The chemical constituents and hypoglycemic activity of alcoholic extract of sea buckthorn leaves / 药学学报

The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.

Xiaojindan Extract Modulated Macrophage Polarization by Targeting PI3K/Akt Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Xiaojindan extract （XJD） on macrophage polarization. MethodLipopolysaccharide （LPS） and interleukin-4 （IL-4） were used to induce M1 and M2 polarization of RAW264.7 cells. The influence of 10-80 mg·L-1 XJD on cell proliferation was detected by Cell Counting Kit-8 （CCK-8） assay. Nitric oxide （NO） and interleukin-6 （IL-6） release was explored by Griess assay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA expression of M1 and M2 macrophage markers was measured by real-time quantitative polymerase chain reaction （Real-time PCR）， and the CD206+ expression was determined by flow cytometry. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway was analyzed by western blot. Result10-80 mg·L-1 XJD showed no marked cytotoxicity in LPS （0.5 mg·L-1）- or IL-4 （20 μg·L-1）-induced RAW264.7 cells. Compared with the control group， LPS significantly promoted the expression of M1 macrophage markers （P<0.01）， including increased NO and IL-6 release （P<0.01） and upregulated mRNA expression of interleukin-1β （IL-1β）， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX-2） and tumor necrosis factor-α （TNF-α） （P<0.01）. Compared with LPS-induced group， 20-80 mg·L-1 XJD decreased the release of NO and IL-6 in a dose-dependent manner （P<0.01）， and similarly 10-80 mg·L-1 XJD suppressed the mRNA expression of IL-1β， iNOS， COX-2 and TNF-α （P<0.01）. Compared with the control group， IL-4 obviously increased the expression of M2 macrophage markers （P<0.01）， including increased CD206+ cell population and upregulated mRNA expression of arginine-1 （Arg-1）， interleukin-10 （IL-10）， interleukin-13 （IL-13） and transforming growth factor-β1 （TGF-β1）. Compared with IL-4-induced group， 10-80 mg·L-1 XJD dose-dependently decreased CD206+ cell population （P<0.01） and inhibited the mRNA expression of Arg-1， IL-10， IL-13 and TGF-β1 （P<0.01）. Western blot showed that XJD significantly downregulated the activation of PI3K/Akt pathway as compared to LPS- and IL-4-induced groups （P<0.05， P<0.01）. ConclusionXJD significantly inhibited the macrophage polarization in the LPS- and IL-4-induced RAW264.7 cells by targeting PI3K/Akt pathway.

A feasibility study of combining hepatectomy with splenectomy in hepatocellular carcinoma patients with severe thrombocytopenia / 中华肝胆外科杂志

Objective:To study the feasibility of combining hepatectomy with splenectomy in hepatocellular carcinoma patients with severe thrombocytopenia (platelet count ≤30×10 9/L). Methods:The data of 46 patients with primary hepatocellular carcinoma with thrombocytopenia treated at Beijing Ditan Hospital, Capital Medical University from January 2016 to January 2021 were analyzed retrospectively. There were 32 males and 14 females, aged (55.0±7.9) years. According to the platelet count one day before operation, the patients were divided into the study group (20×10 9/L < platelet count ≤30×10 9/L, n=20) and the control group (30×10 9/L<platelet count <100×10 9/L, n=26). All patients underwent hepatectomy combined with splenectomy or hepatectomy combined with splenectomy and pericardial devascularization. The liver function (aspartate aminotransferase, alanine aminotransferase, albumin), platelet count, daily abdominal drainage within 3 days after operation, drop in hemoglobin (the difference between hemoglobin on the day after operation versus 1 day before operation) and hospital stay were compared between the two groups. Rebleeding and portal vein thrombosis were studied. Results:There was no significant difference in liver function between the two groups 2 weeks after operation (all P>0.05). The platelet count on the 1st, 3rd and 5th day after operation in the study group was significantly lower than that in the control group (all P<0.05). The platelet count in the study group and the control group returned to the normal range on the 5th and 3rd day after operation, respectively. The daily abdominal drainage volume, drop in hemoglobin and hospital stay in the control group were (407.3±124.2) ml, (31.1±8.6) g and (13.7±3.3) d, respectively, which were significantly better than those in the study group (647.5±209.5) ml, (38.3±12.8) g, (16.9±3.7) d. There were 3 patients (15.0%) who developed esophageal and gastric fundus vein rebleeding and 10 patients (50.0%) with portal vein thrombosis in the study group, versus 2 patients (7.7%) and 12 patients (46.2%) respectively in the control group. There were no significant differences between the two groups (both P>0.05). Conclusion:Severe thrombocytopenia was not an absolute contraindication of combining hepatectomy and splenectomy in patients with hepatocellular carcinoma. After sufficient and reasonable preoperative adjustment and evaluation, the operation was still safe and feasible.

