[Current status and challenges of clinical research and development of new drugs for liver diseases].

Liver disease is a serious public health problem worldwide, affecting human health. However, there are still many unmet needs for the treatment of liver disease, especially with new therapeutic drugs. At present, there is no treatment method to eradicate the hepatitis B virus, nor are there therapeutic drugs for liver fibrosis, liver failure, and others. Chemotherapy and targeted immunotherapy are still unsatisfactory for liver cancer. This article provides an overview of the current status and challenges that arise in new drug research and development for liver diseases.

[The application value of metagenomic next-generation sequencing technology in diagnosis and treatment of pulmonary infection in immunocompromised patients].

Objective: To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. Methods: A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. Results: The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (P<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all P<0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (P<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (P=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (P<0.001). Conclusion: In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.

Muscone alleviates myocardial ischemia-reperfusion injury via inhibition of oxidative stress and enhancement of SIRT3.

This study aimed at probing into the function of muscone in ameliorating myocardial ischemiareperfusion (I/R) injury and exploring the underlying mechanism. To analyze the function of muscone, H9c2 cardiomyocytes were treated with hypoxia/reoxygenation (H/R) and Sprague-Dawley (SD) rats were treated with left anterior descending (LAD) of the coronary artery ligation for 30 min and reperfusion for 2 h to induce myocardial I/R injury. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of SIRT3. MTT assay and TUNEL assay were performed to investigate H9c2 viability and apoptosis, respectively. ELISA was employed to determine the expressions of inflammatory cytokines TNF-α, IL-6 and IL-1ß, and myocardial injury markers CK and LDH. Oxidative stress markers MDA and SOD, and ROS expression levels were also detected. SIRT3 inhibitor 3-TYP was used to further confirm whether muscone worked via the augmentation of SIRT3. Herein, we found that muscone significantly inhibited inflammation and oxidative stress in H9c2 cardiomyocytes in a dose-dependent manner. H9c2 viability was promoted by muscone while apoptosis was inhibited. In SD rats, pre-treatment of muscone alleviated I/R injury-induced cardiac function dysregulation and left ventricle remolding. Furthermore, muscone increased SIRT3 expression at both mRNA and protein levels. With 3-TYP inhibiting SIRT3, the protective effects of muscone in H9c2 cardiomyocytes and SD rats were all significantly alleviated. In summary, muscone can attenuate inflammation, oxidative stress and cardiomyocytes injury in H9c2 cells treated with H/R and alleviate myocardial I/R injury of SD rats, which are dependent on SIRT3.

[Comparison of early outcome between one-stage hybrid technique and frozen elephant thunk technique in the treatment of Stanford A aortic dissection involving the arch].

Objective: To analyze the early outcome of one-stage hybrid technique in the treatment of Stanford type-A aortic dissection involving the arch and compare its therapeutic efficacy with the classical frozen elephant trunk technique (FET). Methods: A total of 106 patients with Stanford type-A aortic dissection involving the arch in Department of Cardiac and Vascular Surgery, 1st Affiliated Hospital of Soochow University from October 2015 to October 2019 was collected. All patients in this group were treated with one-stage hybrid technique (modified arch debranching technique) without deep hypothermia circulation. Meanwhile, 30 patients with Stanford type A dissection involving the arch who underwent FET from January 2014 to September 2015 were collected. The therapeutic effects of the two surgical methods were analyzed and compared. Results: The age [M (Q1, Q3)] of 106 patients in hybrid group was 49.0 (40.0, 55.0) years, including 89 males and 17 females. The age [M(Q1, Q3)] of 30 patients in FET group was 49.5 (41.5, 65.3) years, including 24 males and 6 females. The time [M(Q1, Q3)] of using ventilator in hybrid group was 56.0 (38.0, 72.0) h, which was shorter than 127.0 (92.0, 145.0) h in FET group (P<0.001). The incidence of cerebral infarction in hybrid group was 2.8% (3 cases), which was lower than 13.3% (4 cases) in FET group (P=0.042); the incidence of postoperative renal insufficiency in hybrid group was 7.5% (8 cases), which was lower than 23.3% (7 cases) in FET group (P=0.023); the ICU time [M (Q1, Q3)] in hybrid group was 8.0 (6.0, 10.0) d, which was shorter than 14.0 (8.3, 24.0) d in FET group (P<0.001). Conclusion: Compared with FET, one-stage hybrid technology is safer and more effective in the treatment of Stanford type A aortic dissection involving the arch. Its short-term therapeutic efficacy appears good.

