Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged to be one of the world's greatest health threats. However, not only have recent decades shown a steady decline in the number of approved antimicrobial agents but a disappointing discovery also void. The development of novel antibiotics to treat MDR Gram-negative bacteria has been stagnated over the last half century. Though few compounds have shown activities in vitro, in animal models or even in clinical studies, the global antibiotic pipeline is not encouraging. There are a plethora of unexpected challenges that may arise and cannot always be solved to cause promising drugs to fail. This review intends to summarize recent research and development activities to meet the inevitable challenge in restricting the proliferation of MDR Gram-negative bacteria, with focus on compounds that have entered into clinical development stage. In addition to new analogues of existing antibiotic molecules, attention is also directed to alternative strategies to develop antibacterial agents with novel mechanisms of action.

Orthopedic robotics is an emerging industry in the area of healthcare , mainly used for minimally invasive treatment and accurate treatment .It can provide accurate surgical navigation and planning .Orthopedic robots can be mainly used for articular surgery , osteopathy surgery , spine surgery and traumatic orthopedics .This paper outlines the development and characteristics of orthopedic robots at home and abroad , analyzes the developments of orthopedic robots by combining medical imaging technology with clinical feedback , and predicts the future of this field .

Objective:To compare liver adhesive suspension method and V-shaped liver suspension of anterior abdominal wall in laparoscopic radical gastrectomy.Methods:This study retrospectively evaluated 115 patients who underwent laparoscopic radical gastrectomy from Jan 2018 to Dec 2019 at Shanxi Provincial People′s Hospital, 59 cases were under liver adhesive suspension (study group) and 56 cases under V-shaped liver suspension of anterior abdominal wall (control group). Intraoperative and postoperative conditions were observed and compared between the two groups.Results:All the 115 cases successfully completed surgery. The liver suspension time in study group was (2.4±0.5)min, which was significantly shorter than that of the control group((12.5±2.6) min)( t=-28.100, P<0.01). The total operation time in was (284±69) min and (307±78) min, respectively, ( t=-1.656, P=0.10). There were no statistically significant differences between the two groups in preoperative ALT, AST, total bilirubin, intraoperative incidence of hepatic lacerations and subcapsular hematoma, postoperative total bilirubin level, AST on the day 7 postoperatively, tumor location, TNM staging, surgical method, postoperative duration of hospital stay, and VAS score ( P>0.05). Conclusions:Both methods of liver suspension are safe and feasible in laparoscopic surgery for gastric cancer.Compared with V-shaped liver suspension of anterior abdominal wall, liver adhesive suspension has the advantages of less invasive, safe, and time-saving.

Objective To discus the diagnosis,favorabl management and diagnosis of pilocytastrocytoma.Methods Provided by the information from CT,MRI and operation,we try to discus and confirm the characteristics of this tumor.Results Pilocytastrocytoma commonly occurs in 20 years old or younger.The most frequent location involve by tumor were cerebellum.The most common presenting sympton was increased intracranial pressure,and then cerebellum symptoms such as incoordination.Final diagnosis made depending on mainly pathology.We found the relationship between prognosis and the extent of surgical removal.Conclusions Pilocytastrocytoma usually occur in children and adolescent.The most common site of these tumors are the cerebellum.And the more complete extent of surgical removal,the better prognosis.So it was called as "benign" tumors.If pilocyticastrocytoma were subtotally excised,the addition of postoperative irradiati could significantly prolong survival.

Objective To construct the eukaryotic expression plasmid for the expression of human Connexin26 in COS-7 cells.Methods Total RNA was isolated from human peripheral blood lymphocytes and used as template for the PCR cloning of the human Connexin26 gene.The human Cx26 cDNA containing the 678 bp whole coding region of the human Connexin26 gene was amplified by PCR using specific primers and cloned into the pCI-neo vector to construct the recombinant eukaryotic expression plasmid,pCI-Cx26.The recombinant plasmid was identified by restriction endonuclease digestion,and transfected into COS-7 cells by liposome.The expression of Cx26 mRNA and the protein were analyzed by RT-PCR and SDS-PAGE,respectively.Results Restriction endonuclease digestion analysis verified successful construction of the recombinant plasmid,pCI-Cx26.The expression of Cx26 mRNA and protein in the transfected COS-7 cells were detected by RT-PCR and SDS-PAGE,respectively.Conclusion The eukaryotic expression plasmid for human Cx26 has been constructed successfully with the capability of expression in COS-7 cells.

