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The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.
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Immune tolerance after liver transplantation refers to discontinuing use of immunosuppressants in varying patterns and maintaining the long-term stability of liver function of the recipients. At present, immune tolerance may be achieved by passive immune tolerance, active operational immune tolerance and induced immune tolerance. Multiple clinical trials have confirmed the safety and feasibility of these approaches. Compared with adults, pediatric recipients undergoing liver transplantation have better potential of immune tolerance, especially the living donor liver transplant recipients. Nevertheless, it remains a challenge to predict whether a certain individual may achieve immune tolerance. In this article, research progresses on the characteristics of immune tolerance in pediatric recipients, induction of immune tolerance, operational immune tolerance, induced immune tolerance, screening of recipients and tolerance markers were reviewed, aiming to provide reference for the formulation of postoperative immunosuppressant regimens, reduce the overall exposure to immunosuppressants and lower the risk of adverse reactions induced by immunosuppressants in children undergoing liver transplantation.
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Objective@#This study aimed to identify internal ribosome entry sites (IRESs) in the open reading frame (ORF) of the Coxsackievirus B3 (CVB3) genome.@*Methods@#The sequences of P1, P2, or P3 of the CVB3 genome or the truncated sequences from each antithymocyte globulin (ATG) to the end of the P1, P2, or P3 gene were inserted into the pEGFP-N1 vector. After transfection, possible IRES-dependent green fluorescent protein (GFP)-fused proteins were detected by anti-GFP western blotting. The sequences of possible IRESs were inserted into specific Fluc/Rluc bicistronic vectors, in which the potential IRESs were determined according to the Fluc/Rluc activity ratio. Expression of Fluc and Rluc mRNA of the bicistronic vector was detected by RT-qPCR.@*Results@#After transfection of full length or truncated sequences of the P1, P2, or P3 plasmids, six GFP-fused protein bands in P1, six bands in P2 and nine bands in P3 were detected through western blotting. Two IRESs in VP2 (1461-1646 nt) and VP1 (2784-2983 nt) of P1; one IRES in 2C (4119-4564 nt) of P2; and two IRESs in 3C (5634-5834 nt) and 3D (6870-7087 nt) of P3 were identified according to Fluc/Rluc activity ratio. The cryptic promoter was also excluded by RT-qPCR.@*Conclusion@#Five IRESs are present in the CVB3 coding region.
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Internal Ribosome Entry Sites/genetics , Open Reading Frames , RNA, Messenger/geneticsABSTRACT
With the increasing number of patients waiting for liver transplantation worldwide, the development of living donor liver transplantation can not only alleviate the shortage of donor liver, but also expand the donor pool. Compared with classical liver transplantation, living donor liver transplantation is more complex and delicate in surgical operation, with many problems to be further discussed and solved. The authors retrospectively analyze relevant research results, combined with clinical practice, investigate the selection and evaluation of donor, selection of donor liver, surgical innovation and treatment of hepatocellular carcinoma in living donor liver transplan-tation, in order to provide helps for alleviating the shortage of donor liver and improving the prognosis of recipients.
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Liver transplantation is one of the best approaches for the treatment of hepatocellular carcinoma. The concept of transplant oncology could shed light on the whole process management of hepatocellular carcinoma patients. The success rate of operation and perioperative safety were the major concerns in the past, whereas the focus of treatment is gradually shifting to cancer treatment and improving patient survival and quality of life, with the promotion of neoadjuvant and postoperative adjuvant therapy for hepatocellular carcinoma. The prognosis of different group of patients might be heterogeneous. Therefore, refined stratification should be carried out for heterogeneous patients before and after liver transplantation to achieve the best prognosis. The present study classified patients for three clusters: primary hepatocellular carcinoma patients within the transplant criteria, hepatocellular carcinoma recurrence after liver resection, and patients after down-staging or neoadjuvant therapy. Fine stratified management are essential for the whole process management in the new era of transplant oncology.
