Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Dimethyl fumarate inhibits NLRP3/AIM2 inflammasomes to prevent spleen radiation injury ZHANG / 中国药理学通报

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

Effect of naringenin regulating RIP1-RIP3-MLKL signaling pathway on apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome / 中国药理学通报

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Application of triangle stability mechanical model in the layer separation of transanal total mesorectal excision / 中华胃肠外科杂志

Transanal total mesorectal resection (taTME) has come a long way since it was first used in the clinic in 2010.The learning curve of this procedure is long due to different surgical approaches, different perspectives and different anatomical positions. Many surgeons experience complications during this procedure. Although the advantages and problems of this procedure have been reported in much literature, the anatomy and operation methods of taTME introduced in literatures and training centers are too complicated, which makes many surgeons encounter difficulties in carrying out taTME surgery. According to the author's experience in learning and carrying out this operation, spatial expansion process of ultralow rectal cancer was divided into three stages. At each stage, according to different pulling forces, three different schemes of triangular stability mechanics model were adopted for separation. From point to line, from line to plane, the model can protect the safety of peripheral blood vessels and nerves while ensuring total mesorectal excision . This model simplifies the complex surgical process and is convenient for beginners to master taTME surgical separation skills.

A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Progress of Research on Immune-related Pneumonia in Non-small Cell Lung Cancer / 肿瘤防治研究

In recent years, immunotherapy has made a breakthrough in the field of non-small cell lung cancer, reshaping the pattern of lung cancer treatment. However, with the wide application of immunotherapy in clinical practice, immune-related adverse events have attracted increasing attention. Immune pneumonia, as one of the immune-related toxic side effects of greatest concern, affects the treatment process and curative effect and can be a threat to life in serious cases. Given that immune pneumonia has a complicated pathogenesis and diverse clinical manifestations, strengthening the understanding of immune pneumonia is urgently needed. The treatment of immune pneumonia is limited, and additional therapeutic medicines are still awaiting exploration. Therefore, this paper summarizes the progress of the research on immune pneumonia in the treatment of non-small cell lung cancer.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Application of body temperature rinse in percutaneous transforaminal endoscopic lumbar discectomy through intervertebral approach / 中国骨伤

OBJECTIVE@#To investigate the effects of two types of temperature rinses on body temperature, inflammatory cytokine levels, and bleeding volume in percutaneous endoscopic lumbar discectomy.@*METHODS@#Eighty patients underwent percutaneous endoscopic lumbar discectomy from January 2018 to December 2020 were selected and divided into experimental group (40 cases) and control group(40 cases). In experimental group, there were 19 males and 21 females, aged (38.8±9.8) years old;7patients on L4,5 and 33 patients on L5S1;Body msss index(BMI) was (27.8±7.2) kg·m-2. In contral group, there were 18 males and 22 females, aged (41.5±10.9) years old, 5 patients on L4,5 and 35 patients on L5S1;BMI was (26.4±6.2) kg·m-2. The patients in the control group were received normal saline rinse at room temperature, and the patients in the experimental group were received normal saline rinse heated to 37 ℃. Body temperature, chills, nausea, vomiting, and other adverse reactions were recorded. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in two groups were recorded before and 2 hours after operation. Visual analogue scale (VAS) was used to evaluate the degree of lumbar pain in two groups before and 2 hours after surgery. Fibrinolytic-coagulation indexes with preoperative and 2 hours after surgery, including the D-dimer (DD), fibrinogen degradation products (FDP), activated partial thrombin time (APTT) and prothrombin time (PT) were recorder. Operation time and blood loss in two groups were recorded.@*RESULTS@#The body temperature of both groups showed a downward trend, while the body temperature of the control group was lower than that of the experimental group. The levels of TNF-α, IL-6 and IL-10 in two groups were increased 2 hours after surgery compared with those before surgery(P<0.05), while the levels in experimental group were lower than those in control group(P<0.05). Postoperative VAS in experimental group 2.19±1.13 was significantly lower than that in the control group 3.38±1.35(P<0.05). The levels of DD and FDP at 2 hours after surgery in both groups were higher than those before surgery (P<0.05), while the levels of DD and FDP in the experimental group were higher than those in the control group (P<0.05). There was no significant difference in APTT and PT levels between two groups after operation (P>0.05). The blood loss in the experimental group of (45.2±14.1) ml was lower than that in the control group of (59.52±15.6) ml. The operation time of experimental group (46.7±13.8) min was less than that of control group (58.3±15.2) min(P<0.05).@*CONCLUSION@#Body temperature rinse can reduce the incidence of adverse reactions, alleviate local inflammatory reactions, reduce intraoperative blood loss and shorten the operation time.

