[Analysis of the experience and procedural complications of trans-radial access versus trans-femoral access for hepatic arterial perfusion chemotherapy in patients with advanced hepatic malignancies:a retrospective study].

Objective: To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA. Methods: The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA (n=20, receiving TRA HAIC only), group TFA (n=33, receiving TFA HAIC only), and crossover group [n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group (n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group (n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher's exact test, univariate logistic regression analysis, and multi-factor analysis. Results: TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort (Z=-3.07,P=0.002), postoperative toilet difficulty (Z=-2.12, P=0.034), and walking difficulty (Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group (Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure (χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO (P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions: With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.

[Therapeutic effect of intravenous thrombolysis with tenecteplase on patients with post awakening branch atheromatous disease].

Objective: To investigate the efficacy and safety of intravenous thrombolysis with Tenecteplase (TNK) in patients with post-awakening branch atheromatous disease (BAD). Methods: A retrospective collection was conducted on 178 patients with post-awakening BAD admitted to the Stroke Centre of Zhengzhou People's Hospital from January 2017 to June 2023, who had a mismatch in DWI/FLAIR on magnetic resonance imaging. The patients were divided into thrombolysis group (60 patients) and control group (118 patients) according to whether or not they were applied to intravenous thrombolysis by TNK. Propensity score matching (PSM) was used to pair and balance the confounding factors at 1∶1 between the two groups, and the 90-d long-term prognosis of the patients was assessed using the modified Rankin Scale (mRS) and the Barthel Index (BI). The National Institutes of Health Stroke Scale (NIHSS) score was used to compare the early neurological changes between the two groups.The differences in clinical outcomes were compared between the two groups. Results: Fifty-two pairs of patients, 65 males and 39 females, aged (60±9) years, were successfully matched by PSM. The thrombolysis group had lower NIHSS score than that of the control group at 24 h, 7 d, 14 d after treatment or at discharge [3(2, 5) vs 4(3, 7), 3(2, 5) vs 4(3, 5), and 2(1, 4) vs 3(2, 4)], and shorter hospital stay than that of the control group [9(7, 12) d vs 11(9, 13) d], and at the same time, the thrombolysis group was less likely to experience early neurological deterioration (END) [9.6% (5/52) vs 28.9% (15/52)], and the proportion of 90 d mRS≤1, mRS≤2, and BI scores were higher than those in the control group [63.5% (33/52) vs 30.8% (16/52), 82.7% (43/52) vs 59.6% (31/52), and (91±8) points vs (82±8) points ], all differences were statistically significant (P<0.05). The percentage of mRS≥4 points was higher in the control group than that in the thrombolysis group [23.1% (12/52) vs 7.7% (4/52)]. One case of intracranial haemorrhage occurred in the thrombolysis group, and 1 case in the control group died of pulmonary infection within 90 d of follow-up, with a case-fatality rate of 1.9% (1/52). Conclusion: In the patients with post-awakening BAD screened by MRI, TNK intravenous thrombolysis can significantly reduce the risk of END, improving long-term prognosis and has a high safety.

[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

[Efficacy of intravenous thrombolysis with tenecteplase in treating the branch atheromatous disease].

Objective: To explore the efficacy of intravenous thrombolysis with tenecteplase (TNK) in the treatment of branch atheromatous disease (BAD). Methods: A total of 148 BAD patients hospitalized in the stroke center of Zhengzhou People's Hospital from January 2020 to March 2023 were retrospectively included. According to whether TNK was used for treatment, the patients were divided into the TNK group (52 cases) and the control group (96 cases). The propensity score matching (PSM) method was used to eliminate baseline differences between the two groups, and 46 pairs were successfully matched. Early neurological deterioration (END) was defined as an increase in the national Institutes of Health Stroke Scale (NIHSS) scores within 7 days of stroke≥2. The 90-day modified Rankin Scale (mRS) was used to compare the long-term efficacy between the two groups. A binary logistic regression model was used to analyze the influencing factors of clinical outcomes in patients with BAD. Results: Among the 92 patients, 62 were males and 30 were females, with an average age of (61.0±9.5) years. After PSM, there were statistically significant differences in NIHSS score at discharge [2 (0, 4) vs 4 (3, 8)] and length of hospital stay [9 (6, 13) d vs 11 (9, 14) d] (both P<0.05) between the two groups. The proportion of mRS 0-2 in TNK group was higher than that in the control group [82.6%(38/46) vs 60.8%(28/46)], while the proportion of END and mRS≥4 was lower than that in the control group [10.8%(5/46) vs 30.4%(14/46); 8.7%(4/46) vs 26.0%(12/46)], with statistically significant differences (P<0.05). The 90-day mortality in the control group was 2.2% (1/46), while no death was detected in the TNK group. Conclusion: Intravenous thrombolysis therapy with TNK can not only increase the proportion of 90-day mRS 0-2 in BAD patients, but also reduce the incidence of END.

[Effect of PCSK9 inhibitors on early neurological deterioration in patients with branch atheromatous disease].

Objective: To investigate the effect of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors on the incidence of early neurological deterioration during the treatment of branch atheromatous disease (BAD). Methods: A retrospective analysis of 297 BAD patients admitted to the Department of Neurology in Zhengzhou People's Hospital from January 2020 to April 2023 was made. According to whether to use PCSK9 inhibitor treatment, they were divided into PCSK9 inhibitor group (81 cases) and control group (216 cases). Propensity score matching (PSM) method was used to eliminate the general situation difference between PCSK9 inhibitor group and control group. Seventy-two cases were successfully matched in each group. The early neurological deterioration (END) and low-density lipoprotein cholesterol (LDL-C) were compared. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase≥2 points within 72 hours after stroke. Suspicious influencing factors leading to END were screened for multivariate logistic regression model analysis. Results: After PSM matching, among the 144 patients, 90 were male and 54 were female, aged (61.2±9.6) years. After matching, The hospital stay[M(Q1, Q3)] [9(7, 11)d vs 10(8, 13)d] in PCSK9 and NIHSS score at discharge [2(1, 3) vs 3(1, 4) points] were significantly different from those in the control group (all P<0.05). In addition, the incidence of END was reduced in the PCSK9 inhibitor group [12.5%(9/72) vs 31.9%(23/72),P<0.05]. Multivariate logistic regression analysis found that C-reactive protein (CRP)(OR=1.119,95%CI: 1.010-1.240, P<0.05) and PCSK9 inhibitor (OR=0.298, 95%CI: 0.117-0.755, P<0.05) were factors associated with the development of END. Conclusion: The use of PCSK9 inhibitors in the treatment of patients with BAD can reduce the incidence of END.

[Free anterolateral femoral muscle flap and perforator flap transplantation for repair of the huge wound after periorbital tumor resection and orbital enucleation].

Objective: To observe the clinical effect of free anterolateral femoral muscle flap and perforator flap transplantation for repair of the huge wound and after periorbital tumor resection and orbital enucleation. Methods: It was a retrospective case series study. Twelve patients with orbital tumors admitted to the Department of Burn and Plastic Surgery of the Affiliated Hospital of Zunyi Medical University from February 2017 to April 2021 were included. There were 4 males and 8 females, aged 48 to 87 years. Nine patients had cutaneous squamous cell carcinoma, and 3 had basal cell carcinoma. All patients underwent extended resection of the tumor, resection of orbital contents and wound repair.All patients had the lesion completely removed, chimeric anterolateral thigh flap of the anterolateral femoral flap and perforator flap were transplanted to repair the wound. The donor area of the flaps was closed with tension sutures. The size of intraoperative resection lesion,intraoperative resection flap and muscle flap and the depth of the wound cavity were summarized. The postoperative flap survival, wound healing, surgical area appearance, flap color, thickness and texture, scarring and sensation in the surgical area, and tumor recurrence were observed. Results: The surgical procedures were successfully completed in all the 12 patients. The intraoperative resection lesion ranged from 7.0 cm × 5.0 cm to 15.0 cm × 8.0 cm. The depth of the wound cavity was 4.0 to 5.0 cm. The intraoperative resection flap range was 7.0 cm × 5.0 cm to 19.0 cm × 8.0 cm. The muscle flap size ranged from 4.0 cm × 3.0 cm to 5.0 cm × 4.0 cm. All flaps completely survived after surgery, and the wounds healed. The sutures at the recipient area were removed at 5 to 7 days after surgery, while the sutures at the donor area were removed at 12 to 14 days. All of the patients were followed up for 3 to 30 months. The scar at the periorbital area was concealed, and the color, thickness and texture of the flaps were similar to those of the surrounding normal skin. The scarring in the flap supply area was not hypertrophic, with localized decreased skin sensation around it. None of the patients had any tumor recurrence during the follow-up period. Conclusion: The anterolateral femoral muscle flap and perforator flap transplantation could efficiently repair the huge wound after orbital content removal, achieving satisfactory therapeutic effects.

Moiré graphene nanoribbons: nearly perfect absorptions and highly efficient reflections with wide angles.

The strong absorption and reflection from atomically thin graphene nanoribbons has been demonstrated over the past decade. However, due to the significant band dispersion of graphene nanoribbons, the angle of incident wave has remained limited to a very narrow range. Obtaining strong absorption and reflection with a wide range of incident angles from atomically thin graphene layers has remained an unsolvable problem. Here, we construct a tunable moiré superlattice composed of a pair of graphene nanoribbon arrays to achieve this goal. By designing the interlayer coupling between two graphene nanoribbon arrays with mismatched periods, the moiré flat bands and the localization of their eigen-fields was realized. Based on the moiré flat bands of graphene nanoribbons, highly efficient reflection and nearly perfect absorption was achieved with a wide range of incident angles. Even more interesting, is how these novel phenomena can be tuned through the adjustment of the graphene's Fermi energy, either electrostatically or chemically. Our designed moiré graphene nanoribbons suggest a promising platform to engineer moiré physics with tunable behaviors, and may have potential applications in the field of wide-angle absorbers and reflectors in the mid-infrared region.

Laser-cooled 171Yb+ microwave frequency standard with a short-term frequency instability of 8.5 × 10-13/√τ.

We report on the development of a microwave frequency standard based on a laser-cooled 171 Y b + ion trap system. The electronics , lasers, and magnetic shields are integrated into a single physical package. With over 105 ions are stably trapped, the system offers a high signal-to-noise ratio Ramsey line-shape. In comparison with previous work, the frequency instability of a 171 Y b + microwave clock was further improved to 8.5×10-13/τ for averaging times between 10 and 1000 s. Essential systematic shifts and uncertainties are also estimated.

Differentiating infected focal liver lesions from malignant mimickers: value of ultrasound-based radiomics.

AIM: To establish an ultrasound-based radiomics model through machine learning methods and then to assess the ability of the model to differentiate infected focal liver lesions from malignant mimickers. MATERIALS AND METHODS: A total of 104 patients with infected focal liver lesions and 485 patients with malignant hepatic tumours were included, consisting of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), combined hepatocellular-cholangiocarcinoma (cHCC-CC), and liver metastasis. Radiomics features were extracted from grey-scale ultrasound images. Feature selection and predictive modelling were carried out by dimensionality reduction methods and classifiers. The diagnostic effect of the prediction mode was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: In total, 5,234 radiomics features were extracted from grey-scale ultrasound image of every focal liver lesion. The ultrasound-based radiomics model had a favourable predictive value for differentiating infected focal liver lesions from malignant hepatic tumours, with an area under the curve (AUC) of 0.887 and 0.836 (HCC group), 0.896 and 0.766 (CC group), 0.944 and 0.754 (cHCC-CC group), 0.918 and 0.808 (liver metastasis group), and 0.949 and 0.745 (malignant hepatic tumour group) for the training set and validation set, respectively. CONCLUSIONS: Ultrasound-based radiomics is helpful in differentiating infected focal liver lesions from malignant mimickers and has the potential for use as a supplement to conventional grey-scale ultrasound and contrast-enhanced ultrasound (CEUS).

Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH).

