The past, present and future of heart transplantation / 器官移植

Heart transplantation is one of the most effective strategies to treat end-stage heart failure. Multiple challenges, such as difficulty in preservation of heart allograft, rejection and postoperative complications, emerge in heart allotransplantation. After decades of research and practice, most problems have been resolved. Nevertheless, the shortage of donor organs has become increasingly prominent. To alleviate the shortage of donor organs, artificial heart and heart xenotransplantation have captivated attention, and obtained significant progress in recent years. The application of artificial heart in clinical practice has significantly enhanced the survival rate of patients with end-stage heart failure, which is expected to become the standard treatment for end-stage heart failure. Heart xenotransplantation still faces many challenges, which is still far from clinical application. In this article, the history of heart transplantation, development of heart allotransplantation, use of artificial heart and research progress on heart xenotransplantation were reviewed, and the future development direction of heart transplantation was predicted.

Remnant cholesterol and ischemic stroke / 国际脑血管病杂志

Atherosclerosis (AS) is one of the pathological bases of ischemic stroke. AS caused by elevated low-density lipoprotein cholesterol levels is the main causative factor. However, recent studies have found that the traditional blood lipid indicators can not fully reflect the risk of stroke in high-risk populations. Non-traditional blood lipid parameters are developed from traditional blood lipid parameters, including remnant cholesterol (RC), non-high density lipoprotein cholesterol and a variety of blood lipid ratios, which may play a role in the prevention and treatment of cerebrovascular diseases. Among them, RC is increasingly recognized as a biomarker driving the residual risk of AS. It has been confirmed that RC is closely associated with the risk of cerebrovascular disease in the primary and secondary prevention studies of stroke.

Comparison of clinical efficacy and treatment costs in different regimens for patients with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective:To explore the clinical efficacy and treatment costs of different regimens for newly diagnosed acute promyelocytic leukemia (APL).Methods:The clinical data of 37 newly diagnosed APL patients admitted to Jingjiang People's Hospital from January 2011 to December 2020 were retrospectively analyzed. They received different induction therapy regimens and consolidation therapy after achieving complete remission (CR). Among them, 11 patients received induction chemo therapy with all-trans retinoic acid (ATRA) combined with anthracycline, which was consolidated with ATRA combined with chemotherapy after CR (ATRA+chemotherapy group); 13 patients were treated with ATRA combined with arsenite acid (ATO) and anthracycline, which was consolidated with ATRA combined with chemotherapy after CR(ATRA+ATO+ chemotherapy group). The other 13 patients received double induction therapy of ATRA combined with ATO, which was consolidated with ATRA combined with ATO after CR (ATRA+ATO double induction group). The clinical efficacy and treatment costs of newly diagnosed APL patients in 3 groups were analyzed.Results:There were 10, 12, 12 patients with newly diagnosed APL achieving CR, respectively in ATRA+chemotherapy group, ATRA+ATO+chemotherapy group, ATRA+ATO double induction group, and the difference was statistically significant ( P > 0.05). The differences of hematological, cardiac, gastrointestinal adverse reactions and infection incidence in the 3 groups were not statistically significant (all P > 0.05). The costs of induction therapy in ATRA+chemotherapy group, ATRA+ATO+chemotherapy group and ATRA+ATO double induction group were (73 755±4 820) yuan, (74 101±5 097) yuan, (52 944±4 099) yuan, respectively; the costs of consolidation treatment were (26 366±2 497) yuan, (25 801±2 528) yuan, (19 674±1 940) yuan, and the treatment time was (41±4) d, (39±4) d, (34±3) d, respectively; and the differences were statistically significant ( F value was 84.77, 31.90, 9.62, all P < 0.001). Conclusion:The chemotherapy-free therapy regimen of induction and consolidation with ATRA and ATO has the advantage of high cost-effectiveness with no significant difference in clinical efficacy.