Multi-modal synergistic quantitative analysis and rehabilitation assessment of lower limbs for exoskeleton / 生物医学工程学杂志

In response to the problem that the traditional lower limb rehabilitation scale assessment method is time-consuming and difficult to use in exoskeleton rehabilitation training, this paper proposes a quantitative assessment method for lower limb walking ability based on lower limb exoskeleton robot training with multimodal synergistic information fusion. The method significantly improves the efficiency and reliability of the rehabilitation assessment process by introducing quantitative synergistic indicators fusing electrophysiological and kinematic level information. First, electromyographic and kinematic data of the lower extremity were collected from subjects trained to walk wearing an exoskeleton. Then, based on muscle synergy theory, a synergistic quantification algorithm was used to construct synergistic index features of electromyography and kinematics. Finally, the electrophysiological and kinematic level information was fused to build a modal feature fusion model and output the lower limb motor function score. The experimental results showed that the correlation coefficients of the constructed synergistic features of electromyography and kinematics with the clinical scale were 0.799 and 0.825, respectively. The results of the fused synergistic features in the K-nearest neighbor (KNN) model yielded higher correlation coefficients ( r = 0.921, P < 0.01). This method can modify the rehabilitation training mode of the exoskeleton robot according to the assessment results, which provides a basis for the synchronized assessment-training mode of "human in the loop" and provides a potential method for remote rehabilitation training and assessment of the lower extremity.

Study on the difference of high frequency dielectric properties of biological tissues measured by air and packed coaxial probe / 生物医学工程学杂志

In this paper, the differences between air probe and filled probe for measuring high-frequency dielectric properties of biological tissues are investigated based on the equivalent circuit model to provide a reference for the methodology of high-frequency measurement of biological tissue dielectric properties. Two types of probes were used to measure different concentrations of NaCl solution in the frequency band of 100 MHz-2 GHz. The results showed that the accuracy and reliability of the calculated results of the air probe were lower than that of the filled probe, especially the dielectric coefficient of the measured material, and the higher the concentration of NaCl solution, the higher the error. By laminating the probe terminal, liquid intrusion could be prevented, to a certain extent, to improve the accuracy of measurement. However, as the frequency decreased, the influence of the film on the measurement increased and the measurement accuracy decreased. The results of the study show that the air probe, despite its simple dimensional design and easy calibration, differs from the conventional equivalent circuit model in actual measurements, and the model needs to be re-corrected for actual use. The filled probe matches the equivalent circuit model better, and therefore has better measurement accuracy and reliability.

Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats / 中国中药杂志

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.

Construction and application of a field-scale rapid prediction system for wind field and pollutant dispersion / 中国辐射卫生

