Objective To explore the value of echocardiography in evaluation of pulmonary venous in total anomalous pulmonary venous connection (TAPVC).Methods Fifty-five children with TAPVC were enrolled in the study.The data of echocardiography and CT angiography were retrospectively analyzed and compared with intraoperative findings.Results Totally 55 patients with TAPVC were classified into supra-cardiac type (n=24),cardiac type (n=20),infra-cardiac type (n=7) and mixed type (n=4) according to the sites of drainage of pulmonary venous in echocardiography.In 15 patients with obstruction of pulmonary vertical vein,the sites of obstruction in the supra-cardiac type mostly presented between vertical vein and superior vena cava or innominate vein,and the sites of obstruction in the infra-cardiac presented all between vertical vein and hepatic or portal vein.In 4 patients with pulmonary vein stenosis,3 cases with local pulmonary vein stenosis were all cardiac type,which presented between individual pulmonary vein and common confluence or right atrium;1 patient with diffuse pulmonary vein stenosis was infra-cardiac type.In 9 patients of abnormal individual pulmonary vein,8 cases were not detected by echocardiography,but all were detected by CT angiography.Conclusion Echocardiography is able to make more comprehensive evaluation for the pulmonary venous drainage,obstruction,and proximal stenosis of individual pulmonary vein in TAPVC.CT angiography is superior in evaluation of abnormalities of connection and amount of individual pulmonary vein,and imaging of distal pulmonary vein.

Objective To summarize the clinical efficacy of renal transplantation from donors of donation after brain death (DBD) complicated with acute kidney injury (AKI). Methods Fifty-nine DBD donors successfully undergoing renal transplantation were recruited in this investigation. According to the Scr level upon admission of intensive care unit (ICU), DBD donors were divided into the AKI group (n=14) and control group (n=45). A total of 101 recipients were assigned into the AKI group (n=23) and control group (n=78) correspondingly. The organ donation conditions of 59 donors were summarized. Main parameters of the donors before organ procurement were statistically compared between two groups. Postoperative kidney function, hospitalization condition and clinical outcomes of the recipients were statistically compared between two groups. Results Among 59 donors, 14 cases (24%) suffered from AKI. Two donors received continuous renal replacement therapy during organ maintenance. Compared with the donors in the control group, the APACHE Ⅱ score of the donors was significantly higher (P<0.05), the incidence of central diabetes insipidus was considerably higher (P<0.01), the Scr levels at admission of ICU and before organ procurement were significantly higher (both P<0.01) and the amount of urine at 24 h before organ procurement was dramatically less in the AKI group (P<0.01).Compared with the recipients in the control group, the Scr levels at postoperative 2 and 3 d were significantly higher (both P<0.05), the length of hospital stay was considerably longer (P<0.01) and the hospitalization expanse was significantly higher in the AKI group (P<0.05). No statistical significance was observed in the postoperative delayed recovery of renal graft function, incidence of acute rejection, infection and rehabilitation dialysis in the recipients between two groups (all P>0.05). At 3 months after transplantation, the recipients in two groups were discharged and the graft survival rate was 100%. Conclusions For renal transplantation from DBD donors complicated with AKI, active measures should be taken to maintain the organ and relieve the AKI, which yields similar clinical efficacy to renal transplantation from non-AKI donors and widens the origin of kidney graft.

OBJECTIVEThe aim of the study was to evaluate the effects of cochlear implantation on bilateral perceived tinnitus of postlingually deafened patients.

METHODTotal of 32 postlingually deafened cochlear implant recipients (13 males, 19 females; 31 unilateral,1 bilateral cochlear implantation) with bilateral tinnitus were assessed by Tinnitus Handicap Inventory (THI) before and after implantation. Furthermore, characteristics information of tinnitus were recorded to analyze the variety of tinnitus. Intensity of tinnitus in ispilateral and contralateral ears was investigated when cochlear implant was switched on and off. Statistical analysis was performed by SPSS 18.0.

RESULTSTwenty-two patients (71.0%) got a decreased THI score of more than 20 points after the operation. The average THI score of pre-operation was 56.4±18.1, and post-operation score was 24.7±22.7. A paired-samples t test analysis showed a significant difference of the THI total scores (t=8.037, P<0.05). Tinnitus in the ipsilateral ear improved in 81.9% (27/33) patients and 18.2% (6/33) unchanged. Tinnitus in the contralateral ear improved in 71.0% (22/31) patients, 16.1% (5/31) unchanged and 12.9% (4/31) worsen. Tinnitus of ipsilateral ears improved or abolished in 97.0% (32/33) patients, while 83.9% (26/31) of contralateral ear got reduction or absence of loudness when cochlear implant was switched on.

CONCLUSIONSAs an electrical stimulation treatment method, cochlear implant has the inhibitory effect on tinnitus. However, cases of tinnitus aggravation were found, further data is still necessary before considering CI as a treatment of tinnitus.

Cochlear Implantation ; Cochlear Implants ; Electric Stimulation ; Female ; Humans ; Male ; Perception ; Postoperative Period ; Tinnitus ; surgery

Objective:To explore the clinical efficacy of venovenous extracorporeal membrane oxygenation(V-V ECMO)in patients with severe acute respiratory distress syndrome(ARDS)caused by Pneumocystis pneumonitis(PJP)after kidney transplantation(KT).Methods:Cal data of 9 KT recipients on V-V ECMO were retrospectively analyzed. Timing of V-V ECMO support, complications during treatment and V-V ECMO performance were summarized.Results:All 9 patients with confirmed PJP adopted V-V ECMO with oxygenation index of 25~92 prior to V-V ECMO and average time from admission to initiating V-V ECMO was 5.56(1~17)days. Except for one death from hemorrhagic shock due to abdominal hemorrhage, the remainders were successfully weaned. Another recipient died from sepsis after weaning and there were 7 survivors. V-V ECMO support time was 215.5 h among 8 successfully weaned recipients. Among 7 survivors, 1 had premorbid deterioration of graft function and no fatal complications occurred.Conclusions:V-V ECMO is an effective treatment for severe ARDS caused by P. pneumoniae post-KT. And its early application is recommended for reducing complications and improving patient prognosis.

