To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.

Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.
Humans ; Neurodegenerative Diseases/metabolism* ; alpha-Synuclein/metabolism* ; Amyloid beta-Peptides/metabolism* ; tau Proteins/metabolism* ; Protein Aggregation, Pathological/metabolism* ; DNA-Binding Proteins/metabolism* ; Animals ; Protein Aggregates/physiology*

ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

Objective:To investigate the clinical application effect of enhanced recovery after surgery(ERAS) in the perioperative period of primary repair for children with hypospadias.Methods:Non-randomized controlled study.Retrospective analysis was made on clinical data of 206 children with hypospadias admitted to the Department of Urology, Shanxi Children′s Hospital from March 2018 to March 2022.According to whether the concept of ERAS was adopted for perioperative management of children, they were divided into the ERAS group(109 cases) and the non-ERAS group(97 cases). t-test and Chi-square test were used to analyze the differences between the two groups of patients in hospitalization days, hospitalization costs, pain scores on the first day after surgery, average number of bowel movements within 5 days after surgery, first out-of-bed activity time, hospital satisfaction score, and complication rate. Results:Pediatric patients in the ERAS group showed better outcomes compared to the non-ERAS group: shorter hospital stays[(7.71±1.12) d vs.(21.00±1.07) d], lower hospitalization costs[(10 043.21±1 341.00) yuan vs.(12 993.44±1 081.00) yuan], lower postoperative pain scores on the first day[(5.21±1.32) points vs.(6.09±1.07) points], more frequent bowel movements within 5 days[(5.16±0.65) times vs.(2.91±0.48) times], earlier time to first out-of-bed activity[(5.03±0.61) d vs.(7.12±0.57) d], and higher hospital satisfaction scores[(4.71±0.21) points vs.(4.14±0.15) points], and the differences were statistically significant(all P<0.05).Additionally, the ERAS group had lower rates of fever(6.42%, 7/109) and constipation(3.67%, 4/109) before urinary catheter removal compared to the non-ERAS group[21.64%(21/97) and 28.87%(28/97), respectively](all P<0.05).There were no significant differences in the incidences of complications such as urethral prolapse, infection, delayed wound healing, and bleeding, as well as urethral stricture, urethral fistula, and urethral diverticulum after urinary catheter removal between the two groups(all P>0.05). Conclusions:ERAS protocol applied in the perioperative period of primary repair for children with hypospadias can shorten the hospitalization time, lower the hospitalization costs, and accelerate the rehabilitation of children.It is worth further promotion.

Objective To investigate the clinical value of deep learning reconstruction(DLR)for flow sensitive black blood(FSBB)sequence in MRI of lenticulostriate artery(LSA).Methods Thirty robust volunteers were prospectively selected,performed scans with conventional FSBB sequences,and divided into DLR-FSBB group and conventional FSBB group according to whether DLR method was used.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and number of branches of the two groups of images for bilateral LSA were compared,and the overall image quality was evaluated subjectively using Likert score(5-point scale).A paired t-test was used to compare quantitative indicators,SNR and CNR of image quality between the two groups.The Kappa coefficient was applied to eval-uate the consistency of subjective scores between the two observers.Results The SNR and CNR of DLR-FSBB images of cranial bilateral LSA were considerably higher than those of conventional FSBB images(left SNR 34.45±8.21 vs 16.91±4.67,P＜0.001,and right SNR 31.24±6.35 vs 16.02±3.00,P＜0.001;corresponding CNR 19.38±6.37 vs 9.27±3.12,15.82±4.29 vs 8.01±2.27,P＜0.001).The number of branches of LSA was slightly higher in the DLR-FSBB images[4.00(4.00,5.00)vs 3.00(3.00,4.00)on the left side,P＜0.001;3.00(3.00,4.00)vs 3.00(2.00,3.00)on the right side,P=0.003].The subjective score of overall image quality was higher in DLR-FSBB than that in conventional FSBB[reader 1:4.00(4.00,4.00)points vs 3.00(3.00,3.00)points;reader 2:4.00(4.00,4.00)points vs 3.00(3.00,3.00)points,P＜0.001].Conclusion Compared with conventional FSBB sequences,DLR-FSBB sequences of LSA have lower image noise,and vessel branches are displayed more plainly and slightly more numerous.DLR can improve the overall image quality of LSA in conventional FSBB sequences.

