ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P＜0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P＜0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

Xiaoji Yinzi is one of the classic prescriptions for treating urinary diseases， originated from the Yan's Prescriptions to Aid the Living （Yan Shi Ji Sheng Fang） written by YAN Yonghe in the Song dynasty. Xiaoji Yinzi is composed of Rehmanniae Radix， Cirsii Herba， Talcum， Akebiae Caulis， Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， Angelicae Sinensis Radix， Gardeniae Fructus， and Glycyrrhizae Radix et Rhizoma and has the effects of cooling blood and stopping bleeding， draining water and relieving stranguria. The medical experts of later generations have inherited the original prescription recorded in the Yan's Prescriptions to Aid the Living， while dispute has emerged during the inheritance of this prescription. In this study， the method of bibliometrics was employed to review and analyze the ancient documents and modern clinical studies involving Xiaoji Yinzi. The results showed that Xiaoji Yinzi has two dosage forms： powder and decoction. According to the measurement system in the Song Dynasty， the modern doses of hers in Xiaoji Yinzi were transformed. In the prepration of Xiaoji Yinzi powder， 149.2 g of Rehmanniae Radix and 20.65 g each of Cirsii Herba， Talcum， Akebiae Caulis， stir-fried Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， wine-processed Angelicae Sinensis Radix， stir-fried Gardeniae Fructus， and stir-fried Glycyrrhizae Radix et Rhizoma are grounded into fine powder with the particle size of 4-10 meshes and a decocted with 450 mL water to reach a volume of 240 mL. After removal of the residue， the decoction was taken warm before meals， 3 times a day （i.e.， 7.77 g Rehmanniae Radix and 0.97 g each of the other herbs each time）. In the preparation of Xiaoji Yinzi decoction， 20.65 g each of the above 10 herbs are used， with stir-fried Typhae Pollen， wine-processed Angelica Sinensis Radix， stir-fired Gardeniae Fructus， stir-fired Glycyrrhizae Radix et Rhizoma， and raw materials of other herbs. Xiaoji Yinzi is specialized in treating hematuresis and blood stranguria due to heat accumulation in lower energizer， which causes injury of the blood collaterals of gallbladder and dysfunction of Qi transformation. In modern clinical practice， Xiaoji Yinzi is specifically used for treating urinary diseases and can be expanded to treat diseases of the cardiovascular system and other systems according to pathogenesis. The comprehensive research on the key information could provide a scientific reference for the future development of Xiaoji Yinzi.

OBJECTIVE: To explore the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of chronic cough using data mining. METHODS: The ancient and modern medical record cloud platform, and the databases, i.e. CNKI, Wanfang, VIP, EMbase, Web of Science and PubMed, were searched to screen the ancient and modern literature on acupuncture and moxibustion treatment of chronic cough. The prescription database was established for acupuncture and moxibustion treatment of chronic cough, and the analysis conducted on the frequency and use percentage in the aspects of intervention measures, acupoint selection, acupoint distribution, meridian tropism, special points and acupoint combination, as well as the association rules and clustering rules of acupoint selection. The subgroup analysis was performed in accordance with the etiology of chronic cough and intervention measures. RESULTS: A total of 106 articles were included and 158 prescriptions were extracted. The intervention measures were acupuncture, moxibustion, herbal medication and the combination of several measures. The high-frequency acupoints included Feishu (BL13), Zusanli (ST36), Dazhui (GV14), Pishu (BL20), Danzhong (CV17), Shenshu (BL23), Lieque (LU7), Dingchuan (EX-B1), Tiantu (CV22), and Fenglong (ST40). These acupoints are mainly distributed on the back, lumbar region, chest and abdomen. The involved meridians were bladder meridian of foot-taiyang, conception vessel, and lung meridian of hand-taiyin. The special points covered back-shu points, crossing points and five-shu point. Regarding the compatibility of acupoints, the combination of upper and lower points, and the combination of front and back points were predominant in treatment. The analysis of association rules found that the support of Feishu (BL13)→Zusanli (ST36) was the highest; the cluster analysis obtained 8 clusters of acupoints. The acupoint compatibility and overall rules were similar when cough variant asthma (CVA) or the mixed reasons were involved, and the local treatment approach was adopted if the etiology of disease was related to upper airway cough syndrome (UACS) and gastroesophageal reflux cough (GERC). The acupoint selection was similar among different intervention measures. When two kinds of measures were combined in treatment, Feishu (BL13), Pishu (BL20) and Zusanli (ST36) were the most common. CONCLUSION In treatment with acupuncture and moxibustion for chronic cough, the acupoints are selected on the affected local area, depending on syndrome differentiation, and focusing on back-shu points. The main acupoints are Feishu (BL13), Zusanli (ST36), Dazhui (GV14), Pishu (BL20), Danzhong (CV17) and Shenshu (BL23). The combined therapy is dominant with acupuncture, moxibustion and herbal medicine involved.
Acupuncture Points ; Moxibustion/history* ; Humans ; Cough/history* ; Acupuncture Therapy/history* ; Chronic Disease/therapy* ; Data Mining ; History, Ancient ; Meridians ; Chronic Cough

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95％confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87％.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95％CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63％.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95％CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend＜0.001),and the highest was 5.62(95％CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.