This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/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 explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

Objective:To investigate the predictive value of serum 25 hydroxyvitamin D3[25 (OH) D3], insulin-like growth factor 1 (IGF-1) and bone mineral density (BMD) in the occurrence of osteoporosis (OP) in postmenopausal women.Methods:A total of 87 postmenopausal women admitted to Shanxi Children’s Hospital from Jan. 2020 to Dec. 2023 were chosen and separated into OP group ( n=40) and non-OP group ( n=47) . The differences of clinical features, serum 25 (OH) D3, IGF-1 and BMD were compared, and the correlation analysis between serum 25 (OH) D3, IGF-1 and BMD (including L 1-4 BMD, femoral neck BMD and total hip BMD) was analyzed. Multivariate Logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the influencing factors of OP occurrence in postmenopausal women and the predictive value of serum 25 (OH) D3 and IGF-1 combined with BMD for OP occurrence. Results:Compared with non-OP group, there were no significant differences in age, body mass index (BMI) , menopause time, serum calcium, serum phosphorus, alanine aminotransferase (ALT) , or aspartate aminotransferase (AST) levels in OP group ( t=1.42, 1.03, 1.71, 0.93, 0.76, 0.43, 0.04; P=0.161, 0.306, 0.092, 0.354, 0.452, 0.670, 0.966) , but the proportion of diabetes mellitus significantly increased ( χ2=4.37, P=0.037) . Compared with non-OP group, the levels of serum 25 (OH) D3 and IGF-1 and the values of L1-4 BMD, femoral neck BMD and total hip BMD in OP group significantly decreased ( t=5.37, 4.83, 8.31, 2.01, 3.11; P<0.001, P<0.001, P<0.001, P=0.048, P=0.003) . Correlation analysis showed that serum 25 (OH) D3 and IGF-1 were significantly positively correlated with L 1-4 BMD, femoral neck BMD and total hip BMD ( r=0.37, 0.42, 0.29, 0.33, 0.28, 0.29; P<0.001, P<0.001, P=0.024, P=0.015, P=0.032, P=0.021) . Multivariate Logistic analysis showed that serum 25 (OH) D3, IGF-1 and L 1-4 BMD were independent influencing factors for OP occurrence in postmenopausal women ( P=0.007, 0.019, 0.001) ROC curve showed that the area under the curve (AUC) values of serum 25 (OH) D3, IGF-1, L 1-4 BMD and their combination in the prediction of the occurrence of OP in postmenopausal women were 0.764, 0.752, 0.957 and 0.985, respectively. Conclusion:Serum 25 (OH) D3, IGF-1 and L 1-4 BMD can be used as predictors of OP occurrence in postmenopausal women, and the combined value of the three is higher.

Objective:To investigate the predictive value of serum 25 hydroxyvitamin D3[25 (OH) D3], insulin-like growth factor 1 (IGF-1) and bone mineral density (BMD) in the occurrence of osteoporosis (OP) in postmenopausal women.Methods:A total of 87 postmenopausal women admitted to Shanxi Children’s Hospital from Jan. 2020 to Dec. 2023 were chosen and separated into OP group ( n=40) and non-OP group ( n=47) . The differences of clinical features, serum 25 (OH) D3, IGF-1 and BMD were compared, and the correlation analysis between serum 25 (OH) D3, IGF-1 and BMD (including L 1-4 BMD, femoral neck BMD and total hip BMD) was analyzed. Multivariate Logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the influencing factors of OP occurrence in postmenopausal women and the predictive value of serum 25 (OH) D3 and IGF-1 combined with BMD for OP occurrence. Results:Compared with non-OP group, there were no significant differences in age, body mass index (BMI) , menopause time, serum calcium, serum phosphorus, alanine aminotransferase (ALT) , or aspartate aminotransferase (AST) levels in OP group ( t=1.42, 1.03, 1.71, 0.93, 0.76, 0.43, 0.04; P=0.161, 0.306, 0.092, 0.354, 0.452, 0.670, 0.966) , but the proportion of diabetes mellitus significantly increased ( χ2=4.37, P=0.037) . Compared with non-OP group, the levels of serum 25 (OH) D3 and IGF-1 and the values of L1-4 BMD, femoral neck BMD and total hip BMD in OP group significantly decreased ( t=5.37, 4.83, 8.31, 2.01, 3.11; P<0.001, P<0.001, P<0.001, P=0.048, P=0.003) . Correlation analysis showed that serum 25 (OH) D3 and IGF-1 were significantly positively correlated with L 1-4 BMD, femoral neck BMD and total hip BMD ( r=0.37, 0.42, 0.29, 0.33, 0.28, 0.29; P<0.001, P<0.001, P=0.024, P=0.015, P=0.032, P=0.021) . Multivariate Logistic analysis showed that serum 25 (OH) D3, IGF-1 and L 1-4 BMD were independent influencing factors for OP occurrence in postmenopausal women ( P=0.007, 0.019, 0.001) ROC curve showed that the area under the curve (AUC) values of serum 25 (OH) D3, IGF-1, L 1-4 BMD and their combination in the prediction of the occurrence of OP in postmenopausal women were 0.764, 0.752, 0.957 and 0.985, respectively. Conclusion:Serum 25 (OH) D3, IGF-1 and L 1-4 BMD can be used as predictors of OP occurrence in postmenopausal women, and the combined value of the three is higher.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.