Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

Objective:To investigate the epidemiological characteristics of community acquired pyogenic liver abscess (CA-PLA) as a reference for its early identification, early diagnosis and rational antibacterial treatment.Methods:A single center retrospective study was carried out in patients with CA-PLA hospitalized in First Hospital of China Medical University from January 2011 to December 2017.The symptoms, signs and treatment results were concluded. The underlying diseases and onset symptoms of the cases were grouped by year, and the change trend of the disease characteristics was analyzed. The etiology results were grouped according to whether the patients had underlying diseases of biliary tract, and the etiology characteristics were analyzed. Statistical analysis was performed by using chi-square test.Results:A total of 1 063 CA-PLA cases were included in this study. The analysis on underlying diseases grouped by year showed that the number of patients admitted to the hospital increased annually, and the percentage of patients with underlying hepatobiliary diseases decreased from 17.3% (19/110) in 2011 to 7.3% (14/191) in 2017, the difference was statistically significant ( χ2=13.648, P=0.034), while that of patients with diabetes mellitus kept high at 31.6% to 46.5% in the past seven years without increasing trend. There were 274 patients (25.8%) with extrahepatic manifestations. Totally 445 cases were microbiologically diagnosed, among which single Klebsiella pneumoniae infection was found in 371 cases (83.4%). Klebsiella pneumoniae was the leading pathogen in patients without underlying hepatobiliary diseases (91.6%, 362/395), in contrast to 18.0%(9/50) in patients with underlying hepatobiliary diseases. The other pathogens were Escherichia Coli (32.0%, 16/50) and mixed infection (18.0%, 9/50). The susceptibility rate to second generation and above cephalosporins of clinically defined hypervirulent Klebsiella pneumoniae was ≥97.5%, and that to carbapenems was 100.0%. Most patients had good prognosis, and 1 049 cases were cure or improvement discharged, six cases left hospital voluntarily, and eight cases died. Conclusions:Most of the CA-PLA patients have no underlying hepatobiliary diseases, and more than half of patients have no history of diabetes mellitus. Most of the pathogens are Klebsiella pneumoniae, which are relatively sensitive to antimicrobial agents.

Objective To describe the clinical characteristics of hypervirulent Klebsiella pneumoniae (hvKP) infection.To analyze the antibiotic susceptibility of hvKP to provide the empiric antibiotic options.To investigate capsule serotype and sequence type (ST) of hvKP and their correlation with clinical profiles.Methods hvKP was defined as bacteria isolated from patients with community-acquired pyogenic liver abscess (CA-PLA) with co-infection sites outside liver or a bloodstream infection in a host without underlying biliary tract diseases.Patients with CA-PLA hospitalized in the First Hospital of China Medical University were retrospectively analyzed from January 2011 to December 2017.Antibiotic susceptibility was detected by automatic bacterial identification and antibiotic susceptibility analysis system in vitro.Polymerase chain reaction method and gene sequencing were used to detect the main capsule serotype and ST.Results A total of 140 cases with hvKP infection were enrolled.The co-infections outside liver abscess included 98 bloodstream infections,53 pneumonia,11 perianal abscess,10 urinary system infections,3 subphrenic abscess,3 endophthalmitis,2 spleen abscess,and other miscellaneous infections including 1 peritonitis,1 skin and soft tissue infection,1 myelitis,1 colitis,1 psoas major abscess and 1 myocardial abscess.Among the 140 cases,106 presented with single co-infection site,32 with 2 sites,and 2 with 3 sites.HvKP manifested high antibiotic susceptibility up to 80％ for most commonly used antibiotics.Capsule serotyping of 4,3 revived isolates indicated that K1 serotype accounted for 53.49％ (23/43),K2 34.88 (15/43),K54 2.33％ (1/43),K57 2.33％ (1/43),and other serotypes 6.98％(3/43).There was no significant distribution among K1,K2,K54,and K57 of hvKP capsule serotypes in patients with or without diabetes mellitus (P＞0.05).Multilocus sequence typing (MLST) suggested that ST23 and ST65 were predominant accounting for 39.53％ (17/4.3) and 25.58％ (11/4.3) respectively.No serotype or ST predominance was seen in any of the clinical infections.Conclusion HvKP is related to a wide spectrum of infectious diseases,including multiple extrahepatic sites and bloodstream infections besides CA-PLA with high antibiotic susceptibility.K1 and K2 are the predominant capsule serotypes,and ST 23 and ST65 are the predominant sequence types.