Research progress in nano-drug delivery systems for antitumor multi-drug combinational application / 药学学报

Due to the complexity of tumor pathology, the demand for the combined use of multiple drugs in clinical treatment has become increasingly clear-cut. Multi-drug combination can act on multiple pathways and multiple targets simultaneously to exert synergistic effects. However, the current delivery strategy for multi-drug combination still needs to be optimized. Nano-drug delivery systems can carry drugs to overcome physiological and pathological barrier to target tumor tissues and cells, achieve the goal of continuous, controllable, and targeted delivery, and enhance the efficacy of anti-tumor synergism and detoxification. To meet the new requirements for smarter and more accurate antitumor multi-drug combinational therapy, the nano-drug delivery system has been well-designed to realize more functions. For instance, delivery of multiple drugs in accurate proportions and doses can make the multi-drug synergistic effect more precise; stimulus-responsive drug release can improve selectivity and reduce side effects; controlling the time-course relationship of multiple drugs can realize sequential drug combination effect. It has shown broad prospects in the field of tumor multidrug therapy and has become one of the new directions of research and development. This article reviews the recent developments in the application of tumor drug combination therapy strategies and their delivery systems, and analyzes the new requirements and challenges of multidrug combination for the development of nano-drug delivery systems.

Effects and mechanism of hydrogen peroxide pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells / 中华烧伤杂志

Objective: To investigate the effects and mechanism of hydrogen peroxide (HP) pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs). Methods: The experimental research methods were used. BMSCs were isolated and cultured from two 2-week-old male BALB/c mice by the whole bone marrow culture method. The 3rd-7th passages of cells in logarithmic growth phase were used for the experiments after identification. According to the random number table (the same grouping method below), the cells were divided into 0 μmol/L HP group (without HP, the same below), 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. The apoptosis rate was detected by flow cytometry (n=4) after 24 hours of culture. The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, and 100 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively. After 24 hours of culture, the protein expressions of B-lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) were detected by Western blotting, and the Bcl-2/Bax ratio was calculated (n=3). The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 200 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. After 24 hours of culture, the protein expressions of glycogen synthase kinase-3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) were detected by Western blotting (n=3). The cells were divided into 0 μmol/L HP group, 50 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively, and HP pretreatment group with 50 μmol/L HP being added in advance for 12 h and then 300 μmol/L HP being added. After 24 hours of culture, the morphology and growth of cells were observed by inverted fluorescence microscopy (non-fluorescent condition) and immunofluorescence method, the apoptosis rate was detected by flow cytometry, the protein expressions of Bcl-2, Bax, cysteine aspartic acid specific protease-3 (caspase-3), caspase-9, cleavage caspase-3, cleavage caspase-9, GSK-3β, and p-GSK-3β were detected by Western blotting, and the Bcl-2/Bax ratio was calculated, with all the number of samples being 3. Data were statistically analyzed with one-way analysis of variance and Bonferroni test. Results: After 24 hours of culture, compared with that in 0 μmol/L HP group, the apoptosis rate of cells did not change significantly in 25 μmol/L HP group, 50 μmol/L HP group, or 100 μmol/L HP group (P>0.05) but increased significantly in 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group (P<0.01). After 24 hours of culture, compared with that in 0 μmol/L HP group, the Bcl-2/Bax ratio of cells increased significantly in 25 μmol/L HP group and 50 μmol/L HP group (P<0.05 or P<0.01) but decreased significantly in 100 µmol/L HP group (P<0.05). After 24 hours of culture, compared with those in 0 μmol/L HP group, the protein expression of GSK-3β in cells showed no significant change in 25 μmol/L HP group and 50 μmol/L HP group (P>0.05), the protein expressions of p-GSK-3β in cells significantly increased in 25 μmol/L HP group and 50 μmol/L HP group (P<0.01), the protein expressions of GSK-3β and p-GSK-3β in cells in 100 μmol/L HP group showed no significant change (P>0.05), the protein expressions of GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group were significantly increased (P<0.05). but the protein expression of p-GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group was significantly decreased (P<0.05). After 24 hours of culture, the morphology and growth of cells in 0 μmol/L HP group and 50 μmol/L HP group were similar and normal; in contrast, the cells in 300 µmol/L HP group became smaller and round, with the cell protrusions being shorter or disappeared, the nucleus being cavitated, and the cell abscission being increased significantly; the morphology of most cells in HP pretreatment group was normal, with the shedding of cells being less than that in 300 µmol/L HP group, and the morphology of nucleus being normal. After 24 hours of culture, the protein expression of caspase-9 was similar among the four groups (P>0.05). Compared with that in 0 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 50 μmol/L HP group showed no significant changes (P>0.05), the Bcl-2/Bax ratio of cells in 50 μmol/L HP group increased significantly (P<0.05), the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 300 μmol/L HP group were significantly increased (P<0.01), while the Bcl-2/Bax ratio of cells in 300 μmol/L HP group was significantly decreased (P<0.05). Compared with those in 300 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells were significantly decreased in HP pretreatment group (P<0.05 or P<0.01), while the Bcl-2/Bax ratio of cells was significantly increased in HP pretreatment group (P<0.01). After 24 hours of culture, the protein expressions of GSK-3β and p-GSK-3β of cells in 0 μmol/L HP group, 50 μmol/L HP group, 300 μmol/L HP group, and HP pretreatment group were 1.09±0.14, 0.62±0.17, 1.35±0.21, 0.74±0.34, 0.68±0.03, 0.85±0.08, 0.38±0.10, and 0.54±0.09, respectively. Compared with those in 0 μmol/L HP group, the protein expression of p-GSK-3β of cells was significantly increased in 50 μmol/L HP group (P<0.05) but significantly decreased in 300 μmol/L HP group (P<0.01), while the protein expression of GSK-3β of cells was significantly increased in 300 μmol/L HP group (P<0.05). Compared with those in 300 μmol/L HP group, the protein expression of GSK-3β of cells was significantly decreased in HP pretreatment group (P<0.01), while the protein expression of p-GSK-3β of cells was significantly increased in HP pretreatment group (P<0.01). Conclusions: The molarity of 50 μmol/L may be the optimal molarity of HP to pretreat mouse BMSCs, and 50 μmol/L HP pretreatment can antagonize mitochondrial pathway of oxidative stress induced apoptosis by inhibiting the activity of GSK-3β.