PURPOSE: Fibrosis is the only histological feature reflecting the severity and prognosis of nonalcoholic steatohepatitis (NASH). We aim to explore novel genes associated with fibrosis progression in NASH. METHODS: Two human RNA-seq datasets were downloaded from the public database. Weighted gene co-expression network analysis (WGCNA) was used to identify their co-expressed modules and further bioinformatics analysis was performed to identify hub genes within the modules. Finally, based on two single-cell RNA-seq datasets from mice and one microarray dataset from human, we further observed the expression of hub genes in different cell clusters and liver tissues. RESULTS: 7 hub genes (SPP1, PROM1, SOX9, EPCAM, THY1, CD34 and MCAM) associated with fibrosis progression were identified. Single-cell RNA-seq analysis revealed that those hub genes were expressed by different cell clusters such as cholangiocytes, natural killer (NK) cells, and hepatic stellate cells (HSCs). We also found that SPP1 and CD34 serve as markers of different HSCs clusters, which are associated with inflammatory response and fibrogenesis, respectively. Further study suggested that SPP1, SOX9, MCAM and THY1 might be related to NASH-associated hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of HCC. At the same time, there were significant differences in metabolism-related pathway changes between different HCC subtypes, and SOX9 may be involved in these changes. CONCLUSIONS: The present study identified novel genes associated with NASH fibrosis and explored their effects on fibrosis from a single-cell perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of fibrosis progression in NASH.

[Establishment of quality evaluation criteria for out-patient medical records of cancer pain and assessment of its application effect].

Objective: To establish the quality evaluation criteria for out-patient medical records of cancer pain and evaluate the effect of its application. Methods: The evaluation criterion was established based on Delphi method for out-patient medical records of cancer pain in the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University. Firstly, the weight of each evaluation indicator was calculated by the method of Attribute Hierarchical Model in combination with technique for order preference by similarity to solution (AHM-TOPSIS), and out-patient medical records of 50 cancer pain patients (group A, 150 records) received in June 2020 were assessed comprehensively. Secondly, the relative closeness (Ci value) between the writing quality and the ideal solution was calculated, as well as the proportion of evaluation indicators which were lack of standardization. Thirdly, the corresponding countermeasures were adapted based on the results of assessment. Finally, another 50 medical records (156 records) received in October 2021 were re-evaluated by the same method, and the differences of quality of medical record and proportion of each evaluation indicator which was lack of standardization before and after the intervention were compared. Results: A specific criterion which contained integrity of materials required for the medical records, documents of the complaints and medical history of cancer pain, description of the previous medical treatment for cancer pain, regular assessment of cancer pain and its' document, quantitative assessment and its' document, comprehensive assessment and its' document, dynamic assessment and its' document, reasonable of pain medication, reasonable of the drug usage and dosage, reasonable adjustment of the drug variety or dosage, prevention of adverse reactions of analgesic drugs and its' document, evaluation and management of adverse reactions of analgesic drugs and its' document (12 indicators) was established to evaluate the out-patient medical records of cancer pain. The proportion of medical records which Ci≥0.6 was 62.0% (93/150) in group A before the intervention. It was increased to 84.6% (132/156) in group B after the intervention and the difference was statistically significant (P<0.001). Furthermore, the proportions of comprehensive assessment of cancer pain which were lack of standardization, prevention of adverse reaction, quantitative evaluation and dynamic assessment of cancer pain accounted for a higher level, which was 64.0% (96/150), 55.3% (83/150), 54.7% (93/150) and 52.7% (79/150) respectively in group A before the intervention. However, proportions of such records were decreased to 50.6% (79/156), 35.9% (56/156), 32.1% (50/156) and 39.7% (62/156) respectively in group B after the intervention and the differences were statistically significant (all P<0.05). Conclusions: A specific quality evaluation criterion is established based on Delphi method and AHM-TOPSIS for the out-patient medical records of cancer pain. The quality of medical records has been improved in a certain level after adapting comprehensive evaluation and intervention on the out-patient medical records of cancer pain.

[The effect of steatotic donor livers on the prognosis of donors and recipients after pediatric living donor liver transplantation].

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ2 test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.

Precision determination of the ground-state hyperfine splitting of trapped 113Cd+ ions.

