OBJECTIVE To investigate the analgesic effects and potential mechanisms of the partial agonist of the 5-hydroxytryptamine 1A(5-HT1A)receptor and the selective 5-HT reuptake inhibitor,viladazone(Vil),in various animal models of pain.METHODS ① Mouse acetic acid writhing test:KM mice were divided into the model group,model+morphine 10 mg·kg-1 group,and model+Vil 2,4,8 mg·kg-1 groups.Thirty minutes after ig administration of saline(model group)or corresponding drugs,each group was ip injected with a 2%acetic acid aqueous solution(0.01 mL·g-1),and the writhing frequency of the mice was observed and recorded from 5 to 20 min.② Mouse formalin pain test:KM mice were divided into the model group and model+Vil 2,4 and 8 mg·kg-1 groups.Thirty minutes after ig adminis-tration of saline(model group)or drugs,20 μL of 5%formalin solution was sc injected into the right plantar region of the mice.The licking time(the sum of the duration of licking and biting the paw)of the mice was observed and recorded during two periods:the acute phase(0-5 min after sc formalin injec-tion)and the delayed phase(15-35 min after sc formalin injection).③ Rat chronic constriction injury(CCI)of the sciatic nerve experiment:SD rats successfully examined with a paw withdrawal threshold(PWT)<5 g were randomly divided into a CCI model group and a CCI model+Vil 2,4 and 8 mg·kg-1 group.Solvent(model group)or corresponding drugs were ig administered,and the PWT of the modeled side was measured at 30,60,120 and 240 min after the first administration to evaluate the acute anal-gesic effect of Vil on mechanical pain.Then,Vil was continuously ig administered for 14 d,and the PWT was measured 1 h after Vil administration on the 7th and 14th d to evaluate the long-term analgesic effect of Vil.Immunofluorescence staining was employed to analyze the expression levels of inflamma-tion-related proteins,ionized calcium binding adapter molecule 1(IBA-1),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β),in brain tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IBA-1,TNF-α and IL-1β in the dorsal root ganglion of the spinal cord in the CCI model.RESULTS ① In the mouse model of acetic acid writhing,single ig administration of morphine 10 mg·kg-1 and Vil at varied doses significantly reduced the number of writhings induced by acetic acid compared to the model group.② In the formalin-induced pain model,the average licking time of the model group was 50.5 s during the acute phase of inflammatory pain(0-5 min after intraplantar injec-tion of 5%formalin),and 347.9 s during the delayed phase of inflammatory pain(25-35 min after formalin injection).Compared to the model group,single ig administration of Vil 2-8 mg·kg-1 reduced chronic pain induced by formalin in mice,and each dose of Vil significantly decreased the licking time of mice,but had no notable impact on the licking duration exhibited by mice during acute phase.③ In the CCI model,the PWT values of CCI model rats significantly decreased compared with the control group.Pathological damage to varying extents was observed in brain slices,manifested as enlarged intercellular spaces and the appearance of vacuoles.The expression of IBA-1 in brain tissue significantly increased,while TNF-α and IL-1β hardly changed.The levels of IBA-1,TNF-α and IL-1β in the spinal dorsal root ganglion significantly increased.Compared with the CCI model,after single administration of Vil 2-8 mg·kg-1 for 60,120 and 240 min,Vil significantly reduced the PWT values.After two-week continuous administration,the PWT values in Vil 4 and 8 mg·kg-1 were significantly reduced,and Vil 2-8 mg·kg-1 could alleviate the neuropathic pain to some extent.Vil 8 mg·kg-1 significantly reduced the elevated levels of inflammatory factors compared to CCI rats.CONCLUSION The antidepressant Vil exhibits analgesic effects in mouse models of acetic acid writhing,formalin-induced inflammation,and neuropathic pain induced by CCI in rats,with a more pronounced effect on neuropathic pain.The mechanism of action may be related to the inhibition of inflammatory pathways of IBA-1.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Extracorporeal membrane oxygenation (ECMO), as an important treatment technology for circulatory and respiratory support, is widely used in the treatment of critically ill patients. Nurses play a vital role in the management of ECMO patients during the initiation and operation processes. This article comprehensively reviews the current status of ECMO nursing specialty practice, analyzes existing problems and challenges, and explores the future development trends of ECMO nursing specialty practice. The aim is to provide reference for promoting the standardized development of ECMO nursing specialty practice.