Burden of disease and risk factors among children under 5 years in China from 1990 to 2019: a perspective of international comparison / 中华预防医学杂志

Based on the Global Burden of Disease study 2019, the standardized mortality rate and disability-adjusted life years (DALYs) rate of children under 5 years old were selected as evaluation indicators to compare and analyze the current situation and differences of disease burden of children under 5 years old between China and other regions from 1990 to 2019. The change trend and difference of disease burden of children under 5 years old in China were analyzed by sexes. From 1990 to 2019, the all-cause standardized mortality rate of children under 5 years old in China decreased from 1 153.81/100 000 to 160.39/100 000, and the all-cause standardized DALY rate decreased from 104 426.40/100 000 to 16 479.01/100 000. In 2019, neonatal preterm birth, congenital heart anomalies and lower respiratory infections ranked the top three disease burden of children under 5 years old in China. Except that the disease burden of neonatal preterm birth was lower than that in North America, they were much higher than that in Western Europe and North America in the same period. The burden of unintentional injury diseases, including pulmonary aspiration and foreign body in airway and drowning, was higher than that in Western Europe and North America. The standardized mortality and DALY rate of the top ten diseases and injuries in boys and girls under 5 years old in China showed a downward trend (P<0.05), and most of them were higher in boys than girls (P<0.05). From 1990 to 2019, the disease burden of children under 5 years old in China decreased significantly. However, compared other regions, it is still necessary to strengthen the prevention and control of neonatal premature birth, birth defects and unintentional injuries, and take different sex-specific interventions to improve the overall health of children.

A case report of intracranial infection caused by Aggregatibacter aphrophilus / 中华神经科杂志

Aggregatibacter aphrophilus is a member of the normal flora of the human oral cavity and pharynx, a Gram-negative fastidous bacteria, belonging to agglomerates, which is a normal mixed oropharyngeal flora in humans, most commonly colonized on the surface of oral mucosa. This bacterial infection is rare in clinical practice, and it is difficult to culture and identify the bacteria, which is easy to be missed. A patient with intracranial infection was admitted to Huaihe Hospital, who showed fever and headache as the main clinical manifestations, and Aggregatibacter aphrophilus was detected by the metagenomic next-generation sequencing of cerebrospinal fluid. The patient′s symptoms were significantly improved after anti-infection treatment.