We measured the ground-state hyperfine splitting of trapped 113Cd+ ions to be 15199862855.02799(27) Hz with a fractional uncertainty of 1.8×10-14. The ions were trapped and laser-cooled in a linear quadrupole Paul trap. The fractional frequency stability was measured to be 4.2×10-13/τ, obtained from Ramsey fringes of high signal-to-noise ratios and taken over a measurement time of nearly 5 h, which is close to the short-term stability limit estimated from the Dick effect. Our result is consistent with previously reported values, but the measurement precision is four times better than the best result obtained to date.

Antibacterial potential and mechanism of action of dithiocyano-methane as a bactericidal agent for farm disinfection.

AIMS: This study aimed to investigate the antibacterial ability and action mechanism of dithiocyano-methane against Aeromonas hydrophila, so as to provide a reference for its application in farm disinfection. METHODS AND RESULTS: After exposing the bacteria to dithiocyano-methane, the minimum inhibitory concentration (MIC), minimum bactericide concentration (MBC), activities of alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and electric conductivity in bacterial suspensions were determined, transmission electron microscope images on cellular structure and SDS-PAGE profile of bacterial proteins were analysed and the expression of genes related to the above experimental observations was confirmed by real-time quantitative PCR. The MIC and MBC of dithiocyano-methane against three tested strains was 1·46 and 2·93 mg l-1 respectively. The results showed that dithiocyano-methane significantly damaged bacterial cell structure, inhibited the biosynthesis of bacterial proteins and changed the integrity and permeability of bacterial cell wall and cell membrane. CONCLUSIONS: Dithiocyano-methane showed remarkable antibacterial ability against three tested strains, indicating it is a potential effective bactericidal agent for preventing animal diseases resulted from Aer. hydrophila. SIGNIFICANCE AND IMPACT OF THE STUDY: To our best knowledge, this is the first report to examine the antibacterial ability and action mechanism of dithiocyano-methane against bacteria. The results demonstrate the great potential of dithiocyano-methane as a disinfectant against Aer. hydrophila in settings such as aquaculture ponds and livestock farms.

[Risk factors of blood loss during liver transplantation in children with biliary atresia and its influence on prognosis].

Objectives: To study the risk factors for massive intraoperative blood loss in children with biliary atresia who underwent liver transplantation for the first time,and to analyze their impacts on graft survival,hospital stay and postoperative complications. Methods: The data of 613 children with biliary atresia who underwent liver transplantation at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital from January 2015 to December 2018 were collected and analyzed. There were 270 males and 343 females, aged 7.4 (3.9) months (range: 3.2 to 148.4 months), the body weight of the recipients were (7.8±3.5) kg (range: 4.0 to 43.3 kg).According to the 85th quad of estimated blood loss(EBL),they were divided into two groups:massive EBL group(96 cases) and non massive EBL group(517 cases). The age,height,weight and other factors between the two groups were analyzed and compared. Univariate Logistic regression and multiple stepwise regression were used to determine the risk factors of massive EBL. Then,the postoperative complications of the two groups,including portal vein thrombosis and portal vein anastomotic stenosis etc.,were analyzed and compared by chi square test. Kaplan Meier curve and log rank test were used to analyze the recipient and graft survival rate of the two groups. Results: During the study period,713 transplants were performed and 613 patients were enrolled in the study. Ninety-six patients(15.7%) had massive EBL,and the postoperative hospital stay was 21(16) days(range:2 to 116 days),the hospital stay of non-massive EBL group was 22(12)days(range:3 to 138 days)(U=24 224.0,P=0.32). Univariate Logistic regression analysis showed that the recipient's weight,Kasai portoenterostomy,platelet count,operation time and cold ischemia time were the risk factors of massive EBL during biliary atresia transplantation. Multiple regression analysis showed that cold ischemia time ≥10 hours,prolonged operation time(≥8 hours) and body weight<5.5 kg were important independent risk factors for massive EBL.The incidence of portal vein thrombosis,hepatic vein stenosis,intestinal leakage and pulmonary infection in patients with massive EBL were significantly higher than those without massive EBL(3.1% vs. 0.8%,9.4% vs. 2.1%,6.3% vs. 0.8%,30.2% vs. 20.1%,all P<0.05). The 3-year overall graft and recipient survival rate were significantly lower in patients with massive EBL than those without massive EBL(87.5% vs. 95.7%,P=0.001;84.4% vs. 95.4%,P<0.01,respectively). Conclusions: In children with biliary atresia who underwent liver transplantation for the first time,the effective control of intraoperative bleeding should shorten the operation time and reduce the cold ischemia time as far as possible,on the premise of ensuring the safety of operation. For children without growth disorder,the weight of children should be increased to more than 5.5 kg as far as possible to receive the operation. Reducing intraoperative bleeding is of great significance to the prognosis of children.

