Lung transplantation is the only effective treatment for end-stage lung disease. Acute kidney injury is a common complication after lung transplantation, which is related to the occurrence of chronic kidney disease and increased postoperative fatality. The factors and mechanisms affecting the occurrence of acute kidney injury are very complex. Clinically, it has been found that various risk factors during the perioperative period of lung transplantation may lead to the occurrence of acute kidney injury, including preoperative, intraoperative and postoperative factors. Early diagnosis of acute kidney injury after lung transplantation and timely intervention are of great significance to improving patient prognosis. Therefore, this article reviews the definition of acute kidney injury, non-invasive assessment, risk factors, prognosis, and clinical management of acute kidney injury after lung transplantation, aiming to provide a reference for the diagnosis and treatment of acute kidney injury after lung transplantation in clinical practice and to improve the survival rate of lung transplant recipients.

Objective To investigate the effects of peroxisome proliferator activated receptor-gamma(PPARγ)gene silen-cing in human bone marrow stromal cells(HS-5)on hematopoietic function in bone marrow-suppressed mice,and to explore the potential mechanisms involved.Methods A bone marrow-suppressed mouse model was established by whole-body X-ray irradi-ation.Two hours after modeling,the mice were randomly divided into three groups:experimental group(intravenous injection of PPARγ RNAi-interfered HS-5 cells through the tail vein),control group(intravenous injection of PPARγ RNAi-uninterfered HS-5 cells through the tail vein),and blank group(intravenous injection of an equal amount of saline through the tail vein),with 5 mice in each group.Peripheral blood routine tests were performed before,24 hours after,1 week after,and 2 weeks after radio-therapy.In vitro osteogenic and adipogenic induction was performed in cells,and the cells were divided into experimental group(PPARγ RNAi-interfered HS-5 cells),control group(PPARγ-uninterfered HS-5 cells),and blank group(HS-5 cells without os-teogenic/adipogenic induction).Osteogenic/adipogenic staining was observed.The effects of PPARγ gene-silenced HS-5 cells on mouse bone marrow hematopoietic stem cells(HSCs)were detected by CCK-8 proliferation assay.The groups included experi-mental group(PPARγ RNAi-interfered HS-5 cells were co-cultured with mouse HSCs after 3 days of osteogenic induction dif-ferentiation),positive control group(HS-5 cells treated with 50 μmol/L PPARγ inhibitor were co-cultured with mouse HSCs af-ter 3 days of osteogenic induction differentiation),negative control group(PPARγ RNAi-uninterfered HS-5 cells were co-cul-tured with mouse HSCs after 3 days of osteogenic induction differentiation),and blank group(Mouse HSCs were cultured alone without co-culturing with HS-5 cells).Results After radiotherapy,the hematological parameters of mice in each group showed a decreasing trend initially,and then increased.One week after radiotherapy,there were significant differences in platelet and white blood cell levels among the three groups(experimental group＞control group＞blank group,all P＜0.05).Two weeks after radiotherapy,there were significant differences in the percentage of adipocyte vacuole area among the three groups(experi-mental group＜control group＜blank group,all P＜0.05).Pearson correlation analysis showed a negative correlation between hematological parameters and PPARγ expression levels(all P＜0.05),as well as a negative correlation between hematological parameters and the percentage of adipocyte vacuole area(all P＜0.05).After in vitro osteogenic/adipogenic induction differenti-ation,compared to the control group,the experimental group showed a significantly lower proportion of orange-red cells and a significantly higher proportion of red calcium nodules.After 3 days of osteogenic induction differentiation,the experimental group,positive control group,and negative control group of human bone marrow stromal cells were co-cultured with mouse HSCs,while HSCs were solely cultured in the blank group.The results showed that after 24 h,48 h and 72 h of co-culture,the A values of mouse HSC cells in the experimental group and positive control group were higher than those in the negative control group and blank group(all P＜0.05).Conclusion Silencing of the PPARγ gene in HS-5 cells implanted into bone marrow-sup-pressed mice contributes to enhanced hematopoietic function in mice.After interference and silencing of the PPARγ gene,the os-teogenic differentiation ability of HS-5 cells is enhanced,while the adipogenic differentiation ability is weakened.Furthermore,osteogenic-induced HS-5 cells can further enhance the proliferation capacity of mouse HSCs.