The applications of ionic liquids in drug delivery / 药学学报

Ionic liquids (ILs) are liquid mixtures formed by anions and cations in a certain stoichiometric ratio under certain conditions. They are widely used in various fields because of their simple preparation process, low volatility, high stability, high conductivity and non-flammability. Here, we firstly introduce their formation principles, classification, and physical and chemical properties in detail. Then, we summarize their functions in pharmaceutical preparations, such as improving the solubility of insoluble drugs, enhancing the stability of drugs, and promoting the permeability of drugs, as well as their role as active pharmaceutical ingredients (API) to fabricate new drug delivery systems of API-ILs. Finally, we reviewed the applications of ILs in different administration routes, including oral, transdermal, mucosal, and injection routes, and meanwhile offer perspectives for the further use of ILs.

Malignant tumors in farmers over 60 years old of the high-risk population in a town in Shanghai / 上海预防医学

Objective To screen for malignant tumors and high-risk factors in rural residents over 60 years old， so as to prevent and control the occurrence and development of tumors in the future. Methods The survey was conducted with reference to part of the questionnaire in the "Urban Cancer Early Diagnosis and Treatment Project and Evaluation of High-risk Populations". Clinical examinations included serum tumor marker detection， CT screening for lung cancer， occult blood （+） plus colonoscopy screening for colorectal cancer， and mammography screening. Individuals who were positive in the abovementioned clinical tests were defined as high-risk subjects. Results A total of 271 high-risk subjects （1.91%） were screened out of 14 161. Among the high-risk subjects， 71 cases of malignant tumors （26.19%） were found， with an incidence rate of 501.38 per 105. The top five tumors （63.38% of all diagnosed） were mainly concentrated in lung， upper digestive tract， blood system， urinary system， and rectum-colon. The proportion of malignant tumors detected by positive indicators was 61.54% of blood； 46.15% of carcinoembryonic antigen and carbohydrate antigen 125； 23.08% of alpha-fetoprotein； 16.66% of lung CT； and 3.09% of prostate PSA. The positive indicators in the high-risk subjects were mainly for the tumors in the prostate， lungs， liver， and CEA/CA125. The subjects with positive test indicators had lower average annual income in the last 5 years than the normal subject group （χ2=3.380， P=0.040）. The subjects with positive test indicators had higher proportion in family history of tumors than the normal group （χ2=2.596， P=0.046）. People in thehigh-risk group had a higher proportion than the normal group in suffering from hypertension， liver disease， gastrointestinal disease， respiratory system disease， and surgical treatment. Patients with high-risk tumors were found to have higher proportion than the normal group in showing pre-tumor clinical symptoms in the last 1 year. Study of the tumor-related risk factors found that the high-risk group had a higher proportion of high-fat/high-cholesterol diet， alcohol drinking， passive smoking， and personality depression. Conclusion High tumor risk factors have been identified in this population. It is necessary to strengthen the corresponding intervention and follow-up treatment of precancerous diseases in the future. We recommend the government to conduct tumor screening among high-risk groups to improve cost-effectiveness.

Effect of Polysaccharides from Root， Stem， Leaf and Fruit of Schisandra chinensis on Exercise Endurance in D-galactose-induced Aging Mice / 中国实验方剂学杂志