Objective To study the correlation between lactate/albumin ratio level and incidence of multiple organ dysfunction syndrome (MODS) as well as mortality in patients with severe sepsis or septic shock.Methods In January 2012-September 2013, 54 patients who were admitted to the intensive care unit(ICU) of a hospital developed severe sepsis and septic shock on the first day of admission, clinical data of patients were analyzed.Results On the first and second days of admission, 30(55.56%)and 26(53.06%)patients developed MODS;lactate/albumin ratio between MODS group and non-MODS group on the first and second days of admission were both significantly different (both P<0.05).Multivariate logistic regression analysis showed that lactate/albumin ratio, oxygenation index (PaO2/FiO2), as well as acute physiology and chronic health evaluation (APACHE Ⅱ) were independent risk factors for predicting MODS in patients with severe sepsis.Lactate/albumin ratios between MODS group and non-MODS group, death group and non-death group were both significantly different (both P<0.05);lactate/albumin ratio was correlated with APACHE Ⅱand PaO2/FiO2, the higher the APACHE Ⅱ score and the lower the PaO2/FiO2, the higher of lactate/albumin ratio.The area under the receiver operating curve (ROC curve) analysis showed that incidence and mortality of MODS on the first day of admission predicted by lactate /albumin ratio were 0.85 and 0.84 respectively;sensitivity, specificity, positive predictive value, and negative predictive value of occurrence of MODS predicted by lactate /albumin ratio>1.735 were 80.00%, 79.17%, 82.67%, and 75.92% respectively, sensitivity, specificity, positive predictive value, and negative predictive value of mortality were 100.00%, 51.02%, 17.23%, and 100.00% respectively.Conclusion Lactate/albumin ratio level is closely correlated with incidence and mortality of MODS in patients with severe sepsis or septic shock.

Objective To evaluate the feasibility and efficacy of twin grasper combined with endoloops on closing acute stomach perforation.Methods Two experimental porcines of stomach perforation underwent endoscopic closure by twin grasper combined with endoloops.Survival conditions and closure of perforating were observed.Results Mild infection and abdominal adhesions were observed in one week after operation.The nylon rope fell off and an ulcer-like lesion was presented in the closed position.The methylene blue leak test was negative.Histologic examination revealed chronic inflammatory cells infiltration,granulation,fibroplasias,and regenerative mucous membrane crawling toward the center of perforation.Conclusion The technique of twin grasper combined with nylon ropes in closing the acute stomach perforation is feasible and effective.

Objective To explore the feasibility of intravoxel incoherent motion DWI (IVIM-DWI) in differential diagnosis of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH).Methods A total of 407 patients with clinically-suspected HCC or FNH underwent conventional and dynamic enhanced MRI and IVIM-DWI,60 patients (40 cases of HCC,20 cases of FNH) were enrolled.Parameters of ADC,slow apparent diffusion coefficient (D),fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f) were obtained by monoexponential model and biexponential model respectively.Results The values of ADC,D,D* and f in FNH group were (1.60±-0.25) × 10-3mm2/s,(1.12±0.17)×10-3mm2/s,(44.89±18.23)× 10-3 mm2/s and (34.80 ± 9.68)％,and those in HCC group were (1.32 ± 0.21) × 10-3 mm2/s,(0.82±-0.21) × 10-3mm2/s,(49.82±20.11) × 10 3mm2/s and (28.72±13.84) ％,respectively.Significant inter-group differences were observed in ADC and D (both P＜0.001),however,there were no significant differences in D* and f (both P＞0.05).The areas under the ROC curve of D were 0.90,and taking D=0.96 × 10-3 mm2/s as cut-off value,the sensitivity and specificity of D in diagnosis of HCC were 84.44％ and 90.02％.Conclusion IVIM-DWI is useful to distinguish FNH from HCC,and the D value in biexponential model has the best diagnostic efficacy for differentiations.

