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.

ObjectiveTo investigate the effects of the inoculation of potassium-solubilizing bacteria on the rhizosphere soil microenvironment of Paris polyphylla var. yunnanensis. MethodThe effects of different potassium-solubilizing bacteria on the physical and chemical properties， microbial community structure， and soil enzyme activity in the rhizosphere soil of P. polyphylla var. yunnanensis were investigated by pot planting at room temperature. The correlation of various indexes was analyzed. ResultThe inoculation with different potassium-solubilizing bacteria could significantly affect the physical and chemical properties of rhizosphere soil of P. polyphylla var. yunnanensis. The mass fractions of available nitrogen， available phosphorus， and available potassium were 24.5-90.5 mg·kg^-1， 2.53-25.9 mg·kg^-1， and 132-312 mg·kg^-1， respectively， and the soil pH was 7.08-7.75， which were in line with the optimal ranges of P. polyphylla var. yunnanensis planting. The inoculation of different potassium-solubilizing bacteria could affect the number of bacteria， actinomycetes， and fungi in rhizosphere soil to varying degrees. The transformation of soil from "fungal type" to "bacterial type" marks the improvement of soil fertility. It also affected the enzyme activity of rhizosphere soil， and the activities of neutral phosphatase， protease， and polyphenol oxidase showed an increasing trend. The correlation analysis showed that the number of bacteria was negatively correlated with the number of fungi （r=-0.856， P<0.01）， positively correlated with the number of actinomycetes， the content of available nitrogen and available potassium， and negatively correlated with soil pH. ConclusionThe inoculation of potassium-solubilizing bacteria can effectively improve the content of available potassium， available nitrogen， available phosphorus， and other nutrients in the rhizosphere soil of P. polyphylla var. yunnanensis， improve soil fertility， alleviate the continuous cropping obstacles of P. polyphylla var. yunnanensis， and lay a theoretical foundation for the green and sustainable development of P. polyphylla var. yunnanensis.

Objective: To explore the internal mechanism of short-term mindfulness intervention in reducing individual anxiety and stress perception. Methods: Totally 134 subjects were recruited and randomized into attention group (n=53), acceptance group (n=41) and control group (n=40). Attention group received observation of breathing intervention program, acceptance group received acceptance of negative emotions intervention program and the control group did not intervene mindfulness and read the social science materials of history. Before and after intervention, cancelled tasks were used to stimulate anxiety and stress perception, and self-rating anxiety scale and Chinese perceived stress scale (CPSS) were used to measure anxiety and stress perception level, and the results of cancelled tasks were recorded. Variance analysis and multiple linear regression were used for data statistics. Results: The changes of anxiety in attention group and acceptance group((-1.44±2.42)and(-1.06±2.58)) were significantly higher than that in control group(0.08±2.56)(both P<0.01). On the basis of controlling the changes of gender, age, number of cancellations and pre-test anxiety, the differences between groups had no significantly predictive effect on pre-cancellative anxiety(P>0.05). The attention group had significant predictive effect on anxiety in post-projected cancellative task compared with the control group (t=-2.84, P<0.01), while the acceptance group had no significant predictive effect on anxiety in post-projected cancellative task compared with the control group(P>0.05). Conclusion Attention and acceptance play different roles in short-term mindfulness training. Attention factor in mindfulness plays a key role in reducing anxiety level in individual tasks.