[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.

[Jiangsu Province Coronary Artery Bypass Grafting Registry study: a report of 4 661 patients in 13 centers].

Objective: To examine the overall status of the Jiangsu Province Coronary Artery Bypass Grafting Registry database. Methods: The patients date of Jiangsu Province Coronary Artery Bypass Grafting Registry database from October 2017 to December 2019 was collected retrospectively.Risk factors, history, cardiac function (New York Heart Association class), extent of coronary artery lesion, European system for cardiac operative risk evaluation Ⅱ (EuroSCORE Ⅱ), cardiopulmonary bypss, arterial grafts, the numbers and flow of grafts and postoperative major adverse cardiac and cerebrovascular event(MACCE) information were analyzed. The clinical data of patients underwent on-pump CABG(ONCABG) or off-pump CABG (OPCAB) were compared by t test or χ(2) test. Results: Up till December 2019, the database enrolled 7 138 patients, in which 4 661 patients receiving primary isolated CABG. There were 3 486 males and 1 175 females with the age of (64.6±8.1) years (range:31 to 87 years). There were coronary left main disease in 960 patients, triple vessel disease in 3 934 patients, both left main and triple vessel disease in 837 patients, ejection fraction>50% in 3 841 patients, cardiac function class Ⅲ to Ⅳ in 1 664 patients. EuroSCORE Ⅱ was (2.3±0.7)% (range: 0.5% to 35.8%). There were 2 731 patients (58.59%) underwent ONCABG and 1 930 patients (41.41%) underwent OPCAB. There were 4 144 patients (88.91%) for whom the left internal thoracic artery was harvested. Seven centers (2 centers routinely) used left radial artery, 5 centers (3 centers routinely) used the transit time flow meter. The graft was 3.4±0.7 (range:1 to 7), the aortic crossclamp time was (65.0±20.4) minutes (range: 21 to 196 minutes), the cardiopulmonary bypass time was (90.0±24.2) minutes (range: 33 to 227 minutes). In-hospital death ocurred in 84 patients(1.80%), while re-operation in 93 patients (2.00%), myocardial infarction in 71 patients (1.52%), cerebral infarction in 33 patients (0.71%) and dialysis in 56 patients (1.20%). There were 2 936 patients prescribed with secondary prevention drugs(62.99%).Comparing with OPCAB group, ONCABG group had younger age, more female, more diabetes mellitus, more history of myocardial infarction and percutaneous transluminal coronary angioplasty, poorer cardiac function and coronary lesions, higher EuroSCORE Ⅱ, preoperatively (all P<0.05), and was associated with higher MACCE (135/2 731 vs. 71/1 930, χ(2)=4.280, P=0.039), and of more grafts, transfusion and intra-aortic balloon counterpulsation application (all P<0.05). Conclusions: Jiangsu Province Coronary Artery Bypass Grafting Registry database is generally in good operation, and some parameters still need to be improved. Comparing with OPCAB group, ONCABG has more severe preoperative general conditions, while the outcomes is acceptable.

Genetic association between the NLRP3 gene and acne vulgaris in a Chinese population.

BACKGROUND: Acne vulgaris is a common chronic skin disease. Inflammation is an important pathogenetic mechanism of acne, and NLRP3 polymorphisms have been reported to be involved in the mediation and occurrence of the inflammation. However, only a few studies on NLRP3 and acne have been reported, and the mechanism remains unclear. AIM: To investigate two SNPs in the NLRP3 gene in patients with acne vulgaris (AV) and healthy controls (HCs) in a Chinese population. METHODS: A case-control study was performed with 428 patients with AV and 384 (HCs). The SNPs rs10754558 and rs4612666 of the NLRP3 gene were genotyped using PCR with sequence-specific primers. A dual luciferase reporter assay was performed to determine whether the SNP rs10754558 might be responsible for the altered NLRP3 gene expression in AV by disrupting the interaction between micro-RNA (miR)-4273 and NLRP3 mRNA. Additionally, the mRNA level of NLRP3 was measured by PCR in the two groups. RESULTS: The frequencies of the G allele of rs10754558 were 0.54 in patients and 0.49 in HCs (P < 0.05). No significant difference was observed for SNP rs4612666. Dual luciferase reporter assay revealed that luciferase activity was downregulated by about 40% when the G allele of rs10754558 coexisted with miRNA-4273, indicating that the G allele might interfere with miR-4273 function and alter NLRP3 expression. The level of NLRP3 mRNA in patients with AV was significantly higher than that in HCs. CONCLUSIONS: Our study suggests that the NLRP3 SNP rs10754558 is associated with the incidence of AV. The G allele might be a genetic risk factor for AV in the Chinese population.

[Combined application of multi-parameter semiquantitative Alberta stroke program early CT score to assess infarction severity in acute ischemic stroke].

Objective: To explore the significance of multi-parameter semiquantitative Alberta Stroke Program Early CT Score (ASPECTS) in detecting core infarction in acute ischemic stroke (AIS) patients. Methods: Twenty-one consecutive AIS patients from Beijing Hospital were retrospectively reviewed in this study from August 2016 to August 2017. All the patients presented within 6 hours since symptom onset.All the patients underwent one-stop dynamic whole brain 4D CTA-CTP scan before treatments (intravenous thrombolysis, mechanical thrombectomy, or other endovascular recanalization). MRI scan was performed in all patients 3 to 7 days after initial administration. Multi-parameter ASPECTS was calculated on the affected hemisphere regarding noncontrast CT (NCCT) map, cerebral blood flow (CBF) map, cerebral blood volume (CBV) map, mean transit time (MTT) map and MRI-DWI map by subtracting 1 point from 10 for any abnormalities visually detected. The evaluative consistency and diagnostic efficiency were analyzed by Pearson's χ(2) test, kappa identity test, and Kendall's coefficient of concordance using IBM SPSS statistics 22.0 software. Results: Compared with DWI-ASPECTS or follow-up NCCT-ASPECTS, CBV-ASPECTS had the best performance on both the kappa identity test (kappa coefficient κ=0.74)and Kendall's coefficient of concordance (τ=0.70). All the values of sensitivity (77.8%), specificity (95.5%), positive likelihood ratio (17.27) and AUC(0.87)were the highest in CBV-ASPECTS, followed by dMTT-ASPECTS. Meanwhile, the misdiagnosis rate (4.5%), missed diagnosis rate (22.2%) and negative likelihood ratio were the lowest in CBV-ASPECTS, followed by dMTT-ASPECTS. dMTT-ASPECTS had the same specificity(95.5%) as CBV-ASPECTS did and it could reveal the infarction in the areas where CBV map showed normal. NCCT-ASPECTS had the lowest sensitivity (64.7%) and highest missed diagnosis rate (35.3%). The misdiagnosis rate of CBF-ASPECTS was the highest (25.2%) and AUC was the lowest (0.76). Conclusions: Multi-parameter semiquantitative ASPECTS may predict the infarction accurately in AIS patients. Compared with the single parameter of NCCT-ASPECTS, this new method may have better detectability and diagnostic performance.

[Clinical analysis of de novo HBV infection after liver transplantation in non-HBV- related liver disease].

Objective: The aim of this study was to summarize and analyze the clinical features and characteristics of de novo HBV infection after liver transplantation in non-HBV-related liver disease. Methods: We retrospectively analyzed the clinical data of 13 patients with new HBV infection in 376 cases of liver transplantation patients with non-HBV related liver diseases from April 2002 to December 2013 in our hospital. Results: Among 376 patients with non-HBV-related liver disease after liver transplantation, 13 patients developed new HBV infection, and the rate of new HBV infection was 3.46%. Of the 13 cases, 5 were males and 8 were females. The follow-up time was 14.7 -128.7 months, and the average time from surgery to new HBV infection was 19.06 months. The primary diseases were as follows: 5 cases of primary biliary cholangitis, 3 cases of alcoholic liver disease, 2 cases of drug-induced liver damage, 1 cases of post-hepatitis C cirrhosis, congenital biliary atresia and congenital liver fibrosis. All patients were positive for HBsAg, HBeAg, anti-HBc, 11 were positive for HBV DNA, and 2 were negative for HBV DNA. 6 cases had abnormal liver function and 7 cases had normal liver function. All patients were treated with antiviral therapy with nucleoside (acid) analogues. HBsAg was negative in 6 patients; HBsAg remained positive in 7 cases, including HBsAg, HBeAg, anti-HBc positive in 6 cases, HBsAg, anti-HBe, anti- HBc was positive in 1 case, HBV DNA was still positive in 1 patient, and HBV DNA was negative in 6 patients; liver function was normal in all patients. Conclusion: Non-HBV- related liver transplantation are high-risk group of new HBV infection, with the highest incidence of autoimmune liver disease. It is speculated that it may be related to the long-term use of hormones after the transplantation. The prognosis of newly diagnosed HBV infection after liver transplantation is fine as long as it can be found and treated early.

[Impact of psoas muscle index on early postoperative mortality and complications after liver transplantation].

Objective: To investigate the relationship between psoas muscle index (PMI) and early postoperative survival rate and the incidence of complications after liver transplantation in adults. Methods: The clinical data of 225 patients (male, n=184; female, n=41) underwent liver transplantation at the Organ Transplantation Department of First Central Clinic Institute of Tianjin Medical University from January 2014 to December 2016 were analyzed, retrospectively.Original disease: hepatitis B liver cirrhosis(44 cases), hepatitis C cirrhosis(10 cases), autoimmune liver cirrhosis(29 cases), other benign liver diseases(24 cases), liver cirrhosis with liver cancer(116 cases), hilar cholangiocarcinoma(1 case) and hepatic vascular sarcoma(1 case). The area of bilateral psoas muscle on the lower edge level of the third lumbar vertebral body was measured through preoperative CT image.The PMI was calculated using this formula: bilateral psoas muscle area (mm(2))/the square of the body height (m(2)). According to the receiver operating characteristic curve and cut-off values, the male and female patients were divided into low PMI group and high PMI group respectively.The χ(2) test, Fisher exact test and t-test was used to compare the differences in perioperative data, survival rate and postoperative complications between the two groups, respectively. Results: There were 44 patients in the low PMI group, and 181 patients in the high PMI group. ICU time was longer (82.5(62.0-128.0) hours vs.69.1(56.0-104.0) hours; P=0.006) and preoperative blood urea nitrogen level (5.86(4.35-15.52) mmol/L vs. 4.94(4.05-7.06) mmol/L; P=0.012) was higher in the low PMI group than those in the high PMI group. Incidence rates of grade 5 complication (18.2%) and grade 4a complication (18.2%) were higher in the low PMI group, and 120-day cumulative survival rate was lower than that in high PMI group(81.8% vs. 95.6%, P=0.001). On the other hand, there were no significant differences in preoperative white blood cell count level, serum creatinine level, operative time, anhepatic period time, intraoperative blood loss, and incidence of postoperative grade 3 complications between the two groups(all P>0.05). Conclusions: There is a significant correlation between PMI and early postoperative survival rate and incidence of complications.Patients with lower PMI has poor prognosis after liver transplantation.

[Clinical analysis of liver transplantation in treatment of liver metastatic cancer].

OBJECTIVE: To evaluate the feasibility and outcome of liver transplantation in the treatment of liver metastatic cancer. METHODS: Four patients with pathologically confirmed liver metastatic cancer underwent liver transplantation, including one of liver metastases from pancreatic endocrine tumor, one from rectal endocrine tumor, one from stomach stromal tumor and one from colorectal carcinoma. Classic surgical method was adopted, i. e. orthotopic liver transplantation for the recipients and transplants came from cadaveric donors. RESULTS: All the four patients had a smooth operation, an uneventful early postoperative recovery and good living quality. The patient with liver metastases from pancreatic endocrine tumor had liver tumor recurrence at four and a half years after the transplantation, and then underwent left lateral hepatic lobectomy, without any recurrence until now. The patient with liver metastases from rectal endocrine tumor had right renal and pelvic tumor metastasis at 16 months after the operation, and died of tumor recurrence 5 years after the liver transplantation. The patient with liver metastases from gastric stromal tumor had extensive pelvic metastases at five and a half months after the transplantation, and survived with tumor for 4 years and 6 months after the operation. The patient with liver metastases from colorectal carcinoma had extensive bilateral lung metastases at 3 months after the transplantation and died one and a half years after the operation. CONCLUSION: For well-differentiated unresectable metastatic liver cancers, liver transplantation may serve as a treatment option and better treatment results can be achieved for some highly selected patients.

[Liver transplantation for benign liver tumor: six cases report and literature review].

OBJECTIVE: To analyse and explore the indications and efficacy of liver transplantation for benign liver tumor. METHODS: From Jan.2001 to Dec.2014, 6 patients, incluing 3 males and 3 females, with benign liver tumor underwent liver transplantation in our department.There were 2 cases of hepatic epithelioid hemangioendothelioma, 1 case of hepatic cavernous hemangioma, 1 case of liver mesenchymal hamartoma, 1 case of hilar bile duct mucinous cystadenoma, and 1 case of hepatic adenoma. The data of surgical procedure, perioperative complications, postoperative management, and the outcome of follow-up were analyzed. RESULTS: Six orthotopic liver transplantation from one living donor and five cadaveric donors were performed. One patient died in the perioperative period, and other patients were discharged with normal liver and kidney function. Within the follow-up time of 22 to 88 months, these patients could live the normal lives with stable graft function and nutritional status. CONCLUSIONS: Liver transplantation is the most efficient treatment for unresectable and symptomatic benign lesions, with the favourable outcome.

Association between XRCC1 Arg280His polymorphism and risk of hepatocellular carcinoma: a systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is one of the most life-threatening malignancies worldwide. Defects in DNA repair genes may increase the risk of HCC. X-ray cross-complementing group 1 gene (XRCC1) is a major DNA repair gene involved in base excision re-pair. Recently, several studies have indicated that an association exists between XRCC1 polymorphism and HCC, particularly the Arg280His polymorphism. However, the data is inconsistent and incomplete. In this study, we conducted a meta-analysis to investigate the association between the XRCC1 Arg280His polymorphism and HCC risk. A total of 10 case-control studies included 1848 HCC cases and 1969 controls were examined in this analysis. Our results suggest that variant geno-types of the XRCC1 Arg280His gene are associated with a significantly increased risk of HCC in homozygote comparison (HisHis vs ArgArg, odds ratio, 1.55, 95% confidence interval, 1.10-2.18, P = 0.013); no het-erogeneity was observed (I2 = 0%). Our analysis suggests that the XRCC1 Arg280His polymorphism is associated with a higher risk of HCC.

Risk factors associated with aortic remodeling in patients with Stanford type B aortic dissection after thoracic endovascular aortic repair.

To determine the risk factors associated with adverse aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with Stanford type B aortic dissection, we performed a retrospective analysis of 54 patients between January 2009 and June 2012 at the First Affiliated Hospital of Soochow University. All patients underwent TEVAR of the descending thoracic aorta. Multiple-logistic regression analyses were performed to identify risk factors associated with aortic remodeling. True-lumen and false-lumen volumes were increased (P < 0.001) and decreased (P < 0.001) after surgery, respectively. Therefore, the remodeling index increased after surgery (1.04 ± 0.6 to 2.06 ± 1.12, P < 0.001). Remodeling index and true-lumen volume were higher in the favorable aortic remodeling group compared to the adverse aortic remodeling group (P < 0.001), while the false-lumen volume was lower in the favorable aortic remodeling group (P < 0.001). Multivariate analyses revealed a branch originating from the false lumen (OR = 39.9, P < 0.01) and multiple tears (OR = 27.4, P < 0.01) to be independent risk factors for adverse aortic remodeling. Therefore, a branch originating from the false lumen and multiple tears were determined to be independent risk factors for adverse aortic remodeling after TEVAR in patients with Stanford type B aortic dissection.

Successful transplantation of kidney allografts in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine.