Mechanism of omege-6 PUFA increasing the susceptibility to acute myocardial ischemia injury / 药学学报

The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.

Phospholipid remodeling and Parkinson's disease / 药学学报

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Research progress on the detection methods and their application in ferroptosis / 药学学报

Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.

Effect of Qinggan Xiefei Fang on increasing susceptibility of influenza virus caused by "liver fire invading lung" / 药学学报

In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.

Qingre Xiaoyanning inhibits emotional stress-induced reactivation of latent herpes simplex virus type 1 in mice / 药学学报

In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.

The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

The development of artificial cervical disc replacement from the perspective of orthopedic bionic therapy / 中华外科杂志

The modern surgical treatment of cervical degenerative disc disease can be traced back to the advent of anterior cervical decompression and fusion.With the emergence of fusion-related complications,different scholars have promoted the gradual transformation of cervical degenerative disc diseases from "fusion fixation" to "non-fusion reconstruction" through in-depth fusion with materials science,engineering mechanics and other disciplines.The innovation of this treatment concept is consistent with the original intention of "structural remodeling,functional reconstruction,maximum repair and reconstruction of the morphology and function of skeletal muscle system" in orthopedic bionic treatment,which is essentially in line with the "bionic alternative therapy" in orthopedic bionic therapy.This paper focuses on the surgical treatment of cervical degenerative disc diseases,reviews the development history of artificial cervical disc replacement,analyzes the evolution from orthopedic biomimetic therapy,and explores a new direction for the design of artificial cervical disc prostheses and the treatment of cervical degenerative disc diseases in the future.

Analysis of epidemic characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis isolated from some provinces (autonomous regions). Methods: Surveillance data of anthrax cases reported from 2017 to 2019 in the Infectious Disease Surveillance information System of China Disease Prevention and Control and the Public Health Emergency Reporting and Management Information System were collected, and descriptive epidemiological methods were used to analyze the epidemic characteristics, including the temporal, geographic and demographic distribution of this disease. A total of 47 strains of Bacillus anthracis isolated from 2017 to 2019 were analyzed by canSNP and MLVA15. Results: A total of 951 cases of anthrax were reported from 2017 to 2019, of which 938 were cutaneous anthrax, representing 98.63% of the total number reported. It was mainly distributed in the west and northeast of China, and the three provinces with the highest number of cases were Gansu (215), Sichuan (202) and Qinghai (191). Cases had been reported throughout the year, more cases occurred in the summer and autumn, and August was the month with the most cases,66.35% (211/318), 72.32% (243/336) and 68.01% (202/297) of cases were reported during June to September. The age distribution was mainly between 20 and 59 years old, accounting for more than 80% of all cases. The number of male cases was significantly higher than that of female cases, the ratio of male to female was about 3∶1. The occupations were mainly herdsmen and farmers, accounting for 49.70% to 58.18% and 31.45% to 36.70%, respectively. Public health events occurred every year, and 29 events had been reported from 2017 to 2019. canSNP analysis showed that 37 of the 47 strains belonged to the A.Br.001/002 subgroup and 10 belonged to the A.Br.Ames subgroup. MLVA15 analysis showed that there were 17 genotypes, of which 10 genotypes contained only one strain. Conclusion: Cutaneous anthrax was the predominant clinical type in China from 2017 to 2019.The seasonal, geographic and demographic distribution characteristics were evident.Molecular typing methods such as canSNP and MLVA15 can be used to trace the source of infectious diseases and provide technical support for anthrax prevention and control.

Application of the three-dimensional visualization ablation planning system in radiofrequency ablation for hepatocellular carcinoma / 临床肝胆病杂志

Objective To investigate the significance of the three-dimensional visualization ablation planning system in radiofrequency ablation for liver cancer. Methods A total of 71 patients who received radiofrequency ablation for hepatocellular carcinoma in Beijing Ditan Hospital, Capital Medical University from July 2017 to December 2020 were enrolled as subjects. The 34 patients in the three-dimensional group used the three-dimensional visualization ablation planning system for radiofrequency protocol planning before surgery and the 37 patients in the two-dimensional group used the two-dimensional image for radiofrequency protocol planning before surgery. The two groups were compared in terms of the indices such as the first-attempt success rate of puncture, complete tumor ablation rate, and tumor-free survival. The Fisher's exact test, the chi-square test of continuous correction, or the Pearson chi-square test was used for comparison of categorical data between two groups; the t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank (Mantel-Cox) test was used for comparison of tumor recurrence and survival; the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for tumor-free survival. Results Compared with the two-dimensional group, the three-dimensional group had a significantly higher first-attempt success rate of puncture (94.12% vs 75.68%, Pearson χ 2 =4.183, P =0.041) and a significantly shorter median time of puncture (5 minutes vs 7 minutes, Z =-2.407, P =0.013). There was no significant difference in complete ablation rate between the three-dimensional group and the two-dimensional group (97.06% vs 91.89%, continuous correction χ 2 =0.183, P =0.669). There were significant differences in the 1-, 2-, and 4-year cumulative tumor-free survival rates between the three-dimensional group and the two-dimensional group (90.8%/78.8%/72.8% vs 61.5%/55.9%/44.7%, χ 2 =5.073, P =0.024). The multivariate Cox regression analysis showed that preoperative planning method, complete or incomplete ablation, and alpha-fetoprotein at 1 month after surgery were independent influencing factors for the tumor-free survival of patients with liver cancer after radiofrequency ablation (all P < 0.05). Conclusion Radiofrequency ablation planning via the three-dimensional visualization ablation planning system can ensure the therapeutic effect of radiofrequency ablation, reduce the recurrence rate of liver cancer, and prolong the tumor-free survival of patients.

A retrospective comparative study on Hassab operation combined with either RFA or liver resection in treatment of liver cancer associated with portal hypertension / 中华肝胆外科杂志

Objective:To study the efficacy and safety of Hassab operation combined with either radiofrequency ablation(RFA) or liver resection in treatment of liver cancer associated with portal hypertension.Methods:A retrospective analysis was conducted on the clinical data of patients with primary liver cancer associated with portal hypertension operated at the Department of General Surgery of Beijing Ditan Hospital from June 2013 to June 2015. These patients were divided into the RFA combined with Hassab operation group and the liver resection combined with Hassab operation group according to the surgical procedures. The general patient information, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative hospital stay, postoperative complications and the 1-, 3-, and 5-years cumulative survival rates and recurrence-free survival rates were compared.Results:Of 53 patients who were included in the study, 30 patients were in the RFA combined with Hassab operation group (including 28 males and 2 females, average age 46.3 (27.0~64.0) years, and 23 patients in the liver resection combined with Hassab operation group (including 20 males and 3 females), average age 44.7(33.0~59.0) years. There were no significant differences in the general patient information including age, gender, maximum tumor diameter, preoperative laboratory tests (including blood routine, liver function, tumor markers), and Child-Pugh classification between the two groups (all P>0.05). Intraoperative blood loss in the RFA combined with Hassab operation group was significantly less than those in the liver resection combined with Hassab operation group [(401.67±183.12) ml vs (552.17±333.88) ml, P<0.05]. There were also no significant differences between the two groups in operation time, blood transfusion during operation, postoperative hospital stay, and postoperative complications ( P>0.05). The incidence of severe postoperative complications (Clavein-Dindo grade ≥ IIIb) in the liver resection combined with Hassab operation group was 47.8% (11/23), which was significantly higher than the 20.0% (6/30) in the RFA combined with Hassab operation group ( P<0.05). The 1-, 3-, and 5-year cumulative survival rates of patients in the RFA combined with Hassab operation group were 82.8%, 49.9%, and 33.2%, respectively, while the corresponding survival rates of patients in the liver resection combined with Hassab operation group were 81.0%, 58.2%, 43.7%, respectively. There was no significant difference between the two groups ( P>0.05). The recurrence-free survival rates of patients in the RFA combined with Hassab operation group at 1-, 3-, and 5-years after surgery were 79.2%, 38.8%, and 21.6%, respectively. The corresponding recurrence-free survival rates of patients in the liver resection combined with Hassab operation group were 76.4%, 41.7%, and 27.8%, respectively, and there was no significant difference between the two groups ( P>0.05). Conclusion:RFA combined with Hassab operation was safe and efficacious to treat primary liver cancer associated with portal hypertension.

