Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Hiatal hernia (HH) is a prevalent medical condition characterized by the protrusion of abdominal contents into the thoracic cavity through an enlarged diaphragmatic esophageal hiatus. The most common clinical manifestations of HH include acid reflux, heartburn, belching, coughing, and chest pain. Currently, there is a lack of standardized comprehensive treatment protocols for different types of HH, presenting significant challenges in their clinical management. In light of this, individualized treatment approaches should be followed by surgical practitioners when dealing with HH, in order to formulate the most appropriate clinical treatment plan tailored to each patient′s specific circumstances.

As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.

Objective To compare the difference and effectiveness between Tetra-ataxiametry and Berg balance scale (BBS) in predicting the risk for fall in the elderly inpatients.Methods A total of 401 elderly inpatients were randomly selected using convenience sampling in a class III grade A hospital. Tetra-ataxiametry and BBS were used to monitor the risk for falls of elderly patients in two groups: group with or without fall histories.Results Fall histories were set as the standard. The area ratios under receiver operating characteristic (ROC) of Tetra-ataxiametry fall index (FI) and BBS were 0.762 and 0.705. Youden index showed that the predicted value, the sensibility and the specificity of Tetra-ataxiametry FI were 41, 80.5% and 60.2%; while those for BBS were 46, 67.1% and 65.8%. No statistically significant difference in the area under the curve (AUC) between Tetra-ataxiametry and BBS was observed(P=0.0587).Conclusions There is no statistically significant difference in predicting the risk for fall in the elderly inpatients between Tetra-ataxiametry and BBS, suggesting that Tetra-ataxiametry can replace BBS to evaluate the fall risk, and is better than BBS, since Tetra-ataxiametry has higher sensitivity in objective data provision, body weight and BMI (body mass index).

Objective To investigate the phenotypic and genetic characteristics of the lysostaphin‐resistant Staphylococcus aureus variants induced by recombinant lysostaphin in vitro .Methods Three clinical isolates of S . aureus ,including two resistant to methicillin (MRSA ) and one susceptible to methicillin (MSSA ) were induced by treatment with sub‐MIC of recombinant lysostaphin via one‐step selection in vitro .Susceptibility of the variants to antibiotics were determined and compared with their parental strains .The full length of femABX genes was amplified by polymerase chain reaction and sequenced to identify the potential mutation sites in these genes .The growth‐curve in liquid medium and virulence in a mouse systemic infection model of both parental and variant strains were observed . Results The frequency of lysostaphin resistance in S . aureus was between 10-4 to 10-8 following induction by lysostaphin . Resistance to lysostaphin was associated with a significant decrease in growth rate in vitro and virulence in vivo ,as well as increased susceptibility toβ‐lactams evidenced by the M IC of β‐lactams against the variants as low as 1/4 000 to 1/2 of the M IC against their parental strains . Sequencing of f emA BX genes showed mutation in femA gene in both variants ,which resulted in a premature termination codon .Conclusions Resistance of S . aureus to lysostaphin may develop following induction by recombinant lysostaphin in vitro . The lysostaphin‐resistant S . aureus variants are characteristic of lower growth rate , decreased virulence ,and higher susceptibility to β‐lactams .

The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing, China. 173 A. baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance (HLAR, MIC to gentamicin and amikacin>512 µg/mL) phenotype selection by broth microdilution method. The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes (aac(3)-I, aac(3)-IIc, aac(6')-Ib, aac(6')-II, aph(4)-Ia, aph(3')-I, aph(3')-IIb, aph(3')-IIIa, aph(3')-VIa, aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id, ant(2″)-Ia, ant(3″)-I and ant(4')-Ia) and the 16S rRNA methylase genes (armA, rmtB and rmtC). Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS. Totally 102 (58.96%) HLAR isolates were selected. The HLAR rates for year 2006, 2007, 2008 and 2009 were 52.63%, 65.22%, 51.11% and 70.83%, respectively. Five modifying enzyme genes (aac(3)-I, detection rate of 65.69%; aac(6')-Ib, detection rate of 45.10%; aph(3')-I, detection rate of 47.06%; aph(3')-IIb, detection rate of 0.98%; ant(3″)-I, detection rate of 95.10%) and one methylase gene (armA, detection rate of 98.04%) were detected in the 102 A. baumannii with aac(3)-I+aac(6')-Ib+ant(3″)-I+armA (detection rate of 25.49%), aac(3)-I+aph(3')-I+ant(3″)-I+armA (detection rate of 21.57%) and ant(3″)-I+armA (detection rate of 12.75%) being the most prevalent gene profiles. The values of chi-square tests showed correlation of armA, ant(3″)-I, aac(3)-I, aph(3')-I and aac(6')-Ib with HLAR. armA had significant correlation (contingency coefficient 0.685) and good contingency with HLAR (kappa 0.940). The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A. baumannii infections. As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical important aminoglycosides (gentamicin, amikacin, tobramycin, etc), the function of aminoglycoside modifying enzyme gene(s) in A. baumannii carrying armA deserves further investigation.