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Background:Intestinal microbiota dysbiosis and impaired intestinal barrier,leading to bacterial translocation,are involved in acute pancreatitis(AP)exacerbation.Antimicrobial peptides participate in the regulation of intestinal microbiota,yet their changes and roles in the course of AP are unclear.Aims:To investigate the dynamic changes and significance of antimicrobial peptides in the ileum and pancreas among three classical AP models.Methods:Three AP mouse models were established by using cathelicidin plus lipopolysaccharide(CAE+LPS),sodium taurocholate(N-Tau)and L-arginine(L-Arg),respectively.The pathological changes of pancreatic and ileal tissues were observed and scored.Real-time PCR was applied to detect the expression levels of the proinflammatory cytokines,and antimicrobial peptides including lysozyme(LZM),secretory phospholipase A2(sPLA2),angiogenin 4(Ang4),regenerating islet-derived protein 3(REG3)family,β-defensin family,cathelicidin-related antimicrobial peptide(CRAMP),and glycoprotein 2(GP2)in ileum and/or pancreas.The association between expressions of antimicrobial peptides and the injuries of pancreas and ileum was analyzed.Results:Pancreatic and ileal injuries could be observed in all three AP models in different time points with various degrees.The pathological scores of the CAE+LPS and N-Tau models reached the highest level and then declined from 0-72 h,while those of L-Arg model progressively increased within 72 hours.Compared with the corresponding controls,the mRNA levels of LZM,sPLA2,and Ang4 in ileal tissue,and the mRNA levels of CRAMP,GP2,and β-defensins in pancreatic tissue,were generally downregulated in all three AP models(all P<0.05).CAE+LPS and N-Tau models showed a trend of initial decrease followed by partial recovery,while L-Arg model exhibited a gradual downregulation trend.The mRNA levels of REG3β and REG3γ in ileum upregulated and reached the peak at 48 h or 24 h and downregulated significantly at 72 h in all three AP models(all P<0.05);while in pancreatic tissue,both REG3β and REG3γ were generally upregulated in all three AP models(all P<0.05),but fell back in CAE+LPS and N-Tau models at 72 h.The mRNA levels of ileal β-defensins upregulated significantly in the early stage of the disease(12 h)in all three AP models(all P<0.05),and then gradually decreased.Spearman correlation coefficient analysis showed that the expressions of ileal LZM,sPLA2,and Ang4,as well as the pancreatic CRAMP,GP2,and β-defensins,were significantly negatively correlated with the pancreatic and ileal pathological scores in all three AP models(all P<0.05);but the expression of REG3β in the pancreas was significantly positively correlated with the pancreatic and ileal pathological scores(all P<0.05).Conclusions:The expressions of LZM,sPLA2,and Ang4 in the ileum,as well as the expressions of CRAMP,GP2,β-defensin family,and REG3β in the pancreas of the three classical AP models,dynamically changed with the severity of the disease.Ileal and pancreatic antimicrobial peptides may affect the injuries of pancreas and intestine during AP by regulating intestinal microbiota.

Objective:To explore the risk factors for lymphoproliferative disorders (PTLD) in children with thalassemia major (TM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:This was a retrospective case-control study.A total of 482 children with TM who underwent allo-HSCT at Shenzhen Children′s Hospital between January 2020 and December 2022 were selected and classified into the PTLD and non-PTLD groups according to the occurrence of PTLD.The risk factors for PTLD after allo-HSCT in children with TM were analyzed, and the diagnostic efficiency of relevant risk factors for PTLD was analyzed by receiver operating characteristic (ROC) curve.Results:A total of 25 out of 482 patients (5.2%, 25/482) developed PTLD about 114 (54-271) days after allo-HSCT.Among them, 12 cases (12/25, 48.0%) occurred within 100 days, and 22 cases (22/25, 88.0%) occurred within 1 year after allo-HSCT.Univariate analysis showed that there were significant differences in gender composition, type of transplant donor, number of natural killer cells and B lymphocytes in peripheral blood at 30 days after allo-HSCT, positive rate of plasma Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) and incidence rate of acute graft-versus-host disease (aGVHD) between the 2 groups (all P<0.05).Multivariate Logistic regression analysis showed that female ( OR=3.196, 95% CI: 1.144-8.929), positive plasma EBV-DNA ( OR=17.523, 95% CI: 5.449-56.344) and aGVHD ( OR=3.156, 95% CI: 1.161-8.575) were independent risk factors for PTLD after allo-HSCT in TM children (all P<0.05).The ROC curve analysis showed that positive plasma EBV-DNA had an excellent accuracy in predicting the occurrence of PTLD after allo-HSCT (sensitivity was 0.796, specificity was 0.800, area under the curve was 0.803).If combined with aGVHD and gender, the area under the curve for the prediction of PTLD increased to 0.831. Conclusions:Female, positive plasma EBV-DNA and aGVHD are independent risk factors for PTLD after allo-HSCT in children with TM.It provides useful early warnings for the prediction and prevention of PTLD.