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Objective@#To examine the association between the cross-resistance to ethionamide (Eto) and isoniazid (INH) and mutations of drug resistant genes in Mycobacterium tuberculosis (MTB), so as to provide the evidence for clinical diagnosis and treatment for multidrug-resistant (MDR) tuberculosis.@*Methods@#Totally 126 MTB clinical isolates were selected, including 88 MDR-MTB clinical isolates and 38 INH- and rifampicin (RFP)-sensitive isolates. The resistance to INH and Eto was tested in MTB clinical isolates using the drug susceptibility test, and the mutations in the spacer region of INH and Eto resistance-related katG, inhA, ethA, mshA, ndh, spacer region of oxyR-ahpC and inhA promoter were detected using PCR assay. The phenotypic resistance served as a gold standard, and the sensitivity, specificity and accuracy of gene mutation tests were calculated for detection of MTB clinical isolates cross-resistant to INH and Eto.@*Results@#Of the 126 MTB clinical isolates, there were 37 isolates cross-resistant to INH and Eto (29.37%), 51 isolates with resistance to INH and susceptibility to Eto (40.48%), 4 isolates with susceptibility to INH and resistance to Eto (3.17%) and 34 isolates with susceptibility to INH and Eto (26.98%). Among the 41 Eto-resistant MTB clinical isolates, there were 37 isolates with resistance to INH (90.24%). There were 64 MTB clinical isolates detected with katG mutations (50.79%), 4 isolates with mutation in the spacer region of oxyR-ahpC (3.17%), 2 isolates with inhA mutations (1.59%), and these isolates were all resistant to INH. There were 11 MTB clinical isolates detected with mutation in the inhA promoter (8.73%) and one isolate with ndh mutation, and all these isolates were cross-resistant to INH and Eto. There were 23 MTB clinical isolates detected with ethA mutations (18.25%) and 40 isolates with mshA mutations (31.75%), in which Eto-susceptible and -resistant isolates were detected. The diagnostic sensitivity, specificity and accuracy of inhA promoter tests for detection of cross-resistance to INH and Eto were 29.73% (95%CI: 16.44%-47.17%), 100.00% (95%CI: 87.36%-100.00%) and 63.38% (95%CI: 51.76%-73.63%) in MTB clinical isolates.@*Conclusions@#The prevalence of INH resistance is high in Eto-resistant MTB clinical isolates. Mutation in the inhA promoter region correlates with the cross-resistance to INH and Eto in MTB clinical isolates, and detection of mutation in the inhA promoter may be feasible to detect the cross-resistance to INH and Eto in MTB clinical isolates.
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Objective To evaluate the clinical efficacy of heterozygous living donor liver transplantation for pediatric maple syrup urine disease. Methods A 3-year-old boy was admitted to the hospital on July 5, 2017 due to maple syrup urine disease for half a year. The child presented with paroxysmal dysarthria and motor dysfunction of the lower limbs under fasting status for half a year, accompanied with obvious maple syrup urine odor and slow language development. No other growth abnormality or mental defects were observed. Serum branched chain amino acid (BCAA) assay detected that the level of leucine was 684 μmol/L and 559 μmol/L for the valine. The child was diagnosed with maple syrup urine disease type b based on gene detection combined with BCAA assay. Living donor liver transplantation from his biological father was performed. Postoperatively, routine immunosuppression, anti-virus, anti-infection therapies, maintenance of fluid, electrolyte, and acid-base balance and other necessary nutritional support were given. The dose of tacrolimus was adjusted according to biochemical parameters and cytochrome P450(CYP)3A5 genotype of the recipient. Glucocorticoid administration was terminated at approximately 6 months after operation. Results The liver function of the recipient was recovered to normal range at postoperative 1 month, and basically stabilized at 3 years after surgery. The amino acid level was decreased to normal level immediately after operation, and BCAA was continually declined after normal diet for postoperative 1 month. As of the submission date, the recipient grew well in a stable condition and achieved high quality of life. Conclusions Heterozygous living donor liver transplantation is a safe and effective treatment of maple syrup urine disease, which reduces the possibility of sudden acute metabolic events, significantly improves the quality of life of the recipient and provides a novel idea for surgical treatment of maple syrup urine disease.
