As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients&ge;60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

Objective To determine the improved effect of methylene blue(MB)on cognitive func-tion in brain-inflammatory-aging rats and investigate the underlying mechanism.Methods A total of 38 healthy 12-month-old SD rats were randomly divided into healthy control group,lipopo-lysaccharide(LPS)group,MB vehicle group and MB group,with 8 rats in the control and 10 rats in the other three groups.LPS was injected into the fourth ventricle with aid of a subcutaneous sustained release pump to establish a rat model of brain chronic inflammatory aging.MB of 0.5 mg/(kg·d)was added into the pump in the rats from the MB group.T-maze test and new object recognition test were employed to evaluate the learning and memory abilities of the rats.The acti-vation of microglia and astrocytes in the hippocampal CA1 region of the rats was detected by im-munofluorescence assay.The release of inflammatory factors IL-1β and IL-6 was measured by ELISA,and neuronal death in the CA1 region was assessed by neuronal nuclei(NeuN)fluores-cence staining.Results There was no significant difference in the exploration time for new and old objects between the LPS group and the MB solvent group(P＞0.05).The MB group spent significantly longer time in exploring the new objects than the old object(22.50±4.32 s vs 11.60± 3.01 s,P=0.000).The alternating selection rate of new arm and expression level of NeuN antigen were significantly decreased,and the expression levels of ionized calcium binding adaptor mole-cule-1(Iba-1)and glial fibrillary acidic protein(GFAP)and the contents of IL-1β and IL-6 were obviously increased(P＜0.05)in the LPS group and the MB vehicle group than the healthy con-trol group.Compared with the MB vehicle group,the MB group had notably increased alternating selection rate of new arms and higher NeuN expression level,and decreased Iba-1 and GFAP ex-pression and IL-1β and IL-6 contents(P＜0.05).Conclusion Subcutaneous administration of MB could significantly inhibit the damages of spatial learning and memory abilities in the LPS-induced brain chronic inflammatory aging rats.The mechanism may be closely associated with MB inhibi-ting inflammatory glial cells and protecting hippocampal pyramidal neurons.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients&ge;60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

Objective To investigate the best evidence application of exercise prescription in patients with chronic heart failure in clinical practice and evaluate its effectiveness.Methods The best evidence of exercise prescription for patients with chronic heart failure was summarized,and the evidence-based practice plan was developed,and it was implemented in the cardiology department of a tertiary hospital in Zhejiang Province from August to October,2022.Nurses'exercise prescription knowledge-attitude-practice level,implementation rate of review indicators,the length of hospital stay,exercise endurance,daily living ability and grip strength of both groups before and after the intervention were compared.Results After the application of the best evidence,the score of knowledge dimension was(9.34±0.98)points;the score of attitude dimension was(63.29±1.37)points;the score of practice dimension was(25.49±1.51)points,which were statistically significant compared with the scores before the application of evidence(P<0.05).After the application of the best evidence,the implementation rate of 16 review indicators was higher than that before the application of evidence(P<0.001).The length of hospital stay in the evidence application group was shorter than that in the baseline examination group(Z=-2.610,P<0.001).After intervention,the exercise endurance,daily living ability and grip strength of patients in the evidence application group were improved compared with the baseline review group,and the difference was statistically significant(P<0.05).Conclusion After the application of the best evidence of exercise prescription in patients with chronic heart failure,it can improve the level of knowledge,attitude and practice of nurses on exercise prescription,standardize the compliance of nurses'exercise prescription,reduce the number of days in the hospital,and improve patients'exercise endurance,daily living ability and grip strength.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.