0,M1 and M2 motion range in L5/S1 segment did not change significantly in all directions;M2 overall motion range increased by 8.60%in flexion;M3 increased by 8.23%and 8.26%in L5/S1 right bending and right torsion,and 5.39%and 5.67%in overall motion range in flexion and right bending,with no significant changes in motion range in the rest of working conditions.(2)Compared with M0,M1 showed no significant change in the extremes of Von Mises stress at L5/S1 disc;M2 increased 11.06%,12.50%,18.32%,and 15.48%in flexion,extension,left torsion,and right torsion;M3 increased 12.22%,19.54%,10.05%,and 9.97%in flexion,extension,left torsion,and right torsion,and the rest working conditions and L4/5 disc maximum Von Mises stress did not change significantly.(3)Compared to M0,the maximum Von Mises stress in the left isthmus of L5 of M1 increased by 12.43%in left bending,18.38%,13.29%,13.62%,and 40.00%in the right isthmus in extension,right bending,left torsion,and right torsion.The maximum Von Mises stress in the left isthmus of L5 of M2 increased by 38.87%,42.63%,16.95%,and 19.35%,and that in the right isthmus increased by 12.58%,33.70%,12.92%,and 17.42%in flexion,extension,left bending,and left torsion.The maximum Von Mises stress in the left isthmus of L5 of M3 increased 67.07%,78.14%,32.33%,62.94%,and 89.99%in flexion,extension,left and right bending,and right torsion.(4)The results suggest that foraminoplasty and laminoplasty have a small effect on spinal motion range;there is a mild increase in the extreme values of disc Von Mises stress in the segments operated by interbody laminoplasty and secondary foraminoplasty;there is no significant change in the extreme values of disc Von Mises stress in adjacent segments,and there is a significant increase in the Von Mises stress in the ipsilateral isthmus operated by the interbody laminoplasty model.

Finite element analysis on correction effect of varus foot orthosis based on the three-point force principle / 中国组织工程研究

BACKGROUND:Three-point mechanics is an effective method for ankle foot orthosis correction and prevention of various foot diseases.At present,the clinical application research on 3D printing ankle foot orthosis has been widespread;however,there are relatively few reports on numerical simulation and finite element analysis involving three-point mechanical correction.There is a lack of relevant biomechanical experimental verification. OBJECTIVE:Three-point force was loaded to analyze the composite model of ankle foot orthosis and foot by finite element method,observing the effect of foot correction with ankle foot orthosis under three-point force intervention,verifying the effectiveness of three-point force and the reliability of ankle foot orthosis. METHODS:A three-dimensional foot and ankle model of a healthy volunteer was constructed based on the medical image processing software Mimics.Rodin 4D and Geomagic reverse engineering software were used to optimize the models and design personalized ankle foot orthosis models.Solidworks software was utilized to turn the ankle model inside for 10° to simulate the foot varus disease.Static loading was carried out on the foot force application area by ANSYS software combined with the three-point mechanics principle.The deformation and stress changes of the foot and ankle tissues were analyzed when the human foot pain threshold was met.The display dynamics was used to further verify the effectiveness of the three-point force applied by the ankle foot orthosis. RESULTS AND CONCLUSION:(1)The personalized ankle foot orthosis designed in this paper had the effect of preventing and fixing foot and ankle varus.The ankle varus was 1.81 mm after being loaded with 1 N·m of varus when not wearing ankle foot orthosis,while it was only 0.44 mm after wearing ankle foot orthosis,the deformation rate was reduced by 75.7%,and the effect of preventing varus was significantly enhanced.(2)When only coronal correction was performed,the low calcaneal force would aggravate the varus angle of the front foot.After adjusting the correction force on the inside of the heel and above the medial malleolus,the varus angle of the front foot and the calcaneus position were improved;however,the medial phalangeal region of the foot still had different degrees of adduction and displacement,which would aggravate the adduction deformity of the patient's front foot.(3)The correction effect of the coronal plane and horizontal plane was better than that of the single coronal plane.There was no adduction and displacement of the medial phalanges of the front foot and the varus angle of the front foot decreased under the force(25,10,10,20 N)of the medial heel,the medial shaft of the first metatarsal,below the lateral malleolus and above the medial malleolus,and the valgus along the X-axis was corrected by 1.395 mm,the calcaneus valgus was corrected by 1.227 mm.The calcaneus varus angle was corrected from 10.21° to 7.25°,and the varus angle was improved by 28.9%.(4)The lateral plantar metatarsal load decreased,the medial plantar metatarsal load increased under the action of a two-plane three-point force,and the plantar bone stress was significantly improved after correction.Thus,the reliability of the three-point force principle was further verified.This study provides an important theoretical support for the implementation of ankle foot orthosis in the treatment of varus in clinical practice.

A meta-analysis of risk factors for internalizing problems in adolescents / 中国心理卫生杂志

Objective:To analyze the risk factors of internalizing problems in adolescents aged 12 to 18 years,and provide supporting evidence for the scientific prevention and effective control of internalizing problems in adolescents.Methods:By systematically searching the Chinese and English databases such as CNKI,VIP,Wan-fang,PubMed,Web of Science,Psychology and Behavioral Sciences Collection,PsycInfo,PsycArticles and ERIC,literature on risk factors of internalizing problems among adolescents in the past 22 years was collected,and non-clinical literature using CBCL or YSR or TRF scales to measure related internalizing problems were included.Meta analysis was performed using CMA3.0,with r as the effect size indicator and random effects model combined with the effect size of risk factors.Results:Finally,77 and 18 risk factors literatures were included,including 7 risk fac-tors of individuals,7 risk factors of family,and 4 risk factors of school/community.The average correlation between family risk factors and internalizing problems of adolescents was the highest.Among family risk factors,parent-child attachment had the highest correlation.Conclusion:Individual risk factors,family risk factors and school/com-munity risk factors are significantly positively correlated with adolescent internalizing problems,and family risk fac-tors(especially parent-child attachment quality)have the highest correlation with adolescent internalizing problems.

Effects of Electroacupuncture on the Hippocampus Glutamate System of Acute Myocardial Ischemia Rats / 中国中医药信息杂志

Objective To observe the effects of electroacupuncture(EA)on glutamate(Glu),metabotropic glutamate receptor 2/3(mGluR2/3)and apoptosis related proteins expression in hippocampus in rats with acute myocardial ischemia(AMI);To explore the mechanism of EA against AMI.Methods Totally 50 SD rats were randomly divided into sham-operation group,model group,EA group and inhibitor group,with 10 rats in each group.Except for the sham-operation group,the rats were treated with ligation at the left anterior descending coronary artery to establish AMI model.The rats in the EA group was treated with EA at"Shenmen"and"Tongli",30 minutes each time,once a day for 3 consecutive days.The rats in the inhibitor group were treated with injection of LY341459 via the lateral ventricle 30 min after modeling.HE staining was used to observe myocardial tissue morphology,and ELISA was used to detect Caspase-3 activity in myocardial tissue and Glu content in hippocampal tissue,immunofluorescence staining was used to detect mGluR2/3 expression in hippocampal tissue,TUNEL staining was used to detect apoptosis in hippocampal tissue cells,Western blot was used to detect the expressions of PI3K,Akt,and Caspase-3 protein in hippocampal tissue.Results Compared with the sham-operation group,the myocardial cells of the model group rats showed sparse and swelling with severe infiltration of inflammatory cells;the activity of Caspase-3 in myocardial tissue significantly increased,and the Glu content,positive expression of mGluR2/3,number of apoptotic cells in hippocampal tissue significantly increased(P<0.01),and the expressions of PI3K and Akt proteins in hippocampal tissue were significantly decreased,while the expression of Caspase-3 protein significantly increased(P<0.01).Compared with the model group,myocardial cell edema and inflammatory cell infiltration were reduced in the EA group and inhibitor group,the activity of Caspase-3 in myocardial tissue was significantly decreased,the Glu content,positive expression of mGluR2/3,and number of apoptotic cells in hippocampal tissue were significantly reduced(P<0.01),the expressions of PI3K and Akt proteins in hippocampal tissue significantly increased,while the expression of Caspase-3 protein significantly decreased(P<0.01).Conclusion EA can improve myocardial injury in AMI rats,and its mechanism may be related to activation of PI3K/Akt signaling pathway,inhibition of hippocampal mGluR2/3 overexpression,reduction of Glu accumulation,inhibition of apoptosis of hippocampal neurons and reduction of neurotoxicity.

