OBJECTIVE To study the differences of quinolones-resistant determining region(QRDR) in DNA gyrase A(gyrA) subunit between drug-resistant Klebsiella pneumoniae induced by fluoroquinolone in vitro and strains isolated from clinical isolates.Furthermore,to reveal the relation between different QRDR gene mutations and drug-resistance. METHODS Ten sensitive K.pneumoniae strains were selected and induced into drug-resistant strains by ciprofloxacin.The QRDR in gyrA by polymerase chain reaction(PCR) was amplified and compared their DNA sequences with clinically isolated quinolone-resistant K.pneumoniae. RESULTS We had found several gene mutations of QRDR in fluoroquinolone-resistant K.pneumoniae induced by ciprofloxacin,including Ser 83(TCC)→Phe(TTC) and Ile(ATC);and Gln106(CAG)→Leu(CTG).And the alteration of Gln106(CAG)→Leu(CTG) was a new discovery. CONCLUSIONS There are gene mutations of QRDR in fluoroquinolone-resistant K.pneumoniae induced by ciprofloxacin.The mutation of Ser 83(TCC) and Gln106(CAG) is probably the molecular basis of inducing drug-resistant strains.

Objective To assess the therapeutic effectiveness of monotherapy of adefovir dipivoxil (ADV) and lamivudine (LAM),or ADV administered in combination with LAM,in order to find the effective and secure therapy for decompensated cirrhosis patients following chronic hepatitis B. Methods Totally 64 decompensated cirrhosis patients following chronic hepatitis B were divided into 2 groups by using a prospective randomized grouping method. In group A,patients received the therapy of adefovir dipivoxil (10mg/d) combined with lamivudine (100mg/d); and in group B,a monotherapy of adefovir dipivoxil (10mg/d) was used. The period of treatment was 48 weeks. Levels of serum ALT,HBeAg and HBV-DNA were detected in week 12,24,36 and 48 respectively. The liver function was evaluated with Child scores on these time points. Data were analyzed by a blinded independent investigator. Results After 48 weeks treatment,HBV DNA negative conversion rate of the two groups were 87.1%and 78.8%.The virtual rate were 96.8% and 87.9%;HBeAg negative conversion rate were 83.9%,and 57.6%. HBeAg/anti-HBe seroconversion rates of the two groups were 41.9%and 24.2%. Normalization of serum ALT levels were observed in 96.8% patients of group A and 97.0% of group B. Conclusion The combination therapy of adefovir dipivoxil (ADV) and lamivudine (LAM) could reduce the occurrence of drug resistance,and increase the anti-viral effect. It is a secure management for chronic hepatitis B virus infection.

OBJECTIVETo study the pathological and clinical characteristics of a patient with spontaneous platelet aggregation of his giant and morphologically abnormal platelets.

METHODSPlatelet size and structure were observed under light microscope and electron microscope. Platelet aggregation was measured turbidometrically. Platelet glycoproteins (GP) were analyzed using flow cytometry. PCR and DNA sequencing were performed to identify the gene abnormality.

RESULTSThe patient had spontaneous platelet aggregation of giant platelets with thickened plasma membrane and increased number of granules in various shapes. Aspirin and ticlopidine did not affect the spontaneous aggregation. The expression of GP I b, GP II b, GP III a and P-selectin in the platelet membrane were in normal range. Results of gene analyses for GP I balpha, GP I bbeta and GPIX were also normal.

CONCLUSIONBoth morphological and functional abnormalities of the platelets from the patient were clearly distinguishable from that of other hereditary giant platelet disorders. It would probably represent a novel platelet disorder which had not been reported to date.

Aspirin ; pharmacology ; Bernard-Soulier Syndrome ; metabolism ; pathology ; Blood Platelet Disorders ; metabolism ; pathology ; Cell Size ; physiology ; Child ; Cytoplasmic Granules ; pathology ; ultrastructure ; Female ; Humans ; Platelet Aggregation ; drug effects ; physiology ; Platelet Aggregation Inhibitors ; pharmacology ; Platelet Membrane Glycoproteins ; genetics ; metabolism ; Ticlopidine ; pharmacology

Objective To explore the correlation of waist-to-height ratio (WHtR) and triglycerides (TG) with changes in cerebral hemodynamic index (CVHI) and the risk of stroke. Methods From March 2018 to March 2019, a total of 500 medical examinees were selected from the civil servants who underwent a physical examination in the physical examination department of our hospital. According to the TG level, the subjects were divided into two groups: HTG group (208 cases) and normal group (292 cases). According to WHtR value, the subjects were divided into an abnormal group (216 cases) and a normal group (284 cases). According to the test results, CVHI and other information the stroke risk was analyzed among the 4 groups. Results The right Vmax and bilateral Qmean, Vmean, Vmin, and Dp in the HTG group were significantly lower than those in the normal group (P<0.05), while the bilateral Wv, Zcv, Rv, DR, and Cp were higher than those in the normal group (P<0.05). The parameters of bilateral Vmax, Qmean, Vmean, Vmin, and Dp in the abnormal group were significantly lower than those in the normal group (P<0.05), while the bilateral Wv, Zcv, Rv, DR, and Cp were higher than those in the normal group (P<0.05). The CVHI scores of the HTG group and the abnormal group were lower than those of the normal group (P<0.05), and the FSP scores were higher than those of the normal group (P<0.05). The proportion of high-risk strokes with CVHI<75 and FSP score ≥10 in the HTG group were both higher than that in the normal group (P<0.05). There were 4 predictors including HTG, WHtR, CVHI score, and FSP score. There was a statistically significant difference in the etiology of stroke between CVHI and FSP (P<0.05). The risk of stroke in patients with abnormal WHtR increased by 2.746 times, and the relative risk of stroke in patients with CVHI<75 increased by 3.298 times. Conclusion WHtR abnormality and CVHI<75 were two independent predictors of stroke risk. HTG may increase the risk of stroke by affecting cerebral hemodynamic indicators.

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome