S-propargyl-cysteine delays the progression of atherosclerosis and increases eNOS phosphorylation in endothelial cells / 生理学报

The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.

Advances in the treatment of hypertrophic cardiomyopathy with cardiac myosin inhibitors / 中国药房

In recent years， with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy， novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin， thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient， the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers， and improve New York Heart Association （NYHA） cardiac function class. They are safe， have mild adverse reactions， and can be tolerated by patients. Compared to Mavacamten， Aficamten， as a structurally optimized product， has a shorter half-life and fewer drug-drug interactions， which is more conducive to drug- targeted dose titration.

Effect of electroacupuncture at different time points on postoperative urination function in patients with mixed hemorrhoids surgery / 中国针灸

OBJECTIVE@#To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery.@*METHODS@#A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group.@*RESULTS@#In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05).@*CONCLUSION@#EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.

Effects of etoricoxib and sodium hyaluronate on pain and inflammatory factors in patients with knee osteoarthritis / 中国医师进修杂志

Objective:To explore the effects of etoricoxib combined with sodium hyaluronate on pain and inflammatory factors in patients with knee osteoarthritis (KOA).Methods:A total of 106 KOA patients admitted to Zhujiang Hospital of Southern Medical University were selected as the research objects from March 2018 to October 2020, and they were divided into a control group and a study group using a random number table method, with 53 cases in each group. The control group was treated with sodium hyaluronate, and the study group was treated with etoricoxib on the basis of the control group. The effects of both groups were observed after continuous treatment for 4 weeks. The clinical efficacy and changes of knee joint function, pain and inflammatory factors before and after treatment were compared between the two groups, and the occurrence of adverse reactions during the treatment period was recorded.Results:The total effective rate of the study group was higher than that of the control group: 92.45%(49/53) vs. 77.36%(41/53), the difference was statistically significant ( P<0.05). The American Knee Association score (AKS) and Lysholm score after treatment in the two groups were higher than before treatment ( P<0.05), and the AKS score and Lysholm score in the study group after treatment were higher than control group: (171.84 ± 24.16) scores vs. (159.09 ± 22.21) scores, (81.62 ± 14.76) scores vs. (75.41 ± 13.58) scores, the difference was statistically significant ( P<0.05). The visual analogue score (VAS) of pain after treatment in the two groups was lower than before treatment, and the VAS score of the study group after treatment was lower than the control group: (3.01 ± 0.54) scores vs. (3.45 ± 0.64) scores. the difference was statistically significant ( P<0.05). The levels of interleukin-1β (IL-1β), matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) after treatment in the two groups were lower than before treatment, TIL-1β, MMP-3, and MMP-9 of the study group after treatment were lower than the control group: (56.38 ± 9.67) μg/L vs. (62.19 ± 10.73) μg/L, (91.56 ± 15.18) μg/L vs. (98.09 ± 16.74) μg/L, (30.46 ± 5.59) μg/L vs. (35.03 ± 6.27) μg/L, the difference was statistically significant ( P<0.05). There was no statistically significant difference in the incidence of total adverse reactions between the two groups ( P>0.05). Conclusions:Tocoxib combined with sodium hyaluronate in the treatment of KOA can improve the clinical efficacy, improve knee joint function, relieve pain, reduce the level of inflammatory factors, and have good safety.

Therapeutic effect of small extracellular vesicles derived from mesenchymal stem cells on retinal light injury and its mechanism / 中华实验眼科杂志

Objective:To investigate the effect of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) in mouse model of retinal light injury and the possible mechanism.Methods:Human umbilical cord derived MSCs were identified by flow cytometry.Supernatants of passage 3-5 MSCs were collected.sEVs were harvested by ultracentrifugation and were identified by transmission electron microscopy.Sixty-five healthy female SPF-grade BALB/c mice aged 8-10 weeks were randomly divided into normal group (17 mice), phosphate buffered saline (PBS) group (24 mice) and sEVs group (24 mice). Mice in PBS and sEVs groups were intravitreally injected with 2 μl of PBS and sEVs, respectively, and were exposed to 930 lx blue light for 6 hours.No intervention was administered to the normal group.Three days after lighting, mice retinal structure was observed by hematoxylin-eosin staining.Apoptotic retinal cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Retinal function was tested by electroretinogram.Differentially expressed mRNAs between PBS group and sEVs group were assayed by mRNA transcriptome sequencing and were analyzed through KEGG cluster analysis.The differential mRNAs were verified via real-time quantitative PCR.The study protocol was approved by the Animal Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221035).Results:MSCs were positive for CD90 and CD105, negative for CD34 and CD45.The extracted MSC-sEVs showed a bilayer membrane vesicle with a diameter of 80-140 nm.Hematoxylin-eosin staining showed the arrangement of photoreceptor nuclei was disordered in outer nuclear layer in PBS group.The disorder of photoreceptor nuclei arrangement of sEVs group was slighter than that of PBS group.The apoptotic cell number of sEVs group was (14.60±4.04)/visual field, which was lower than (24.00±8.52)/visual field of PBS group, with a statistically significant difference ( t=2.37, P<0.05). The a-wave amplitude of sEVs group was (64.38±16.70)μV, which was higher than (16.78±6.37) μV of PBS group, showing a statistically significant difference ( P<0.05). The b-wave amplitudes of PBS and sEVs groups were (132.40±39.41) μV and (154.86±34.08) μV, respectively, which were lower than (338.38±27.41) μV of normal group, and the differences were statistically significant (both at P<0.05). A total of 110 differentially expressed mRNAs were detected.There were 109 downregulated mRNAs in sEVs group.Differentially expressed mRNAs were mainly inflammation- and immune-related pathways.PCR showed that the expression level of C-C motif chemokine ligand 2, C-C motif chemokine receptor 2, leukotriene B4, leukocyte Ig-like receptor A6 and interleukin-1β in sEVs group were significantly decreased in comparison with PBS group (all at P<0.05). Conclusions:MSC-sEVs can ameliorate blue light-induced retinal structural and functional damage.The protective effect may be achieved through inhibiting inflammatory response.

Electromyographic signals and the starting threshold voltage of orbicularis oris muscle in healthy rhesus monkeys / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.

Mechanism study of platelet derived growth factor receptor alpha on the bidirectional differentiation regulation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells in mice / 中华口腔医学杂志

Objective: To investigate the role of platelet derived growth factor receptor alpha (PDGFRα) on bidirectional differentiation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells (Gli1+-MSC). Methods: Breeding double reporter transgenic mice ROSAmT/mG/Gli1-CreERt2/PDGFRαfl (Experimental group) and ROSAmT/mG/Gli1-CreERt2 (Control group), 20 mice in each of the two groups at four weeks of age were selected, MSC were isolated from the mouse aortic epithelium. After tamoxifen inducement, the two groups of Gli1+-MSC were screened by green fluorescent protein (GFP) labeling and flow cytometry sorting. PDGFRα was conditionally knocked out in the experimental group, and the control group Gli1+-MSC expressed PDGFRα normally. The two groups of Gli1+-MSC were subjected to adipogenic induction and fibrogenic induction, the Western blotting was performed to detect PDGFRα, adipocyte markers [perilipin and CCAAT/enhancer binding protein alpha (C/EBPα)] and fibrogenic markers [alpha smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1)] and semi-quantitative analysis was performed. The degree of cellular adipose differentiation after bidirectional induction of Gli1+-MSC in both groups was observed by oil red O staining and analyzed semi-quantitatively. Results: After tamoxifen induction, Gli1+-MSC could be accurately isolated from flow cytometry by GFP labeling. Via adipogenic differentiation, the expression of PDGFRα in the experimental group (0.017±0.002) was significantly lower than that in the control group (0.184±0.012) (t=25.48，P=0.002). The protein expressions of perilipin (3.138±0.414) and C/EBPα (3.565±0.289) were significantly higher than those in the control group (2.312±0.218 and 2.179±0.103, respectively) (t=6.21，P=0.025；t=6.69，P=0.022). Thus, the knock-out of PDGFRα enhanced the adipogenic differentiation ability of Gli1+-MSC. After fibrogenesis induction, the protein expressions of PDGFRα, α-SMA and FSP-1 in the experimental group (0.030±0.001, 0.932±0.177 and 0.276±0.020, respectively) were significantly lower than those in the control group (0.439±0.006, 1.352±0.170 and 0.835±0.097, respectively) (t=149.40, P<0.001; t=66.38,P<0.001; t=11.41,P<0.08). This suggested that the knock-out of PDGFRα significantly inhibited Gli1+-MSC differentiation toward fibroblasts. After bidirectional induction, significantly less adipocyte formation was seen in the control group and more in the experimental group. Quantitative analysis showed that the amount of oil red O staining in the experimental group (0.461±0.042) was significantly higher than that in the control group (0.017±0.007) after bidirectional induction (t=23.20, P<0.01). Conclusions: PDGFRα plays an important role in the regulation of bidirectional differentiation of vascular adventitial Gli1+-MSC.

