In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective:To explore the effect of multiple modified process management intervention on cardiac func-tion,psychological state,stress level,sleep quality and adverse events in patients with severe coronary atherosclerot-ic heart disease(CHD).Methods:This randomized controlled study enrolled 130 severe CHD patients who were treated in Affiliated Beijing Shijitan Hospital of Capital Medical University between January 2020 and May 2023.Patients were randomly divided into control group(n=65)and intervention group(n=65).Patients in the control group were treated with routine management intervention,while those in the intervention group were given addi-tional multiple modified process management interventions.Both groups were intervened for 4 weeks.Cardiac func-tion,levels of norepinephrine(NE)and cortisol(COR),scores of Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),General Comfort Questionnaire(GCQ),Pittsburgh Sleep Quality Index(PSQI),and the incidence of adverse events during intervention were compared between the two groups.Results:Compared to those in control group after intervention,patients in intervention group had significant higher left ventricular ejection fraction(LVEF)[(57.81±2.15)％vs.(50.11±2.99)％]and GCQ score[(95.88±5.37)points vs.(75.81±6.67)points](P＜0.001 all),and significant lower left ventricular end-diastolic volume(LVEDV)[(109.81±5.37)ml vs.(129.26±5.17)ml],left ventricular end-systolic volume(LVESV)[(50.85±3.08)ml vs.(66.02±3.77)ml],levels of NE[(61.56±5.49)pg/ml vs.(69.86±5.03)pg/ml],COR[(85.63±5.19)ng/ml vs.(92.28±6.57)ng/ml],scores of SAS[(30.06±5.19)points vs.(49.51±5.85)points],SDS[(31.86±4.51)points vs.(40.00±5.10)points]and PSQI[(8.72±1.58)points vs.(13.89±2.40)points],and incidence of ad-verse events(4.69％vs.23.44％)(P＜0.01 all).Conclusion:The multiple modified process management interven-tion may improve the cardiac function,adverse psychological state,stress level,sleep quality and reduce the inci-dence of adverse events in patients with severe CHD.

Objective:To explore any effect of excitatory and inhibitory multi-focal transcranial direct current stimulation (m-tDCS) on cortical functioning in healthy adults.Methods:Fifteen healthy participants received 20-minute excitatory and inhibitory episodes of m-tDCS targeting C1-C2-FC1-FC2. Finite element analysis and functional near-infrared spectroscopy were then used to model the normal component of the electric field (En) applied and to monitor the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (THb) concentrations in the targeted regions during the stimulation.Results:The excitatory protocol induced En values of 0.057V/m and 0.058V/m in the left and right hemispheres, respectively, with an average of 0.058V/m, while the inhibitory one evoked corresponding En values of -0.057V/m and -0.058V/m with an average of -0.058V/m. During excitatory m-tDCS, HbO and THb concentrations in the target cortices were higher than in the inhibitory protocol, with significant differences at FC1, FC2, and C2 for HbO, and at FC2 and C2 for THb. However, no significant inter-group differences in HbR concentrations were observed. Moreover, either protocol induced severe adverse reactions including pain, though the pain decreased with prolonged stimulation.Conclusions:Both excitatory and inhibitory m-tDCS modulate cortical function among healthy individuals. Excitatory m-tDCS is the more effective in enhancing cortical excitability.

Objective:To investigate genetic findings and pregnancy outcomes in fetuses with omphalocele.Methods:This retrospective study analyzed data from 502 fetuses with prenatally diagnosed omphalocele who underwent genetic testing at Guangzhou Women and Children's Medical Center and Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2014 and March 2024. Testing methods included karyotyping, chromosomal microarray analysis (CMA), methylation-specific multiplex ligation-dependent probe amplification, and whole-exome sequencing (WES). Cases were categorized as non-isolated ( n=340) or isolated ( n=162) based on ultrasound findings. Differences in genetic abnormality detection rates and pregnancy outcomes were analyzed using Mann-Whitney U test, independent samples t-test, and Chi-square test (or Fisher's exact test). Results:Among 502 fetuses, karyotyping plus CMA detected chromosomal abnormalities in 223 cases (44.4%, 223/502), including trisomy 18 (57.0%, 127/223) and trisomy 13 (23.3%, 52/223). CMA additionally identified nine pathogenic copy number variations (1.8%, 9/502) and five uniparental disomies (1.0%, 5/502), increasing the total diagnostic yield from 44.4% to 47.2%. The genetic abnormality rate was significantly lower in isolated (14.8%, 24/162) versus non-isolated omphalocele (64.7%, 220/340) ( χ2=109.34, P<0.001). WES detected variants in nine of 16 karyotype/CMA-negative cases, including five pathogenic variants involving PIK3CA and CDKN1C. Eight imprinting disorders (1.6%, 8/502) were identified, including five Beckwith-Wiedemann syndrome cases. Among 499 cases with follow-up, 401 (80.4%, 401/499) underwent pregnancy termination. Live birth rate was higher in isolated versus non-isolated groups [42.5% (69/162) vs. 8.5% (29/340), χ2=77.67, P<0.001]. Three cases were lost to follow-up. The one-year survival rate was 93.9% (92/98) in live-born infants. Conclusion:Aneuploidy (particularly trisomy 18) is the primary genetic etiology of omphalocele. CMA and WES significantly improve diagnostic yield. Isolated omphalocele has a more favorable prognosis, while non-isolated cases show significantly higher genetic abnormality rates. A stratified testing strategy is recommended: karyotyping plus CMA for isolated cases and prioritization of WES for multiple anomalies.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.