Objective:To summarize evidence for physical activity management in cancer patients based on the Joanna Briggs Institute (JBI) approach for evidence synthesis in health care, providing a scientific basis for the clinical standardization of physical activity management in cancer patients.Methods:Literature was searched according to the "6S" pyramid model of evidence, using BMJ Best Practice, UpToDate, JBI Evidence-Based Practice Database, Cochrane Library, global guideline websites, professional cancer association websites, and relevant Chinese and English databases for all evidence regarding physical activity in cancer patients. The search covered the period from February 13, 2018, to February 13, 2023. Guided by the JBI approach for evidence synthesis, two researchers independently evaluated the quality of the literature and extracted relevant evidence in accordance with clinical scenarios.Results:Thirty articles were included, comprising two guidelines, three expert consensuses, one evidence summary, 21 systematic reviews, and three randomized controlled trials. A total of 29 best evidence points were summarized in six aspects: benefits of physical activity, physically active people, pre-activity assessment, implementation of physical activity programs, safety monitoring of physical activity, and ongoing support strategies.Conclusions:This study supplements and updates 15 pieces of evidence based on existing evidence, ultimately forming a best evidence summary for the management of physical activity in cancer patients, providing evidence-based support for clinical management. Most evidence comes from international studies. It is recommended that Chinese researchers consider the activity ability and willingness of cancer patients when applying these findings in future research, and consider the specific clinical context, or conduct foundational research to further validate the evidence, to comprehensively improve the quality of life of cancer patients.

Abstract: Objective　To retrospectively analyze the clinical characteristics of patients with Talaromyces marneffei infection (TSM) complicated by osteolytic lesions in non-HIV infected individuals, aiming to improve the diagnosis and treatment of TSM in non-HIV patients. Methods　Clinical characteristics and laboratory data, of non-HIV adults diagnosed with TSM complicated by osteolytic destruction were collected from the People's Hospital of Liuzhou City from January 2019 to October 2023, covering nearly five years. Results　All 14 patients were healthy hosts without HIV infection or any underlying diseases. All patients had systemic manifestations such as fever, anemia, and weight loss, while 7 patients experienced bone pain. The initial symptoms mainly included neck mass, ulceration, and purulent discharge from the skin. Laboratory tests showed elevated white blood cell counts, C-reactive protein, and erythrocyte sedimentation rate. The CD4+ lymphocyte count ranged from 157 to 1 477 cells/μL, and CD8+ lymphocyte counts from 112 to 1 779 cells/μL, with CD4+/CD8+ ratios from 0.651 to 3.797. Pathogenic evidence was obtained from positive cultures of purulent or ulcerative secretions from the neck, chest, face, and joints in 9 cases, positive metagenome sequencing of mediastinal lymph nodes in 1 case, positive cultures of sputum and bronchoalveolar lavage fluid in 4 cases, and positive blood cultures in 1 case. Imaging findings showed osteolytic destruction involving any part of the skeleton. Nine patients improved with treatment, 2 died, 3 showed no improvement, and 6 cases were misdiagnosed as lung cancer or metastatic tumors. After antifungal treatment, 7 patients developed non-tuberculous mycobacterial infection, and 4 cases were co-infected with TSM and Mycobacterium tuberculosis. Conclusions　TSM complicated by osteolytic destruction is more common in non-HIV infected, with prominent manifestations of severe bone or joint pain. Early diagnosis is difficult, and it is prone to be complicated by non-tuberculous mycobacterial or Mycobacterium tuberculosis infection, leading to frequent misdiagnosed as cancer and tumors clinically.