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Objective@#To explore school bullying in middle school and the associated socio-ecological factors.@*Methods@#Totally 1 169 middle school students were selected from urban areas of Nantong and were selected to complete the Campus Bullying Questionnaire and a self-designed questionnaire.@*Results@#The bullying scores of junior school students were higher than senior school students( t=3.61, 2.53, P <0.05). The bullying scores of ordinary middle school students were higher than the key middle school students( t=12.52, 8.34, P <0.01). The bullying scores of students with poor peer relationship were higher than the students with good peer relationship( F=8.98, 25.89, P <0.01). The bullying scores of students with poor school discipline were higher than the students with good school discipline （F=8.50, 10.00, P <0.01). Students from schools with poor school bullying prevention and control policies reported higher rates of campus bullying than students from schools with general and perfect school policies( F= 8.30 , 2.67, P <0.05). The bullying scores of intervention type and neglect type students were higher than the negotiation type students( F=3.66, P <0.05). Multivariate Logistic regression analysis showed that high school section, key middle school, good peer relationship, deliberative education mode, good school style and discipline, and improvement of campus bullying prevention and control policies were the protective factors that affect middle school students’ Campus bullying( OR=1.68-4.28, P <0.05), gender and only child were risk factors for chool bullying( OR=1.54, 1.68, P <0.05). Structural equation model analysis showed that the path of campus bullying was centered on individual factors, through interaction with interpersonal, organizational and policy factors.@*Conclusion@#Campus bullying prevention and intervention should be considered from individual, interpersonal, organizational and policy levels of students, through the collaborative efforts of school, family and society.
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Objective To summarize the therapeutic effects of living related donor liver transplantation for Crigler-Najjar syndrome type Ⅰ (CNS type Ⅰ). Methods A 3-month-old male infant had appeared a progressive xanthochromia of the skin and sclera 4 d after birth without obvious cause. Other causative factors were eliminated after relevant tests were completed, and identified as CNS type Ⅰ by genetic testing. Living related donor liver transplantation was performed with his mother as the donor. An immunosuppression regimen was routinely applied postoperatively and tacrolimus doses were adjusted according to biochemical indicators and cytochrome P450 (CYP) 3A5 genotype of the recipient. Results The liver enzymes of the recipient returned to normal at 7 d postoperatively, and bilirubin decreased daily and fell to the normal range at 22 d postoperatively. Followed up to the submission date, the recipient's xanthochromia of skin and scleral faded with normal bilirubin and stable liver enzymes. The condition of the recipient was generally good with high quality of life. Conclusions Living donor liver transplantation can treat unconjugated hyperbilirubinemia and other diseases caused by CNS type Ⅰ, which greatly improve the quality of life of patients.
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Insect antimicrobial peptides (AMPs) are small cationic molecules with various biological activities induced by many factors. Insect AMPs, which are essential components of insect innate immune system, may have functionsof anti-infection, anti-tumor and immune modulation in the medicine field. Many different types of insect AMPs, such as cecropin-like AMPs extracted from Saturniidae, defensin-like AMPs purified from Catharsius molossus L., and Pro-rich and Gly-rich peptides from drosophilid fly and silkworm, respectively, have been identified, and been reported to have anti-infective and anti-tumor functions. However, relatively few reports have focused on the immunomodulatory activities and their possible mechanisms of insect AMPs. It has been found that insect AMPs could activate immune cells, enhance the activities of NK cells and cytotoxic T lymphocytes, induce cytokine production, and inhibit the activities of inflammatory cytokines and inflammatory mediators. Furthermore, Toll-like receptor pathways, nuclear factor-κB signaling pathway and mitogen-activated protein kinase signaling pathway were also reported to be involved in their immunomodulatory mechanisms. In this paper, the immunomodulatory effects of some classes of insect AMPs (Lepidoptera, Diptera, Coleoptera, and Hymenoptera are involved),and their signaling pathway - related mechanisms are reviewed. It was hoped that these data could provide references for the future research in the field of insect AMPs.
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Liver transplantation is a mature treatment for children with end-stage liver disease. With the development of surgical techniques, immunosuppressive therapy, and infection monitoring in recent years, there have been significant increases in the survival rates of patients and liver transplants, helping children to achieve long-term survival. Meanwhile, several issues have emerged, such as viral infection, complications, new-onset tumors, quality of life, and self-management. Therefore, this article reviews related issues in long-term survival in children after liver transplantation from the two aspects of medical treatment and nursing and provides several regimens for reference, so as to provide a basis for long-term high-quality survival in children after liver transplantation. Here, these issues are reviewed.
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Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.