Structure identification and content analysis of active components in Xiaoyao pills / 药学学报

Xiaoyao pills are a famous traditional Chinese medicine collected in Welfare Pharmacy, which is a classic prescription for treating liver depression and spleen deficiency. However, its composition is complex. In order to better control the quality of Xiaoyao pills, in this study, HPLC-ion-trap time-of-flight mass spectrometry (LC-IT-TOF/MS) was used to identify the main ingredients of Xiaoyao pills, paeoniflorin, albiflorin, glycyrrhizic acid, saikosaponin A and saikosaponin B2. Then a liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed for simultaneous determination and quantification of the main compounds. Fragmentation pathways of five active components were obtained. The method was validated. Five active ingredients in Xiaoyao pills had a good linear relationship, and the values of RSD (%) of repeatability were all less than 5%, the recovery ranges were between 90% and 115%, and the values of RSD (%) of each substance were less than 10% after the sample solution is placed for 24 hours. Three batches of Xiaoyao pills (concentrated pellets) and two batches of Xiaoyao pills (water pellets) were determined, the contents of paeoniflorin in concentrated pills were more than 4.0 mg·g-1, and those in water pills were more than 2.5 mg·g-1, which was accordance with Chinese Pharmacopoeia. However, other compounds behave differently. This method has high sensitivity and reliable measurement results, which provides basis for quality control of Xiaoyao pills and material basis for pharmacology research.

Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Impacts of muscular strength training on boxers' endurance / Impactos do treinamento de força muscular na resistência de boxeadores / Impacto del entrenamiento de la fuerza muscular en la resistencia de los boxeadores

ABSTRACT Introduction Strength and endurance training of boxers are the main parts to pay attention to in the training protocol due to the particularities of Chinese boxing. Objective Study the effect of strength training on the muscles and endurance of Chinese boxing athletes. Methods This paper adopts experimental control. The control group practiced the traditional martial arts training while in the experimental group, other daily training properly protocoled was added. One class was selected for strength training on Monday, Tuesday, and Friday of each week. Before the experiment began, the physiological data of the athletes were evaluated and recorded. After the experiment, the data was again acquired and compared. By comparing the data, the effectiveness of the training can be analyzed. Results After strength training, the experimental group's results were significantly higher than those of the control group. Conclusion Adopting properly targeted special strength training can increase the effectiveness and anaerobic endurance of Chinese boxers, increasing the chances of exploiting their maximum potential in combat. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O treino de força e de resistência dos boxeadores são as principais partes a se prestar atenção no protocolo de treinamento devido às particularidades do boxe chinês. Objetivo Estudar o efeito do treinamento de força sobre os músculos e a resistência dos atletas de boxe chinês. Métodos Este trabalho adota o controle experimental. O grupo de controle pratica o tradicional treino das artes marciais enquanto ao grupo experimental, acrescentou-se outros treinamentos diários devidamente protocolados. Nas segundas, terças e sextas-feiras de cada semana, uma classe foi selecionada para o treinamento de força. Antes do início do experimento, os dados fisiológicos dos atletas foram avaliados e registrados. Após o experimento, os dados novamente foram adquiridos e comparados. Através da comparação dos dados, a eficácia do treinamento pode ser analisada. Resultados Após o treinamento de força, os resultados do grupo experimental foram significativamente maiores do que os do grupo de controle. Conclusão A adoção de treinamento de força especial devidamente direcionado pode aumentar a eficácia e resistência anaeróbica dos boxeadores chineses, aumentando as chances de explorar o seu máximo potencial em combate. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El entrenamiento de la fuerza y la resistencia de los boxeadores son las partes principales a las que hay que prestar atención en el protocolo de entrenamiento debido a las particularidades del boxeo chino. Objetivo Estudiar el efecto del entrenamiento de fuerza en los músculos y la resistencia de los atletas chinos de boxeo. Métodos Este trabajo adopta el control experimental. El grupo de control practica el entrenamiento tradicional de artes marciales mientras que al grupo experimental se le añadió otro entrenamiento diario debidamente protocolizado. Los lunes, martes y viernes de cada semana, se seleccionó una clase para el entrenamiento de fuerza. Antes de comenzar el experimento, se evaluaron y registraron los datos fisiológicos de los atletas. Tras el experimento, se volvieron a adquirir los datos y se compararon. La comparación de los datos permite analizar la eficacia de la formación. Resultados Tras el entrenamiento de fuerza, los resultados del grupo experimental fueron significativamente superiores a los del grupo de control. Conclusión La adopción de un entrenamiento de fuerza especial adecuadamente dirigido puede aumentar la eficacia y la resistencia anaeróbica de los boxeadores chinos, incrementando las posibilidades de explotar su máximo potencial en el combate. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Loss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging / 国际口腔科学杂志·英文版

Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.