Qingre Xiaoyanning Capsules alleviate HSV-1 susceptibility induced by emotional stress / 中国中药杂志

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.

Phospholipid peroxidation: a key factor in "susceptibility" to neurodegenerative diseases / 药学学报

The biochemical integrity of the brain is necessary to maintain normal function. Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity. The nervous system is enriched in phospholipid and polyunsaturated fatty acids (PUFAs). Due to the nature of high oxygen-consumption and rich lipids, brain is particularly vulnerable to oxidative damages. Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system. Once the antioxidant system is insufficient to resist oxidative damage, membrane phospholipids will be prone to free radical attack. Phospholipid peroxidation leads to a variety of toxic oxidation products, including membrane damage, mitochondrial dysfunction, rapid accumulation of amyloid, etc. Multiple proteins and nucleic acids can be covalently modified by peroxidation products, resulting in the loss of the protein functions, which eventually triggers programmed cell death and general neuroinflammation in brain, and ends up with an increased susceptibility to neurodegenerative diseases. Based on the knowledge of mechanisms of phospholipid peroxidation, this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases, in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.

Imaging signs for predicting hematoma enlargement in patients with intracerebral hemorrhage / 国际脑血管病杂志

Hematoma enlargement is a common harmful event after cerebral hemorrhage, which can lead to deterioration of neurological function and poor outcome. Early detection of high-risk patients can help prevent hematoma enlargement and improve the outcome of patients. Although the exact mechanism of hematoma enlargement is unclear, more and more evidence shows that many imaging signs may be related to hematoma enlargement, such as dot sign, mixed sign, black hole sign, island sign, etc. This article mainly reviews the relevant imaging prediction factors of hematoma enlargement from the perspective of imaging.

Application of deep convolutional neural networks in the diagnosis of laryngeal squamous cell carcinoma based on narrow band imaging endoscopy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the possibility of using artificial intelligence (AI) technology based on convolutional neural network (CNN) to assist the clinical diagnosis of laryngeal squamous cell carcinoma (LSCC) through deep learning algorithm. Methods: A deep CNN was developed and applied in narrow band imaging (NBI) endoscopy of 4 799 patients with laryngeal lesions, including 3 168 males and 1 631 females, aged from 21 to 87 years, from 2015 to 2017 in Beijing Tongren Hospital, Capital Medical University. A simple randomization method was used to select the laryngeal NBI images of 2 427 patients (1 388 benign lesions and 1 039 LSCC lesions) for the training and correction the CNN model. The remaining laryngeal NBI images of 2 372 patients (including 1 276 benign lesions and 1 096 LSCC lesions) were used as validation data set to compare performance between CNN and otolaryngologists. SPSS 21.0 software was used for Chi-square test to calculate the accuracy, sensitivity and specificity of AI and otolaryngologists. The area under the curve (AUC) of receiver operating curve (ROC) was used to evaluate the diagnostic ability of the algorithm for NBI images. Results: The accuracy, sensitivity and specificity for NBI predictions were respectively 90.91% (AUC=0.96), 90.12% and 91.53%, which were equivalent to those for otolaryngologists' predictions (accuracy, sensitivity and specificity were (91.93±3.20)%, (91.33±3.25)% and (93.02±2.59)%, t values were 0.64, 0.75 and 1.17, and P values were 0.32, 0.28 and 0.21, respectively). The diagnostic efficiency of CNN was significantly higher than that of otolaryngologists (0.01 vs. 5.50, t =9.15, P<0.001). Conclusion: AI based on deep CNN is effective for using in the laryngeal NBI image diagnosis, showing a good application prospect in the diagnosis of LSCC.