Effect of Yiqi Tongmai Formula in Intervening in Liver Inflammation and Lipidosis in ApoE-∕- Mice Based on NF-κB/NLRP3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E-∕- （ApoE-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

Suicide attitude, ideation and their relationship with family environment in adolescents with depression / 中国儿童保健杂志

【Objective】 To investigate the suicidal attitude, ideation of adolescent patients with depression, and to analyze their relationships with family environment, in order to provide evidence for the clinical treatment of adolesent depression and to reduce the suicide rate. 【Methods】 Totally 376 adolescents diagnosed with depression in Lu′an area from March 2019 to October 2021 were selected as the case group, and 376 normal adolescents were selected as the control group.The suicide attitude questionnaire (QSA), Beck scale for suicide ideation (BSS) and family environment scale (FES-CV) were used to investigate the suicide attitude, suicidal ideation and family environment of adolescents in two groups. Logistic regression analysis was used to analyze the influencing factors of suicide attitude and ideation of adolescent depression patients.Pearson correlation test was used to analyze the correlations between suicidal attitude, ideation and family environment of adolescent patients with depression. 【Results】 The scores of QSA and BSS in the case group were significantly higher than those in the control group (t=43.352, 96.527, P<0.001).The scores of intimacy, emotional expression, knowledge and entertainment in FES-CV of the case group were lower than those of the control group (t=25.487, 14.573, 22.160, 18.906), the score of contradiction was higher than that of the control group (t=30.311), and the differences were statistically significant (P<0.001).Logistic regression analysis showed that age of 20 - 25 years old (OR=2.016,2.261), severe illness (OR=2.115, 2.192), dwelling in city (OR=2.442, 2.557) were all risk factors for suicidal attitude and ideation in adolescent depression patients (P<0.05).The scores of QSA and BSS in the case group were negatively correlated with the scores of intimacy, emotional expression, knowledge and entertainment in FES-CV (QSA: r=-0.891,-0.933,-0.788,-0.698, BSS: r=-0.901,-0.832,-0.725,-0.637, P<0.05), but they were positively correlated with the score of contradiction (r=0.848, 0.883, P<0.05). 【Conclusions】 The suicidal attitude, ideation of adolescents with depression are higher than those of normal adolescents. Age, illness and growth environment are all influencing factors for suicidal attitudes and ideation in adolescent depression patients, of which the suicide attitude, ideation of patients are closely related to family environment.

Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

Comparative analysis of clinicopathological characteristics of central necrotizing breast cancer and basal cell-like breast cancer.

Purpose: This study aims to compare the clinicopathological and immunohistochemical characteristics of centrally necrotizing carcinoma of the breast (CNC) and basal-like breast cancer (BLBC), as well as to analyze the characteristics of the molecular typing of the CNC. Methods: The clinicopathological features of 69 cases of CNC and 48 cases of BLBC were observed and compared. EnVision immunohistochemical staining was performed to detect the expressions of hypoxia-inducible factor 1α (HIF-1α), breast cancer susceptibility gene 1 (BRCA1), and vascular endothelial growth factor (VEGF) in CNC and BLBC. Results: The age of the 69 patients ranged from 32 to 80 years, with an average of 54.55 years. Gross examination showed that most tumors were well-defined single central nodules with a diameter of 1.2~5.0 cm. Microscopically, there is a large necrotic or acellular area in the center of the tumor, mainly composed of tumor coagulative necrosis with varying degrees of fibrosis or hyaline degeneration. A small amount of cancer tissue remained in the form of a ribbon or small nest around the necrotic focus. Among 69 cases of CNC, the proportion of basal cell type (56.5%) was significantly higher than that of lumen type A (18.84%), lumen type B (13.04%), HER2 overexpression (5.8%), and nonexpression (5.8%). A total of 31 cases were followed up for 8~50 months, with an average of 33.94 months. There have been nine cases of disease progression. When compared to BLBC, there were no significant differences in BRCA1 and VEGF protein expression in response to CNC (p > 0.05), but there were significant differences in protein expression in HIF-1α (p < 0.05). Conclusion: The molecular typing of CNC showed that over half of those were BLBC. No statistically significant difference in the expression of BRCA1 was observed between CNC and BLBC; thus, we predict that targeted therapy for BRCA1 in BLBC may also have considerable effects in CNC patients. The expression of HIF-1α is significantly different in CNC and BLBC, and perhaps HIF-1α can be used as a new entry point to distinguish between the two. There is a significant correlation between the expression of VEGF and HIF-1α in BLBC, and there was no significant correlation between the expression levels of the two proteins in CNC.