OBJECTIVE To study the pharmacokinetics and tissue distribution of cannabidiol（CBD）-cholesterol succinate monoester-g-carboxymethyl chitosan （CCMC） nano-micelles in rats， and to evaluate its anti-inflammatory effect. METHODS CBD- CCMC nano-micelles were prepared by dialysis method and the properties were characterized. SD rats were divided into CBD group and CBD-CCMC nano-micelles group with 6 rats in each group. The rats were given 100 mg/kg CBD and CBD-CCMC nano- micelle by intragastric administration， respectively （based on the CBD load）. Blood was collected from the posterior ophthalmic venous plexus at 0.5， 1， 1.33， 1.5， 1.75， 2， 4， 8， 24， 48 h after administration. The heart， liver， spleen， lung， kidney and muscle tissues of rats were separated at 0.25， 1.5， 10 and 24 h after administration of CBD and CBD-CCMC nano-micelle with the same dose. The drug content in plasma and tissues was determined， the pharmacokinetic parameters were calculated， and the tissue distribution was analyzed. The inflammatory model of Caco-2 cells was induced by lipopolysaccharide， after 24 h of treatment with 5， 10， and 15 µg/mL CBD and CBD-CCMC nanomicelles （based on loaded CBD）， its anti-inflammatory activity was investigated by measuring cell viability， transepithelial electrical resistance （TEER） and inflammatory cytokines IL-1β， IL-8 and TNF-α. RESULTS The prepared CBD- CCMC nano-micelles had a particle size of （230.6±1.8） nm， a polydispersity index of 0.170±0.053， a Zeta potential of （－13.5± 1.2） mV， an encapsulation rate of （86.35±0.56）% and a drug loading of （9.18±0.32）%， respectively； the solubility was 68.240 μg/mL. The pharmacokinetic results showed that the AUC0-48 h， AUC0-∞， half-life time and peak concentration of CBD-CCMC nano- micelle group were significantly increased/extended compared with CBD group （P＜0.05 or P＜0.01）. The results of the tissue distribution study showed that at the same time point， the drug distribution concentration of CBD-CCMC nanomicelles in the rat tissue was higher than that in the CBD group. Research on anti-inflammatory effects shows that compared with CBD of the same mass concentration, CBD-CCMC nano-micelles can significantly increase cell viability （P＜0.05 or P＜0.01）， enhance TEER， and reduce the levels of IL-8， IL-1β and TNF-α in cells （P＜0.01）， and the secretion levels of inflammatory cytokines IL-8， IL-1β and TNF- α were significantly decreased （P＜0.01）. CONCLUSIONS CBD-CCMC nano-micelles can increase the plasma concentration and tissue distribution concentration of CBD， and improve anti-inflammatory activity of CBD.

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.

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor. Its malignancy is between benign hemangioma and highly malignant angiosarcoma. It originates from vascular endothelial cells or pre-endothelial cells. It is characterized by the proliferation of vascular endothelial cells with a skin-like or histiocyte-like appearance. The incidence of EHE is less than 1% in all vascular tumors, and it can occur in multiple parts of the body, most often in the liver, followed by simultaneous involvement of the liver and lung, the lung alone, and the bone alone. At present, there is no report of epithelioid hemangioendothelioma diagnosed by bone marrow cell morphological examination in China. In this case, abnormal cells were found through bone marrow cell morphological examination, which guided the direction of further diagnosis and treatment. And finally the patient was diagnosed as epithelioid hemangioendothelioma. The bone marrow cell morphological examination can provided an important basis for clinical diagnosis and treatment. Epithelioid hemangioendothelioma needs to be differentiated from a variety of benign and malignant angiogenic tumors, especially other types of epithelioid angiogenic tumors. At present, it has been found that the disease has characters of cytogenetic and molecular biological abnormalities. Combined with histopathological morphology and immunohistochemical examination, we can make the diagnosis and differential diagnosis.

Skin is a kind of tissue that surrounds the surface of body, it is the first barrier for animals to resist mechanical, chemical and pathogenic microorganisms. Skin wound is one of the most common surgical diseases. The process of wound healing can be summarized as three stages: inflammation stage, fibrous tissue proliferation stage, and scar formation and repair stage. Incomplete repair of the wound leads to skin scarring, which causes the tissue to lose its normal structure and function, and seriously affects the aesthetic appearance. Traditional treatment methods can not restore the normal function of the skin and have obvious adverse reactions, which can not meet people's needs. Stem cell therapy, especially adipose derived stem cells (ADSCs) plays a essential rule in the process of wound healing making it a research hotspot in recent years. ADSCs can secrete a variety of growth factors during wound healing to reduce wound inflammatory response, promote wound regeneration epithelialization and vascular reconstruction, thereby promoting wound healing. In this paper, the wound healing process and its regulation mechanism were summarized, and the role of ADSCs in wound healing at home and abroad and its clinical application progress were reviewed.

The periosteum is a special connective tissue enveloping bone,which not only contains the mesenchymal cells required for bone repair,i.e.periosteum derived stem cells (PDSCs),but also provides the microenvironment required for PDSCs and the necessary biomechanical support.Periostea play a vital role in bone tissue repair.Clinical periosteal transplantation has been widely applied to restore bone defects,which is an important research field in regenerative medicine.In this paper,the structure characters of periosteal cells isolation and characterization of PDSCs were reviewed.The research progress of periosteum and PDSCs in bone defect restoration was reviewed.The related signal pathways involved in the restoration of PDSCs were discussed.Periostea and PDSCs are not only crucial for bone defect repair but also play important role in bone regeneration.The differences in proliferation and differentiation potential of PDSCs in human/mouse amputation,the amphibian epimorphic regeneration and the annual regeneration of deer antler were compared and analyzed.The results showed that the proliferative potential of PDSCs and abundant blood supply may be the key factors determining bone regeneration.

Colorectal cancer is a malignancy with poor prognosis and high mortality and is caused by multiple factors. Colonoscopy,flexible sigmoidoscopy,guaiac-based fecal occult blood test,immunochemical fecal occult blood test,fecal DNA test,CT colonoscopy and serum carcinoembryonic antigen test are the methods frequently used for screening of colorectal cancer,but they all have certain limitations. Elevation of methylation of SEPT9 is associated with the pathogenesis of colorectal cancer,and detection of the level of methylation of SEPT9 in peripheral blood can be used for screening of colorectal cancer in susceptible population. This article reviewed the application of peripheral blood SEPT9 DNA methylation assay for screening of colorectal cancer.