Objective:To investigate the learning curves of gastroscopy and colonoscopy for surgeons.Methods:Clinical data of ordinary digestive endoscopy performed by gastrointestinal surgeons in Peking University People's Hospital from March, 2022 to March, 2024 were collected retrospectively. Learning curves were plotted according to the number of examinations and learning time, and the cumulative sum control chart method was used to determine the number of cases required to achieve proficiency in endoscopic examination.Results:Six gastrointestinal surgeons (sequentially) received training in gastroscopy and colonoscopy. All surgeons were male physicians with a doctoral degree and the professional title of attending physician. The average age was (33.0 ±1.9) years, and the average job tenure was (4.0±1.8) years. The median time required for proficiency in gastroscopy was 31 weeks, with a median number of cases of 624. Similarly, the median time required for proficiency in colonoscopy was also 31 weeks but with a median number of cases of 470.Conclusions:Surgeons need at least 31 weeks of independent operation to become proficient in endoscopic examination and more than 600 cases to be proficient in gastroscopy. Surgeons with gastroscopy experience also need 31 weeks of independent operation but at least 450 cases to become proficient in colonoscopy.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Objective Based on multi-objective optimization,a design method for Voronoi bionic porous scaffolds tailored to different degrees of bone defects was proposed.Methods First,the effects of design parameters on mechanical and biological properties of the scaffolds were investigated.The response surface models were then established respectively for the design parameters and performance indicators(specific surface area,elastic modulus,yield strength,and permeability).Using a cubic scaffold with side length of 15 mm as an example(assuming a corresponding bone defect of the same dimension),multi-objective optimization of the scaffold was finally conducted using the non-dominated genetic algorithm-Ⅱ algorithm,while considering the elastic modulus and permeability ranges of bone tissues as performance constraints.Results The degree of anisotropy in Voronoi scaffolds was influenced by the number of seed points,while the size and scaling factors of the scaffolds exclusively impacted the rod diameter and rod length.Using the design method of this study,the optimal scaffold with specific defect size satisfying mechanical and biological properties was designed.The optimal scaffold meeting different strength requirements was designed by adjusting the yield strength to change the utopia point.Conclusions A design method for Voronoi bionic porous scaffolds based on multi-objective optimization is proposed.This method can be applied to bone defects at varying degrees and provides a new idea for the personalized design of bone tissue engineering scaffolds.

To investigate the characteristics and differences of immune cell infiltration between different SDHx gene expression and pheochromocytoma/paraganglioma(PPGL).

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

Objective:To investigate the correlation between the hemodynamic pattern of non-culprit vessel stenosis and long-term vessel-oriented composite outcome(VOCO) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:From January 2019 to December 2021, 233 consecutive patients with STEMI and non-culprit vessel stenosis were prospectively enrolled at Shanghai East Hospital. The median follow-up duration was 3.9 years. The 367 non-culprit vessels of the 233 patients were divided into the VOCO group (33 vessels, 9.0%) and the non-VOCO group (334 vessels, 91.0%). Parameters pertaining to the hemodynamic pattern of non-culprit vessel stenosis between the two groups were compared. Receiver operating characteristic (ROC) curves were used to assess the correlation between hemodynamic pattern and VOCO, and Cox multivariate regression and logistic multivariate regression analyses were applied to identify independent predictors of VOCO.Results:The 233 enrolled patients were aged (62.5±12.9) years, with 193 males (82.8%). In the VOCO group, the maximum quantitative flow ratio (QFR) decreased within 20 mm of the QFR-assessed segment, the difference in QFR across the entire vessel, the length of functionally significant vessel, and the maximum gradient of QFR decrease (dQFR/dsmax) were significantly greater than those in the non-VOCO group. ROC curve analysis showed that the optimal threshold for predicting VOCO using dQFR/dsmax was 0.009 6 (area under the curve: 0.691, 95% CI: 0.606-0.775, P<0.001). Multivariable Cox regression analysis revealed that dQFR/dsmax was an independent predictor of VOCO ( HR=1.199, 95% CI: 1.070-1.343, P=0.002). When anatomical and functional stenosis severities were included in the model, a high pullback pressure gradient (PPG) index ( HR=1.572, 95% CI: 1.052-2.351, P=0.027) emerged as an independent predictor of VOCO. Multivariable logistic regression analysis revealed that a low PPG index( OR=2.851, 95% CI: 1.945-4.178, P<0.001) was an independent predictor of QFR≤0.80 without long-term VOCO. Conclusion:In patients with STEMI, localized hemodynamic patterns of coronary artery stenosis, characterized by high dQFR/dsmax and high PPG index, are associated with long-term VOCO.