ObjectiveTo observe the effect of polysaccharides from root， stem， leaf and fruit of Schisandra chinensis on exercise endurance in the aging mice induced by D-galactose. MethodMale ICR mice were randomly assigned into six groups： blank control group， model group， root polysaccharide group， stem polysaccharide group， leaf polysaccharide group and fruit polysaccharide group. The mice were administrated with distilled water or root， stem， leaf and fruit polysaccharide （total sugar content of 35 mg·kg-1） by gavage. Thirty minutes after the administration， the blank control group was subcutaneously injected with normal saline， and the other groups with D-galactose （300 mg·kg-1）， once daily for 6 weeks. The anti-fatigue effects were evaluated by rotarod test， forelimb grip strength test， and weight-loaded swimming test. The fatigue and oxidation indicators such as blood urea nitrogen （BUN）， serum lactic acid （LD）， lactic dehydrogenase （LDH）， creatine kinase （CK）， superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and reactive oxygen species （ROS） were measured by chemical colorimetry. The protein levels of pro-apoptotic protein B cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， anti-apoptotic Bcl-2 and cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3） in mouse skeletal muscle were detected by Western blot. ResultIn the rotarod test， the time on rod was shorter in the model group than in the blank control group （P<0.01） and the root， stem and fruit polysaccharide groups （P<0.01）. In the forelimb grip strength test， the forelimb grip strength in the model group was lower than that in the blank control group （P<0.01） and the root， stem， leaf and fruit polysaccharide groups （P<0.01）. In the weight-loaded swimming test， the weight-loaded swimming time in the model group was shorter than that in the blank control group （P<0.01） and the root， stem， leaf and fruit polysaccharide groups （P<0.01）. Compared with those in the blank control group， the BUN， LD， LDH and CK levels significantly increased in the model group （P<0.05， P<0.01）. The increases in BUN and LDH levels were decreased by the root， stem and fruit polysaccharides （P<0.05， P<0.01） and those in LD and CK by the root， stem， leaf and fruit polysaccharides （P<0.05， P<0.01）. Compared with the blank control group， the model group showed decreased SOD and GSH-Px activities （P<0.01） and increased MDA and ROS content （P<0.01）. Compared with the model group， the root， stem， and fruit polysaccharide increased the SOD activity （P<0.05， P<0.01） and decreased ROS content （P<0.01）. The root and stem polysaccharides decreased the MDA content （P<0.01） and increased the GSH-Px activity （P<0.05， P<0.01）. Compared with the blank control group， the model group showed up-regulated protein levels of Bax and cleaved Caspase-3 and down-regulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the root， and stem polysaccharides down-regulated the protein levels of cleaved Caspase-3 （P<0.05） and up-regulated protein level of Bcl-2 （P<0.01）. ConclusionThe polysaccharides from the root， stem， leaf， and fruit of S. chinensis have anti-fatigue effect in D-galactose-induced aging mice. The polysaccharides may exert such effect by improving the antioxidant capacity and inhibiting the apoptosis of skeletal muscle cells.

Status Analysis and Improvement Suggestions on Filing Review Trial Implementation of Shanghai's Class II Passive Medical Device Registration / 中国医疗器械杂志

This article collected the statistics of Shanghai's class II passive medical device registration filing review trial implementation. It summarized and analyzed the common issues in the filing review stage, and gave suggestions for registration applicants and reviewers in order to further improve the quality of application materials and improve the efficiency of review.

Effective fraction from Simiao Wan prevents hepatic insulin resistant by inhibition of lipolysis via AMPK activation / 中国天然药物

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.

Continuous purification and culture of rat type 1 and type 2 alveolar epithelial cells by magnetic cell sorting / 中华创伤杂志(英文版)

PURPOSE@#The incidence of acute lung injury (ALI) in severe trauma patients is 48% and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%. Alveolar epithelial type 1 cells (AEC1s) and type 2 cells (AEC2s) are the key cells in the repair of injured lungs as well as fetal lung development. Therefore, the purification and culture of AEC1s and AEC2s play an important role in the research of repair and regeneration of lung tissue.@*METHODS@#Sprague-Dawley rats (3-4 weeks, 120-150 g) were purchased for experiment. Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells, and then magnetic bead cell sorting was performed to isolate T1α positive cells as AEC1s from the single-cell suspension by using polyclonal rabbit anti-T1a (a specific AEC1s membrane protein) antibodies combined with anti-rabbit IgG microbeads. Afterwards, alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining T1α-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads. Cell purity was identified by immunofluorescence staining and flow cytometry.@*RESULTS@#The purity of AEC1s and AEC2s was 88.3% ± 3.8% and 92.6% ± 2.7%, respectively. The cell growth was observed as follows: AEC1s stretched within the 12-16 h, but the cells proliferated slowly; while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days.@*CONCLUSION@#AEC1s and AEC2s sorted by this method have high purity and good viability. Therefore, our method provides a new approach for the isolation and culture of AEC1s and AEC2s as well as a new strategy for the research of lung repair and regeneration.

Research Progress of Targeted Ultrasound Contrast Agent BR55 / 中国医学科学院学报

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.

Association of the duration of systemic inflammatory response syndrome with infectious pancreatic necrosis at the initial stage of acute pancreatitis / 临床肝胆病杂志

ObjectiveTo investigate the potential association between early-stage inflammatory response and late-stage infectious pancreatic necrosis (IPN) in patients with acute pancreatitis (AP). MethodsA retrospective analysis was performed for the clinical data of 219 patients with moderate-severe acute pancreatitis (MSAP) and 53 patients with severe acute pancreatitis (SAP) who were admitted to The Affiliated Hospital of Southwest Medical University from June 2019 to June 2020, and according to the presence or absence of systemic inflammatory response syndrome (SIRS) at the initial stage of the disease, they were divided into SIRS group with 160 patients and non-SRIS group with 112 patients. Baseline data, serological markers, complications, and mortality rate were included for analysis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between multiple groups, and the Bonferroni method was used for further comparison between two groups. A logistic regression analysis was used to screen out valuable variables; the receiver operating characteristic (ROC) curve was used to compare the diagnostic value of variables, and the Z-test was used for pairwise comparison of area under the ROC curve (AUC). ResultsCompared with the non-SIRS group, the SIRS group had significantly higher white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (all P＜0.05) and a significantly higher proportion of patients with acute peripancreatic necrosis (ANC), IPN, pancreatic necrosis (PN), organ dysfunction, multiple organ dysfunction syndrome (MODS), SAP, critically-ill acute pancreatitis (CAP), death, BISAP score ＞2, CTSI score ＞2,or RANSON score ＞2 (all P＜0.05). The univariate analysis showed that SIRS duration, obesity, CRP, WBC, blood urea nitrogen, PN, ANC, SAP, MODS, RANSON score, BISAP score, and CTSI score were risk factors for IPN in patients with AP (all P＜005), and the multivariate analysis showed that SIRS duration (odds ratio ［OR］=1.307, 95% confidence interval ［CI］: 1.081-1580, P=0006) and ANC (OR=42.247, 95% CI: 10.829-164.818, P＜0.001) were risk factors for IPN; when ANC was excluded, SIRS duration (OR=1.430, 95% CI: 1.207-1.694, P＜0.001) and PN (OR=5.296, 95% CI: 1.845-15.203, P=0.002) were risk factors for IPN. The ROC curve showed that SIRS duration (AUC=0.772, Youden index=0.521), RANSON score (AUC=0701, Youden index=0.319), BISAP score (AUC=0.741, Youden index=0.377), and CTSI score (AUC=0.765, Youden Index=0.414) had a certain value in predicting IPN, and there was no significant difference in AUC between any two indices. The long-duration SIRS group(＞4 d) had a significantly higher proportion of patients with PN, ANC, IPN, SAP, or CAP than the non-SIRS group(0 d), the transient SIRS group(1~2 d), and the persistent SIRS group(3~4 d) (all P＜0.05), and the persistent SIRS group had a significantly higher proportion of patients with SAP than the non-SIRS group (P＜0.05). ConclusionAP patients with SIRS in the early stage are likely to develop organ failure and local complications, and there is a significant increase in the risk of IPN when SIRS duration is ＞4.5 days.