Objective:To investigate the effect of internal fixation of medial support and lateral wall on initial weight-bearing stability of femoral intertrochanteric fracture after reconstruction of intertrochanteric fracture.Methods:Based on the digital model of Sawbones femur, intertrochanteric fracture models with different medial support and lateral wall states were constructed. Combined with various intramedullary and extramedullary fixation methods, the mechanical models after fixation were simplified, and seven mechanical simplified models were obtained. The individual body weight load (70 kg) was simulated by applying concentrated force (700 N) to the end nodes of the femoral head. Through the analysis and calculation of each model in StrucMaster software, the axial force, shear force, bending moment, displacement deformation, and support reaction force of each bar in each mechanical model were obtained, and the results were output through the supporting SMConsole.Results:The median bending moment of model 1 was 11.55(5.57, 18.00) N·m, and the median bending moment was 2.89(2.81, 2.94) rad. The median bending moment of model 2 was 13.72(9.30, 20.05) N·m, and the median bending moment was 2.93(2.77, 3.05) rad. The median bending moment of model 3 was 19.65(10.23, 26.11) N·m, and the median bending moment was 2.93 (2.77, 3.05) rad. The median bending moment of model 4 was 25.95(25.14, 36.70) N·m, and the median bending moment was 4.38(3.16, 5.15) rad. The median bending moment of model 5 was 13.66(7.99, 25.62) N·m, and the median bending moment was 3.50(3.32, 3.56) rad. The median bending moment of model 6 was 24.60(9.33, 29.37) N·m, and the median bending moment was 3.90(3.69, 4.10) rad. The median bending moment of model 7 was 41.14(0.16, 41.30) N·m, and the median bending moment was 5.50(5.50, 7.05) rad. The mechanical properties of model 1 were better than those of the other six models.Conclusion:The simplified mechanical model and its mechanical calculation analysis based on the lever reconstruction balance theory can be used to preliminarily reveal the mechanical characteristics of femoral intertrochanteric fractures after internal fixation. The internal fixation methods of the medial support and lateral wall of femoral intertrochanteric fracture reconstruction can improve the initial stability of the weight bearing after internal fixation of femoral intertrochanteric fractures and have guiding significance for the functional rehabilitation of early postoperative weight bearing.

Objective To evaluate the application effect of ciprofol-alfentanil in short urological surgery.Methods A total of 80 patients who were to undergo urological general anesthesia surgery in this hospital were divided into two groups by random number method:ciprofol-alfentanil group(group C)and propofol-alfentanil group(group P).Group C was injected with ciprofol 0.4 mg/kg,group P was injected with propofol 1.5-2.0 mg/kg,and when the bispectral index(BIS)was<60,the intravenous injection of alfen-tanil(10 μg/kg)and rocuronium bromide(0.6 mg/kg)was continued.When the modified alertness/sedation score(MOAA/S score)was 0,the laryngeal mask was placed and mechanical ventilation was used.During the maintenance period,ciprofol 0.8-1.2 mg·kg-1·h-1 was infused intravenously in group C,and propofol 4-6 mg·kg-1·h-1 was infused intravenously in group P.The heart rate(HR),blood pressure(BP),oxygen saturation(SpO2),end-tidal carbon dioxide(PetCO2),BIS and MOAA/S score were recorded at the begin-ning of anesthesia induction(T0),laryngeal mask insertion(T1),ureteroscopy entry(T2),10 min after sur-gery(T3)and the end of surgery(T4).The consciousness disappearance time,operation time,anesthesia re-covery time,drug dosage,injection pain during induction,hypotension,bradycardia and other adverse reactions during the operation were recorded.Results There was no significant difference in HR,SpO2,PetCO2,BIS value,MOAA/S score,operation time,consciousness disappearance time,and anesthesia recovery time be-tween the two groups at each time point(P>0.05).The dosage of sedative drugs in group C was less than that in group P(P<0.05).Compared with group P,systolic blood pressure and diastolic blood pressure at T1-T3 and diastolic blood pressure at T4 increased in group C(P<0.05).Compared with T0,systolic blood pressure at T1-T4 in group C and group P decreased,diastolic blood pressure at T2-T4 in group C de-creased,and diastolic blood pressure at T1-T4 in group P decreased(P<0.05).Compared with group P,the injection pain and the incidence of intraoperative hypotension were reduced in group C(P<0.05).Conclusion Cipro-fol-alfentanil is superior to propofol-alfentanil in short urological surgery.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.