ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

OBJECTIVE: To investigate the effects of bone density, plate bending degree and proximal screw type on the stress fracture of clavicle hook. METHODS: Three sows weighing between 45 and 50 kg were selected, from which a total of 40 rivs were collected. The 15 ribs of sows were divided into 3 groups according to bone density and bone hardness with 5 rivs in each group. And then the 3 groups were fixed with 6-hole collarbone hook plates and 3 locking screws. Measure the maximum torsion force when the ribs were fractured by force. The same size 15 rids were divided into 3 groups, named forward bending group, 0° group(the angle between the plate surface and the rib surface) and reverse bending group. All fixed with 6-hole collarbone hook plates and locking screws to measure the maximum torsion force of rib stress fracture. Then the same size 10 rids were divided into 2 groups, the normal screw group and the locking screw group with 5 ribs in each group. Both groups were fixed with 6-hole collarbone hook plates and screws. The normal screw group was a normal screw, fixed in proximal end, and two locking screws. The locking screw group was fixed by locking screws. Measure the maximum torsion force of the two groups when the ribs fracture by force. RESULTS: In the bone density experiment, the torque force of hard bone group (104.51±6.27) N was greater than the normal bone group (75.04±3.81) N(t=8.979, P<0.05). The force of normal bone group was greater than the osteoporosis group (49.99±2.12) N(t=12.832, P<0.05). In the bending collarbone hook experiment, the order of the torque force generated by each group as follow:the forward bending group (343.59±6.18) N greater than the 0° group (106.01±5.29) N(t=65.279, P<0.05) greater than the reverse bending group (95.82±4.12) N(t=3.398, P<0.05). The force of the normal screw group (98.68±0.70) N was greater than the locking screw group (50.20±0.95) N(t=91.484, P<0.05). The data comparisons of each group were statistically significant. CONCLUSION Bone density, plate bending degree and proximal screw type had an impact on stress fracture of clavicle hook plate. Higher bone density, forward bending of the steel plate, and ordinary screws in proximal end can reduce the rates of stress fractures of clavicle hooks.
Animals ; Bone Plates ; Clavicle/surgery* ; Swine ; Fractures, Stress/etiology* ; Female ; Risk Factors ; Fracture Fixation, Internal/instrumentation* ; Bone Screws ; Biomechanical Phenomena ; Bone Density

PURPOSE: Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure. METHODS: A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis. RESULTS: A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850.00, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%. CONCLUSION The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.
Adult ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China ; Logistic Models ; Resuscitation/mortality* ; Retrospective Studies ; Survival Rate ; Thoracotomy/methods* ; Trauma Centers/statistics & numerical data* ; Wounds, Nonpenetrating/surgery*

PURPOSE: Although there are significant differences between China and the United States (US) in trauma medical services, there has been no direct comparative research on the epidemiological data of trauma centers between the 2 countries. This study aims to fill this research gap by directly comparing trauma centers in China and the US, providing valuable data and insights for the development of trauma centers in both countries, promoting academic exchange and cooperation internationally, and enhancing the level of global trauma medical care. METHODS: This is a multicenter retrospective descriptive study. Data were collected for trauma patients with an injury severity score ≥16 treated from September 2013 to September 2019 at 2 hospital trauma centers in these 2 countries. Detailed clinical data (including injury mechanism, age, injury site, injury severity score, pre-hospital transport time, whether blood transfusion was performed, whether resuscitative thoracotomy was conducted, hospital and intensive care unit stay duration, the number of organ donor patients, mortality rates, and costs) were meticulously compiled and retrospectively analyzed to identify differences between the 2 trauma centers. The comparison was conducted using SPSS 23 software. Continuous variables are reported as median (Q₁, Q₃), and Mann Whitney U test is used to compare the median of continuous variables. Use clinically relevant critical points to classify continuous variables, with categorical variables represented as n (%), and comparisons were made between the 2 groups using the χ² test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05. RESULTS: These results point to significant differences in trauma center capacity, pre-hospital transport times, treatment procedures, hospital stay duration, mortality rates, and costs between the 2 centers. The volume of patients in trauma centers is less in China (2465 vs. 5288). Pre-hospital transport time was notably longer in China (180 min vs. 14 min), and the rate of emergency blood transfusions was lower in China (18.4% vs. 50.6%), Emergency thoracotomy was not performed in China but was conducted in 9.8% of cases in the US. Hospitalization costs were significantly lower in China than in the US ($5847 vs. $75,671). CONCLUSION There are clear differences in trauma center capacity (number of patients treated), pre-hospital transport time, age distribution of injured patients, injury mechanisms, injury sites, whether emergency thoracotomy is performed, hospital costs, and length of stay between the 2 trauma centers in China and America. Understanding these differences can help us further recognize the characteristics of Eastern and Western trauma patients.
Humans ; China/epidemiology* ; Trauma Centers/statistics & numerical data* ; Retrospective Studies ; United States/epidemiology* ; Male ; Female ; Wounds and Injuries/therapy* ; Middle Aged ; Adult ; Injury Severity Score ; Length of Stay/statistics & numerical data* ; Treatment Outcome

