OBJECTIVE To establish fingerprint， chemical pattern recognition and multi-component quantification analysis of Sanzi powder， and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection （VIP） value greater than 1 was used as the index to screen the differential markers， and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated， and the similarities of them were 0.994- 0.999； 6 common peaks were identified， including gallic acid （peak 3）， garminoside （peak 10）， corilagin （peak 11）， chebulinic acid （peak 16）， ellagic acid （peak 18）， crocin Ⅰ （peak 19）. According to the results of cluster analysis， YKD2024LH005，No.YKD2023LH062） principal component analysis and orthogonal partial least squares-discriminant analysis， 15 batches of samples could be clustered into two categories： S1， S5， S7， S9， S14 were clustered into one category； S2-S4， S6， S8， S10-S13， S15 were clustered into one category. VIP values of 11 differential components such as corilagin， chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples， the contents of corilagin， chebulinic acid and ellagic acid ranged 2.667-5.152， 9.506- 13.522， 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple， and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin， chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Objective To evaluate the differential diagnostic value of synthetic magnetic resonance imaging(syMRI)and field of view optimized and constrained undistorted single shot diffusion weighted imaging(FOCUS DWI)in patient with breast imaging reporting and data system(BI-RADS)4 breast lesions.Methods A total of 68 patients who underwent breast MRI and were classified as BI-RADS category 4 were prospectively enrolled.Among them,there were 31 cases of benign lesions(benign group)and 37 cases of malignant lesions(malignant group).All patients underwent T1WI,T2WI,FOCUS DWI,dynamic contrast-enhanced magnetic resonance ima-ging(DCE-MRI)and syMRI.Two radiologists delineated the region of interest(ROI)on quantitative parameters images of syMRI and the apparent diffusion coefficient(ADC)images generated from FOCUS DWI and calculated T1,T2,proton density(PD)and ADC values,respectively.The thresholds and diagnostic efficacy of syMRI and FOCUS DWI parameters were evaluated by the receiver op-erating characteristic(ROC)curve.Logistic regression analysis was used to combine the parameters of the two sequences and evalu-ate the diagnostic efficacy.Results The T2,PD,and ADC values in the malignant group were significantly lower than those in the benign group(P＜0.05),but there were no statistically significant difference in T1 values between the groups(P＞0.05).T2 and ADC values could be used as important diagnostic indexes in patient with malignant lesions of BI-RADS 4 breast lesions,and the area under the curve(AUC)of T2 and ADC was 0.833 and 0.867,respec-tively.There was no significant difference in AUC of T2 and ADC between benign and malignant groups(Z=0.485,P=0.627).The AUC of T2 value combined with ADC value was 0.910,and the sensitivity and specificity was 90.3％and 89.2％,respectively.Conclusion T2 value of syMRI and ADC value of FOCUS DWI can be used as quantitative diagnostic indicators in patients with BI-RADS 4 breast lesions.The combination of T2 and ADC values can further improve the differential diagnosis efficiency.

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

ObjectiveTo analyze the measures and effects of comprehensive noise control in an automobile engine manufacturing enterprise. Methods An automobile engine manufacturing enterprise with noise exposure work-sites was selected as the research subject. The noise hazard status of the enterprise was investigated. The noise hazard exceeded the national standard in work-sites was comprehensively treated. The treatment effect was analyzed. Results A total of 395 work-sites exposed to noise were detected. Among them, 16 work-sites exceeded the national noise standard, with the rate of 4.1%. The work-sites with noise exceeding the national standard were mainly in the machine workshop and the casting workshop, with normalization of equivalent continuous A-weighted sound pressure level to a nominal eight hours working day (L_EX,8h) ranging from 86.8 to 89.2 and 85.2 to 90.2 dB(A), respectively. In addition, the classification of occupational noise exposure of the mold protection group in the casting workshop was level Ⅱ, and classification of occupational noise exposure of other work-sites with excessive national standard was grade Ⅰ. After the enterprise implemented noise control measures such as process reform, equipment replacement, sound insulation, noise reduction, sound absorption, and vibration isolation, the L_EX,8h of nine positions were lower than those before rectification ［(86.7±1.1) vs (83.3±1.3) dB(A), P<0.01］. Conclusion The use of comprehensive control measures can achieve the purpose of reducing noise from the sources, and can be used for reference by relevant enterprises with noise hazards.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