Clinical features of elderly patients with acute pancreatitis aged ≥80 years / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of elderly patients with acute pancreatitis (AP) aged ≥80 years. MethodsA retrospective analysis was performed for 3642 patients with pancreatitis who were admitted to Department of Gastroenterology in The Affiliated Hospital of Southwest Medical University from January 2013 to December 2019, and according to age, they were divided into young group (aged ＜65 years) with 2955 patients, middle-aged group (aged 65-79 years) with 558 patients, and elderly group (aged ≥80 years) with 129 patients. Related clinical data were collected and analyzed, including sex, age, etiology, predisposing factors, past medical history, disease severity, complication, and clinical outcome. The independent samples one-way ANOVA-test was used for comparison of normally distributed continuous data between groups and the least significant difference t-test was used for comparison within each group; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; the Kruskal-Wallis H test was used for comparison of ordinal categorical variables. ResultsIn the young group, there were 1721 male patients and 1234 female patients; in the middle-aged group, there were 214 male patients and 334 female patients; in the elderly group, there were 48 male patients and 81 female patients; the middle-aged group and the elderly group had a significantly higher proportion of female patients than the young group (62.8% vs 61.6% vs 41.8%, P＜0.05). High-fat diet was the main predisposing factor for all three groups, and compared with the young group, the elderly group had a significantly lower proportion of patients with AP induced by alcohol or high-fat diet+alcohol (P＜0.05). The elderly group had a significantly higher proportion of patients with the etiology of biliary diseases than the middle-aged group and the young group (798% vs 69.2% vs 41.4%, χ2=204.127, P＜0.05), as well as a significantly lower proportion of patients with the etiology of hyperlipidemia, alcohol, or biliary diseases+hyperlipidemia (all P＜0.05). Among the 129 patients in the elderly group, 83 (64.3%) had mild AP, 23 (17.8%) had moderate-severe AP, and 23 (17.8%) had severe AP; there was a significant difference in the constituent ratio of disease severity between the elderly group and the middle-aged/young groups (H=1972.5, P＜005). The elderly group and the middle-aged group had a significantly lower proportion of patients with recurrence than the young group (both P＜0.05). There were no significant differences in local complications between the three groups (all P＞0.05), and as for systemic complications, compared with the young group, the elderly group had a significantly higher proportion of patients with pneumonia (3.9% vs 2.2%, P＜0.05), acute kidney injury (AKI) (6.2% vs 2.5%, P＜0.05), or multiple organ dysfunction syndrome (MODS) (7.8% vs 4.0%, P＜0.05). Compared with the middle-aged group and the young group, the elderly group had a significantly lower proportion of cured patients (67.4% vs 76.3% vs 820%, P＜0.05) and a significantly higher proportion of patients with improvement (23.3% vs 147%/12.7%, P＜0.05). The elderly group and the middle-aged group had a significantly higher proportion of patients withdrawn from treatment than the young group (8.5%/5.9% vs 3.4%, P＜0.05). There was 1 death in the elderly group (0.8%), 9 deaths in the middle-aged group (1.6%), and 16 deaths in the young group (0.5%), and there was no significant difference between the three groups (P＞0.05). There were no significant differences in length of hospital stay and hospital costs between the three groups (P＞0.05). ConclusionAP patients aged ≥80 years are mainly female and are often caused by biliary factors, and they are likely to develop the complications such as pneumonia, AKI, and MODS.

Clinical efficacy of extracorporeal membrane oxygenation on severe acute respiratory distress syndrome caused by Pneumocystis jersima pneumonia after renal transplantation / 中华器官移植杂志

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

Current status of acute pancreatitis related clinical trial registrations in China / 中华胰腺病杂志

Objective:To analyze the registration status of acute pancreatitis-related clinical studies registered on the Chinese Clinical Trial Registry (ChiCTR) and USA ClinicalTrials.gov database.Methods:The ChiCTR and ClinicalTrials.gov database were searched to collect, sort and analyze the clinical studies related to acute pancreatitis registered from the establishment of the database to December 31, 2020. The clinical trials were manually grouped, and the features of clinical researches were compared based on different registered data (2007-2014 vs 2015-2020) and different financial sources (self-support, enterprise support or public support). Results:A total of 157 registered clinical studies related to acute pancreatitis have been included (ChiCTR n=99; ClinicalTrial.gov n=58). The top three areas with the greatest number of registered clinical studies were Sichuan (28.0%), Shanghai (14.6%) and Jiangsu (12.1%), totally accounting for 54.7%. There were 91 interventional studies, 41 observational studies and 25 other type studies. Masking was performed in 34 studies (21.6%). Randomized parallel controlling was performed in 84 studies (53.5%). 30 trials (19.1%) were at Ⅳ phase, and 7 trials (4.4%) were at Ⅱ or Ⅲ phase. 2007-2014 group tended to use randomized parallel controlled design (68.3% vs 45.4%, P=0.005) and randomization grouping (76.7% vs 47.4%, P=0.001). 2015-2020 group tended to use relatively large sample (72.6% vs 47.4%, P=0.002)and data management committee (53.6% vs 25.0%, P=0.001). The differences between the two groups were statistically significant. Of 92 trials from ChiCTR database, 48 were self-supported, 5 was supported by enterprise, and 38 was supported by the public. The percentage of self-support and public support was 86.9%. Conclusions:The number of acute pancreatitis-related clinical studies registered on ChiCTR was generally on the increase. Most registered studies were funded by public finances or by the researchers' institutions self. There was a lack of phaseⅡ or phase Ⅲ.

Treatment of Thin Endometrium in Infertility Based on Thought of "Blood Being Basis of Women" / 中国实验方剂学杂志

Infertility is commonly seen but difficult to treat in the department of obstetrics and gynecology. The incidence of infertility in women of childbearing age has reached as high as 25% in China， which seriously affects social harmony and people's happiness. As the lifestyle of modern women changes， thin endometrium has gradually become an important reason for infertility and embryo transfer failure. Such factors as repeated operations in uterine cavity and oral intake of hormones have resulted in destructed blood vessels and reduced blood flow in endometrium， impaired growth of glandular epithelial cells， insufficient local blood supply， retarded development of endometrium， reduced receptivity， and therefore poor acceptance of endometrium to the implanted gestational sac， which is not conducive to the implantation of fertilized eggs. As a result， the infertility will occur. Traditional Chinese medicine （TCM） has a long history of treating infertility. During the long-term clinical practice， physicians of ancient and modern times have gained rich experience in the diagnosis and treatment of infertility. The idea of "blood being the basis of women" sprouted in the Spring and Autumn and Warring States Periods and determined in the Song Dynasty as an important guiding principle that can be applied in various physiological periods of women. It emphasizes "blood regulation" for gynecological diseases to ensure sufficient blood in blood vessels and its normal circulation， thus allowing the thoroughfare and conception vessels and endometrium to be nourished and the pregnancy to be facilitated. With blood as the basis， the paper explored the physiopathological correlations of five zang organs and thoroughfare and conception vessels with blood， pointed out the preference for "blood harmonization" in ancient literature based on the differentiation of infertility into blood stasis， blood cold， blood heat， and blood deficiency syndromes， reviewed the key methods of modern physicians in assisting pregnancy including tonifying kidney and nourishing blood， tonifying kidney and activating blood， tonifying kidney and invigorating spleen， as well as invigorating kidney and soothing liver， and summarized the efficacy of integrated TCM and western medicine in promoting ovulation， regulating hormones， improving blood supply， and nourishing endometrium to assist pregnancy. All these would contribute to the clinical treatment and scientific research of thin endometrium in infertility from multiple angles.

Treatment of Perimenopausal Anovulatory Dysfunctional Uterine Bleeding Based on Thought of Liver Being Innate Basis of Women / 中国实验方剂学杂志

Perimenopausal anovulatory dysfunctional uterine bleeding （ADUB） is a severe acute disease that is difficult to be dealt with in gynecology， accounting for about 70% of abnormal uterine bleeding. The significant differences in bleeding patterns make it particularly challenging to treat. The main manifestations of perimenopausal ADUB are prolonged menstrual period， inexhaustible menstrual bleeding， or heavy inter-menstrual vaginal bleeding， which allow it to be classified into the category of metrorrhagia and metrostaxis in traditional Chinese medicine （TCM）. After conducting in-depth research on this disease， physicians of the past dynasties have figured out its etiology and pathogenesis and accumulated rich experience in its differentiation and treatment， thus forming a relatively systematic theoretical system. The existing literature mainly focuses on four types of its pathogenesis， namely blood heat， blood stasis， spleen deficiency， and kidney deficiency， and there are few discussions on liver. However， patients with metrorrhagia and metrostaxis due to liver dysfunction are commonly seen in clinical practice. The theory of liver being innate basis of women explores the special physiological and pathological characteristics of women and emphasizes the important role of liver in the treatment of this disease based on its characteristic functions and meridian circulation. Considering the close relationship of liver Qi and blood with spleen， kidney， and thoroughfare and conception vessels， this paper discussed the TCM treatment of perimenopausal ADUB from the following four aspects： soothing liver Qi and nourishing liver blood， liver and kidney sharing the same source， simultaneous regulation of liver and spleen， and liver meridian circulation， so as to broaden the clinical treatment options. Perimenopause is a unique physiological period when women tend to suffer from Qi stagnation and blood deficiency. Liver， characterized by Yin in property and Yang in function， governs the free flow of Qi， induces ovulation， stores blood， and regulates blood volume. Therefore， the liver should be emphasized in the treatment of perimenopausal ADUB， which contributes to correcting the hormone disorder caused by abnormal ovulation， stopping bleeding， and alleviating perimenopausal symptoms. This paper has provided a new direction for the clinical treatment of perimenopausal ADUB .