OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*

Objective:To investigate the early diagnosis value of Pentraxin-3(PTX-3)promoter methylation for complicated appendicitis.Methods:Patients with appendicitis and healthy physical examination from Qingdao Hiser Medical Group were selected as the research objects,and they were divided into complicated appendicitis group(CA),simple appendicitis group(SA)and healthy control group(HCs).Plasma PTX-3 levels,mRNA expression,promoter methylation status,and clinical parameters—including total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(Alb),white blood cell count(WBC),neutrophil count(NEU),C-reactive protein(CRP),and procalcitonin(PCT)—were analyzed.in each group.Spearman correlation analysis was used to test the correlation of variables.Multivariate Logistic regression analysis was used to test the correlation between PTX-3 gene methylation and clinical parameters.The area under the receiver operating characteristic curve(AUC)was used to analyze the diagnostic value of PTX-3 methylation for CA.Results:The mRNA level and plasma concentration of PTX-3 in CA group were significantly higher than those in SA group and HCs group,while the methylation frequency of PTX-3 in CA group was significantly lower than that in SA group and HCs group(P<0.05).The methylation status of PTX-3 gene was significantly correlated with inflammatory markers(WBC,NEU,PCT,CRP)(P<0.05).Multivariate Logistic regression analysis showed that WBC,CRP and PCT were independent influencing factors of PTX-3 gene promoter methylation(P<0.05).Spearman correlation analysis showed that the PTX-3 mRNA level in peripheral blood of CA patients was negatively correlated with its methylation status(P<0.001).PTX-3 mRNA level was positively correlated with WBC,NEU,CRP and PCT levels(P<0.05).The sensitivity and specificity of PTX-3 gene methylation in the diagnosis of CA were 94.67%and 76.67%,re-spectively.When CA was diagnosed from SA patients,the AUCs of PTX-3 methylation were significantly higher than those of WBC,NEU,CRP and PCT(P<0.001).Conclusion:PTX-3 promoter methylation is involved in the pathogen-esis of AA by regulating the expression of PTX-3.It can be used to monitor the inflammatory state of patients with com-plicated appendicitis and serve as a non-invasive early diagnosis biomarker for complicated appendicitis.

Objective To explore the anesthetic effects of remimazolam combined with nalbuphine on patients undergoing painless gastroscopy.Methods A total of 120 patients who underwent painless gastroscopy in Handan Central Hospital from August 2019 to May 2021 were selected and randomly divided into the observation group(60 cases)and the control group(60 cases).Patients in the observation group anesthetized with remimazolam and nalbuphine,while patients in the control group anesthetized with propofol and alfentanil.The vital signs,sedative effect,recovery quality,cognitive function,and adverse reactions of patients were compared between the two groups.Results The heart rate(HR),respiratory rate(RR),and the level of pulse oxygen saturation(SpO2)of patients in the observation group were significantly higher than those in the control group(P<0.05).Five minutes after the examination,the Narcotrend score of patients in the observation group was significantly lower than that in the control group(P<0.05).The time from the last administration to awakening,the time from gastroscopy removal to awakening,and the time of leaving the anesthesia recovery room of patients in the observation group were significantly shorter than those in the control group(P<0.05).Five minutes after the examination,the score of the mini-mental state examination(MMSE)of patients in the observation group was significantly higher than that in the control group(P<0.05),while the incidence of adverse reactions was significantly lower than that in the control group(P<0.05).Conclusion The application of remimazolam combined with nalbuphine anesthesia in painless gastroscopy has a relatively ideal effect,which can effectively reduce the adverse reactions of patients and promote rapid postoperative recovery.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To investigate the effects of curcumin,berberine,and puerarin combination therapy on lipid levels in hyperlipidemic mice.Methods:A total of 40 male C57BL/6J mice were randomly divided into eight groups:normal control group(A),high-fat control group(B),curcumin group(C),berberine group(D),puerarin group(E),low-dose combination group of curcumin,berberine,and puerarin(F),high-dose combination group of curcumin,berberine,and puerarin(G),and positive control group(H),with 5 mice in each group.The normal control group was fed a standard diet,while the other groups were given a high-fat diet.After establishing the hyperlipidemic model,the mice were administered with physiological saline,curcumin(200 mg/kg),berberine(200 mg/kg),puerarin(300 mg/kg),low-dose combination of curcumin(50 mg/kg),berberine(50 mg/kg),and puerarin(100 mg/kg),high-dose combination of curcumin(200 mg/kg),berberine(200 mg/kg),and puerarin(300 mg/kg),or simvastatin(6 mg/kg)via gavage for three weeks.After treatment,serum was collected from the mice for biochemical analysis of lipid levels and liver function.Liver tissues were subjected to HE staining,Western blot analysis and real-time quantitative PCR.Results:Curcumin,berberine,and puerarin,whether administered individually or in combination,can reduce the body weight of hyperlipidemic mice(P＜0.01).Treatment with curcumin,berberine,and puerarin individually significantly reduced lipid levels in hyperlipidemic mice(P＜0.05)and alleviated liver damage caused by hyperlipidemia(P＜0.05).Furthermore,the high-dose combination of curcumin,berberine,and puerarin exhibited a more pronounced effect on improving lipid levels(P＜0.01)and provided greater protective effects on the liver compared to the positive control group(P＜0.05).Additionally,curcumin,berberine,and puerarin administered individually can each promote the expression of the LDLR gene in high-fat diet mice(increased by 90％,85％,and 98％,respectively)and reduce the expression of the ACC gene(decreased by 42％,45％,and 43％,respectively).The combination of all three compounds enhances the expression of the LDLR gene in high-fat diet mice(increased by 90％with low-dose combination and 169％with high-dose combination)and reduces the expression of the ACC gene(decreased by 38％with low-dose combination and 42％with high-dose combination).Conclusion:The combination of curcumin,berberine,and puerarin significantly improves lipid levels in hyperlipidemic mice and mitigates liver damage associated with hyperlipidemia.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.