Objective:To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in tuberculous meningitis (TBM).Methods:From August 1, 2020 to August 31, 2022, 99 patients with suspected TBM admitted to the Tuberculosis Diagnosis and Treatment Center, Hangzhou Chest Hospital, Zhejiang University School of Medicine were enrolled. The cerebrospinal fluid (CSF) was tested for mNGS, GeneXpert Mycobacterium tuberculosis/rifampin (GeneXpert MTB/RIF) and mycobacterium culture. The sensitivity, specificity, positive predictive value, negative predictive value, agreement rate, Kappa value of the diagnostic efficacy of the three test methods were compared.The receiver-operating characteristic (ROC) curve of the diagnostic efficacy of mNGS was drawn. Chi-square test and rank sum test were used for statistical analysis. Results:Among the 99 suspected patients with TBM, 67 were diagnosed with TBM and 32 were non-TBM. Based on the results of 67 cases clinically diagnosed with TBM, the sensitivity, specificity, positive predictive value, negative predictive value, agreement rate and Kappa value of mNGS for the diagnosis of TBM were 82.1%, 100.0%, 100.0%, 72.7%, 87.9% and 0.748, respectively. The sensitivity of mNGS was higher than that of GeneXpert MTB/RIF (50.7%) and mycobacterium culture (28.4%). The differences were statistically significant ( χ2=12.61 and 32.42, respectively, both P<0.01). The detection time of mNGS was 1.0 (1.0, 2.0) day, which was shorter than 42.0 (42.0, 42.0) days of mycobacterium culture with statistical significance ( Z=10.80, P<0.001). ROC curve analysis showed that mNGS had the best diagnostic efficacy when the number of Mycobacterium tuberculosis sequences in CSF was one. Conclusions:The sensitivity and specificity of mNGS in the diagnosis of TBM are high, and the detection time is shorter, which could be used in the early diagnosis of TBM.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Trichoderma reesei Rut-C30 is widely used in industrial cellulase production, and development of cellulase hyper-producer is of great importance for economic lignocellulosic biorefinery. In this study, T. reesei Rut-C30 was engineered with an artificial zinc finger proteins (AZFPs) library. Two mutants T. reesei M1 and M2 with improved cellulase production were obtained. Compared to the parent strain, the filter paper activity (FPase) of T. reesei M1 and M2 increased 100% and 53%, respectively. In addition, the total amount of extracellular protein from the M1 mutant increased 69%, whereas the endo-β-glucanase (CMCase) activity of the M2 mutant is 64% higher compared to the parental strain. Furthermore, RT-qPCR analysis showed that the major cellulase genes exhibited significantly increased expression in both mutants, but different patterns were observed in the two mutants. On the other hand, the cellulase transcriptional repressor ace1 was down-regulated in both mutants, but the transcription level of the activator xyr1 was only up-regulated in the strain M1. These results demonstrated that different AZFPs exert diverse regulatory mechanisms on cellulase production in T. reesei. Analysis of the target genes of AZFPs from T. reesei M1 and M2 will not only benefit further exploration of the regulatory mechanisms of cellulase biosynthesis in T. reesei, but also enable development of cellulase hyper-producing strains by metabolic engineering.
Cellulase ; Gene Library ; Transcription Factors ; Trichoderma ; Zinc Fingers

BACKGROUNDSurfactant protein A (SP-A) contributes to the regulation of sepsis-induced acute lung injury. In a previous study, we demonstrated the expression and localization of SP-A in the kidneys. The present study evaluated the effect of SP-A on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-α) expression and its underlying mechanisms in the human renal tubular epithelial (HK-2) cells.

METHODSIndirect immunofluorescence assay was used to detect SP-A distribution and expression in HK-2 cells. HK-2 cells were treated with various concentrations of LPS (0, 0.1, 1, 2, 5, and 10 mg/L) for 8 hours and with 5 mg/L LPS for different times (0, 2, 4, 8, 16, and 24 hours) to determine the effects of LPS on SP-A and TNF-α expression. Then, HK-2 cells were transfected with SP-A siRNA to analyze nuclear factor κB (NF-κB) P65 and TNF-α expression of HK-2 cells after LPS-treatment.

RESULTSIndirect immunofluorescence assay revealed that SP-A is localized to the membrane and cytoplasm of HK-2 cells. Interestingly, SP-A1/SP-A2 and TNF-a expression were found to be significantly increased in HK-2 cells upon LPS treatment. Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant increases in the levels of NF-κB P65 protein and TNF-α mRNA and protein compared to those in non-transfected LPS-treated HK-2 cells.

CONCLUSIONSP-A plays an important role in protecting cells against sepsis-induced acute kidney injury by inhibiting NF-κB activity to modulate LPS-induced increase in TNF-α expression.

Cell Line ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Fluorescent Antibody Technique, Indirect ; Humans ; Kidney Tubules, Proximal ; cytology ; Lipopolysaccharides ; pharmacology ; Pulmonary Surfactant-Associated Protein A ; metabolism ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism