UNC-51-like kinase 1(ULK1)is an important factor involved in regulating the initiation of autophagy.ULK1 regu-lates inflammatory cytokines through autophagy and mitochondrial oxidative stress,and is involved in the pathological processes of var-ious diseases.ULK1 and its complexes are regulated by rapamycin(mTOR)and AMP-activated protein kinase(AMPK)to initiate au-tophagy,thereby exerting differential effects on a variety of inflammatory diseases.In inflammatory diseases,mitochondrial oxidative stress can induce ULK1 into the nucleus to accelerate apoptosis.Therefore,ULK1 plays different important roles in inflammatory dis-eases.For example,ULK1 initiates airway epithelial mitochondrial autophagy in asthma,participates in mitochondrial oxidative stress in acute liver failure,affects related inflammatory factors in atherosclerosis,and modulates beneficial effects of autophagy in diabetes.This article reviews the biological function of ULK1,its impact on inflammatory diseases and the research progress of targeted drugs.

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Objective:To understand the etiological characteristics of the patients with fever of unknown origin in Guizhou province through the isolation and identification of Leptospira interrogans and provide evidence for the control, prevention and treatment of human leptospirosis. Methods:Blood and urine samples were collected from patients with fever symptoms in Qiandongnan, an epidemic area, in Guizhou. The suspected Leptospira strains were primarily identified using pathogenic Leptospira specific G1/G2-PCR, and subsequently identified by using Leptospira serogroups specific PCR. The Leptospira strains were then genotyped with multiple locus sequence typing. MLST data based cluster analysis on the isolates and Leptospira reference strains of common serogroups were analyzed by using software NTsys 2.10e. Results:Three suspected strains of Leptospira were isolated from human blood samples, the isolation rate was 8.６%, which were designated as strain 17BX002, 17BX003 and 17AJX008. Strain 17BX002 was further identified as serogroup grippotyphosa by using Leptospira serogroup specific PCR, while the other two strains were negative (excluded as iterohaemorrhagiae, sejroe, canicola, autumnalis, grippotyphosa and hebdomadis). MLST genotyping showed that strain 17BX002 was typed as ST106, most closely clustered with Leptospira grippotyphosa, while strain 17BX003 and 17AJX008 were typed as ST96, the same as serogroup badaviae. Conclusion:There are leptospirosis cases in epidemic area of Guizhou in high incidence season, grippotyphosa and bataviae are the newly discovered serogroups of Leptospira in Guizhou.

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on social function and life quality of schizophrenia in long-term hospitalization.Methods Sixty patients met with ICD-10 for schizophrenia in long-term hospitalization were enrolled in this study.The group was divided randomly into research (n =40) and control (n =40) groups.They were given rTMS or sham stimulation,respectively.The treatment was given 20 times,and the course of treatment was 4 weeks.The research and control groups were assessed with measured the scale of social function in psychosis inpatients and personal and social function scale and schizophrenia quality of life scale before and'after 4 weeks treatment.Each test result of all groups before and after treatment was compared with each other,respectively.Results Compared to rTMS before treatment,the study group scale of social function in psychosis inpatients (SSPI) total score,factor Ⅰ,Ⅱ and personal and social function scale (PSP) scores were significantly increased (P ＜ 0.05),no change of SSPI factor (P ＞ 0.05);the study group Schizophrenia Quality of Life Scale (SQLS) total score,psychological and social power,the energy scale scores were significantly reduced (P ＜ 0.05),SQLS symptoms and side effects scale showed no significant difference (P ＞ 0.05).No significant change was found in the scores of project SSPI,PSP and SQLS in control group before and after treatment (P ＞ 0.05);the difference of each parameter between two groups after treatment were statistically significant (P ＜ 0.05).Conclusions Repetitive transcranial magnetic stimulation could improve on social function and life quality of schizophrenia in long-term hospitalization,rTMS could provide a new way for the individual rehabilitation of schizophrenia in long-term hospitalization.

Objective To investigate the bacterial resistance profile of clinical isolates collected in the hospitals across Chuzhou in 2016. Methods Antimicrobial susceptibility testing was carried out by Kirby-Bauer method. The data were analyzed using WHONET 5.6 software according to CLSI 2015 breakpoints. Results A total of 5 465 clinical isolates were collected during 2016, of which gram positive organisms and gram negative organisms accounted for 25.9％ (1 416/5 465) and 74.1％ (4 049/5 465), respectively. Prevalence of MRSA was 37.6％ among S. aureus and the prevalence of MRCNS was 78.1％ in CNS. All Staphylococcus, E. faecalis and E. faecium isolates were sensitive to vancomycin and linezolid. The prevalence of extended spectrum-lactamases (ESBLs) positive strains was 51.2％ in E. coli, 23.4％ in Klebsiella spp. (K. pneumoniae and K. oxytoca), and 23.6％ in P. mirabilis isolates, respectively. The Enterobacteriaceae strains were highly sensitive to carbapenems. The percentage of the P. aeruginosa isolates resistant to the antimicrobials tested was lower than 30％. The percentage of the Acinetobacter strains resistant to meropenem and imipenem was 65.6％ and 67.4％, respectively. Conclusions The situation of antibiotic resistance is still very serious, especially multi-drug or pan-drug resistant strains, which is of great concern.

Objective: To conduct an epidemiological investigation of two leptospirosis death cases reported in Guizhou Province in 2014. Methods: The information of the patients were investigated and analyzed. The serological detection, samples of the two patients was detected using ELISA and microscopic agglutination test (MAT). Leptospira carrier status of murine host animal in the living environment of the two patients was investigated in October and November of 2014. Leptospires in the kidney were cultured and isolated, the isolates were identified using Leptospira specific PCR and further identified with serogroup specific PCR and the conventional MAT. The relativity between the carrier status of murine and the death cases of human leptospirosis was analyzed. Results: The two death cases of human leptospirosis came from Liping County and the clinical symptoms were consistent with the diagnosis criteria for Leptospirosis. The results of ELISA detection showed that the anti-Leptospira antibody was positive for one of the death cases, MAT identified the serum reacted with sera-group icterohaemorrhagiae Leptospira, while the serum sample of the other case was failed to perform antibody detection due to hemolysis. 1 600 traps were placed in the living environment of the two death cases and 183 murine rodents were trapped. The murine density was 11.44% (183/1 600); 40 leptospirea suspected strains were isolated and all of them were isolated from Apodemus agrarius. The positive rate was 21.86% (40/183); 95 Apodemus agrarius were trapped and the murine density was 5.93% (95/1 600). Species specific PCR identified all the 40 strains as Leptospire. Serogroup specific PCR further identification showed that they were iterohaemorrahgiae serogroup Leptospria. interrogans. Conclusion Anti-iterohaemorrahgiae Leptospira antibody was detected from one of the two patients. 40 strains of iterohaemorrahgiae serogroup Leptospira interrogans were isolated and all of them were isolated from Apodemus agrarius in the living environment and the serogroup of the Leptospira matched with the serological detection results from patients, which indicated that the two death cases were caused by the infection of iterohaemorrahgiae serogroup Leptospira interrogans, and Apodemus agrarius were the potential source of infection.

Aim To study the effects of pyrin recombi-nant protein ( PRP ) on VEGF/VEGFR2/ MMP-9 sig-naling pathway in bleomycin-induced pulmonary fibro-sis of rats. Methods Sixty male Wistar rats were ran-domly divided into groups of control ( n=10 ) , model ( n=20 ) , PRP ( n=20 ) , and SU5416 ( n=10 ) . All the rats, except for those in control group, were estab-lished as the model of interstitial pulmonary fibrosis by perfusion of bleomycin (5 mg·kg-1 ) through tracheal intubation. From the second day after modeling, all rats were intragastrically administered with drugs or sa-line, according to different groups designed. The rats were sacrificed on the 14th and 28th day, and lung samples were taken out. The pathological changes of interstitial pulmonary fibrosis were observed by HE staining and Masson staining to evaluate the degree of alveolitis and pulmonary fibrosis. Expressions of VEGF, VEGFR2, MMP-9 protein and mRNA were de-tected by immunohistochemistry and RT-PCR. Results On the 14th and 28th day, the alveolitis, pulmonary fibrosis, expression of VEGF, VEGFR2, MMP-9 and mRNA increased significantly in the model group com-pared with in the control group ( P <0. 05 ) , and de-creased significantly in PRP group than those in the model group ( P <0. 05 ) . Conclusion PRP plays a role of anti-pulmonary fibrosis via the down-regulation of VEGF/VEGFR2/MMP-9 signaling pathway.