Aim To explore the relationship between Mre11/Rad50/Nbs1 ( MRN ) complex focus formation and DNA double-strand breaks( DSBs) caused by cinob-ufagin in human hepatocellular carcinoma HepG2 cells. Methods The Na+,K+-ATPaseα1 subunit expression level in liver cancer tissues was detected by immunohis-tochemistry. After HepG2 cells were treated with 5μmol·L-1 cinobufagin for 6, 12 and 24 h, the drug-in-duced DSBs were assessed by single cell gel electro-phroesis ( SCGE ) , the gene transcription and protein levels of Mrel1, Nbs1, Rad50 and p53 were evaluated by Real time-PCR and Western blot. The cell cycle in parallel was analyzed by flow cytometry. Results The Na+, K+-ATPase α1 subunit expression level in liver cancer tissues was significantly increased compared with the tissue adjacent to carcinoma ( P <0. 05 ) . The 5μmol · L-1 cinobufagin could induce the DSBs in a time-dependent manner (P <0. 05), and it could up-regulate the gene expression levels of Mre11, Nbs1, Rad50 and p53 in HepG2 cells ( P<0. 05 ) . The pro-portions of HepG2 cells in S phase were ( 21. 32 ± 4. 21) % in the control group, and (33. 25 ± 5. 72) %, (56. 72 ± 6. 29) % and (67. 32 ± 9. 42) % in HepG2 cells treated with 5 μmol · L-1 cinobufagin for 6, 12 and 24 h, respectively. The proportions of cells in S phase in cinobufagin groups were significantly increased compared with the control group ( P<0. 05 ) . Conclu-sion Cinobufagin could induce the cell cycle arrest in liver cancer HepG2 cells by activation of Mre11/Rad50/Nbs1 Complex.

Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1 076,1 010)and vulcanizing agent in the range of 0.5-100 μg·mL-1 with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Authors summarized a case report of characteristics and treatment measures for three female patients (3 eyes) with sutures dislodged into the eyelids during blepharoplasty were admitted to the Department of Oculoplastics, Shandong Eye Hospital from December 2017 to February 2019. The ages of patients ranged from 19 to 35 years, with an average of 25 years. The needles were removed 1-14 days after the previous operation. None of the eyelid wounds showed infection, the height of bilateral palpebral fissures were symmetrical in all the patients, and no significant abnormalities were seen on ophthalmic examination. Orbit CT scan showed that all the stitches were located in the upper eyelid. All patients underwent skin incisions along the original double eyelid line, and needles were successfully removed under the direction of a magnet. The needles removed were whole in one case and partial in other two cases. All needles were stainless steel needles. The patients were followed up for 1 month to 4 years. One case was followed up for 4 years, the palpebral fissure height was almost symmetrical, and the double eyelid disappeared in the affected eye. Blepharoplasty was recommended. Another case was followed up for 1.5 years, the double eyelid was symmetrical. The eyelid edema of the other case resolved 1 month after the operation, and the patient was lost to follow-up half a year after surgery. The risk of surgical needle breaking and buried into the tissues in the process of double blepharoplasty should not be neglected. These accidents tend to occur in the temporal eyelid. Orbital CT scan and permanent magnet are helpful in locating and surgically removing these foreign bodies.

Authors summarized a case report of characteristics and treatment measures for three female patients (3 eyes) with sutures dislodged into the eyelids during blepharoplasty were admitted to the Department of Oculoplastics, Shandong Eye Hospital from December 2017 to February 2019. The ages of patients ranged from 19 to 35 years, with an average of 25 years. The needles were removed 1-14 days after the previous operation. None of the eyelid wounds showed infection, the height of bilateral palpebral fissures were symmetrical in all the patients, and no significant abnormalities were seen on ophthalmic examination. Orbit CT scan showed that all the stitches were located in the upper eyelid. All patients underwent skin incisions along the original double eyelid line, and needles were successfully removed under the direction of a magnet. The needles removed were whole in one case and partial in other two cases. All needles were stainless steel needles. The patients were followed up for 1 month to 4 years. One case was followed up for 4 years, the palpebral fissure height was almost symmetrical, and the double eyelid disappeared in the affected eye. Blepharoplasty was recommended. Another case was followed up for 1.5 years, the double eyelid was symmetrical. The eyelid edema of the other case resolved 1 month after the operation, and the patient was lost to follow-up half a year after surgery. The risk of surgical needle breaking and buried into the tissues in the process of double blepharoplasty should not be neglected. These accidents tend to occur in the temporal eyelid. Orbital CT scan and permanent magnet are helpful in locating and surgically removing these foreign bodies.

Objective:To analyze the clinical characteristics and treatment outcomes of chronic dacryocystitis-related corneal ulcers and to provide a basis for the rational clinical diagnosis and treatment.Methods:An observational case series study was performed.A total of 31 patients (31 eyes) diagnosed with chronic dacryocystitis-related corneal ulcers in Eye Hospital of Shandong First Medical University were enrolled from January 2016 to January 2020, with an average age of (53.0±10.8) years.The typical ocular signs, results of the etiological examination and microbial sensitivity test, treatment process and outcomes were analyzed.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.20191020-1).Written informed consent was obtained from each subject before any medical examination.Results:The average history of chronic dacryocystitis was (3.6±1.9) years.Corneal ulcers were mostly located in the peripheral cornea and had a rounded morphology with clear borders.The positive rate of corneal scraping was 74.2%(23/31), with bacteria in 19 eyes, fungal hyphae in 3 eyes, and both gram-positive cocci and fungal hyphae in 1 eye.The positive rate of microbial culture was 74.2%(23/31), with positive bacterial culture in 20 eyes (gram-positive cocci in 16 eyes and gram-negative bacilli in 4 eyes) and fungal growth in 3 eyes.The sensitivity rates of gram-positive cocci to vancomycin, rifampicin, moxifloxacin, and levofloxacin were 100%(16/16), 87.5%(14/16), 81.3%(13/16), and 75.0%(12/16), respectively.All patients were treated with surgery for chronic dacryocystitis, including 22 cases of endoscopic dacryocystorhinostomy, 7 cases of dacryocystectomy, and 2 cases of lacrimal duct probing combined with intubation.Among the 9 cases with an ulcer depth of <1/3 of the corneal thickness (CT), 6 cases were cured after (10.8±3.2) days of drug treatment and 3 cases underwent corneal lesion resection.The 6 patients with an ulcer depth of 1/3-2/3 of the CT underwent conjunctival flap covering surgery.Among the 16 patients with an ulcer depth of >2/3 of the CT, lamellar keratoplasty was performed in 6 cases, penetrating keratoplasty in 8 cases and evisceration in 2 cases with infectious endophthalmitis.Conclusions:Chronic dacryocystitis-related corneal ulcers are mainly located at the periphery of the cornea, and gram-positive cocci infections are the most common pathogenic bacteria.In patients with mild symptoms, corneal ulcers heal gradually after treatment with sensitive antibiotics.For patients with severe infections, appropriate surgery should be selected according to the depth of the corneal ulcer.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

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.