ObjectiveA growing body of research suggests a strong link between metabolic imbalance and Alzheimer’s disease (AD). In recent years, the development of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in AD. Serum levels of tryptophan and tyrosine were associated with mild cognitive impairment (MCI) and AD. The purpose of this study is to further characterize tryptophan and tyrosine levels in MCI and AD. MethodsWe stratified 765 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort into cognitively normal (CN; n=207), stable mild cognitive impairment (sMCI; n=201), progressive mild cognitive impairment (pMCI; n=171), and dementia due to AD (n=186). Serum tryptophan and tyrosine were analyzed for diagnostic value of MCI and AD. To evaluate the relationships between serum tryptophan and tyrosine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (¹⁸F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. ResultsSerum tryptophan was decreased in patients with AD, pMCI or sMCI compared with CN. Serum tyrosine was decreased in patients with AD or pMCI compared with CN. Serum tryptophan has diagnostic value for pMCI and AD. Serum tyrosine has diagnostic value for AD. ConclusionSerum tryptophan and tyrosine contribute to the early diagnosis of AD. The detection of tryptophan and tyrosine can contribute to the pathogenesis of AD. Serum tryptophan and tyrosine were not significantly associated with core AD markers, cognitive function, brain structure and brain metabolism, so serum tryptophan and tyrosine may not be good peripheral AD biomarkers.

AIM To identify the chemical components of Longmu Qingxin Mixture by UPLC-Q-TOF-MS and study its material basis for the treatment of attention deficit hyperactivity disorder.METHODS The sample was detected by mass spectrometry in positive and negative ion mode on a Waters CORTECS? UPLC? T3 chromatographic column.The data were analyzed with Peakview 1.2 software and matched with the Natural Products HR-MS/MS Spectral Library 1.0 database,and the components were identified in combination with literature reports.The material basis of Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder was analysed according to the identified components.RESULTS Forty chemical components were identified,including 11 flavonoids,6 monoterpene glycosides,4 triterpene saponins,3 phenolic acids,6 alkaloids etc.,which mainly derived from Radix Astragali,Radix Paeoniae Alba,Radix Scutellariae,licorice root,Ramulus Uncariae cum,etc.,baicalein,formononetin,astragaloside Ⅳ and rhynchophylline may be the material basis for the therapeutic effect of Longmu Qingxin Mixture.CONCLUSION UPLC-Q-TOF-MS can quickly identify the chemical components of Longmu Qingxin Mixture.Flavonoids,triterpene saponins and alkaloids may be the material basis for Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder,which can provide the basis for its material basis research,quality standard establishment and pharmacological study of the dismantled formula.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the therapeutic effects and mechanism of enalapril maleate tablet on doxorubicin-induced heart failure rats based on mitogen-activated protein kinase(MAPK)signaling pathway.Methods Eleven of the 40 male SD rats were randomly selected as the normal group(equivalent to 0.9％NaCl),and the remaining 29 were prepared with intraperitoneal injection of 3 mg·kg-1·w-1 doxorubicin to prepare heart failure model.After successful modeling,they were randomly divided into model group(n=15 cases)and experimental group(n=14 cases).Experimental group was given 1.8 mg·kg-1·d-1 enalapril maleate suspension for gavage;normal and model groups were given the same amount of 0.9％NaCl by gavage.After 8 weeks,the rats were subjected to cardiac ultrasound,the left ventricular ejection fractions(LVEF)of each group were recorded,the serum myocardial injury index level was detected by enzyme-linked immunosorbent assay,and the expression levels of mRNA and protein related to the MAPK signaling pathway were detected by real-time quantitative polymerase chain reaction and Western blot.Results The LVEF values of control,model and experimental groups were(77.85±3.34％)％,(41.39±2.87％)％and(60.10±6.53％)％;serum brain natriuretic peptide contents were(219.30±10.59),(333.90±61.19)and(260.00±16.10)pg·mL-1;the relative expression levels of Mapk8ip2 were 1.00±0.01,2.60±0.12 and 2.00±0.08;the relative expression levels of Mapk8ip3 were 1.00±0.00,6.77±1.04 and 3.66±0.54;the relative expression levels of Mapk1 were 1.00±0.00,4.40±0.14 and 2.71±0.24;the relative expression levels of Mapk3 were 1.00±0.01,7.83±0.34 and 2.71±0.24;the relative expression levels of P38-MAPK were 1.00±0.05,1.14±0.02 and 1.02±0.03;the relative expression levels of extracellular regulated protein kinase 1/2 protein were 1.00±0.07,1.49±0.03 and 1.16±0.10;the relative expression levels of c-Jun N-terminal kinase 1/2 protein were 1.00±0.03,1.65±0.19 and 1.14±0.01,respectively.Compared with the model group,the differences of above indexes in the normal and experimental groups were statistically significant(all P＜0.01).Conclusion Enalapril maleate tablets have therapeutic effects on rats with heart failure,and the mechanism may be achieved by regulating the MAPK signaling pathway.