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

Oligodendrocyte precursor cells (OPCs) represent the fourth major cell type within the central nervous system (CNS), ubiquitous beyond neurons, astrocytes, and microglia, constituting 5%-8% of the total cell population. They exhibit widespread distribution throughout the central nervous system, including brain, spinal cord, and optic nerve. OPCs showcase distinct protein expression, featuring platelet-derived growth factor receptor alpha (PDGFRα), neural/glial antigen 2 (NG2), SRY-related HMG-box protein 10 (Sox10), and oligodendrocyte transcription factor 2 (Olig2), endowing them with robust proliferation and migration capabilities. This capacity persists into adulthood and even later stages, contributing to the maintenance of normal neurological functions such as learning, memory, and sleep, while playing crucial roles in various neurological disorders. OPCs also display significant heterogeneity, influenced by developmental programs, stimulus-specific cellular responses, CNS locations, cell-cell interactions, and other regulatory mechanisms. Dysregulation of OPC function has been observed in various diseases, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Pelizaeus-Merzbacher disease, as well as psychiatric disorders such as schizophrenia, depression, emotional disorders, and autism spectrum disorders. In addition to differentiating into oligodendrocytes to form myelin sheaths and supporting axonal protection, fast signal transmission, and metabolic support, OPCs actively participate in regulating neural development, circuit formation, and neural plasticity. They respond to environmental factors and are closely associated with neurological disorders. This comprehensive exploration of OPCs delves into their development, functional diversity, and associations with neurological disorders. Firstly, the article introduces the complex regulatory mechanisms of OPCs during embryonic development, encompassing transcription factors, chromatin regulatory factors, post-translational modifications of proteins, microRNA, and intercellular communication, emphasizing their significance in the nervous system. Subsequently, it reviews recent research findings on various functions of OPCs, not only in neuronal development, phagocytosis, and reshaping activities, but also involving their secretion of factors, interactions with surrounding blood vessels, and regulation of inflammatory responses. Furthermore, the review highlights the connections between OPCs and neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis) and psychiatric disorders (such as schizophrenia and depression), indicating their potential roles in disease occurrence and progression. The review then explores emerging trends in OPC research, addressing the evolving understanding of their roles in neurological health and disease. Recent studies have unveiled novel aspects of OPC functionality, shedding light on their ability to modulate immune responses, interact with the extracellular matrix, and contribute to neurovascular coupling. Additionally, insights into the role of OPCs in neuroinflammation and the crosstalk between OPCs and neurons have expanded our comprehension of their impact on neural circuits and plasticity. In conclusion, the comprehensive review summarizes the current understanding of OPC functional impairments and discusses future research directions. Emphasizing the importance of in-depth analysis of OPC heterogeneity and their roles in the development, repair, and diseases of the nervous system, this review not only provides profound insights into the multifaceted functions of OPCs in the nervous system but also sets the stage for future investigations into the intricate interplay between OPCs and the broader neural environment. With an expanded scope encompassing recent advances and emerging research trends, this review contributes to the ongoing dialogue in the field of neuroscience, fostering a deeper understanding of OPC biology and its implications for therapeutic interventions in neurological disorders.

OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.

Objective Based on the affective events theory,explore the influence of the cmerged county-based medical community reform on the conscientiousness of physicians in township health centers and its internal mechanism,and provide references for improving their conscientiousness.Methods Self-designed questionnaire was used to conduct the survey,including the basic personal information,physician's conscientiousness,county-based integrated service delivery networks and efficacy emotional feeling.Select physicians from 23 township health centers of 2 merged county-based medical community in Hubei Province as the investigation objects and use structural equation model to analyze the the influence of compact county-based integrated service delivery networks on the conscientiousness.Results The county-based integrated service delivery networks efficacy had a positive impact on the emotional feeling.Emotional feeling had a positive impact on the conscientiousness.The county-based integrated service delivery networks efficacy on the was conscientiousness 0.044,while the indirect effect was 0.236,and the ratio of indirect effect to the total effect was 84.3%.Conclusions The emotional feeling plays a fully mediating role between county-based integrated service delivery networks efficacy and physician's conscientiousness of township health centers.