Objective:To explore the effect of probiotics Lactiplantibacillus plantarum(LP) WCFS1 by gavage on acute necrotizing pancreatitis (ANP) and associated ileum injury in mice. Methods:Twenty-four healthy male mice were gavaged with broad-spectrum antibiotics for 3 weeks to establish microbiota-depleted mice, and then randomly divided into control group (CON), ANP model group (ANP), LP gavage group (LP) and LP gavage and ANP induced group (LP+ ANP) , with 6 mice in each group. Mice in LP and LP+ ANP group were treated by gavage of LP (1×10 9 CFU/ml, 0.2 ml/day per mouse) for 1 week, while CON and ANP were gavaged with sterile phosphate buffered saline for 1 week instead. The ANP model was induced by intraperitoneal injection with caerulein (100 μg/kg) for 10 times with 1-hour interval between two injections and the 10th injection with lipopolysaccharide(LPS) 5 mg/kg intraperitoneally, and the mice were sacrificed 2 h later. Levels of LP in stool and ileal mucosa were detected by real-time PCR; the pancreas and ileum were collected for pathological examination to observe the extent of tissue inflammation and to score the pathology. Serum amylase activities were determined by enzymatic kinetic chemistry; serum inflammators levels and intestinal permeability were detected by ELISA; levels of inflammators in pancreatic and ileal tissues were detected by real-time PCR; ileal tight-junction proteins (occludin, claudin-1 and ZO-1) were measured by immunofluorescence staining. Results:LP levels in the stool and ileal mucosa of mice were significantly increased after LP gavage, and the differences were statistically significant (913.30±39.12 vs 2.39±1.39, 23.11±0.50 vs 1.38±0.28, all P value <0.05). The pathological scores of pancreatic tissue of CON, LP, ANP and LP+ ANP group were (0.26±0.41), (0.17±0.26), (8.55±0.46) and (6.30±0.45); the serum amylase activities were (219.70±19.73), (217.60±11.30), (2896.24±98.32) and (1837.13±131.60)U/L, IL-1β were (0.87±0.28), (1.4±0.85), (67.41±6.45) and (36.33±5.65)pg/ml, IL-6 were (0.74±0.27), (0.16±0.16), (280586.12±39163.92) and (107912.75±31283.47)pg/ml, IL-10 were (35.52±5.27), (50.99±15.34), (2008.45±184.83) and (3070.35±403.71)pg/ml; the expression level of pancreatic IL-1β mRNA was 1.42±0.39, 0.95±25, 20.53±0.50 and 10.69±1.01, IL-6 mRNA was 1.31±0.44, 0.93±0.023, 21.97±1.71 and 11.54±1.75, IL-10 mRNA was 0.93±0.14, 0.75±0.15, 0.99±0.21 and 1.76±0.19; there was no significant difference between LP and CON group, and pancreatic pathological scores, serum amylase、IL-1β and IL-6 levels, and the expression level of pancreatic IL-1β and IL-6 mRNA were significantly decreased in LP+ ANP group compared with those in ANP group, while serum IL-10 levels and the expression level of pancreatic IL-10 mRNA were significantly increased compared with ANP group, and all the differences were statistically significant (all P values <0.05). The pathological scores of ileal tissue of CON, LP, ANP and LP+ ANP group were 0, 0, (3.17±0.41) and (1.67±0.52); the levels of serum DAO of CON, LP, ANP and LP+ ANP group were (0.03±0.03), (0.02±0.02), (0.50±0.05) and (0.49±0.06)ng/ml; LPS levels were (2.75±0.35), (3.74±0.28), (7.19±0.92) and (5.88±0.38)ng/ml; the expression level of ileal IL-1β mRNA was 1.21±0.20, 1.17±0.09, 1.81±0.25 and 1.63±0.21; IL-6 mRNA was 1.01±0.29, 2.83±0.42, 54.45±8.50 and 16.87±4.42; IL-10 mRNA was 1.12±0.41, 6.09±2.51, 11.65±1.47 and 29.86±2.93. There was no significant difference between LP and CON group, except that the ileal IL-10 mRNA expression was significantly higher than that of CON group. Ileal pathological scores, serum LPS levels and the expression level of ileal IL-6 mRNA were significantly lower in LP+ ANP group than those in ANP group, while the expression level of ileal IL-10 mRNA was significantly higher than that of ANP group; the expression of ileal tight junction proteins (ocludin, claudin-1, ZO-1) was significantly higher than those in ANP group, and all the differences were statistically significant (all P values <0.05). Conclusions:LP WCFS1 gavage could ameliorate the injury of pancreatic and ileal barrier in caerulein-induced ANP mice.

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.