[Clinical study of causes and outcomes in pediatric liver retransplantation].

Objective: To investigate the etiology,clinical features and prognosis of pediatric liver retransplantation. Methods: The data of 1 024 cases of pediatric liver transplantation (<18 years old) from January 2014 to December 2019 operated at Tianjin First Central Hospital were collected,retrospectively. Retransplantation was performed in 26 cases,among which 25 cases received secondary liver transplantation and 1 case received a third liver transplantation. There were 13 male and 12 female patients among the 25 patients. The median age was 12.9(20.5) months(range: 5.8 to 134.8 months), the body weight was 8.0(5.6) kg(range: 5.0 to 30.0 kg) at the time of retransplantation. The pediatric end-stage liver disease(PELD) score was 17.0(21.3) (range: 0 to 45) before retransplantation. The etiology of retransplantation was biliary complications in 7 cases,primary nonfunction of liver graft in 5 cases,antibody-mediated rejection in 4 cases,hepatic artery thrombosis in 3 cases,portal vein thrombosis in 3 cases,concomitant hepatic artery and portal vein thrombosis in 2 cases,thrombogenesis of inferior Vena Cava in 1 case and sinusoidal obstruction syndrome in 1 case. The patients were divided into two groups according to the time interval(30 days) between two liver transplantations,8 patients were classified into early-retransplantation(≤30 days) group and 18 patients were classified into late-retransplantation (>30 days) group. The etiology of liver retransplantation,pre-transplant score,time interval between two transplantations,surgical aspects,major complications and survival rates were compared between the two groups. Continuous variables with normal distribution were compared with t test,while Mann-Whitney U test was applied to compare variables without normal distribution. Categorical variables were compared with chi-square test. The survival curves were created by Kaplan-Meier method and compared by Log Rank test. Results: The median follow-up time was 26.8(30.2) months(range: 1 day to 85.7 months), and the incidence of retransplantation was 1.9%. In the early-retransplantation group,the duration of surgery was (439.8±151.0)minutes,the graft-to-recipient weight ratio was 5.0(1.8)%(range:3.6% to 6.1%),the main cause for retransplantation were primary nonfunction and vascular complications. In the late-retransplantation group,the duration of surgery was (604.4±158.0)minutes,the graft-to-recipient weight ratio was 3.4(2.1)%(range:1.4% to 5.3%),the main cause for retransplantation were biliary complications,antibody mediated rejection and vascular complications.The 3-month,1-year and 2-year recipient survival rates in the early-retransplantation group were all 62.3%,while the recipient survival rates in the late-retransplantation group were 100%,93.8% and 93.8%,respectively. The difference of recipient survival rates was significant between the early-retransplantation group and the late-retransplantation group(P=0.019). The overall 3-month,1-year and 3-year recipient survival rates after the primary liver transplantation were 97.1%,95.4%,94.1%,respectively. Conclusions: The vascular complications,biliary complications,primary nonfunction and antibody-mediated rejection are the main causes of liver retransplantation.The PELD score is higher in patients receiving early retransplantation,while the surgery is relatively more complex in patients receiving late retransplantation,which is reflected by longer duration of surgeries. Patients in the late-retransplantation group showed similar recipient survival rates with primary liver transplantation recipients,and the survival rates are superior to those of patients in the early-retransplantation group. Infection and multiple organ failure are the most common fatal causes after retransplantation.