Objective To investigate the changes of serum leptin levels and the influential factors in maintenance peritoneal dialysis patients.Methods Seventy-six peritoneal dialysis patients were chosen at the time before,and 3 months,6 months,12 months,18 months and 24 months after they began the peritoneal dialysis therapy,to examine body mass index (BMI),triceps skinfold thickness (TSF),abdominal circumference,homeostasis model assessment of insulin resistance (HOMA-IR),the plasma lipid profile,and leptin in the same situation.Results For 24 months,these patients showed higher serum leptin level than the values before commencing peritoneal dialysis treatment (P ＜ 0.01).The level of leptin was positively correlated with the BMI(r =0.412,P ＜ 0.01),TSF(r =0.308,P ＜ 0.01),abdominal circumference(r =0.284,P ＜ 0.01),HOMA-IR(r =0.184,P ＜ 0.01) and TG(r =0.288,P ＜ 0.01),negatively corelated with the high-density lipoprotein cholesterol(HDL-C)(r =-0.285,P ＜ 0.01).Multiple logistic regression analysis showed that BMI (β =0.339,P ＜ 0.01),TGβ =0.157,P ＜ 0.01) and HDL (β =-0.126,P ＜ 0.05)were significant predictive factors for the changes of serum leptin levels.Conclusion Leptin maybe involve in the occurrence and the development of cardiovascular events like other metabolic parameters in peritoneal dialysis therapy.

Objective To investigate the pathogens,drug resistance and outcomes of continuous ambulatory peritoneal dialysis(CAPD) patients with peritoneal dialysis-related peritonitis in our peritoneal dialysis(PD) centers. Method Data including clinical manifestations,pathogens,treatment,outcome of 93 CAPD cases with peritoneal dialysis-related peritonitis in our peritoneal dialysis(PD) centers were retrospectively analyzed.Results Dialysate culture of 75cases was positive with a positive rate of 80.2％,including 45 cases of gram-positive cocci,21cases of gram-negative bacilli,2 cases of fungi and 5 cases of mixed infection.Coagulase-negative staphylococci were the most common gram-positive cocci.All the gram-positive cocci were sensitive to vancomycin,but the resistance rate to cefazolin was 60.0％ with an increasing tendence year by year.Resistance rate of gram-negative bacilli to ceftazidime was 46.1％.All the gram-negative bacilli were sensitive to imipenem.The withdraw rate of CAPD was 17.2％(16/93) because of peritonitis. Noobviousside-effectofperitonealadministrationofvancomycinwasfound.Conclusions Gram-positive cocci are major pathogens in CAPD-related peritonitis.Now cefasolin is not suitable for the empiric initial treatment.Peritoneal administration of vancomycin should be recommended for peritonitis caused by gram-positive cocci.

Allergic rhinitis (AR), with an increasing uptrend of the prevalence in many developed and developing countries, is a global health problem that affects people of all ages and ethnic groups. However, data on the prevalence of self-reported AR in western China are rare. This study investigated the epidemiological features of self-reported AR in western China. In the cross-sectional, population-based study, a validated questionnaire survey on self-reported AR was carried out in 4 major cities in western China by multistage, stratified and cluster sampling, from January to December 2008. The total prevalence rate was 34.3%, with 32.3% (Chongqing), 34.3% (Chengdu), 37.9% (Urumqi), 30.3% (Nanning), respectively. The prevalence presented to increase with age before 30 years old while decrease with age after 30 years old, and the highest prevalence was in 19-30 years group in Chongqing, Chengdu and Nanning which significantly showed "persistent and moderate-severe" type (P<0.0001); In Urumqi, there wasn't a significant increasing or decreasing trend of prevalence rate with age but with an "intermittent and mild"predominance (P<0.0001). There were no distinct sexual differences in prevalence rates in the 4 cities. The morbidity was positively related to monthly average temperature and sunshine (r=0.76645, P=0.0036; r=0.67303, P=0.0165), but negatively associated with relative humidity (r=-0.64391, P=0.0238) in Urumqi. Interestingly, the monthly morbidity was negatively associate with average temperature, sunshine and precipitation in Nanning (r=-0.81997, P=0.0011; r=-0.60787, P=0.0360; r=-0.59443, P=0.0415). Self-reported AR is becoming common in western China with a rapid development in recent years, affecting about three persons out of ten. The climatic factors may have an indirect impact on the prevalence rate through the effects on the local allergens.

Allergic rhinitis (AR),with an increasing uptrend of the prevalence in many developed and developing countries,is a global health problem that affects people of all ages and ethnic groups.However,data on the prevalence of self-reported AR in western China are rare.This study investigated the epidemiological features of self-reported AR in western China.In the cross-sectional,population-based study,a validated questionnaire survey on self-reported AR was carried out in 4 major cities in western China by multistage,stratified and cluster sampling,from January to December 2008.The total prevalence rate was 34.3％,with 32.3％ (Chongqing),34.3％ (Chengdu),37.9％ (Urumqi),30.3％ (Nanning),respectively.The prevalence presented to increase with age before 30 years old while decrease with age after 30 years old,and the highest prevalence was in 19-30 years group in Chongqing,Chengdu and Nanning which significantly showed “persistent and moderate-severe” type (P＜0.0001); In Urumqi,there wasn't a significant increasing or decreasing trend of prevalence rate with age but with an “intermittent and mild”predominance (P＜0.0001).There were no distinct sexual differences in prevalence rates in the 4 cities.The morbidity was positively related to monthly average temperature and sunshine (r=0.76645,P=0.0036; r=0.67303,P=0.0165),but negatively associated with relative humidity (r=-0.64391,P=0.0238) in Urumqi.Interestingly,the monthly morbidity was negatively associate with average temperature,sunshine and precipitation in Nanning (r=-0.81997,P=0.0011; r=-0.60787,P=0.0360; r=-0.59443,P=0.0415).Self-reported AR is becoming common in western China with a rapid development in recent years,affecting about three persons out of ten.The climatic factors may have an indirect impact on the prevalence rate through the effects on the local allergens.