Objective: To investigate the effect of silencing troponin I3 (Tnni3) gene expression on biological property of rat embryonic H9C2 cardiomyocytes. Methods: The rat embryonic H9C2 cardiomyocytes were cultured and divided into 2 groups: control group transfected with negative control small interfering RNA (NC-siRNA group) and experimental group transfected with Tnni3 small interfering RNA (Tnni3-siRNA group). At 48 h, 72 h after transfection, the cells were collected, and real time quantitative polymerase chain reaction (qPCR)was used to detect the mRNA expressions of Tnni3 and Caspase-3, and Western blot was used to detect the protein expressions of Tnni3, Cyclin A1 and Cyclin B1.Annexin V-fluorescein isothiocyanate(FITC) apoptosis detection kit was used to analyze cell apoptosis.Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) solution and cell cycle was detected by flow cytometry. Results: At 48 h post-transfection with Tnni3-siRNA, H9C2 cells exhibited a significant decrease in Tnni3 mRNA (0.27±0.05 vs. 1.00±0.00) and protein (0.18±0.03 vs. 1.00±0.00) compared with those transfected with NC-siRNA, and the differences were statistically significant (t=25.26, 47.40, all P<0.01). Apoptotic cells were observed in the NC-siRNA group and the Tnni3-siRNA group.At 72 h post-transfection, the percentage of apoptotic cells significantly increased in H9C2 cells transfected with Tnni3-siRNA [(11.30±1.85)% vs. (0.33±0.15)%] compared with those transfected with NC-siRNA, an increased expression of Caspase-3 mRNA was also observed in Tnni3-siRNA-transfected H9C2 cells (1.39±0.13 vs. 1.00±0.00), and the differences were statistically significant (t=10.24, 5.19, all P<0.01). Compared with NC-siRNA-transfected H9C2 cells, a time-dependent reduction in cell proliferation was observed in Tnni3-siRNA-transfected H9C2 cells (48 h: 0.32±0.06 vs. 0.46±0.03; 72 h: 0.31±0.01 vs. 0.63±0.04; 96 h: 0.36±0.01 vs 0.75±0.04), and the differences were statistically significant (t=3.62, 13.45, 16.39, all P<0.01). At 72 h post-transfection with Tnni3-siRNA, the percentage of G1 phase, S phase and G2 phase cells was (71.25±3.82)%, (18.28±2.78)% and (9.94±1.09)%, respectively.There was a significant increase in the proportion of G2 phase cells [(9.94±1.09)% vs. (4.54±0.99)%] in H9C2 cells transfected with Tnni3-siRNA compared with those transfected with NC-siRNA, an increased expression of Cyclin A1 protein (1.89±0.09 vs.1.00±0.00) and a decreased expression of Cyclin B1 protein (0.47±0.06 vs.1.00±0.00) were observed in Tnni3-siRNA-transfected H9C2 cells, respectively, and the differences were statistically significant (t=6.35, 17.12, 15.32, all P<0.01). Conclusions Silencing Tnni3 gene expression in rat embryonic H9C2 cardiomyocytes can induce cell apoptosis, suppress cell proliferation, and led to G2 cell cycle arrest.

Objective To investigate the effects of metformin on myocardial fibrosis induced by isoproterenol(ISO) in rats and its mechanism. Methods A total of 48 SD male rats were randomly divided into four groups,normal control group,model control group,valsartan group and metformin group. Cardiac fibrosis models were induced in model group, Valsartan group and metformin group by subcutaneous injection of ISO 10 mg·kg-1·d-1in the 1stday, 5 mg·kg-1·d-1in the 2ndday, 3 mg·kg-1·d-1in the 3rd-10thday. Valsartan group and metformin group were fed valsartan 10 mg·kg-1, qd or metformin 100 mg·kg-1,bid for 28 days respectively.Rats were killed at the 3rdday,the 7thday,the 14thday and the 28thday.The value of HMI,LVMI,LVW/TL were measured,and pathological alteration were observed by HE staining and Masson staining,TGF-β and Smad3 protein expression in left ventricular myocardium were detected by western blotting,and IL-6 level in serum were detected by ELISA. Results The serum levels of IL-6 in control group, model group, valsartan group and metformin group were (59.18± 0.86) pg·mL-1, (71.90±1.35) pg·mL-1, (64.33±2.59) pg·mL-1and (65.45±1.92) pg·mL-1respectively on the 28th day. Compared with control group, the serum levels of IL-6 in model group were significantly increased(P<0.01), while their levels significantly reduced in rats received metformin (P<0.05). Conclusion Metformin may inhibit myocardial firbosis by TGF-β/Smads pathway.

Objective To evaluate the protective effect of ACEI drugs on radiation pneumonitis,and to compare ACEI with ARB,statin, steroid, and NSAID on the treatment of radiation induced lung injury through the network Meta-analysis. Methods A computer-based online search of PubMed, EMbase, Cochrane Library, as well as CNKI, CBM, VIP, Wanfang database was conduce. The NOS score was used to evaluate the quality of studies,and the results were analyzed by stata14. 0 software. Results ACEI drugs showed desired effect on the treatment of radiation pneumonia,which can effectively reduce the incidence of radiation-induced lung injury,but can not prolong the survival time of the patients.The protective effects of statins and non-steroid anti-inflammatory drugs are second only to those of ACEI.Meta-analysis results were proved to be stable and credible by the sensitive-analysis.The therapeutic effect of ACEI on radiation induced lung injury is not affected by sex and age of patients. Conclusion ACEI drugs have an optimum protective effect on radiation induced lung injury.

Objective To explore the safety and feasibility of vagus nerve-preserving Da Vinci robotassisted radical gastrectomy for gastric cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 12 gastric cancer patients who underwent vagus nerve-preserving Da Vinci robotassisted radical gastrectomy at the Southwest Hospital of the Third Military Medical University from January 2015 to November 2016 were collected.All patients underwent vagus nerve-preserving Da Vinci robot-assisted radical gastrectomy for gastric cancer.During operation,lymph node dissection of the pyloric region,the right side of the cardia and the superior margin of the pancreas were noticed,and other surgical procedures were the same as the traditional Da Vinci robot-assisted radical gastrectomy.Observation indicators:(1) intra-and post-operative situations:surgical methods,digestive tract reconstruction,operation time,volume of intraoperative blood loss,number of lymph node dissected,results of postoperative pathological examination,recovery time of gastrointestinal function,time for liquid diet intake,duration of postoperative hospital stay,short-term surgery-related complications (postoperative bleeding,anastomotic fistula,obstruction and intra-abdominal infection);(2)follow-up situations:postoperative long-term complications (gastric retention,alkaline reflux gastritis,dumping syndrome,gallbladder disease and cholelithiasis),postoperative quality of life (diet,upper abdominal discomfort,nausea,vomiting and diarrhea),postoperative nutritional status [body weight,hemoglobin (Hb),total protein (TP),albumin (Alb)] and tumor recurrence.Follow-up using telephone interview and outpatient examination was performed up to December 2016.Telephone interview included detecting diet of patients,digestive tract symptoms and body weight.Routine blood test,liver and kidney functions,tumor markers,chest X-ray,abdominal computed tomography (CT) or color Doppler ultrasound and gastroscopy of outpatient examinations were performed to detect tumor recurrence and metastasis.Measurement data with normal distribution were represented as x±s and measurement data with skewed distribution were described as M (range).Results (1) Intra-and post-operative situations:all the 12 patients underwent successful vagus nerve-preserving Da Vinci robot-assisted radical gastrectomy for gastric cancer,without conversion to laparoscopic surgery or open surgery,including 2 patients with D1 lymphadenectomy,2 patients with extended D1 lymphadenectomy and 8 patients with D2 lymphadenectomy.Five and 7 patients underwent respectively Billroth Ⅰ anastomosis and Billroth Ⅱ anastomosis of digestive tract reconstruction.Operation time,volume of intraoperative blood loss and number of lymph node dissected of 12 patients were (247± 34) minutes,(94 ± 23) mL and 27 ± 7,respectively.Results of postoperative pathological examination showed that distal and proximal surgical margins of 12 patients were negative and achieved R0 resection;326 lymph nodes were dissected,6 patients didn't have lymph node metastasis and 18 positive lymph nodes were detected in 6 patients.Recovery time of gastrointestinal function,time for liquid diet intake and duration of postoperative hospital stay in 12 patients were (57±14)hours,(64± 14)hours and (7.3±0.9)days,respectively.There was no occurrence of short-term surgery-related complications.(2) Follow-up situations:12 patients were followed up by telephone interview (10 receiving outpatient exaninations) for 9 months (range,1-20 months).Of 12 patients with long-term complications,2 had loss of appetite,1 had diarrhea,without occurrence of cholelithiasis,cholecystitis,gastric retention and dumping syndrome.Of 10 patients receiving outpatient examinations,body weight,Hb,TP and Alb were (56± 12) kg,(126± 10) g/L,(69.9±5.1) g/L,(43.2±3.3)g/L at 1 month postoperatively and (52±13)kg,(126±10)g/L,(72.1±2.4)g/L,(45.2±1.6)g/L at 3 months postoperatively,respectively,with negative carcinoembryonic antigen.There was no tumor recurrence and metastasis in 12 patients.Conclusion Vagus nerve-preserving Da Vinci robot-assisted radical gastrectomy is safe and feasible for gastric cancer,which has not affected the lymph node dissection and incidence of surgeryrelated complications,and it also can improve the postoperative quality of life and maintain good nutritional status.

Objective To evaluate the efficacy of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in the treatment of idiopathic pulmonary fibrosis through the method of system evaluation. Methods A computer-based online search of Pubmed, Embase, Cochrane Library, CNKI, CBM and Wanfang were used for database retrieval. Revman 5.0 was used to assess the bias of the included studies. The Stata 14.0 was used to evaluate the extraction indexes of efficacy, p (O2), p (CO2), DLco, FEV1 and VC. GRADE score was used to evaluate the level of evidence. Results A total of 17 articles (related with 1381 patients) were included in this study, including 14 studies using ARB and 3 studies using ACEI. Compared with the control group ACEI and ARB drugs showed advantages in the treatment of pulmonary fibrosis (RR=1.34, 95%CI:1.24-1.44, Z=7.81, P<0.001). Auxiliary index analysis showed that the test groups were treated with enalapril (SMD=0.72, 95%CI:0.21-1.22, Z=2.77, P=0.006), telmisartan (SMD=3.86, 95%CI:2.44-5.27, Z=5.35, P<0.001), valsartan (SMD=1.94, 95%CI:1.33-2.55, Z=6.27, P<0.001) and captopril (SMD=0.60, 95%CI:0.11-1.09, Z=2.41, P=0.016), the p(O2) levels were significantly improved in patients ≥65 years old (SMD=0.76, 95%CI:0.52-1.00, Z=6.18, P<0.001) and patients < 65 years old (SMD=3.97, 95%CI:2.61-5.32, Z=5.73, P<0.001), and disease duration≥5 years (SMD=1.39, 95%CI:0.45-2.33, Z=2.89, P=0.004) and disease duration<5 years (SMD=3.26, 95%CI:2.06-4.46, Z=5.34, P<0.001) compared with those of control group (SMD=2.95, 95%CI:1.95-3.94, Z=5.82, P<0.001). The curative effect of telmisartan was better than that of other drug groups (P < 0.001), and which was much better for patients under 65 years old (P<0.001). There was no significant difference in the disease duration between two groups (P=0.307). The p (CO2) levels were significantly improved in patients treated with telmisartan [SMD=-12.94,95%CI:(-14.01)-(-11.86),Z=23.51,P<0.001), valsartan [SMD=-1.95,95%CI:(-2.56)-(-1.34),Z=6.29,P<0.001] compared with those of control group [SMD=-11.13,95%CI:(-17.03)-(-5.24),Z=3.70,P<0.001]. The effect of telmisartan was better than that of valsartan (P<0.001). In addition, values of DLco (SMD=0.64, 95%CI:0.45-0.83, Z=6.72, P<0.001), FEV1 (SMD=1.19, 95%CI:0.52-1.86, Z=3.47, P<0.001) and VC (SMD=0.51, 95%CI:0.16-0.85, Z=2.85, P=0.004) were improved in test group compare with those of control group. And the GRADE scores of relevant indexes were low quality to moderate quality. Conclusion ACEI and ARB can improve the efficacy, the p (O2) and p (CO2) in the treatment of pulmonary fibrosis. Patients with age<65 years old and treated with telmisartan have the best curative effect, and which is not related to the disease duration.

Objective To investigate the safety and feasibility of totally Da Vinci robotic surgical system in the radical gastrectomy of gastric cancer.Methods The retrospective cross-sectional study was conducted.The clinical data of 30 patients who underwent radical gastrectomy of gastric cancer via totally Da Vinci robotic surgical system in the Southwest Hospital of Army Medical University between June 2016 and August 2017 were collected.Surgical methods were selected according to Expert consensus on enhanced recovery after gastrectomy for gastric cancer (2016 edition).Observation indicators:(1) surgical and postoperative situations;(2) follow-up.Followup using outpatient examination and telephone interview was performed to detect the patients' postoperative survival and tumor recurrence and metastases up to September 2017.Measurement data with normal distribution were represented as (x)±s and measurement data with skewed distribution were represented as median (range).Results (1) Surgical and postoperative situations:30 patients underwent radical gastrectomy of gastric cancer using totally Da Vinci robotic surgical system,without conversion to laparoscopic or open surgery.Of 30 patients,21 underwent distal subtotal gastrectomy including 1 with Billroth Ⅰ anastomosis and 20 with Billroth Ⅱ anastomosis,9 underwent total gastrectomy with Roux-en-Y anastomosis.Of 30 patients,1 underwent D1 radical gastrectomy,24 underwent D2 radical gastrectomy and 5 underwent D2+ radical gastrectomy.The number of lymph node detected,length of abdominal incision,operation time and time of digestive tract reconstruction were 34±12,(4.1 ±0.5)cm,(269±52) minutes and (49±9) minutes in 30 patients,including 31 ±21,(4.0±0.9) cm,(253±61) minutes,35 minutes (1 with Billroth Ⅰ anastomosis) and (38 ± 10) minutes (20 with Billroth Ⅱ anastomosis) in 21patients undergoing distal subtotal gastrectomy and 46± 12,(4.0±0.5) cm,(325±30) minutes,(64± 12) minutes in 9 patients undergoing total gastrectomy.The volume of intraoperative blood loss,postoperative pain score,time for out-of-bed activity,time of gastrointestinal function recovery,time for fluid food intake and time of drainage tube removal were (78±43) mL,2.5±0.5,(33±8) hours,(59± 13) hours,(66± 32) hours and (64±21) hours,respectively.Of 30 patients,2 with postoperative complications were cured by conservative treatment,including 1 of left lower lobe infection and 1 of abdominal abscess.Duration of postoperative hospital stay was (7± 5)days.(2) Follow-up:30 patients were followed up for 1.0-15.0 months,with a median time of 7.5 momths.During follow-up,2 patients died of tumor recurrence at postoperative half year and 1 year,1 patient still survived with tumor recurrence and other 27 patients had tumor-free survival.Conclusion The totally Da Vinci robotic surgical system is safe and feasible in the radical gastrectomy of gastric cancer,with good short-term outcomes.