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Animals , Cell Adhesion Molecules, Neuronal , Physiology , Cells, Cultured , Cerebral Cortex , Embryology , Physiology , GABAergic Neurons , Physiology , Interneurons , Physiology , Membrane Proteins , Physiology , Nerve Tissue Proteins , Physiology , Protein Isoforms , Physiology , Pyramidal Cells , Physiology , Rats, Sprague-Dawley , Synapses , PhysiologyABSTRACT
Objective To study the function and mechanism of receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis in liver ischemia-reperfusion injury (IRI) in mice.Methods Sixty mice were randomly divided into four groups using Stata statistical software:Wild-type (WT)-sham group,WT-IRI group,HKO (HKO:RIPK3 liver-specific knockout)-sham group and HKO-IRI group.Sham operation was used as a control in which only the hepatic portal blood vessels were freed after laparotomy,and blood flow was not blocked.In the WT-IRI group and the HKO-IRI group,the hepatic portal vein was freed,and the blood supply of left hepatic lobe and the mid-hepatic lobe wer blocked for 90 min,then the blood vessels were opened for 6 h.Blood and liver tissue samples of each group of mice were taken to detect liver function.Inflammatory infiltration and liver injury were detected by immunohistochemistry and hematoxylin and eosin (HE) staining,and autophagyassociated protein LC3-Ⅱ and P62 were detected by Western blotting.The primary hepatocytes of WT mice and HKO mice were extracted and divided into control group and hypoxia-reoxygenation group (HIR group).After attachment of primary hepatocytes,the HIR group was given hypoxia for 6 h and reoxygenated for 4 h.The supernatant was taken for detecting ALT and AST,and the cell extract protein was used to detect LC3-Ⅱ and P62.Results As compared with the control groups,the liver functions of the IRI groups were significantly impaired,and as compared with the WT-IRI group,the liver damage was significantly aggravated in the HKI-IRI group (P ＜ 0.05),and the LC3-Ⅱ protein content was significantly decreased and the P62 protein content was increased.Similarly,after hepatocytes were were given hypoxia and reoxygenated,HKO-derived hepatocytes were more severely damaged than WT-derived hepatocytes.Conclusions Blocking RIPK3-mediated necroptosis of hepatocytes could induce autophagy inhibition,which aggravates hepatic ischemia-reperfusion injury.
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Objective To compare the clinical efficacy of laparoscopiceft and open left lateral lobe hepatectomy for living donor liver transplantation in children.Methods The retrospective cohort study was conducted.The clinical data of 65 cases (14 males and 51 females) receiving laparoscopic living donor liver resection from October 2016 to October 2018 were analyzed.At the same time,the same number of male and female donors who underwent open left lateral lobe hepatectomy performed by the same group during the same period were randomly selected as the control group.The occurrence of complications and long-term follow-up of physical and mental health were compared between the two groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative recovery and complications up to November 2018.Results Intraoperative conditions:In the laparoscopic operation group,one donor was converted to open operation due to the confluence of the middle hepatic vein branches bleeding during the operation,and the rest donors successfully completed the laparoscopic left lateral lobe hepatectomy.The operation time of laparoscopic group was (216.0 ± 36.5) min,the amount of bleeding during operation was (56.0 ± 44.3) mL,and the warm ischemia time of donor liver was (6.4 ± 3.8) min.All 65 donors in open operation group successfully completed the operation.The operation time was (167.0 ± 19.7)min,the amount of bleeding was (138.0 ± 59.4) mL,and the time of warm ischemia of donor liver was (1.4 ± 0.5) min.There were significant differences in the above indexes between the two groups (P＜0.05).Postoperative complications:The incidence of incision fat liquefaction was 3.54％ and 2.51％ respectively in laparoscopic group and open group.The time to first anal exhaust after operation of laparoscopic and open groups was (52.3 ± 4.9) h vs.(62.6 ± 4.1) h,P ＜ 0.05.The average length of hospitalization in laparoscopic and open groups was (4.2 ± 0.4) days vs.(5.0 ± 0.6)days,P ＞ 0.05.Conclusions Laparoscopic left lateral lobe living donor liver resection can achieve the same safety as traditional open surgery,and can reduce the physical and mental injury of donors.It is a reasonable choice for living donor liver transplantation.
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Objective To explore the diagnosis and treatment of parvovirus B19 infection-associated anemia after pediatric liver transplantation (LT) .Methods The clinical data were retrospectively reviewed for 2 children with severe anemia caused by parvovirus B19 infection after LT .Case 1 was a 2-year-old girl with a weight of 10 .7 kg .Classical orthotopic LT was performed due to ornithine carbamoyltransferase deficiency . Hemoglobin level began to progressively decline since Day 2 post-transplantation .And case 2 was a 5-month-old girl with an age of 5 months and a weight of 7 .2 kg .She underwent classic orthotopic LT for biliary atresia and decompensated liver cirrhosis .Hemoglobin level progressively declined at nearly 2 months post-transplantation . Results In case 1 ,bone marrow aspiration was performed at Day 54 post-transplantation .There was pure red cell aplasia and the detection of microvirus B19 nucleic acid was positive .Intravenous immunoglobulin was prescribed at a dose of 2 .5 g/day for 10 days ,tacrolimus was switched to cyclosporine and hemoglobin level spiked from 62 to 105 g/L after one-month treatment .In case 2 ,hemoglobin decreased to 44 g/L at 2 .5 months post-transplantation and the result of polymerase chain reaction of parvovirus B 19 was 9 .7 × 107 copies/ml .Then intravenous immunoglobulin was dosed at 2 .5 g/day for 10 days and hemoglobin level rose to 122 g/L at 25 days after treatment . Hemoglobin level decreased to 63 g/L again at 4 .5 months post-transplantation .Anemia was corrected by intravenous immunoglobulin injection plus a temporary discontinuation of tacrolimus and a reduced dose of tacrolimus .Conclusions Infection of parvovirus B19 can cause pure red cell aplasia after LT in children . Early diagnosis with intravenous immunoglobulin and modification of immunosuppressive regimen can obtain excellent therapeutic efficacies .
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Objective To explore the experience of infantile liver transplantation ,reconstructing portal vein (PV) and avoid the higher incidence of portal vein low flow and complications .Methods The clinical data were reviewed for 152 infantile liver transplantations performed by a single surgery group .And 114 cases with PV risk factors underwent customized PV reconstructions .All of them were diagnosed as cholestatic liver diseases and 106 (93％ ) belonged to biliary atresia .Forty-two cases (36％ ) had 2 or more risk factors .Results Most cases (n= 106 ,93％ ) underwent living donor transplantations using lateral left graft while another 8 cases had deceased donor transplantations . Four types of PV reconstructions were adopted based upon individual conditions :left/right branch of PV trunk (n= 103) ,autogenous patch PV venoplastic reconstruction (n= 3) ,duct-to-duct of PV trunk (n= 5) and donor PV duct-to-recipient confluence of SMV/CV and SV (n= 3) .Graft size reduction was performed when GRWR > 4 .5％ (n= 16) .During a median follow-up period of 6 .5 (1 .5-13) months ,there were 3 LPVF (2 .6％ ) ,2PVS (1 .7％ ) and 1 PVT (0 .8％ ) .Three LPVF cases was corrected by PV stenting ,two cases of PVS were stable after anticoagulation therapy while one PVT case undergoing thromboectomy plus PV stenting resumed a normal PV flow .Conclusions PV reconstruction of high-risk infants require comprehensive risk evaluations ,precise surgical skills and customized strategies .For PV complications ,stenting is both safe and feasible .
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Objective To employ high-throughput next generation sequencing (NGS) for analyzing the expression of lneRNAs and mRNAs in donor samples from pediatric living donor liver transplantation and search differentially expressed lncRNAs and drag metabolic gene for individualized guidance of immunosuppressive agents.Methods Between October 2016 and December 2017,10 liver tissue specimens from living donor liver transplantation children were collected and divided into fast and slow metabolic groups (n =5 each) according to the postoperative profiles of drug metabolism.Samples were assayed for high-throughput NGS.Target analysis was used for functional pathways and screening target genes prediction.Results There were differentially expressed 908 mRNAs and 1228 lncRNAs between slow metabolic and fast metabolic groups (P＜0.05).According to the abundance and difference,22 up-regulated and 18 down-regulated mRNAs,13 up-regulated and 24 down-regulated lncRNAs were selected.In addition to CYP3A5,CYP2C19,CYP1A2 and UGT1A1 might affect the metabolism of tacrolimus.At the same time,NONHSAT108617.2 in differemially expressed lncRNAs might regulate the expression of CYP3A5 gene.Conclusions This study has comprehensively analyzed the expression of lncRNAs in donor liver from pediatric liver transplantation.Some differentially expressed drug metabolism related genes may affect tacrolimus metabolism in vivo and thus the postoperative use of immunosuppressive drugs.
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Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.
