Objective To investigate the incidence of acute kidney injury (AKI) post-orthotopic liver transplant (OLT) and its association with prognosis. Methods Data of 28 patients received single OLT in our hospital from 2004 to 2006 were retrospectively analyzed. The incidence of AKI was investigated by new acute kidney injury network (AKIN) criteria. The follow-up was over one year. The prognosis of AKI patients at day 28 and 1 year was evaluated by Kaplan-Meier survival analysis. The association between AKI and prognosis was examined. Results A total of 193 patients were enrolled. The average age was (48.07±10.02) years old. The ratio of male to female was 4:1. One hundred and sixteen (60.1%) patients of post-OLT AKI were found, whose AKI stage 1, 2 and 3 were 50.0%, 21.6% and 28.4% respectively. Ten (8.6%) patients required renal replacement therapy (RRT) after OLT. In AKI post-OLT patients, day 28 and 1 year mortality were significantly higher than those in non-AKI patients (15.5% vs 0, 25.9% vs 3.9%, respectively, both P<0.05). Kaplan-Meier survival analysis showed the 1-year survival rates of AKI stage 1, 2, 3 post-OLT and non-AKl were 84.0%, 81.0%, 42.4% and 90.9%, respectively. The 1-year survival rate of non-AKI was significantly higher than that of AKI stage 1, 2, 3. The 1-year survival rate of AKI stage 3 was significantly lower than that of stage 1 and 2. There was no significant difference between AKI stage 1 and 2. Sct at 1 year post-OLT was significantly higher than that of baseline [(88.35±37.15) vs (73.70±33.88) μmol/L, P<0.05). The change of Scr value at 1 year compared to baseline in AKI patients was similar to non-AKI patients. However such change in AKI stage 2 and 3 was higher than that in stage 1. Conclusions The incidence of AKI post-OLT is quite high and associated to the poor prognosis in short and long periods. Renal function may decrease gradually which is associated to the AKI stage pest-OLTI.

Objective: To summarize and review the clinical and genetic features of neonatal sclerosing cholangitis (NSC) caused by DCDC2 variations. Methods: Whole exome sequencing was performed to identify DCDC2 variants in two Chinese siblings with NSC who were diagnosed in Children's Hospital of Fudan University in May 2017. Clinical, laboratory and genetic data of the two cases were summarized. Key words of "DCDC2" "neonatal sclerosing cholangitis" were searched in Chinese databases and PubMed for articles published until April 2018, and all the relevant literature were reviewed. Results: Patient 1 was a 3-year-and-2-month-old boy. He was admitted to our hospital due to cholestasis for 3 years. Laboratory findings showed elevated levels of gamma-glutamyl transpeptidase (161-1 092 U/L) and total cholesterol (5.4-7.7 mmol/L). Magnetic resonance cholangiopancreatography showed multiple dilations of intrahepatic bile ducts and bilateral hydronephrosis. Patient 2, the older brother of patient 1, was a 9-year-and-9-month-old boy. He was admitted to our hospital due to "cholestasis for 9 years" . CT angiography showed hydrocephalus and left internal carotid artery aneurysms with vascular malformations. A homozygous variant c.529dupA (NM_001195610) in DCDC2 gene was identified in patient 1 by whole exome sequencing. Patient 2 was a homozygote and his parents were heterozygotes with the variation. There has been 2 relevant articles published (Chinese 0, English 2), which reported 11 cases of DCDC2-related NSC in total. All the 13 patients, including the 2 cases reported here, had an onset of symptoms at 0 to 6 months of age. The most common clinical manifestation was cholestasis with high gamma-glutamyl transpeptidase levels, acholic stool, and progression to portal hypertension. Renal and neurological abnormalities were also frequently present. Hypercholesterolemia was observed in one case. Radiological findings revealed the characteristic strictures and dilatations of the intrahepatic and (or) extrahepatic biliary tree. Liver histological examination showed peripheral ductopenia, ductal plate malformation, fibrosis, and cirrhosis. Among the 13 patients, 10 patients required liver transplantation. A total of 7 types of DCDC2 variants were detected in 13 patients. Conclusions DCDC2-related NSC is characterized by the onset of cholestasis with high gamma-glutamyl transpeptidase level and acholic stool in early infancy, which was likely to progress to cirrhosis in early childhood. Renal and neurological abnormalities are also frequently present.Cholangiography or magnetic resonance cholangiopancreatography show strictures and dilatations of the intrahepatic or (and) extrahepatic biliary tree. Identification of pathogenic DCDC2 variants would aid the diagnosis of NSC.