Current methods to remove donor-specific HLA antibody (DSA) from sensitized patients remain imperfect. We tested novel approaches to desensitization using an animal model of allogeneic sensitization with skin grafts from dark agouti (DA) to Lewis rats. At the peak IgG alloantibody response we transplanted DA kidneys into nephrectomized Lewis recipients (n = 6) and all died within 10 days from antibody-mediated rejection (AMR). Allogeneic hematopoietic stem cell transplants (HSCT) from DA donors failed to engraft after lethal or sub-lethal irradiation. Sensitized rats given lethal irradiation plus syngeneic green fluorescent protein (GFP) + HSCT had repopulation of blood, spleen, thymus and lymph nodes by GFP+ cells. At 2 months after HSCT, serum DSA levels were reduced 60-70% and DSA (IgG) production in cultured splenocytes was also significantly decreased. However, there was only a modest improvement in graft survival from an average of 6.5 to 13.9 (n = 9) days. Adding seven daily doses of fludarabine to the preconditioning regimen resulted in long-term survival (>90 days) in 7 out of 10 rat kidney allografts. We conclude that syngeneic HSCT performed after preconditioning with irradiation and fludarabine can reduce DSA, prevent DSA rebound and AMR, enabling successful transplantation in animals with strong antibody reactivity to the donor MHC.

Establishment of tacrolimus-induced diabetes in rat model and assessment of clinical treatments for post-transplant diabetes mellitus in liver transplant recipients.

BACKGROUND: To establish a tacrolimus-induced diabetes rat model and assess efficacy and safety of insulin glargine combined with repaglinide in Chinese patients with diabetes after liver transplantation. METHODS: Animal experiments and clinical trial were conducted. Animal experiments: Male SD rats were randomly divided into tacrolimus (4 mg/kg daily) and control group (saline). Rats were sacrificed after five months of treatment and blood was collected through heart puncture. Patients who underwent liver transplantation were selected and followed up regularly. If HbA1c was < 9%, repaglinide was administered; if HbA1c was > or = 9%, glargine plus repaglinide was administered. RESULTS: For rat model studies, in the tacrolimus group, fasting blood glucose (FBG) levels were increased after three months (p < 0.01). After five months, the insulin secretion index and the sensitivity index in the tacrolimus group was significantly lower than in the control group (p < 0.01). For studies of post-transplant diabetes mellitus (PTDM), eighty-six liver transplant recipients were enrolled. 51 were given repaglinide and 35 were given repaglinide combined with glargine. After treatment for 1, 6, and 12 months, FBG, post-prandial blood glucose (PPBG), and HbA1c levels decreased (p < 0.05) in both groups, and no statistically significant changes were observed in the liver and kidney function indicators (p > 0.05). No severe hypoglycemia episodes were reported. CONCLUSIONS: Tacrolimus caused islet cell necrosis, reduced insulin secretion, increased insulin resistance, and increased blood glucose in the model. The blood glucose levels increased in a time-dependent manner. Combination of glargine and repaglinide was effective and safe for Chinese patients with post liver transplant diabetes mellitus.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

The psoas muscle depletion index is related to the degree of cirrhosis and skeletal muscle loss in patients with end-stage liver disease.

Objective: To establish a new psoas muscle depletion index (PDI) from healthy young donors and to explore the correlation between the PDI and the severity of cirrhosis in patients with endstage liver disease (ESLD). Methods: Clinical data of 461 healthy donors were collected during the period 2014-2019, and clinical data of 331 patients with ESLD were collected during the period 2014-2018. The patients were divided into four groups by PDI severity: PDI ≥ 0.90, PDI = 0.75-0.90, PDI = 0.50-0.75 and PDI ≤ 0.50 (Gsev). Differences in international normalised ratio (INR), total bilirubin and serum creatinine levels, and Child-Pugh (CP) and model for end-stage liver disease (MELD) scores were compared. The sarcopenia incidence according to the PDI and the psoas muscle index (PMI) in different weight groups were also compared. Results: Gsev had the highest CP (10.2 ± 2.1) and MELD (20.1 ± 7.4) scores and total bilirubin (166.3 ± 192.0 umol/L) and blood creatinine (92.9 ± 90.2 umol/L) levels and the lowest haemoglobin (93.8 ± 21.7 g/L) and blood albumin (30.9 ± 5.8 g/L) levels. Gsev showed significant changes in INR (1.74 ± 0.65) and blood sodium (135.3 ± 5.65 mmol/L). If PDI <0.75 was used as the diagnostic criterion for sarcopenia, the incidence was 53.3% in patients weighing >90 kg and 53.6% in those weighing <60 kg. This differed from the PMI, with an incidence of 3.3% in patients weighing >90 kg. Conclusions: The PDI had no significant correlation with body height, body weight or body mass index (BMI) in healthy individuals and patients with ESLD. The PDI was significantly correlated with the severity of cirrhosis and loss of skeletal muscle.