Strategic Exploration of Targeted Therapy for BRAF Non-V600E Mutant Lung Cancer / 中国肺癌杂志

BACKGROUND@#Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment.@*METHODS@#Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature.@*RESULTS@#There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib.@*CONCLUSIONS@#At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.

Mechanism of Tibetan medicine Ershiwuwei Shanhu Pills on scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway / 中国中药杂志

This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice / 中国中药杂志

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.

Mechanism of Tibetan medicine Ershiwuwei Songshi Pills in regulating intestinal flora and improving non-alcoholic steatohepatitis / 中国中药杂志

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.

Research progress on precious Tibetan medicine formula in prevention and treatment of central nervous system diseases / 中国中药杂志

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.

Strengthening the role of evidence-based medicine in the training of cardiovascular specialists / 中华医学教育探索杂志

The standardized training of medical specialists in China is far from perfect. The training contents, training system, training methods, supervision and assessment methods need to be improved. The First Clinical College of The First Hospital of China Medical University have guided the trainees to strengthen the study of guidelines and consensus by emphasizing the concept of evidence-based medicine (EBM) of training teachers by means of Sino-U.S. exchanges, case discussions and other ways. At the same time, with the help of the modern network education platform and the problem-based learning teaching mode, the concept of EBM education has been further developed, which greatly enhances the ability of specialists to analyze and solve problems, and improves the training effect.

A novel sesquiterpenoid from Curcuma longa L / 药学学报

A new compound was isolated from the 95% ethanolic extract of the rhizomes of Curcuma longa L. using silica gel column chromatography, medium pressure liquid chromatography, and semi-preparative high performance liquid chromatography. The structure and absolute configuration of the compound was elucidated by HR-ESI-MS, NMR, and electronic circular dichroism (ECD) calculations. It is a novel sesquiterpenoid, which is named as isoturmeronol B (1). The carbon skeleton of compound 1 is similar to that of bisabolane-type sesquiterpenoid. The only difference is that the methyl group at C-4 in bisabolene-type sesquiterpenoid is migrated to C-5 in compound 1. Besides, the anti-inflammatory and antioxidant activities of the compound 1 were evaluated. The results showed that 1 has no anti-inflammatory and antioxidant activities.

Infective endocarditis in pregnancy: A case report / 北京大学学报(医学版)

Infective endocarditis in pregnancy is extremely rare in clinical practice. Guidelines addressing prophylaxis and management of infective endocarditis do not extensively deal with concomitant pregnancy, and case reports on infective endocarditis are scarce. Due to increased blood volume and hemodynamic changes in late pregnancy, endocardial neoplasms are easy to fall off and cause systemic or pulmonary embolism, respiratory, cardiac arrest and sudden death may occur in pregnant women, the fetus can suffer from intrauterine distress and stillbirth at any time, leading to adverse outcomes for pregnant women and fetuses. The disease is dangerous and difficult to treat, which seriously threatens the lives of mothers and babies. Early diagnosis and reasonable treatment can effectively improve the prognosis of patients. The most important method for the treatment of infective endocarditis requires early, adequate, long-term and combined antibiotic therapy. Moreover, surgical controversies regarding indication and timing of treatment exist, especially in pregnancy. In terms of the timing of termination of pregnancy, the timing of cardiac surgery, and the method of surgery, individualized programs must be adopted. A pregnant woman with 30+5 weeks of gestation is reported. She was admitted to hospital due to intermittent chest tightness, suffocation and fever, with grade Ⅲ cardiac insufficiency. Imaging revealed large mitral valve vegetation, 22.0 mm×4.1 mm and 22.0 mm×5.1 mm, respectively, and severe valve regurgitation. Mitral valve perforation was more likely, blood culture suggested Staphylococcus epidermidis infection, after antibiotic conservative treatment, the effect was poor. After the joint consultation including cardiology, neonatology, interventional vascular surgery, anesthesiology, and obstetrics, the combined operation of obstetrics and cardiac surgery was performed in time. The heart was blocked for 60 minutes, the bleeding was 1 200 mL, the newborn was mildly asphyxiated after birth, and the birth weight was 1 890 g. Nine days after the operation, the patient was discharged from the hospital, and the newborn was discharged with the weight of 2 020 g. Critical cases like this require a thorough weighing of risks and benefits followed by swift action to protect the mother and her unborn child. An optimal outcome in a challenging case like this greatly depends on effective interdisciplinary communication, informed consent of the patient, and concerted action among the specialists involved.

The success rate of His-Purkinje system pacing in patients with various sites of atrioventricular block / 中华心血管病杂志

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.