Objective:To evaluate the service capacity of township hospitals in the counties freed from poverty in Hubei province, for reference in improving their service capacity.Methods:An evaluation index system was constructed based on literature analysis. The service ability of such hospitals was comprehensively evaluated by both entropy weight-TOPSIS and rank-sum ratio method based on the 2022 performance evaluation data of township hospitals of Hubei Health Commission.Results:The evaluation index system of service capacity of township hospitals was constructed, using basic medical service, public health service, health resources and service efficiency as first-level indexes and 11 second-level indexes.A total of 299 township hospitals in 32 such counties were finally included in the analysis, and the results of entropy weight-TOPSIS method showed that the first-level indexes of the highest weight coefficient was health resources (0.43), and the second-level index was annual average number of discharged patients and surgeries in each township hospital (0.17). The mean Ci values of township hospitals in the 32 counties freed from poverty in terms of basic medical services, public health services, health resources, service efficiency, and comprehensive service capacity were 0.304, 0.420, 0.329, 0.576, and 0.352, respectively. The results of RSR method showed that 6, 21 and 5 hospitals in such counties were rated as " good, average and poor" in terms of service capacity. Conclusions:The medical service capacity of township hospitals was relatively weak, with a clear gap in their service capacity among such counties. The focus of improving their service capacity should be placed on health resources and surgical operation capacity.

Objective To evaluate the short-term efficacy and safety of sevelamer hydrochloride in treating maintenance hemodialysis (MHD) patients with hyperphosphemia.Methods A multicenter,open-labeled,self-control study was performed.Phosphate binders were discontinued during a two-week washout period.Patients with more than 1.78 mmol/L serum phosphorus after two-week washout period were eligible for the trial.The dose was adjusted every two weeks as necessary to achieve serum phosphorus control. Sevelamer hydrochloride was administered to 138 MHD patients for 10 weeks and a second two-week washout period followed.Results A total of 111 from 138 patients fulfilled the whole 14-week study. Mean serum phosphorus and calcium-phosphate products starte to decline after two-week sevelamer hydrochloride treatment. By the end of 10-week sevelamer hydrochloride treatment, mean serum level of phosphorus [(1.85±0.50) vs (2.57±0.54) mmol/L,P＜0.01],calcium-phosphate product [(4.16± 1.72) vs (5.79 ± 1.50) mmol2/L2,P＜0.01 ] and low density lipoprotein [(1.64±0.76) vs (2.31 ±0.87) mmol/L,P＜0.01] were significantly decreased,while the adjusted serum level of calcium and serum intact parathyroid hormone kept steady.Both serum phosphorus and calcium-phosphrus product increased after the second washout period, but the levels were still lower as compared to pre-treatment [(2.26±0.71) vs (2.57±0.54) mmol/L; (5.12±1.63) vs (5.79±1.50) mmol2/L2,P＜0.01].Of the 138 patients involved,214 episodes in 106 patients and 121 episodes in 89 patients were reported as adverse events and adverse drug reaction respectively. Gastrointestinal symptoms,of which most were mild or moderate,happened to 68.1％ (94/138) patients. Conclusions Sevelamer hydrochloride can control serum phosphorus and reduce the levels of calcium-phosphorus product and cholesterol.Slight gastrointestinal symptoms like constipation are common during the treatment.

Objective:To investigate the signaling pathway of inhibiting macrophage phagocytosis of TIR domain-containing protein encoded by Escherichia coli (TcpC) N-terminal ubiquitin ligase active fragments of uropathogenic Escherichia coli. Methods:Bioinformatics software was used to analyze the amino acid sequences and the function of TcpC N-terminal ubiquitin ligase active fragments as well as the functional sites. PCR was performed to amplify tcpc-330, tcpc-450 and tcpc-510 genes and a prokaryotic expression system was constructed to express the target proteins. The recombinant proteins rTcpC-N110, rTcpC-N150 and rTcpC-N170 were purified by Ni-NTA affinity chromatography. LPS in the recombinant proteins was removed by Detoxi-gel chromatography. The expression of MyD88 at protein and mRNA levels in macrophages incubated with rTcpC-N110, rTcpC-N150, rTcpC-N170 or rTcpC-TIR was detected by Western blot and qRT-PCR. The activation of NF-κB signal pathway and the levels of proinflammatory factors in macrophages incubated with the above TcpC protein fragments were measured by Western blot and ELISA, respectively. Results:Cys12, Trp104 and Trp106 in the N-terminal fragment of TcpC were crucial amino acids in maintaining its ubiquitin ligase activity. The target recombinant proteins rTcpC-N110, rTcpC-N150 and rTcpC-N170 were successfully expressed and purified. After Detoxi-gel chromatography, rTcpC-N110, rTcpC-N150 and rTcpC-N170 extracts were undetectable for LPS. TcpC ubiquitin ligase fragments inhibited the expression of MyD88 at protein level, but not affect its expression at mRNA level in macrophages. LPS-induced phosphorylation of NF-κB signaling pathway-related proteins p50 and p65 was significantly inhibited in macrophages treated with TcpC ubiquitin ligase fragments. Moreover, LPS-induced production of pro-inflammatory factors was also significantly inhibited.Conclusions:The recombinant proteins rTcpC-N110, rTcpC-N150 and rTcpC-N170 could inhibit the expression of MyD88 at protein level and suppress the activation of NF-κB signaling pathway, suggesting that they were closely related to the inhibition of innate immune activity of macrophages.

Objective:To investigate the role of TcpC in uropathogenic Escherichia coli (UPEC)-induced cystitis in mice and to preliminarily analyze the pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 CFU wild-type UPEC CFT073 (CFT073 wt) or tcpc gene-deleted mutant (CFT073 Δ tcpc) from urethra into bladder to construct the mouse model of cystitis. The mice were sacrificed 3 d after infection and the bladders were taken to observe the gross pathological changes. Histopathological changes in bladder tissues were observed after HE staining. Immunohistochemistry was used to detect TcpC in bladder tissues. Bacterial loads in urine samples of UPEC-infected mice were counted by tenfold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from the bladder and urine samples of CFT073 wt-infected mice was measured by PCR. Real-time quantitative RT-PCR (qRT-PCR) and Western blot were performed to detect the expression of TcpC at mRNA and protein levels in macrophages after CFT073 wt infection. The influence of UPEC strains on the activation of NF-κB signaling pathway in macrophages were determined by Western blot. The levels of proinflammatory factors and the bacterial and cell activity after infecting macrophages with UPEC strains were detected by ELISA, laser confocal microscope and fluorescence microscope, respectively. Results:Compared with the mice with CFT073 Δ tcpc infection, CFT073 wt-infected mice had significantly enlarged bladder and severe neutrophil infiltration and abundant TcpC in bladder tissues. The number of bacteria in the urine of CFT073 wt-infected mice was significantly greater than that of the CFT073 Δ tcpc group. PCR results showed that the bacteria in bladder or urine were CFT073 wt. The expression of TcpC at both mRNA and protein levels in macrophages increased significantly after CFT073 wt infection. Moreover, in CFT073 wt-infected macrophages, the expression of IκBα was promoted and the phosphorylation of p65 and the production of proinflammatory factors were suppressed. TcpC was instrumental in the survival and invasion of CFT073 wt in macrophages. Conclusions:TcpC expression increased significantly in mice with CFT073 wt-induced cystitis. TcpC inhibited the activation of NF-κB signaling pathway and the production of proinflammatory factors in macrophages to improve the survival rate of CFT073 wt, which was closely related to the pathogenesis and immune evasion of UPEC.

