Research on the reform of pathology online-offline teaching mode / 中华医学教育探索杂志

Objective:To study the effect of the reform of pathology teaching mode.Methods:The Batch 2017 Class 1 and Class 3 students of clinical medicine who had pathology courses in the second semester of the 2019-2020 school year were selected in the controlled study, and they were divided into the study group (56 students from Class 1) and the control group (57 students from Class 3). For the pathology course, the control group used conventional teaching, and the study group used online-offline mixed teaching combined with problem-based learning (PBL). Both groups were taught for 1 semester. The theoretical assessment scores, practical assessment scores and excellent rate of the two groups after teaching were compared, the abilities of autonomous learning, problem solving, teamwork, and multidisciplinary thinking were compared between the two groups before and after teaching, and the satisfaction with the teaching mode was compared between the two groups. SPSS 23.0 software was used for t test and chi-square test. Results:The theoretical assessment scores [(93.86±5.42) vs. (86.74±5.33)] and practical assessment scores [(92.91±5.37) vs. (84.86±5.26)] of the study group were significantly higher than those of the control group ( P<0.05); the differences in grades distribution were statistically significant, and the excellent and good rate of the study group was higher than that of the control group ( P<0.05). The scores of autonomous learning, problem solving, teamwork and multidisciplinary thinking in the two groups were higher than those before the teaching, and the scores of the study group were higher than those of the control group ( P<0.05); after the teaching, the study group had higher satisfaction scores than the control group in enhancing clinical thinking ability, deepening the perception of life value and other aspects ( P<0.05). Conclusion:The combination of online and offline teaching combined with PBL can not only improve the assessment performance and excellent rate of medical students majoring in clinical medicine, but also enhance the ability of medical students to study independently, solve problems, teamwork and multidisciplinary thinking, and improve their satisfaction with the teaching mode.

Baicalein Mediated FAK Protein Regulates PI3K/Akt Signaling Pathway to Inhibit Proliferation and Migration of Gastric Cancer HGC-27 Cells / 中国实验方剂学杂志

ObjectiveTo study the possible molecular mechanism of baicalein （BAI）-mediated focal adhesion kinase （FAK） in the regulation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the proliferation and migration of gastric cancer HGC-27 cells. MethodThe gastric epithelial GES-1 cells and gastric cancer HGC-27 cells were respectively treated with BAI （0， 5， 15， 25， and 50 μmol·L-1） for 48 h， and then methyl thiazolyl tetrazolium （MTT） assay was adopted to detect effect of BAI on cell proliferation. Western blot （WB） was employed to detect the expression of FAK and the proteins related to epithelial-mesenchymal transition （EMT） and PI3K signaling pathway after intervention with different concentrations of BAI. The HGC-27 cells stably overexpressing FAK were constructed with lentivirus-mediated transfection technique， and the transfection of FAK was detected through WB and green fluorescent protein （GFP）. The cells were divided into empty vector （NC） group， BAI group， FAK overexpression group， and BAI-treated FAK overexpression group， and cell proliferation activity was detected by MTT assay. The colony formation and cell migration were observed via colony formation assay and Transwell migration assay， respectively. The expression of proteins involved in EMT and PI3K signaling pathways were detected by Western blot. ResultCompared with the NC group， BAI （15， 25 and 50 μmol·L-1） inhibited the proliferation of HGC-27 cells in a dose-dependent manner （P<0.05， P<0.01） while did not affect that of GES-1 cells. BAI （5， 15 and 25 μmol·L-1） down-regulated the expression level of p-FAK （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed up-regulated expression level of FAK in HGC-27 cells. The HGC-27 cells in both NC group and FAK overexpression group had green fluorescence. Compared with NC group， BAI inhibited the growth， colony formation， and migration， while FAK overexpression promoted those of HGC-27 cells. The treatment of FAK overexpression group with BAI inhibited the enhancement of cell proliferation and migration （P<0.05）. WB showed that compared with NC group， BAI （15， 25 μmol·L-1） significantly up-regulated the expression of E-cadherin protein and down-regulated that of Vimentin， Snail， p-PI3K， and p-Akt protein in HGC-27 cells （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed down-regulated expression of E-cadherin， up-regulated expression of p-FAK， Vimentin， and Snail， and increased ratios of p-FAK/FAK， p-PI3K/PI3K and p-Akt/Akt （P<0.05）. This phenomenon would be reversed after BAI treatment. ConclusionBAI can affect the proliferation and migration of gastric cancer HGC-27 cells by mediating FAK to regulate PI3K/Akt signaling pathway.