Objective To prepare a conjugate vaccine by linking Haemophilus influenzae type b (Hib)polysaccharide to PsaA protein carrier and evaluate the immunogenicity and efficacy of the conjugate vaccine. Methods A recombinant protein rPsaA,expressed by using the genetic engineering technology, was used as a protein carrier to prepare conjugate vaccine together with Hib polysaccharide. Ten mice at age of 3 weeks were immunized with the conjugate vaccine,while another 10 age-matched mice were immunized with Hib-tetanus toxoid(Hib-TT)vaccine which was produced formerly as a control. The mice treated with equal volume of PBS were set up as the negative control. The IgG antibodies in serum samples against PsaA and Hib polysaccharide were detected in two weeks after the final immunization. A suspension of Pneumococ-cus was injected into the middle ears of mice from experiment and control group. Histopathological analysis was performed to measure the clearance of bacteria in the middle ears and the severity of infection on days 3 and 7 after bacterial challenge. Results The rPsaA protein was prepared by the genetic engineering tech-nology and purified successfully with anion-exchange column. The Hib polysaccharide-PsaA protein conju-gate vaccine was prepared through a series of amide condensation reactions. The detection of IgG antibodies against PsaA protein and Hib polysaccharide in the immunized mice demonstrated that there was no signifi-cant difference with the titer of IgG against Hib polysaccharide between the mice immunized with the Hib-PsaA conjugate vaccine and those immunized with the Hib-TT vaccine. Less Pneumococcus strains were de-tected in the middle ears of mice immunized with the conjugate vaccine than those mice immunized with the Hib-TT vaccine three days after challenge. The mice from control group showed severe inflammation in the middle ears than those from experiment group. The Hib polysaccharide-PsaA protein conjugate vaccine im-proved protection against Pneumococcus infections as compared with the Hib-TT vaccine. Conclusion The rPsaA protein could be produced by genetic engineering technology and purified by anion-exchange column. The Hib polysaccharide was successfully conjugated with the rPsaA protein through amide condensation reac-tion. Both anti-PsaA and anti-Hib immune responses were induced in young mice by the injection of Hib pol-ysaccharide-PsaA protein conjugate vaccine. Apart from providing protection against Hib infection,the con-jugate vaccine might also be used for the prevention of acute otitis media caused by Pneumococcus infection.

Objective:To explore management experience for post-adolescent postoperative urethral stricture of hypospadias in a single center.Methods:The clinical data of 71 cases of postoperative urethral stricture of post-adolescent hypospadias from January 2015 to December 2019 were retrospectively analyzed. The average age was 27.7(12-65) years. The mean duration of urethral stricture was 33.4(1-240) months. The number of prior surgeries was 2.5(1-9). There were 32 cases of ectopic urethral orifice, including 22 on penile, 8 on scrotum and 2 on perineum. There were 17 cases of urethral stricture with penile curvature, 11 with urethra-cutaneous fistula, 9 with urethral diverticulum, 11 with urethral calculus and 25 with urethral infection. Ten patients kept suprapubic tubes; 61 patients were able to urinate on their own, but suffered from dysuria and weak steam. The average maximum uroflow rate of 71 cases was 4.7(0-11.2) ml/s. The primary urethral reconstruction procedures were performed on 33 cases, included 11 penile or scrotal septum flap urethroplasty, 2 urethral diverticulum wall flap urethroplasty, 12 oral mucosal urethroplasty and 8 urethrotomy. Thirty-three cases underwent two-staged surgery. For patients with penile curvature greater than 30 degrees, the penis was straightened with a urethrotomy in first stage. Besides, the dorsal skin of penis or oral mucosal graft were transferred to the ventral side of the penis to the preset urethral plate. In second-stage, Denis Brown urethroplasty was performed on 23 patients, tubularized incised plate (Snodgrass) urethroplasty on 6, and oral mucosa inlay urethral plate (Snodgraft) urethroplasty on 4. In 5 cases, preplacing of oral mucosa was done in the second stage with a third-staged urethroplasty. Penile curvature was relieved by ventral scar resection with the folding the dorsal tunica albuginea of corpus cavernosum when necessary.Results:The mean follow-up time was 30.5(4-59) months. Sixty-one patients got satisfying postoperative urination, with an average maximum uroflow rate of 22.7 ml/s (15.8-37.2 ml/s). Restenosis occurred in 10 cases, and urethral fistula in 7 cases. Re-stricture patients underwent urethrotomy in 5 cases, augmented urethroplasty with flap in 4 cases, and urethroplasty with oral mucosal graft in 1 case. Among the 7 patients with urethral fistula, 5 were cured by one fistula repair, and 1 cured by second repair; the rest one was left untreated. 2 patients still had penile curvature after operation.Conclusions:It is difficult to manage post-adolescent postoperative urethral stricture of hypospadias, especially for patients with residual penile curvature greater than 30 degrees and lack of penile skin. Performing correction of the curvature and reconstruction of the urethral plate in first stage and Denis Brown urethroplasty or Snodgrass urethroplasty in second or third stage could achieve good results.