Objective To study the difference between piperacillin-tazobactam and other anti-infective agents in the treatment of blood stream infection caused by extended spectrum beta-lactamase (ESBL )-producing Enterobacteriaceae by systematic review and meta-analysis . Methods PubMed , Cochrane library ,Web of Science , CNKI , Weipu DATA , and CPVIP were systematically searched . Literatures were reviewed and data regarding mortality of mono -drug treatment with different antibiotics were collected . All data were pooled using the technique of meta-analysis by Revman 5 .3 , and heterogeneity tests were performed .Results Eleven articles containing 1620 patients were included . Escherichia coli and K lebsiella pneumonia were the main pathogens ,and there were 31 cases caused by Enterobacter cloacae .There was no statistically significant difference in mortality between carbapenems and piperacillin-tazobactam mono-therapy for the empirical treatment (RR = 0 .86 ;95％ CI :0 .62 - 1 .20 , P> 0 .05) or for definitive treatment (RR = 0 .63 ;95％ CI :0 .20 - 1 .97 ,P > 0 .05) .Carbapenems were used as the main antibiotics for definitive treatment as well as empirical treatment . Conclusion Piperacillin-tazobactam treatment is not associated with increased mortality of the patients with ESBL -positive enterobacteria bloodstream infection ,which can be used as an alternative antibiotics .

Objective To investigate the risk factors of bloodstream infections caused by multiple drug resistant Acinetobacter baumannii (MDRAB) and those associated with 30-day clinical outcomes of MDRAB patients. Methods A case-control study was designed to retrospectively analyze 49 cases of MDRAB-related bloodstream infections treated in our hospital during the period from January 2013 to December 2014. Additional 29 cases of non-MDRAB bloodstream infections were included as control group. Univariate and multivariate logistic analysis were used to identify the risk factors of MDRAB bloodstream infections. The prognostic factors were analyzed similarly for all the 78 cases of bloodstream infections by comparing the relevant factors between survival group (38 cases) and non-survival group (40 cases) based on the survival status 30 days after collecting blood samples. Results Univariate analysis revealed that the risk factors for MDRAB bloodstream infection included use of carbapenems, quinolones, or at least 2 antibiotics, mechanical ventilation, nasogastric tube, indwelled central venous catheter, and ICU stay prior to infection. Subsequent multivariate logistic analysis showed that ICU stay (OR=7.118) and prior use of at least 2 antibiotics (OR=8.073) were independent risk factors for MDRAB bloodstream infection. Univariate analysis revealed that ICU stay, mechanical ventilation,and MDRAB in blood sample were the prognostic factors of 30-day survival. Multiple logistic regression analysis showed that MDRAB infection (OR=5.837) and mechanical ventilation (OR=4.926) were the independent risk factors predicting of 30-day patient death. Conclusions ICU stay and prior use of at least 2 antibiotics were independent risk factors for MDRAB bloodstream infection. MDRAB infection and mechanical ventilation were the independent risk factors predicting 30-day patient death in MDRAB bloodstream infections.

Objective To understand the adverse reaction profile of linezolid during clinical treatment,especially lactic acidosis and pancytopenia.Methods One case of linezolid-induced lactic acidosis and pancytopenia was described in a patient receiving long-term treatment in our hospital.Similar cases were searched and identified from literatures reports both in China and abroad from 2000 to 2015 for further review.The data were analyzed in terms of patient age,sex,underlying conditions,as well as onset time,clinical characteristics,and outcomes of the adverse reaction.Results A total of 50 similar cases (male/female ratio:1.78∶1) were analyzed,42.0％ of which were old patients (at least 65 years old).Liver and/or renal insufficiency was found in 20 cases (40.0％).The onset of lactic acidosis was at 5.5 weeks after initiation of linezolid on average,and the onset of pancytopenia was at 3.5 weeks after initiation of linezolid.Conclusions Linezolid-induced lactic acidosis or pancytopenia is more frequently found in the elderly patients with hepatic dysfunction and long-term treatment.

Objective To investigate the antibiotic resistance and resistance genes of carbapenem-resistant Enterobacteriaceaes (CRE) isolated from 5 hospitals in Northeast China.Methods This study collected 85 CRE isolates during January 2013 to June 2015 from five hospitals in Northeast China.Drug sensitivities of 14 antimicrobial agents were determined by the broth microdilution method.The phenotypes of carbapenemases were screened by modified Hodge test and EDTA test respectively.The genotypes of carbapenemases and other extended spectrum β-lactamases (ESBL) were detected by PCR gene amplification and DNA sequencing method.Using the PCR result as gold standard, the performances of other two carbapenemase detection methods were evaluated.Results Among the 85 CRE strains collected in this study, Klebsiella pneumoniae was the most frequently isolated species (61/85,71.8%).The results of antimicrobial agent sensitivity showed that the 85 CRE strains had resistance rate of cephalosporin and β-lactams/enzyme inhibitor (piperacillin-tazobactam) over 80.0%.The resistance rate of carbapenem was high, with ertapenem 100.0% (85/85), meropenem 65.9% (56/85), imipenem 71.8% (61/85).There were 36 isolates resistant to both meropenem and imipenem.For fluoroquinolones, the resistance rates of levofloxacin and ciprofloxacin were 72.9% (62/85) and 65.9% (56/85), respectively.The resistance rate to fosfomycin and amikacin were 65.0% (55/85) and 54.1% (46/85), respectively.The resistance rate of colistin (21.2%, 18/85) and tigecycline (20.5%, 17/85) were low.Forty-nine strains were modified Hodge test positive and 12 strains were EDTA test positive.By PCR gene amplification and DNA sequencing method, 64 strains carried carbapenemase-encoding genes, of which KPC-2 was the main type (53/85, 62.4%), followed by IMP-4 (10/85, 11.8%), NDM-5 (7/85, 8.2%) and NDM-6 (1/85, 1.2%).At the same time, 85 CRE isolates had the ESBL gene detection and 47 isolates were CTX-M type ESBLs (47/85, 55.3%), with no TEM or SHV type.Conclusions Klebsiella pneumoniae is the majority of CRE strains from 5 large hospitals in Northeastern China.The CRE strains are resistant to most of antimicrobials.Most carbapenemases-producing isolates have the KPC-2 type.Nearly half of the carbapenemase-producing strains also carry ESBL genes, which makes the resistance mechanisms more complicated.

Objective To identify the clinical features of patients with brucellosis in Liaoning Province in recent 5 years, and to improve the diagnostic level of the disease.Methods The clinical data including epidemiology, clinical features, laboratory data and diagnosis of 82 hospitalized patients who were diagnosed with brucellosis in the First Affiliated Hospital of China Medical University from 2011 to 2015 were collected and reviewed retrospectively.Results The majority of the 82 patients were middle-aged (45-59 years old) (47.6%) and male gender (63.4%).Fever (90.2%), muscle and joint pain (61.0%), hepatosplenomegaly (36.6%), lymphadenopathy (24.4%) and weight lose (32.9%) were the main complaints.The peripheral leucocyte counts were usually normal (70.7%).C-reactive protein (81.3%), procalcitonin (81.8%) and erythrocyte sedimentation rate (64.2%) increased in most cases.The results of the serum agglutination test in 67 patients were all positive (100.0%).The pathogen isolation was conducted in 60 patients and 49 patients were positive for Brucella species.Among them, 35(71.3%) isolates were identified as Brucella melitensis.A total of 90.2%(74/82) cases were firstly diagnosed with fever of unknown origin and were hospitalized.Misdiagnosis accounted for 52.4(43/82)%.Conclusions Contact history with cow and sheep should be inquired thoroughly in patients with clinical manifestations of fever, muscle and joint pain and hepatosplenomegaly.Pathogen isolation, agglutination test and other specific tests should be performed as soon as possible to diagnose the disease early.

Objective To investigate the homology of carbapenem-resistant Klebsiella pneumoniae (CR-KPN) isolates by multilocus sequence typing (MLST) method,and profile CR-KPN infections in terms of MLST sequence types (STs).Methods A total of 61 CR-KPN isolates were collected in five hospitals from Liaoning Province from January 2013 to June 2015.The MICs of 14 antimicrobial agents against these isolates were determined by broth microdilution method.The genotypes of carbapenemases were analyzed by PCR and DNA sequencing techniques.The homology of CR-KPN isolates were analyzed by MLST method.The clinical data of patients with CR-KPN infection were reviewed to characterize CR-KPN infections.Results A total of 18 STs were identified among the 61 CR-KPN strains according to MLST data.More than 50 ％ of the isolates belonged to ST11 (53.3 ％).ST11 strains showed higher resistance rate to carbapenems and higher prevalence of KPC-2 type carbapenemase.Univariate analysis indicated that more ST 11-infected patients were treated in ICU and with mechanical ventilation than non-ST11 CR-KPN-infected patients (P＜0.05).ST2033,ST2135,ST2193,ST2194,ST2195 and ST2196 were the STs firstly registered in the world.The eBURST analysis showed that ST2193,ST2194,ST2195 and ST 11 were closely related.Clinical data indicated that the prevalent CR-KPN strains during the same period in the same hospital usually belonged to the same ST clone.Conclusions MLST of CR-KPN showed 18 sequence types,of which ST11 was the predominant type.Clinical data indicated that the prevalent CR-KPN strains during the same period in the same hospital usually belonged to the same ST clone.This suggests the potential of local CR-KPN outbreak.The ICU patients and those receiving mechanical ventilation may be prone to CRKPN (especially ST11) infection.Such patients should be managed appropriately.