Objective:To investigate whether the hypervirulent Klebsiella pneumoniae (hvKP) induces liver abscess through activating NLRP3 inflammasome. Methods:K1-hvKP and K35-non-hvKP bacterial suspensions were intraperitoneally injected into C57BL/6 mice to establish the models of liver abscess. Human peripheral blood neutrophils were sorted by immunomagnetic beads with CD45 + and Gr-1 + , and the purity was detected by flow cytometry. The concentrations of capsular polysaccharide of K1-hvKP and K35-non-hvKP were detected by total carbohydrate assay kit. The expression of IL-18 and IL-33 by neutrophils at mRNA and protein levels was detected by real-time fluorescence quantitative PCR and ELISA, respectively. The activation of NLRP3 inflammasome in neutrophils was detected by Western blot. Neutrophil extracellular trap formation (NETosis) was observed under confocal laser scanning microscope. Results:The C57BL/6 mice with K1-hvKP infection had significantly serious liver abscess as compared with the K35-non-hvKP-infected mice. The purity of human neutrophils was more than 95%. The concentration of capsular polysaccharide in K1-hvKP was significantly higher than that in K35-non-hvKP. Compared with K35-non-hvKP, K1-hvKP significantly promoted the neutrophils to express IL-18 and IL-33 at both mRNA and protein levels, enhanced the activation of NLRP3 and induced NETosis.Conclusions:This study suggested that hvKP could promote NETosis by activating NLRP3 inflammasome to cause liver abscess.

Objective To explore the predictive value of CT radiomics and morphological features for the prognosis and survival in non-small cell lung cancer(NSCLC)patients.Methods The clinic data of 300 NSCLC patients(300 lesions)were downloaded from the Cancer Imaging Archive,with 210 randomly selected as the training set and 90 as the test set.According to the prognosis and survival,the patients were divided into two groups with survival period≤3 and＞3 years.3D Slicer software was used to delineate the regions of interest layer by layer in CT images,and the radiomics features were extracted from each region of interest.Both t-test and least absolute shrinkage and selection operator were utilized for radiomics feature screening.Three types of prediction models,namely radiomics model,morphological model and combined model,were constructed with Logistic regression,whose performances were evaluated using the receiver operating characteristic(ROC)curve.Results The differences in radiomics labels and mediastinal lymph node metastasis between the training set and the test set were statistically significant.For radiomics model,morphological model and combined model,the area under the ROC curve was 0.784(95%CI:0.722-0.847),0.734(95%CI:0.664-0.804)and 0.748(95%CI:0.680-0.815)in the training set,and 0.737(95%CI:0.630-0.844),0.665(95%CI:0.554-0.777)and 0.687(95%CI:0.578-0.797)in the test set,which demonstrated that radiomics model had the best diagnostic performance.Conclusion The CT radiomics model can effectively predict the prognosis and survival in NSCLC patients.

Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.

【Objective】 To investigate the environmental pollution of blood collection and supply institutions by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and evaluate its application value. 【Methods】 Colonies of air from blood donation sites, skin puncture sites of blood donors, platelet storage boxes, platelet collection equipment, object surfaces of related experimental consumables and cuff surfaces of staff after disinfection were collected, and typical colonies after cultivation were selected for microbial identification by microbial mass spectrometry and then compared with bacteria results detected in blood components from May 2017 to May 2021. 【Results】 Aseptic growth, the number of colonies ≤4.0 CFU/ dish, and the number of colonies > 4.0 CFU/dish accounted for 21.20%, 62.20% and 16.60%, respectively. The qualified rate from high to low was platelet storage box, bacteria settling in the air of blood donation room after disinfection, platelet collection equipment, skin puncture site of blood donors after disinfection, the surface of platelet consumables and the surface of medical staff's overalls. After disinfection, the blood donors' skin puncture sites were compared with other collection sites, and the t values were 2.0371, 1.508, 2.109, 1.961 and 1.778, respectively, with no significant difference (P>0.05). Thirty cases of bacterial contamination of blood components were detected from May 2017 to May 2021, among which the detection rate of apheresis platelets was the highest, and the t values were 1.731 and 2.272, relative to the contamination frequency of erythrocytes and plasma bacteria (P>0.05), while the t value was 2.875, relative to concentrated platelets, with significant difference (P<0.05). 【Conclusion】 Bacterial contamination of blood components mostly come from air bacteria settling, blood donors' arms and skin after disinfection, and surfaces of related equipment and materials. Therefore, it is of clinical significance to conduct strict disinfection of working sites, establish disinfection monitoring methods and formulate disinfection hygiene standards in blood stations.