Treatment efficiency evaluation of left cardiac sympathetic denervation for patients with inherited arrhythmia by exercise-stress test / 中华心血管病杂志

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

Analyses of triggers for recurrent cardiac events in 38 patients with symptomatic long QT syndrome / 中华心血管病杂志

Objective: To evaluate the main triggers of recurrent cardiac events in patients with symptomatic congenital long QT syndrome (cLQTS). Methods: In this retrospective case analysis study, clinical characteristics were reviewed from 38 patients with recurrent cardiac events after first visit out of 66 symptomatic cLQTS patients. General clinical data such as gender, age, clinical presentation, family history and treatment were collected, auxiliary examination results such as electrocardiogram and gene detection were analyzed. LQTS-related cardiac events were defined as arrhythmogenic syncope, implantable cardioverter defibrillator (ICD) shock, inappropriate ICD shock, aborted cardiac arrest, sudden cardiac death or ventricular tachycardia. Results: A total of 38 patients with recurrent symptoms were enrolled in this study, including 30 females (79%) and 14 children (37%). The average age of onset was (15.6±14.6) years, and the recurrence time was (3.6±3.5) years. Subtype analysis showed that there were 11 cases (29%) of LQT1 (including 2 cases of jervel-Lange Nielson syndrome), 19 cases (50%) of LQT2, 5 cases (13%) of LQT3 and 3 cases (8%) of other rare subtypes (1 LQT5, 1 LQT7 and 1 LQT11) in this patient cohort. LQT1 patients experienced recurrent cardiac event due to drug withdrawal (6 (55%)), specific triggers (exercise and emotional excitement) (4 (36%)) and medication adjustment (1 (9%)). For LQT2 patients, main triggers for cardiac events were drug withdrawal (16 (84%)), specific triggers (shock, sound stimulation, waking up (6 (32%)). One patient (5%) had recurrent syncope after pregnancy. One patient (20%) had inappropriate ICD shock. For LQT3 patients, 4 (80%) patients developed syncope during resting state, and 1 (20%) developed ventricular tachycardia during exercise test. One LQT5 patients experienced syncope and ICD shock under specific triggers (emotional excitement). One LQT11 patient had repeated ICD shocks under specific inducement (fatigue). One LQT7 patient experienced inappropriate ICD shock. Left cardiac sympathetic denervation (LCSD) significantly alleviated the symptoms in 2 children with Jervell-Lange Nielson syndrome (JLNS) post ineffective β-blocker medication. Nadolol succeeded in eliminating cardiac events in one patient with LQT2 post ineffective metoprolol medication. Mexiletine significantly improved symptoms in 2 patients with LQT2 post ineffective β-blocker medication. Conclusions: Medication withdrawal is an important trigger of the recurrence of cardiac events among patients with symptomatic congenital long QT syndrome.

Variant analysis on steroid 5-reductase type 2 deficiency caused by a novel SRD5A2 mutation / 中国当代儿科杂志

This article reported the clinical characteristics and SRD5A2 gene mutation pattern of a child with steroid 5-α reductase type 2 deficiency. The 2-month-old boy showed hypospadias and short penis shortly after birth. DNA was extracted from the peripheral blood of the child and his parents. The endocrine disease-related genes were captured and sequenced by high-throughput sequencing technology, and the family DNA samples were verified by Sanger sequencing. The results showed that c.680G>A(p.R227Q) and c.608G>A(p.G203D) compound heterozygous mutations existed in the SRD5A2 gene of the child. The c.680G>A mutation inherited from his father, which was a known pathogenic mutation. The c.608G>A mutation originated from his mother, which was a novel mutation discovered in this study. These results provide molecular evidence for the etiological diagnosis of the child and genetic counseling for the family, as well as extend the mutation spectrum of SRD5A2 gene.