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Cytokines , Hand , Immune System , Inflammation , Ischemia , Kupffer Cells , Liver Transplantation , Liver , Macrophages , Receptors, Pattern Recognition , Reperfusion Injury , Reperfusion , Toll-Like ReceptorsABSTRACT
Objective To investigate the distribution of common carbapenem resistance genes and virulence genes in and understand the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains.Methods A total of 84 non-duplicate CRKP isolates were collected from Renji Hospital,Shanghai Jiao Tong University School of Medicine and Changzheng Hospital,the Second Military Medical University,in 2015.Kirby-Bauer disk diffusion method was used to test their susceptibility to 15 antimicrobial agents.The HM phenotype of K.pneumoniae was determined by string test.Carbapenem-resistant genes and virulence genes were detected by polymerase chain reaction (PCR).The molecular epidemiology of the 84 isolates were further analyzed by multi locus sequence typing (MLST).The population structure of CRKPs was evaluated by eBURST with the results of MLST.Results Antimicrobial susceptibility test showed that 84 isolates were highly resistant to most antimicrobial agents such as carbapenems,penicillins,cephalosporins and aztreonam.More than 90％ of the strains were resistant to most of the antibiotics tested except ciprofloxacin (77.4％,65/84) and amikacin (82.1％,69/84).Two strains showed HM phenotype.PCR results showed that 90.5％ (76/84) of the strains were positive for blaKPC-2,1.2％ (1/84) positive for blaNDM and blaIMP each,but either blaOXA or blaVIM was not identified.The overall prevalence of virulence genes was low except for mrkD (97.6％,82/84),ybtS (92.9％,78/84) and entB (100％,84/84).Eight sequence types (STs) were obtained.The dominant clone was ST11 (84.5％,71/84),and the two strains of HM phenotype were ST11.eBURST analysis identified 2 ST groups among the 84 CRKPs.Each ST group includes 2 ST types (ST11 and ST1869,ST15 and ST709),respectively.The other four ST types were single ST type.In this study,71 strains of ST11,4 ST15 and 4 ST323 belonged to CC258,CC15 and CC163 clones,respectively.Conclusions CRKP is highly resistant to the commonly used antibiotics.The multidrug resistance or pandrug-resistance of K.pneumoniae is mainly associated with the expression of blaKPC-2 gene.Three virulence genes mrkD,ybtS and entB are highly prevalent in the CRKP isolates.The dominant clone of KPC-producing K.pneumoniae is ST11 in both hospitals.
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Objective To investigate the effect of short course chemotherapy combined with broncho-vaxom on the prognosis of new smear positive pulmonary tuberculosis patients.Methods 80 patients with new smear positive pulmonary tuberculosis were selected as the research subjects.According to the random number table method,they were divided into observation group and control group,40 cases in each group.The control group was treated with 2HRZE/4HR chemotherapy,the observation group was treated with broncho-vaxom tablets based on the treatment of the control group.After 6 months of treatment,the sputum negative conversion rate,pulmonary lesions absorption,the incidence rate of adverse reaction and immune function were compared between the two groups.Results After 2,4,6 months of treatmentt,the sputum negative conversion rates of the observation group were 90.00％,95.00％ and 97.50％,respectively,which were significantly higher than those of the control group(x2 =4.020,4.114,3.914,all P ＜ 0.05).After 2,6 months of treatment,the total effective rates of the observation group were 87.50％ and 97.50％,which were significantly higher than those of the control group (x2 =4.588,5.000,all P ＜ 0.05).After 6 months of treatment,the IgA,IgG,IgM,CD3+,CD4+,CD4+/CD8+ in the observation group were (70.24 ± 6.19) ％,(46.89 ± 6.25) ％,(2.21 ± 0.39),(3.86 ± 1.43) g/L,(14.76 ± 2.58) g/L,(1.47 ± 0.65) g/L,respectively,which were significantly higher than those of the control group(t =-2.116,-2.575,-2.322,-2.138,-4.513,-2.599,all P ＜ 0.05),the CD8+ was (18.85 ± 2.08) ％,which was significantly lower than that in the control group (t =2.609,P ＜ 0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups (x2 =0.251,P ＞ 0.05).Conclusion Short course chemotherapy regimen combined with bronchovaxom can improve the new smear positive pulmonary tuberculosis patients with recent sputum negative conversion rate and lung lesions absorption effect,improve the immune function of patients and without increasing the incidence of adverse reactions,it is worthy of clinical attention.