OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.

Objective:The evidence on the use of bedside ultrasound to assess muscle mass in critically ill adults was retrieved and screened, and the best evidence was summarized.Methods:A computer search was conducted for relevant literature on ultrasound measurement of muscle mass in critically ill adults in domestic and foreign databases such as BMJ Best Clinical Practice, UpToDate, PubMed, CNKI, and guide website and professional association website. The search time limit was from the establishment of the database to August 30, 2023. Literature quality was evaluated by four researchers trained in systematic evidence-based courses according to literature type.Results:A total of 15 literatures were included, including 2 guideline, 4 expert consensus, 5 systematic reviews and 4 randomized controlled studies. A total of 22 pieces of evidence were summarized, including 6 aspects: position and patient preparation, feasibility of implementation by nursing staff, selection of probe and matters needing attention, muscle positioning, evaluation of muscle structure by ultrasound and the guiding significance of ultrasound evaluation of muscle mass.Conclusions:The best evidence summary of bedside ultrasound assessment of muscle mass in critically ill adults summarized in this study is scientific and systematic, and provides evidence-based basis for establishing standardized ultrasound assessment procedures in clinic.

With the increasing incidence of diabetes mellitus in recent years， cardiomyopathy caused by diabetes mellitus has aroused wide concern and this disease is characterized by high insidiousness and high mortality. The early pathological changes of diabetic cardiomyopathy （DCM） are mitochondrial structural disorders and loss of myocardial metabolic flexibility. The turbulence of mitochondrial quality control （MQC） is a key mechanism leading to the accumulation of damaged mitochondria and loss of myocardial metabolic flexibility， which， together with elevated levels of oxidative stress and inflammation， trigger changes in myocardial structure and function. Qi deficiency and stagnation is caused by the loss of healthy Qi， and the dysfunction of Qi transformation results in the accumulation of pathogenic Qi， which further triggers injuries. According to the theory of traditional Chinese medicine （TCM）， DCM is rooted in Qi deficiency of the heart， spleen， and kidney. The dysfunction of Qi transformation leads to the generation and lingering of turbidity， stasis， and toxin in the nutrient-blood and vessels， ultimately damaging the heart. Therefore， Qi deficiency and stagnation is the basic pathologic mechanism of DCM. Mitochondria， similar to Qi in substance and function， are one of the microscopic manifestations of Qi. The role of MQC is consistent with the defense function of Qi. In the case of MQC turbulence， mitochondrial structure and function are impaired. As a result， Qi deficiency gradually emerges and triggers pathological changes， which make it difficult to remove the stagnant pathogenic factor and aggravates the MQC turbulence. Ultimately， DCM occurs. Targeting MQC to treat DCM has become the focus of current research， and TCM has the advantages of acting on multiple targets and pathways. According to the pathogenesis of Qi deficiency and stagnation in DCM and the modern medical understanding of MQC， the treatment should follow the principles of invigorating healthy Qi， tonifying deficiency， and regulating Qi movement. This paper aims to provide ideas for formulating prescriptions and clinical references for the TCM treatment of DCM by targeting MQC.

Nitric oxide(NO)is an endothelial-derived relaxing factor produced by endothelial cells and catalyzed by nitric oxide synthase(NOS), which is present in many organs and tissues of the human body. NO is a key gaseous signaling molecule that mediates a variety of physiopathological processes in organisms. NO and NOS have many functions including the regulation of vascular tone, the relaxation of smooth muscle, activation of immune responses and modulation of neuro-transmission. They have been used in the treatment of diseases in a certain field. In recent years, the incidence of ophthalmic diseases has been on the rise, and the quality of life of patients has been reduced. However, treatment for most diseases is limited. It is find that NO and NOS can be detected in various tissue of ocular parts, and they are involved in the occurrence and transformation of many ocular surface and fundus diseases. This article reviews the correlation between them and ocular diseases, analyzes the mechanism and principle of the occurrence and development of diseases, and provides new ideas for the clinical treatment of ophthalmic diseases in the future.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

To establish the amplification-refractory mutation system quantitative real-time PCR (ARMS-qPCR) method based on qPCR technique for detecting the c.2T>C mutation of SLC25A13 gene and validate its diagnostic performance. According to the principle of ARMS-qPCR primer design, the specific primers were designed for the conserved sequence of SLC25A13. The c.2T>C mutation ARMS-qPCR detection assay of SLC25A13 gene and the corresponding Sanger sequencing system were established through the use of the synthetic plasmids of homozygous mutation and 200 human peripheral blood specimens which were verified by Sanger sequencing as templates, and the diagnostic efficacy of the qPCR assay was validated by using nucleic acid extracted from another 200 human peripheral blood specimens and the results obtained were compared with the Sanger sequencing results as the gold standard, and the consistency of the two detection methods was analyzed. The results showed that the qPCR assay could accurately identify artificial plasmids carrying different mutations of SLC25A13 gene, and distinguish between wild type SLC25A13 gene and the c.2T>C mutation. This method was used to detect the mutation status of SLC25A13 c.2T>C in human peripheral blood, and the detection results were 100% consistent with the Sanger sequencing results. Among the 200 blood samples, 8 samples (4%) carried the c.2T>C mutation of SLC25A13 gene and 192 samples (96%) did not carry it. In conclusion, the ARMS-qPCR test established in this study can quickly, simply and accurately detect the c.2T>C mutation of SLC25A13 gene, which is helpful for the diagnosis of citrin deficiency (CD).