OBJECTIVETo explore the efficacy and prognostic factors of induction therapy combined with autogenetic peripheral blood stem cells transplantation (APBSCT)in patients with multiple myeloma (MM).

METHODSFrom January 1998 to May 2015, 201 patients with MM were enrolled. All patients received APBSCT after induction therapy. With the follow up to 20 June 2015, the overall survival (OS), progression free survival (PFS)and prognostic factor were analyzed.

RESULTS① With a media follow up of 36.67 months, the median PFS and OS were 22.87 (17.48- 28.26)and 69.63 (63.57- 75.69)months, 5-year PFS and OS were 17% and 49%, respectively. ②After APBSCT, when the subgroup (n= 112) achieved complete response (CR)compared with the subgroup (n=89) not achieved CR, the median PFS were 32.93 (21.03-44.83) and 18.13 (14.46-21.80) months (P<0.001), respectively; And the media OS were 96.77 (71.79- 121.75)and 54.70 (49.53- 59.87) months (P=0.004), respectively. The risks for disease progression and death declined in CR subgroup. ③ Two subgroups included or not included bortezomib/thalidomide at induction therapy (123 patientsvs 21 patients), the media PFS were 31.67 (24.36- 38.98)and 15.20 (10.11- 20.29) months (P=0.013), respectively; And the media OS were 76.30 (55.44- 97.15)and 52.03 (33.76- 70.30) months (P=0.014), respectively. ④According to the ISS stage, the media OS of stageⅠ, Ⅱ, Ⅲ were 99.47 (59.58-139.36), 66.77 (52.17-81.37), 53.97 (28.71-79.23) (P< 0.001), respectively. The risk for death of stage Ⅱ, Ⅲ were 2.16 and 3.04 times higher than stage Ⅰ, with no difference in terms of PFS. ⑤ The media PFS in IgD (n=22) and IgG (n=101) type MM were 11.17 (10.27- 13.13)and 35.43 (22.69- 48.17)months (P=0.007) , respectively; The media OS were 30.83 (0.24-61.42)and 70.70 (53.52-87.88) months (P=0.039), respectively. The risk for disease progression of IgD type was 2.47 times higher than IgG type. ⑥ Patients received 1 line induction therapy (n=132) compared with more than 1 line (n=69), the media PFS were 25.43 (16.09- 34.77)and 20.27 (15.04- 25.50) months (P=0.042). ⑦Cox analysis showed that CR after APBSCT and ISS stage were independent prognostic factors for OS. IgD type MM and CR after APBSCT were independent prognosis factor for PFS.

CONCLUSIONCR after APBSCT and ISS stage were independent prognostic factors for OS in MM. CR after APBSCT was independent prognostic factor for PFS in MM. However, disease progression more likely occurred in IgD type MM, which was independent negative prognostic factor for PFS in MM.

Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; therapeutic use ; Disease-Free Survival ; Humans ; Multiple Myeloma ; diagnosis ; therapy ; Neoadjuvant Therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Remission Induction ; Survival Rate ; Thalidomide ; therapeutic use ; Transplantation, Autologous ; Treatment Outcome