Multidrug resistant organism refers to bacteria that are insensitive to three or more antibiotics commonly used in clinic, including Pseudomonas aeruginosa, Acinetobacter Baumannii and Klebsiella pneumoniae, etc. MDRO infection is a major factor affecting the survival rate after lung transplantation (LTx), accounting for 30% of the causes of death in the first year after transplantation. Antibiotic treatment has low specificity and is prone to drug resistance. The development of new drugs has a long cycle and high cost, with significant limitations. Phage has high specificity for bacteria, which can proliferate in large quantities in the infected lesion and co-evolve with bacteria during the action process. Phage also have a good killing effect on MDRO, which is expected to make up for the deficiencies of existing antibiotic therapy. This article reviews the development background and mechanism of action of phage therapy, and summarizes its application status and early clinical trial results in the field of LTx, in order to providing new thinking paths for clinical work.

Objective To analyze the correlation between the lung allocation score (LAS) and the risk of early death and complications in patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 275 patients with IPF were retrospectively analyzed. The correlation between LAS and the risk of early death in IPF patients after lung transplantation and the correlation between LAS and complications at postoperative 1 year was assessed by univariate and multivariate Cox regression analyses. Results Among 275 recipients, 62, 83, 95 and 108 cases died within postoperative 30, 90, 180 and 365 d, respectively. LAS was correlated with 30-, 90-, 180- and 365-d fatality of IPF patients (all P<0.05), whereas it was not correlated with the incidence of primary graft dysfunction (PGD) and acute kidney injury (AKI) at 365 d after lung transplantation (both P>0.05). Conclusions LAS is correlated with the risk of early death of IPF patients after lung transplantation. While, it is not correlated the incidence of PGD and AKI early after lung transplantation. Special attention should be paid to the effect of comprehensive factors upon PGD and AKI.

Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

OBJECTIVE To investigate the improve-ment functions of flavonoid compounds on temozolomide(TMZ)-,aging-or AD model-induced dysregulation of hip-pocampal NSC lineage progression,retardancy of den-dritic spine maturation in new-born neurons,as well as impairment of hippocampal-related learning and memory.METHODS We applied 30-week-old neural stem cell(NSC)specific promoter Nestin-GFP and NestinCreERT2:Rosa26-LSL-tdTomato transgenic mice and 16-week-old AD model 5XFAD transgenic mice,together with hippo-campal microinjection(ih),endogenous fluorescence trac-ing and immunofluorescent staining.RESULTS Both fla-vonoid compound A and its functional derivative flavo-noid compound B dose-dependently improved TMZ-,aging-or AD-induced defects of hippocampal NSC lin-eage progression and the maturation of dendritic spines of newborn neurons,thereby improving hippocampus related learning and memory.CONCLUSION This paper provides a new idea and treatment strategy for the devel-opment of new flavonoids that can promote neurogene-sis for neurodegenerative diseases and aging.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To compare the effect of extracorporeal membrane oxygenation(ECMO)on pulmonary transplantation(LTx)in patients with idiopathic pulmonary fibrosis(IPF)complicated with pulmonary hypertension(PH).Methods:From January 2017 to December 2020, clinical data were retrospectively reviewed for 112 IPF patients complicated with PH undergoing LTx assisted by venous ECMO(VV-ECMO group, n=68)or venous arterial ECMO(VA-ECMO group, n=44). Gender, age, mechanical ventilation time, oxygenation index, cold ischemic time, preoperative gender, age, smoking history, PO 2, PCO 2, PH degree, NYHA cardiac function grade, right cardiac function, ejection fraction(EF)and complications(hypertension & diabetes)of two groups were compared. Intraoperative approach, operative duration, ECMO transfer time, blood loss, blood transfusion, urine volume, postoperative blood transfusion, mechanical ventilation time, ICU stay time, re-thoracotomy, pulmonary infection, primary graft dysfunction(PGD)and renal insufficiency were recorded. And the effects of two different diversion modes on early postoperative complications and short-term outcomes of LTx were further analyzed by multiple factors. Cox proportional risk model was employed for comparing VV-ECMO and VA-ECMO flow patterns with factors related to recipient survival after transplantation. Results:The preoperative PO 2 of 58.3(51.3, 72.0)mmHg was significantly lower in VV-ECMO bypass group than that of 73.2(63.3, 96.8)mmHg in VA-ECMO group and the difference was statistically significant( P<0.006). Compared with VV-ECMO group, 24(54.5%), 15(34.1%)and 22(50.0%)had NYHA class Ⅲ, severe PH and preoperative right heart enlargement in VA-ECMO group respectively and the differences were statistically significant compared with 17(25.0%), 6(8.8%)and 16(23.5%)in VV-ECMO group( P<0.05 for all). No significant inter-group differences existed in postoperative PGD, postoperative mechanical ventilation time(≥3 d), pulmonary infection, postoperative thoracotomy ratio, postoperative renal insufficiency, ICU stay, hospital stay and other aspects( P>0.05). And 6-month postoperative survival rates of VV-ECMO and VA-ECMO groups were 80.9% and 61.4%, respectively and no significant inter-group difference existed in short-term survival rate(6 months)after adjustment by multivariate Cox regression model( P>0.05). Multivariate statistics indicated that the risk of delayed postoperative withdrawal was 14.452-fold higher in VV-ECMO group than in VA-ECMO group and the inter-group difference was statistically significant(95% CI: 2.448-85.323, P=0.03). Conclusions:No differences exist in postoperative complications or short-term survival rate between IPF recipients with mild PH on VV-ECMO mode and IPF recipients with severe PH on VA-ECMO mode. VV-ECMO flow reversal can delay the transplant back-off time.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective To evaluate the effect of interleukin (IL)-10 on donor lung function after ex vivo lung perfusion (EVLP) in rats of cardiac death. Methods Twenty adult male SD rats were randomly divided into the simple perfusion group (group A, n=10) and modified perfusion group (group B, n=10). Perfusate A (without IL-10) and perfusate B (supplemented with IL-10) was administered in group A and B, respectively. The EVLP rat models of cardiac death were established. The appearance of donor lung, dry-to-wet (D/W) ratio of donor lung tissues, the function and metabolism of donor lung, the morphology of donor lung and the levels of inflammatory markers of donor lung were statistically compared between two groups. Results After perfusion, evident edema of the whole donor lung, poor compliance and a large amount of edema fluid discharged from the airway were observed in group A, whereas no obvious edema and good compliance were found in group B. Compared with group A, the D/W ratio of lung tissues in group B was higher (P < 0.05). In both groups, the pulmonary vein partial pressure of oxygen reached the peak at 2 h after perfusion, which did not significantly differ between two groups (P > 0.05). In group B, the pulmonary artery pressure was increased at a lower speed and significantly lower after perfusion, and the lactic acid level in the perfusate was significantly lower than those in group A (all P < 0.05). In group A, the alveolar structure was largely destroyed and the cells was rare. In group B, the alveolar structure was relatively normal without evident cell edema. The incidence of cell apoptosis of donor lung was high in group A, whereas no obvious cell apoptosis of donor lung was noted in group B. After perfusion for 4 h, the levels of monocyte chemoattractant protein (MCP)-1 and IL-6 were significantly increased, the IL-4 levels were remarkably decreased (all P < 0.05), but the levels of tumor necrosis factor (TNF)-α, IL-1α and inducible nitric oxide synthase (iNOS) did not significantly change in both groups (all P > 0.05). Conclusions IL-10 may improve the function of donor lung after EVLP in rat of cardiac death by reducing cell apoptosis.

Traumatic brain injury（TBI）in combination with its sequelae is currently a public health problem that seriously endangers human health. Accumulating studies have deeply investigated the pathological processes of TBI to find possible therapeutic targets. In recent years，the relationship between TBI pathogenesis and gut-brain axis changes in aspects of microflora，metabolites，inflammatory factors and neurohumoral changes has drawn widespread attention，which not only provides a better understanding how TBI affects gut-brain axis，but also provides new therapeutic targets in improving cure rate and recovery level after TBI. However，due to the existence of complicated gut-brain axis self-regulation as well as the individual differences of TBI patients，the recognition and transformation for the latest experimental research are largely limited. In this review，the authors summarize how TBI event influences gut-brain axis balance，as well as how gut-brain axis regulates TBI pathogenesis mutually，so as to provide a better understanding of the interaction between gut-brain axis and TBI.

This paper summarized the operation cooperation and management of the first case of bilateral lung transplantation assisted with double extracorporeal membrane oxygenation (ECMO) for the recipient with novel coronavirus pneumonia (COVID-19) in the world. The bilateral lung transplantation assisted by double ECMO had been accomplished successfully on a recipient with COVID-19, who was supported by ventilator and ECMO, with other organs function basically normal. The operation took 405 min and went smoothly. The cooperation and management guidelines of the operation room included the following: setting up of COVID-19 emergency operation group quickly; listing and preparing of the detailed operation supplies; transferring of the whole system of lung transplantation operating room in Wuxi People's Hospital to the Wuxi No.5 People's Hospital (isolation hospital); reconstruction of a negative pressure operating room for lung transplantation; formulating and strictly implementing the guidelines and management process for the operation of patient with COVID-19.