Objective To construct a rapid prediction system to improve the accuracy and efficiency of evaluation of the consequences of nuclear accidents at a field scale. Methods Base on a diagnostic wind field model and Lagrangian particle diffusion, we established a rapid prediction method for wind field and pollutant dispersion around complex underlying surfaces within a field scale, in a way of visual discrimination of buildings and vegetation distribution. With data simulation and the use of a real urban field example, the simulated results were compared with wind tunnel test measurements and computational fluid dynamics results to study the influence of complex underlying surfaces on wind field and pollutant transport in the region. Results The rapid prediction system could clearly simulate the high-resolution wind field and pollutant concentration distribution of the region in about five minutes. It could interface with geographic information software and couple with a mesoscale weather prediction model. In terms of accuracy, the system performed well in wind field simulation, with the fractional deviations of wind speed and wind direction being 0.33 and −0.08, respectively. Concentration field simulation was greatly affected by the wind field, and the ratios of simulated concentrations to observed concentrations were between 0.05 and 3.4, except for a few low concentration points. Conclusion The rapid prediction system can effectively simulate the distribution characteristics of the flow field and improve calculation efficiency when ensuring calculation accuracy, which provides an important reference for emergency response to nuclear accidents.

Effect of three intrinsic foot muscle exercises on cross-sectional area of abductor hallucis muscle and foot morphology in subjects with flatfoot / 中国康复理论与实践

ObjectiveTo compare the effect of three kinds of intrinsic foot muscle exercise on flatfoot. MethodsFrom September to November, 2022, 45 subjects with flatfoot from Capital University of Physical Education and Sports were randomly divided into short foot exercise (SFE) group (n = 15), toe-spread-out exercise (TSOE) group (n = 15) and short foot & toe-spread-out exercise (SF+TSOE) group (n = 15), who received SFE, TSOE and SF+TSOE, respectively, for eight weeks. The cross-sectional area of abductor hallucis muscle, navicular drop test (NDT) and Chippaux-Smirak index (CSI) were measured before treatment, four weeks after treatment and eight weeks after treatment. ResultsThree subjects dropped out in each group. The main effect of time was significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F > 13.906, P < 0.001). The main effect of group was not significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F < 1.934, P > 0.05). The interaction effect of group and time was significant for left and right NDT (F > 3.044，P < 0.05), and it was better in SF+TSOE group than in SFE group and TSOE group (P < 0.05). ConclusionSF and TSOE can improve the cross-sectional area of abductor hallucis muscle and foot morphology in subjects with flatfoot, and the combination of them may be more effective.

Modified Mohs micrographic surgery for the treatment of five cases of eccrine porocarcinoma / 中华皮肤科杂志

Objective:To investigate the efficacy of modified Mohs micrographic surgery in the treatment of eccrine porocarcinoma.Methods:Clinical data were collected from 5 patients with eccrine porocarcinoma, who treated with modified Mohs micrographic surgery in Department of Dermatology, Wuhan No.1 Hospital from 2016 to 2020, and retrospectively analyzed.Results:Among the 5 patients, 2 were males and 3 were females, their age ranged from 52 to 80 years, and the course of disease ranged from 1 to 50 years. Skin lesions were located on the scalp, face, abdomen, thighs and feet, with diameters ranging from 1 to 6 cm. Tumor excision was performed with 1-cm margins, and was deep to the superficial fascial layers. For histopathologically negative surgical margins, the defects were closed with skin flaps or grafts; for histopathologically positive margins, the excision margin continued to be widened until it was clean. The 5 patients were followed up for 1 - 5 years without recurrence, and 1 died 2 years later due to liver cancer metastasis.Conclusion:Modified Mohs micrographic surgery can ensure clean resection margins and reduce the loss of normal tissues in the treatment of eccrine porocarcinoma.

Application value of ventricular intracranial pressure monitoring in the treatment of unilateral temporal lobe cerebral contusion / 中华创伤杂志