Plasma mtDNA copy numbers are associated with GSTK1 expression and inflammation in type 2 diabetes.

AIMS: Mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes. Glutathione S-transferase kappa 1 (GSTK1) is critical to maintain mitochondrial function and homeostasis. We aimed to investigate whether a potential link exists between mitochondrial DNA (mtDNA) copy numbers and inflammation, non-esterified fatty acids (NEFA) and GSTK1 expression in type 2 diabetes. METHODS: We assessed mtDNA copy numbers in plasma and GSTK1 expression in white blood cells in 123 people with type 2 diabetes and in 121 healthy controls using a quantitative polymerase chain reaction (qPCR). An automatic chemistry or immunoassay analyser was used to determine serum glucose, lipids and inflammatory markers. Multiple linear regression and multivariable logistic regression models were used to evaluate associations and risks. RESULTS: Compared with healthy controls, individuals with diabetes showed higher mtDNA copy numbers (t = -3.938, P < 0.001) and lower GSTK1 expression (Z = -2.985, P = 0.002). mtDNA copy number was associated with type 2 diabetes risk [odds ratio (OR) = 1.80, 95% confidence intervals (CI) 1.25-2.58, P = 0.001] after controlling for confounding factors. In individuals with diabetes, mtDNA copy number was negatively associated with GSTK1 expression (ß = -0.235, P = 0.036) and positively associated with serum high-sensitive C-reactive protein (hsCRP) (ß = 0.839, P < 0.001), tumour necrosis factor alpha (TNF-α) (ß = 0.549, P < 0.001), interleukin-6 (IL-6) (ß = 0.589, P = 0.006) and NEFA (ß = 0.001, P = 0.020). In the diabetic group, individuals with an abnormal increase in NEFA, hsCRP, TNF-α and IL-6 showed significantly elevated mtDNA copy numbers (all P < 0.05). CONCLUSIONS: mtDNA copy numbers in plasma might have an important role in the progression of diabetic chronic inflammation via inhibition of GSTK1 and could be a potential biomarker for type 2 diabetes.

MRI-based radiogenomics analysis for predicting genetic alterations in oncogenic signalling pathways in invasive breast carcinoma.

AIM: To investigate the effect of radiomics in the assessment of alterations in canonical cancer pathways in breast cancer. MATERIALS AND METHODS: Eighty-eight biopsy-proven breast cancer cases were included in the present study. Radiomics features were extracted from T1-weighted sagittal dynamic contrast-enhanced magnetic resonance imaging (MRI) images. Radiomics signatures were developed to predict genetic alterations in the cell cycle, Myc, PI3K, RTK/RAS, and p53 signalling pathways by using hypothesis testing combined with least absolute shrinkage and selection operator (LASSO) regression analysis. The predictive powers of the models were examined by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A total of 5,234 radiomics features were obtained from MRI images based on the tumour region of interest. Hypothesis tests screened 250, 229, 156, 785, and 319 radiomics features that were differentially displayed between cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations and no alteration status. According to the LASSO algorithm, 11, 12, 12, 15, and 13 features were identified for the construction of the radiomics signatures to predict cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations, with AUC values of 0.933, 0.926, 0.956, 0.940, and 0.886, respectively. The cell cycle radiomics score correlated closely with the RTK/RAS and p53 radiomics scores. These signatures were also dysregulated in patients with different oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 statuses. CONCLUSION: MRI-based radiogenomics analysis exhibits excellent performance in predicting genetic pathways alterations, thus providing a novel approach for non-invasively obtaining genetic-level molecular characteristics of tumours.

[Subcellular localization of GTPase of immunity-associated protein 2].

OBJECTIVE: To analyze the subcellular localization of GTPase of immunity-associated protein 2 (GIMAP2) for the further functional study. METHODS: In the study, we first obtained the protein sequences of GTPase of immunity-associated protein 2 (GIMAP2) from National Center for Biotechnology Information (NCBI) database, and then performed a prediction analysis of its transmembrane structure, nuclear localization signal (NLS), nuclear export signal (NES) and subcellular localization through bioinformatics online tools. GIMAP2 gene amplified by PCR was inserted into the expression vector pQCXIP-mCherry-N1 and positive clones were selected by ampicillin resistance. After using methods to extract and purify, the sequenced recombinant plasmid pQCXIP-GIMAP2-mCherry, together with the retroviral packaging plasmids VSVG and Gag/pol, was transferred into HEK293FT cells by liposomes for virus packaging. The virus supernatant was collected 48 h after transfection and directly infected the human breast cancer cell line MDA-MB-436. Immunofluorescence staining was constructed to detect the localization of endogenous and exogenous GIMAP2 in MDA-MB-436 cells. Meanwhile, green fluorescent chemical dyes were used to label mitochondria, endoplasmic reticulum, and lipid droplets in living MDA-MB-436 cells stably expressing the GIMAP2-mCherry fusion protein. Images for the three dye-labeled organelles and GIMAP2-mCherry fusion protein were captured by super-resolution microscope N-SIM. RESULTS: Bioinformatics analysis data showed that GIMAP2 protein composed of 337 amino acids might contain two transmembrane helix (TM) structures at the carboxyl terminus, of which TMs were estimated to contain 40-41 expected amino acids, followed by the residual protein structures toward the cytoplasmic side. NES was located at the 279-281 amino acids of the carboxyl terminus whereas NLS was not found. GIMAP2 might locate in the lumen of the endoplasmic reticulum. Sequencing results indicated that the expression vector pQCXIP-GIMAP2-mCherry was successfully constructed. Fluorescent staining confirmed that GIMAP2-mCherry fusion protein, co-localized well with endogenous GIMAP2, expressed successfully in the endoplasmic reticulum and on the surface of lipid droplets in MDA-MB-436 cells. CONCLUSION: GIMAP2 localizes in the endoplasmic reticulum and on the surface of LDs, suggesting potential involvement of GIMAP2 in lipid metabolism.

[Study on the role and possible mechanism of hemeoxygenase-1/carbon monoxide system in protection of quercetin against ethanol-induced hepatocytes oxidative injury].

Objective: To study the protective effect and potential mechanism of heme oxygenase (HO-1)/carbon monoxide (CO)-mediated quercetin on alcoholic oxidative damage of primary rat hepatocytes. Methods: Primary rat hepatocytes were isolated and cultured by two-step collagenase technique. Ethanol exposed primary rat hepatocytes were simultaneously added with quercetin (100 µmol/L) and/or hemoglobin (100 µmol/L) or different doses of CO-releasing molecules (CORM-2, 5-50 µmol/L) for their combined action. After polling, LDH, AST activities and MDA and GSH levels were measured in the supernatant of cell culture. The alone or combined effects of quercetin, CORM-2, hemoglobin and zinc protoporphyrin IX exposed to ethanol were detected by the activity of CYP2E1 in liver microsomes. Statistical analysis of data was performed by analysis of variance (ANOVA) and intergroup comparison was done by SNK-test. Results: Simultaneous addition of 100 µmol/L quercetin had significantly reduced ethanol-induced AST and LDH release, and GSH consumption and MDA elevation extent. Moreover, quercetin had not only lost the hemoglobin (CO blocker) protective effect but also had further exacerbated ethanol-induced lipid peroxidation. CORM-2 had reduced ethanol-induced AST and LDH release, and GSH consumption and MDA production in liver cells, and thus had dose-dependent protective effect. Ethanol had increased significantly CYP2E1 activity. Quercetin or CORM-2 had inhibited CYP2E1 activity, while hemoglobin or protoporphyrin IX had eliminated quercetin inhibitory effect and had increased the CYP2E1 activity. Quercetin, and CYP2E1 activity was constant as compared to ethanol group when CORM-2, zinc protoporphyrin IX and ethanol were incubated with hepatocytes, but the CYP2E1 activity was significantly decreased (P < 0.05), and the differences were statistically significant. Conclusion: CO/HO-1 metabolite mediates the protective effect of quercetin on alcoholic oxidative damage of hepatocytes, which may be related to the inhibition of CYP2E1 activity.