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As an effective treatment for end-stage liver disease, liver transplantation has been widely carried out worldwide and gradually captivated widespread recognition. With the advancement of liver transplantation techniques, the incidence of postoperative complications has been gradually declined, and the short-term and long-term prognosis of recipients have been constantly improved. However, a huge gap has existed between the supply and demand of donor organs, which is a major factors restricting the development of liver transplantation. The amount of liver transplantation operation in China is increasing year by year, the shortage of donor liver is becoming more and more prominent, and marginal donor liver is increasingly used in clinic. In recent years, the selection criteria of donor organs, organ preservation and functional maintenance have been continuously improved. In this article, the application and development trend of different techniques were reviewed from the perspectives of donor liver preservation and functional maintenance, and recent technical development and research results were summarized, aiming to provide reference for further enhancing the survival rate of grafts and recipients and promoting the development of liver transplantation in China.
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The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.
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Objective To evaluate nPEP willingness and uptake among MSM in Shanghai. Methods MSM were recruited through a NGO-based HIV voluntary counseling testing clinic and several virtual communities using snowball sampling. Results A total of 606 MSM were successfully recruited in which 82.8% （502/606） had heard of nPEP and 81.2% （492/606） were willing to use nPEP. MSM who had been diagnosed with sexually transmitted diseases （STD） were more likely to hold willingness in using nPEP. High cost was the most common reason for being unwilling to use nPEP. 9.9% （60/606） had used nPEP in which 51.7% （31/60） had used twice or more， and 50%（30/60） had missed medication in the last nPEP. MSM who were heterosexual or with other sex orientations except for being bisexuality （OR=2.943， 95%CI： 1.057‒8.191）， being receptor in anal intercourse （OR=3.361， 95%CI： 1.552‒7.282）， having 2 or more sexual partners in the last 30 days （OR=2.242， 95%CI： 1.225‒4.105）， having been diagnosed with STI （OR=2.317， 95%CI： 1.223‒4.389）， and using drugs （OR=2.177，95%CI： 1.052‒4.503） were more likely to use nPEP. Conclusion MSM in Shanghai have a relatively high willingness to use and uptake of nPEP. Comprehensive strategies need to be developed on improving adherence and reducing HIV-risk behaviors.
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Objective:To explore the expression and clinical significance of Janus protein tyrosine kinase/signal transducer and activator of transcription (JAK3/STAT5) signaling pathway in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Peripheral blood, clinical data and laboratory tests were collected from 50 patients with acute gout (AG), 50 patients with intermittent gout (IG) and 50 healthy controls (HC). Quantitative real-time-polymerase chain reaction (RT-qPCR) was used to detect mRNA expression level of JAK3/STAT5 related genes (JAK3, STAT5a, STAT5b). Enzyme linked immune sorbent assay (ELISA) was used to detect interleukin-2 (IL-2) concentration in subject′s plasma. Measurement data among the three groups that was in accordance with normal distribution was analyzed by one-way analysis of variance, pairwise comparisons using LSD, non-normal distribution data was analyzed by Mann-Whitney test or Kruskal-Wallis H test, and correlation analysis between variables was analyzed using Spearman correlation analysis. Results:① The mRNA expression levels of JAK3, STAT5a and STAT5b were significantly different among the three groups ( F=50.13, P<0.01; F=7.573, P=0.000 7; F=12.14, P<0.01), of which the JAK3 mRNA expression level in the HC group [(606±65)×10 -4] was significantly higher than that in the AG group [(103±13)×10 -4] and IG group [(114±24)×10 -4], and the difference was statistically significant (both P<0.01), while the STAT5a mRNA expression level in the AG group [(89±9)×10 -4] was significantly higher than that in the IG group [(59±4)×10 -4] and HC group [(61±4)×10 -4], and the difference was statistically significant ( P=0.002, P=0.003 9), and the expression level of STAT5b mRNA in HC group [(60±5)×10 -4] was significantly lower than that in AG group [(95±7)×10 -4] and IG group [(98±7)×10 -4], and the difference was statistically significant ( P=0.000 2, P<0.000 1). ② The difference of IL-2 concentration in plasma among the three groups was statistically significant ( F=22.87, P<0.01), and the serum IL-2 concentration in the AG group [(87.9±8.4) pg/ml] was significantly higher than that in the IG group [(32±4) pg/ml] and HC group [(44±4) pg/ml], and the difference was statistically significant (both P<0.01). ③ Spearman correlation analysis showed that the mRNA expression of STAT5a and STAT5b was positively correlated with the absolute value of neutrophils in patients with gout ( r=0.282, P<0.05; r=0.257, P<0.05). Conclusion:The IL-2/JAK3/STAT5 signaling pathway is involved in the occurrence and development of gout, suggesting that this pathway may play a key role in the pathogenesis of gout.
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OBJECTIVE@#To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage.@*METHODS@#The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI- group and DWI+ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared.@*RESULTS@#The plasma cell percentage of the patients in DWI+ group was higher than those in DWI- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI+ group were significantly higher than those in DWI- group and normal control group. The ADC values of each part of the patients in DWI- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ.@*CONCLUSION@#DWI+ in MM patients is related to higher tumor invasion. The ADC values of the DWI+ group are higher than those of the DWI- group; the bone ADC values of the DWI- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.
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Bone Diseases , Diffusion Magnetic Resonance Imaging , Humans , Multiple Myeloma/diagnostic imaging , Retrospective Studies , Whole Body ImagingABSTRACT
OBJECTIVE@#To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia.@*METHODS@#Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons.@*CONCLUSION@#HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).
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Acupuncture Therapy , Aphasia/rehabilitation , Humans , Ischemic Stroke , Language , Prostate-Specific Antigen , Randomized Controlled Trials as Topic , Stroke/therapyABSTRACT
Objective@#To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. @*Materials and Methods@#Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. @*Results@#Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. @*Conclusion@#The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.
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OBJECTIVE@#To compare the clinicopathologic features and prognosis of the different types of fibrous dysplasia (FD) of cranio-maxillofacial region, so as to provide a new reference for clinicians to treat these patients and make prognostic judgement.@*METHODS@#Clinical records, radiographic data and pathological information of 105 patients diagnosed with FD or McCune-Albright syndrome (MAS) at the Department of Oral Pathology, Peking University Hospital of Stomatology from January 2013 to December 2020 were collected. The patients were divided into 4 groups: monostotic FDs, polyostotic FDs, MAS and a specific type called craniofacial fibrous dysplasia (CFD) limited in the craniofacial region. The clinicopathological characteristics, treatment and follow-up data of each type were analyzed.@*RESULTS@#Of all the 105 patients, 46 were males and 59 were females, with a male-to-female ratio of 1 ∶1.3. The onset age ranged from 0 to 56 years and the median age was 12 years. On the basis of different involvement conditions, 4 types were divided. The most common type was monostotic FDs (43 cases, 40.95%), including maxilla (29 cases), mandibular (12 cases) and zygoma (2 cases). 32 cases (30.48%) were diagnosed with polyostotic FDs, 7 cases (6.67%) were MAS, and 23 cases (21.90%) were CFDs confirmed by computed tomography (CT) analysis. CFD was clearly distinct from other types of FD, such as the patient gender and the serum alkaline phosphatase level in peripheral blood before operative surgery. The pathologic findings of various types FD were quite similar, whilst the predominant fibrous tissue hyperplasia could be observed in polyostotic FDs and MAS types.@*CONCLUSION@#The clinicopathologic features of FD in the cranio-maxillofacial region are different from the FD lesions in other parts of the body. The clinicopathological features of CFD are significantly different from those of monostotic and polyostotic FDs in the cranio-maxillofacial region. Therefore, the clinicians should pay attention to distinguish CFD in clinic, imaging and pathology aspects, so as to further clarify its features in clinic management and prognosis.
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Adolescent , Adult , Child , Child, Preschool , Female , Fibrous Dysplasia, Polyostotic , Humans , Infant , Infant, Newborn , Male , Mandible , Middle Aged , Prognosis , Tomography, X-Ray Computed , Young AdultABSTRACT
The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is now the second largest indication for liver transplantation in Western countries, but viral hepatitis B and end-stage alcohol-related liver disease are still the main indications in China. With the improvement of people's living standards, the prevalence of metabolic syndrome, and the number of NAFLD patients has also gradually increased. At the same time, with the hepatitis B vaccination popularization and the nucleos(t)ide analogues and other drugs uses, it is predicted that NAFLD-related end-stage liver disease may become one of the main indications for liver transplantation in our country in the future. This article reviews the research progress of NAFLD and liver transplantation.
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End Stage Liver Disease , Humans , Liver Transplantation/adverse effects , Metabolic Syndrome , Non-alcoholic Fatty Liver Disease/epidemiology , PrevalenceABSTRACT
Objective: To study the effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits. Methods: Thirty-two 3.5-month-old New Zealand rabbits were randomly divided into low-intensity group, medium-intensity group, high-intensity group and control group, with 8 rabbits in each group. The rabbits in the experimental group were subjected to hind limb vibration load test for 45 days. The vibration intensity of the high intensity group was 12.26 m/s(2), the medium intensity group was 6.13 m/s(2), and the low intensity group was 3.02 m/s(2) according to the effective value of weighted acceleration[a(hw (4))] for 4 hours of equal energy frequency. The control group was exposed to noise only in the same experimental environment as the medium-intensity group. The noise levels of each group were measured during the vibration load experiment. After the test, the mRNA expression of mitochondrial fusion gene (Mfn1/Mfn2) and fission gene (Fis1, Drp1) by RT-PCR in the skeletal muscles were measured and the ultrastructure of the skeletal muscles were observed in high intensity group. Results: The mRNA expression of mitochondrial in the skeletal muscle tissues of control group, low intensity group, medium intensity group and high intensity group were Mfn1: 3.25±1.36, 3.85±1.90, 4.53±2.31 and 11.63±7.68; Mfn2: 0.68±0.25, 1.02±0.40, 0.94±0.33 and 1.40±0.45; Fis1: 1.05±0.62, 1.15±0.59, 1.53±1.06 and 2.46±1.51 and Drp1: 3.72±1.76, 2.91±1.63, 3.27±2.01 and 4.21±2.46, respectively. Compared with the control group, the expressions of Mfn1 mRNA, Mfn2 mRNA and Fis1 mRNA in the high-intensity group increased significantly (P<0.05) , and the expressions of Mfn2 mRNA in the medium-intensity group and the low-intensity group increased significantly (P<0.05) . Compared with the control group, the ultrastructure of skeletal muscle of high intensity group showed mitochondrial focal accumulation, cristae membrane damage, vacuole-like changes; Z-line irregularity of muscle fibers, and deficiency of sarcomere. Conclusion: Vibration must be lead to the abnormal mitochondrial morphology and structure and the disorder of energy metabolism due to the expression imbalance of mitochondrial fusion and fission genes in skeletal muscles of rabbits, which may be an important target of vibration-induced skeletal muscle injury.
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Animals , Hindlimb/metabolism , Mitochondria/metabolism , Mitochondrial Dynamics , Mitochondrial Proteins/pharmacology , Muscle, Skeletal , Rabbits , Vibration/adverse effectsABSTRACT
The present study explored the effect and mechanism of repeatedly steamed and sundried Rehmanniae Radix Praeparata(RRP) in delaying brain aging in ovariectomized mice. After ovariectomy, the mice were randomly divided into a model group, an estradiol valerate group(0.3 mg·kg~(-1)), and low-(1.0 g·kg~(-1)), medium-(2.0 g·kg~(-1)), and high-dose(4.0 g·kg~(-1)) RRP groups, and a sham operation group was also set up, with 15 mice in each group. One week after the operation, intragastric administration was carried out for 15 consecutive weeks. The step-down test and Morris water maze test were used to detect the behavioral changes of mice. HE staining and Nissl staining were used to observe the morphological changes of mouse brain tissues. Immunohistochemistry was used to detect the expression of Aβ and ER_β in mouse brain tissues. The serum estrogen levels and cholinesterase and cholinesterase transferase levels in brain tissues of mice were detected by assay kits. The extracted hippocampal protein was detected by the Nano-ESI-LC-MS system, identified by the Protein Discovery, and analyzed quantitatively and qualitatively by the SIEVE. The PANTHER Classification System was used for GO analysis and KEGG pathway enrichment analysis of the differential proteins. Compared with the sham operation group, the model group showed decreased learning and memory ability, shortened step-down latency(P<0.05), prolonged escape latency(P<0.05), reduced platform crossings and residence time in the target quadrant, scattered nerve cells in the hippocampus with enlarged intercellular space, increased expression of Aβ-positive cells(P<0.05), declining expression of ER_β-positive cells and estrogen level(P<0.05), and weakened cholinergic function(P<0.05). Compared with the model group, the RRP groups showed improved learning and memory ability, prolonged step-down latency(P<0.05), increased estrogen level(P<0.05), neatly arranged nerve cells in the hippocampus with complete morphology, declining Aβ-positive cells, and elevated expression of ER_β-positive cells. A total of 146 differential proteins were screened out by proteomics, and KEGG pathway enrichment yielded 75 signaling pathways. The number of proteins involved in the dopaminergic synapse signaling pathway was the largest, with 13 proteins involved. In summary, RRP can delay brain aging presumedly by increasing the level of estrogen, mediating the dopaminergic synapse signaling pathway, and improving cholinergic function.
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Aging , Animals , Female , Hippocampus/metabolism , Learning , Mice , Plant Extracts , Proteomics , RehmanniaABSTRACT
Objective To develop a new model for predicting recurrence after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria based on related preoperative and postoperative indicators. Methods A retrospective analysis was performed for the clinical data of the patients with HCC beyond Milan criteria who underwent orthotopic liver transplantation for the first time in Tianjin First Central Hospital from August 2014 to July 2018, and according to the presence or absence of recurrence during follow-up, the patients were divided into recurrence group and no-recurrence group. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the risk factors for recurrence-free survival after surgery. A new model was developed for recurrence after liver transplantation in the patients with HCC beyond Milan criteria based on the risk factors identified. The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive performance, and the Hosmer-Lemeshow test was used to assess the goodness of fit of the model. Results A total of 117 patients with HCC beyond Milan criteria were enrolled in this study, with a median follow-up time of 24 (1-74) months. A total of 53 patients (45.3%) experienced recurrence after surgery, among whom 52 (98.1%) had recurrence within 3 years after surgery, with a median time to recurrence of 6 (1-52) months. The Cox proportional hazards regression analysis showed that preoperative serum alpha-fetoprotein (AFP) >769 ng/mL, neutrophil-lymphocyte ratio (NLR) >3.75, and ki67 index >0.25 were independent risk factors for recurrence-free survival after liver transplantation. The model established based on these three risk factors had an AUC of 0.843, with good sensitivity (88.7%) and specificity (70.3%). The optimal cut-off value was selected according to the maximization of Youden index, and then the patients were divided into low-risk group (0-1 point) and high-risk group (1.5-4 points). The log-rank test showed that the low-risk group had significantly higher 3-and 5-year recurrence-free survival rates than the high-risk group (84.1%/72.0% vs 10.9%/10.9%, χ 2 =29.425, P < 0.001). Conclusion Liver transplantation for HCC beyond Milan criteria should be performed with caution, and the predictive model established based on preoperative AFP, NLR, and ki67 index can accurately assess the indication for liver transplantation in such patients.
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Objective To summarize the experience of diagnosis and treatment of Takotsubo syndrome (TTS) after liver transplantation. Methods Clinical data of one TTS patient after liver transplantation was retrospectively analyzed. Clinical features, diagnosis and treatment strategies were summarized, and literature review was conducted. Results A 43-year-old female patient successfully underwent split liver transplantation due to primary biliary cirrhosis for 8 years. At postoperative 3 d, the patient developed anxiety, irritation, dyspnea, disorientation, hypotension, N-terminal pro-brain natriuretic peptide (NT-proBNP) of > 35 000 pg/mL, creatine kinase isoenzyme (CK-MB) of 5.9 U/L and troponin I (TnI) of 1.78 μg/L. Electrocardiogram indicated the signs of sinus rhythm. Echocardiography indicated diffuse weakening of the left ventricular wall motion and spherical dilatation of the apex, accompanied with moderate and severe regurgitation of the mitral valve and tricuspid valve. The left ventricular ejection fraction (LVEF) declined to 23%, whereas no abnormal segmental motion of ventricular wall or corresponding electrocardiogram changes were observed. The possibility of acute coronary syndrome was excluded. The InterTAK diagnostic score was 73. The diagnosis of TTS after liver transplantation was considered. Metoprolol, coenzyme Q10, recombinant human brain natriuretic peptide, deacetyl lanatoside and lorazepam were given. Echocardiography at postoperative 10 d showed that the left ventricular function was significantly improved and the LVEF recovered to 50%. The patient was discharged 40 d after liver transplantation. The liver function was recovered well. During postoperative follow-up, she was given with metoprolol till the submission date, and no recurrence was reported. Conclusions TTS after liver transplantation is rare in clinical practice. It is difficult to make the diagnosis. The condition of TTS is severe and clinical prognosis is poor. Prompt diagnosis and interventions should be implemented.
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Objective:To evaluate the therapeutic effect of 177Lu-prostate specific membrane antigen (PSMA)-I&T on prostate cancer. Methods:The culture medium of 1.85, 18.50, 185.00, 555.00 and 925.00 MBq/L 177Lu-PSMA-I&T was added into LNCaP cells (200 μl/well, 5 experimental groups and 1 control group, 3 replicates in each group) for 24 h, and the cell viability in each group was detected. The culture medium of 3.7 MBq 177Lu-PSMA-I&T was added into LNCaP cells (1 experimental group, 1 control group, 3 replicates in each group) for 48 h to detect the changes of cell cycle. LNCaP cells (3 experimental groups and 1 control group, 3 replicates in each group) were added into the culture medium of 3.7, 19.5 and 37.0 MBq 177Lu-PSMA-I&T for 48 h to detect cell apoptosis. Tumor-bearing mice models were established (BALB/c-nu/nu nude mice, n=32). The changes of tumor volume and body mass of tumor-bearing mice were observed within 20 d after treatment. On the 7th day after treatment, tumor tissues of tumor-bearing mice were stained with HE staining and fluorescently stained with Ki-67 protein, and apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. On the 20th day after treatment, pathological analysis was performed on the main viscera of the tumor-bearing mice. One-way analysis of variance, the least significant difference t test and paired t test were used to analyze the data. Results:Compared with the control group ((100.00±12.35)%), the cell survival rates were significantly decreased after 177Lu-PSMA-I&T intervention in 185.00, 555.00, 925.00 MBq/L groups ((57.56±6.35)%, (38.65±3.39)%, (27.95±4.48)%; F=78.91, t values: 8.312-14.106, all P<0.01). Cell survival rates were significantly reduced in 185.00 MBq/L group at different time points (24, 48 and 72 h; F=78.28, t values: 6.628-14.384, all P<0.01). The proportion of LNCaP cells in G2/M phase was increased from (12.36±0.28)% to (19.92±0.48)% ( t=17.180, P<0.01). The apoptosis rates of cells were significantly increased in 18.5 and 37.0 MBq groups ( F=71.86, t values: -6.138, -13.050, both P<0.05). The difference of relative tumor volume (RTV%) was statistically significant among 3.7, 14.8 and 29.6 MBq groups and control group (136.7±7.4, 59.2±23.8, 47.3±13.8 vs 240.3±3.7; F=78.20, t values: 7.549-13.345, all P<0.01). But there was no significant difference in body mass of tumor-bearing mice among groups. Compared with the control group, the positive rates of Ki-67 staining cells ((37.23±3.04)% vs (14.89±3.80)%, (5.60±1.83)%, (3.46±0.71)%) and TUNEL-fluorescein isothiocyanate (TUNEL-FITC) staining ((0.74±0.18)% vs (1.61±0.30)%, (3.19±0.44)%, (3.54±0.47)%) in tumor tissues of 3.7, 14.8 and 29.6 MBq groups were statistically significant ( F=103.91, t values: 10.429-15.762; F=38.66, t values: from -9.312 to -2.881, all P<0.01). Conclusions:177Lu-PSMA-I&T has a good therapeutic effect on prostate cancer, with no obvious therapeutic side effects. Therefore, 177Lu-PSMA-I&T is expected to be an ideal drug for treating prostate cancer.
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Objective:To compare the treatment outcomes of neoadjoint therapy combined with liver transplantation versus radical hepatectomy for patients with surgically resectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on the data of 64 patients with resectable hilar cholangiocarcinoma operated from January 2009 to December 2014 at the Organ Transplantation Department of the First Central Hospital of Tianjin. There were 43 males and 21 females, with an average age of 61.2 years. There were 45 patients who underwent radical hepatectomy in the liver resection group, and 19 patients who underwent combined neoadjuvant therapy (radiotherapy combined with 5-fluorouracil intravenous drip, transcatheter lumen radiotherapy, capecitabine oral administration) and liver transplantation in the liver transplantation group. The recurrence rates and survival rate were compared between groups.Results:The 1, 3 and 5 years cumulative survival rates of the liver transplantation group were 89.5%, 73.7% and 63.2%, respectively, which were significantly better than those of the liver resection group (80.0%, 53.3% and 35.6%) ( P<0.05). The postoperative tumor recurrence rate in the liver transplantation group was 31.6% (6/19), which was significantly lower than that in the liver resection group of 60.0% (27/45) ( P<0.05). Subgroup analysis using postoperative pathological results showed the cumulative survival rates of patients without lymph node metastasis (N 0) and those with negative resection margins (R 0) were not significantly different between groups ( P>0.05). However, for patients with regional lymph node invasion (N 1) and with R 0 resection margin, the cumulative survival rates at 1, 3 and 5 years after liver transplantation were 83.3%, 66.7% and 50.0%, respectively, which were significantly superior to the 64.3%, 28.6% and 14.3% of the liver resection group ( P<0.05). Conclusion:Hepatectomy is recommended for patients with N 0 R 0 resectable hilar cholangiocarcinoma. For patients with hilar cholangiocarcinoma with marginally resectable N 1R 0, neoadjuvant therapy combined with liver transplantation resulted in significantly better long-term overall survival than resection.
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Chimeric antigen receptor T (CAR-T) cell has achieved excellent efficacy in hematological tumors, especially for lymphoma. Many products have been approved to market all over the world, and 2 products targeting CD19 have been approved to treat relapsed and refractory large B-cell lymphoma in China. The current experiences of using CAR-T cells come from previous clinical studies. How to use CAR-T cells in a standardized and rationalized way is still a challenge faced by our clinicians. Based on the CAR-T cell treatment experiences from Peking University Cancer Hospital and the latest research progresses in CAR-T in China and abroad, this article will elaborate on patient screening, peripheral blood mononuclear cell collection, bridging treatment, lymphocyte depletion chemotherapy, CAR-T cell infusion, the monitoring and treatment of adverse events after infusion, and long-term follow-up after infusion, in order to guide clinicians to better use CAR-T cell and to bring maximum benefits to patients.
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Objective:To investigate the effects of Huanglian Jiedutang on learning and memory ability and the cholinergic system in Alzheimer's disease（AD） rats induced by amyloid <italic>β</italic>-protein（A<italic>β</italic>）<sub>1-42</sub>. Method:Sixty male SD rats were divided into normal group， model group， huperzine A group （2.1×10<sup>-5</sup> g·kg<sup>-1</sup>）， high-， medium- and low dose of Huanglian Jiedutang groups （6，3，1.5 g·kg<sup>-1</sup>）. AD rat model was replicated by hippocampal injection of A<italic>β</italic><sub>1-42</sub>. After 4 weeks of treatment， Morris water maze test was performed. Hematoxylineosin （HE） staining was used to observe the pathological changes of rat hippocampus. Sampling blood from abdominal aorta was taken. Acetylcholine （ACh）， acetylcholinesterase （AchE） and choline acetyltransferase （ChAT） in serum and hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of hippocampal <italic>α</italic>7 nicotinic acetylcholine receptor （<italic>α</italic>7nAChR） protein was detected by Western blot. The expression of hippocampal <italic>α</italic>7nAChR mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， there were obvious pathological changes in the model group，such as neuron necrosis in the cerebral cortex，pyramidal cell or granular cell necrosis in the hippocampus，disorder of arrangement and inflammatory cell infiltration，prolonged escape latency，decreased escape platform times，decreased residence time in the effective area and swimming path in the effective area （<italic>P<</italic>0.05，<italic>P<</italic>0.01）. The contents of <italic>α</italic>7nAChR mRNA，ACh，AchE，ChAT，<italic>α</italic>7nAChR in the hippocampus decreased （<italic>P<</italic>0.01）. Compared with the model group，the escape latency of the middle dose group was shorter （<italic>P<</italic>0.05）， the escape platform times，the swimming path in the effective area and the residence time in the effective area increased （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， the contents of serum ACh，ChAT， hippocampal AchE，ChAT and <italic>α</italic>7nAChR increased （<italic>P<</italic>0.05，）. The expression of hippocampal <italic>α</italic>7nAChR protein significantly increased （<italic>P<</italic>0.01）， the residence time of effective area in high dose group was prolonged （<italic>P<</italic>0.01）， the times of escape platform increased，and the contents of serum ACh，ChAT and hippocampal ACh，AchE，<italic>α</italic>7nAChR protein and <italic>α</italic>7nAChR mRNA increased （<italic>P<</italic>0.05）. Conclusion:Huanglian Jiedutang can significantly improve the learning and memory ability of AD rats induced by A<italic>β</italic><sub>1-42</sub>，and its mechanism may be related to the improvement of cholinergic system damage and enhancement of cholinergic system function induced by A<italic>β</italic><sub>1-42</sub>.
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Background@#Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. @*Methods@#Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. @*Results@#Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. @*Conclusion@#Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.
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Objective:To evaluate the efficacy of comprehensive anti-cancer treatment for lung metastases after liver transplantation (LT) for hepatocellular carcinoma (HCC).Methods:From March 2012 to July 2016, A total of 36 patients with lung metastasis after LT were divided into comprehensive anti-cancer treatment group (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib, n=22) and maintenance supportive care group ( n=14). The survival profiles of two groups were evaluated. Results:No significant inter-group differences existed in preoperative basic data, tumor pathology, time of pulmonary metastatic tumor after operation and lung metastasis tumor burden.In comprehensive anti-cancer treatment group, there were partial remission ( n=3), disease stability ( n=12) and disease progression after treatment ( n=7). In maintenance supportive care group, there were disease stability ( n=3) and disease progression after treatment ( n=11). And comprehensive anti-cancer treatment was superior to maintenance supportive care ( χ2=7.901, P=0.019). The median survival time after metastasis was 23 months (95%CI: 19.68-26.32) in comprehensive anti-cancer treatment group and 7 months (95%CI: 3.33-10.67) in maintenance supportive care group; 1-year survival rate 91% and 9%, 2-year survival rate 45% and 0% and 3-year survival rate 10% and 0% respectively.The survival rate of comprehensive anti-cancer treatment group was significantly better than that of maintenance supportive care group ( P<0.001). Conclusions:Comprehensive anti-cancer treatment (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib) can improve the survival time of patients with lung metastasis after liver transplantation for HCC.
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OBJECTIVE@#To investigate the effects of chidamide combined with anti-myeloma drugs on the proliferation and apoptosis of myeloma cells.@*METHODS@#The proliferation inhibition of the cells was detected by CCK-8 method, and flow cytometry was used to detected the apoptosis of the cells.@*RESULTS@#Chidamide could inhibit the proliferation of myeloma cells and promote the apoptosis of primary myeloma plasma cells in a time- and dose-dependent manner (P<0.05). In NCI-H929 cell line, chidamide combined with low-dose bortezomib and lenalidomide showed synergistic effect, while combined with dexamethasone and pomalidomide showed additive effect. In MM.1s cell line, chidamide combined with bortezomib, dexamethasone, lenalidomide and pomalidomide all showed synergistic effects.@*CONCLUSION@#Chidamide inhibits proliferation of myeloma cells in a time- and dose-dependent manner and promotes apoptosis of primary myeloma plasma cells. Furthermore, it can enhance the inhibitory effect of anti-myeloma drugs.