Objective:To explore the application value of ventricular intracranial pressure monitoring (V-ICPM) in the treatment of unilateral temporal lobe cerebral contusion.Methods:A retrospective cohort study was conducted to analyze the clinical data of 295 patients with unilateral temporal lobe cerebral contusion admitted to 904th Hospital of PLA Joint Support Force from January 2014 to August 2021, including 172 males and 123 females; aged 14-78 years [(46.3±14.7)years]. V-ICPM was used in 136 patients (V-ICPM group), who received surgical or non-surgical treatment according to the monitoring, while not in 159 patients (non-V-ICPM group), who received routine surgery or non-surgical treatment. The two groups were compared in terms of the rates of intracranial hematoma clearance by craniotomy, decompressive craniectomy (DC) and dehydration and osmotic therapy during hospitalization, use time of 20% mass fraction of mannitol and 30 g/L hypertonic salt, displacement rate of brain midline structure of head CT≥10 mm after discharge, rate of intracranial infection, hydrocephalus and epilepsy, and Glasgow Outcome Scale (GOS) at 6 months after discharge.Results:All patients were followed up for 6-12 months [(8.9±2.1)months]. During hospitalization, the rate of intracranial hematoma clearance by craniotomy and the rate of DC in V-ICPM group were 35.3% (48/136) and 8.1% (11/136), lower than 47.2% (75/159) and 22.0% (35/159) in non-V-ICPM group ( P<0.05 or 0.01). There was no significant difference between the two groups in the rate of dehydration and osmotic therapy or the use time of mannitol (all P>0.05). The use time of hypertonic salt in V-ICPM group was (7.2±2.5)days, more than (4.1±1.8)days in non-V-ICPM group ( P<0.05). After discharge, the displacement rate of brain midline structure of head CT in V-ICPM group was 29.4% (40/136), lower than 42.8% (68/159) in non-V-ICPM group ( P<0.05). There was no significant difference between the two groups in the rate of intracranial infection, hydrocephalus and epilepsy (all P>0.05). Six months after discharge, the good rate of GOS in V-ICPM group was 91.2% (124/136), significantly better than 81.8% (130/159) in non-V-ICPM group ( P<0.05). Conclusion:For unilateral temporal lobe cerebral contusion, V-ICPM is associated with reduced rate of craniotomy exploration and DC, decreased incidence of complications and improved prognosis of the patients in spite of longer use time of hypertonic salt.

Application of "group-based" TA guidance model in the construction of homogenized clinical skill training system / 中华医学教育探索杂志

Objective:To evaluate the application effect of the "group-based" teaching assistant (TA) guidance model in homogenized clinical skill training.Methods:A pilot study was conducted on the cardiopulmonary resuscitation training course, and 32 students majoring in clinical integrative Chinese and Western medicine (five-year program) who were admitted to Shanghai University of Traditional Chinese Medicine in 2018 were randomly divided into control group ( n = 16) and TA group ( n = 16). The control group received traditional teaching methods, and the TA group was further divided into subgroups A, B, C, and D, with four graduate TAs providing group-based teaching. The groups were compared in terms of their satisfaction and test scores. SPSS 25.0 was used for t-test and analysis of variance. Results:The satisfaction survey showed that compared with the control group, the TA group had significantly higher degree of satisfaction with the increased practical opportunities, clinical skill practical ability, learning effect, and overall satisfaction. The immediate test showed that there was no significant difference in test score between the TA group (85.19±2.93) points and the control group (82.75±4.52) points. The test 30 days later showed that the TA group (83.50±5.13) points had a significantly higher test score than the control group (74.68±3.87) points, and the control group had a significantly lower test score than that in the immediate test ( P <0.001); however, there was no significant difference in the TA group's score between the immediate test and the test 30 days later. Conclusion:The "group-based" TA guidance model has a good effect in homogenized clinical skill training, and has a stable long-term effect, with high student satisfaction.

Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats / 解剖学报

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect / 解剖学报

Objective To observe the effect of polyinosinic-polycytidylic acid ( Poly-IC ) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion ( I / R ) injury in fryperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I /R injury in fryperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I /R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly (P<0. 05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group (P<0. 05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0. 05) , and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability ( P < 0. 05 ) . No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0. 05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group ( P < 0 .05 ) , while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0. 05 ) . The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0. 05) , the expression of Bcl-2 was significantly decreased(P<0. 05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly ( P < 0. 05 ) , the expression of Bcl-2 increased significantly(P<0. 05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.