In-hospital mortality and related risk factors after knee replacement in China: based on national hospital quality monitoring system data / 中华骨科杂志

Objective:To estimate in-hospital mortality after knee replacement (KR) and to assess its trend and risk factors in China.Methods:We included patients undergoing KR in the Hospital Quality Monitoring System in China (2013-2019) to estimate in-hospital mortality after KR and assessed relation of patient's and hospital's characteristics (year of surgery, age, gender, marital status, primary indication, Charlson comorbidity index, geographic location, hospital type, hospital volume of KR, and surgery type) to in-hospital mortality using multivariable Poisson regression.Results:The annual amount of KR has increased from 20 307 in 2013 to 35 757 in 2019, and has maintained an upward trend for 7 years. The mean age of patients having KR increased from 64.9 years in 2013 to 66.6 years in 2019. Of the total 218 923 KRs, 63 deaths (0.29‰) occurred within 30 days before discharging. Older age was associated with higher in-hospital mortality ( P for trend <0.001). Male gender had higher incidence of in-hospital mortality compared with female [relative risk (RR), 2.5; 95% CI: 1.5, 4.1]. Single marital status was associated with higher, albeit non-statistically significant, in-hospital mortality than married patients (RR, 2.1; 95% CI: 0.9, 4.6). Higher Charlson comorbidity index was associated with increased risk of in-hospital mortality ( P for trend <0.001). Risk of in-hospital mortality decreased with more hospital-year knee replacement surgeries ( P for trend <0.001). In-hospital mortality varied by geographic regions, with the lowest mortality in East region (0.16‰), followed by South-West (0.31‰), South-Central (0.31‰), North region (0.33‰), North-West (0.54‰) and North-East (0.59‰). Conclusion:In-hospital mortality after KR in China was relatively low. Older age, male gender, higher Charlson comorbidity index and lower hospital-year knee replacement surgeries were risk factors for in-hospital mortality. The mortality varied greatly according to the geographic location of hospital.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

The role of IL-1 related receptor SIGIRR in immune related diseases / 中华微生物学和免疫学杂志

SIGIRR, a member of the interleukin 1 receptor superfamily, is also known as a single immunoglobulin (Ig)-related receptor, which is believed to play a key role in the development of inflammation and the regulation of anti-inflammatory effects. Some studies believe that the abnormal down-regulation of SIGIRR can lead to intestinal inflammation, pyelonephritis, systemic lupus erythematosus and other diseases, but it can promote tumor growth and potentially cause anti-tumor immune damage when its genes are overexpressed. Therefore, the role of SIGIRR in disease occurrence and development is considered a double-edged sword. At present, the detailed molecular mechanism of SIGIRR′s biological role is not fully understood. This article reviews the functions of SIGIRR in the occurrence and development of immune-related diseases and immune regulation, as well as related cell signaling pathways, which have been discovered and confirmed.

Effects of mechanical ventilation with different tidal volumes on right ventricular hemodynamics in acute respiratory distress syndrome rats / 中华危重病急救医学

Objective:To explore the effect of different tidal volumes (VT) on the hemodynamics of right heart in acute respiratory distress syndrome (ARDS) rats induced by oleic acid (OA).Methods:Sixty adult male Sprague-Dawley (SD) rats were divided into control group ( n = 20), ARDS model group ( n = 20), low VT (LVT) group ( n = 10) and high VT (HVT) group ( n = 10) by random number table. ARDS model was reproduced by injecting OA 0.15 mL/kg through a jugular vein. The control group was given the same amount of normal saline. The success of modeling was judged by the oxygenation index (PaO 2/FiO 2) 2 hours after modeling, at the same time, the lung tissues were collected, the wet/dry weight (W/D) ratio was determined, and the lung histopathological changes were measured by lung injury score. The rats in the LVT group and HVT group were given mechanical ventilation with VT of 6 mL/kg or 20 mL/kg for 4 hours, respectively at 2 hours after modeling. The rats in the control group and the ARDS model group maintained spontaneous breathing. After mechanical ventilation for 4 hours, the heart rate (HR), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (dp/dt max), and the blood pressure (BP) were measured. Meanwhile, arterial blood samples were collected for blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2) and PaO 2/FiO 2. Results:The rats in the ARDS model group showed symptoms of respiratory distress 1 hour after modeling, and the lung tissue samples showed obvious patchy bleeding 2 hours after modeling, while the control group showed no such changes. The PaO 2/FiO 2 in the ARDS model group was significantly lower than that in the control group [mmHg (1 mmHg = 0.133 kPa): 294.3±5.9 vs. 459.0±4.4, P < 0.01], and the lung W/D ratio and lung injury score were significantly higher (lung W/D ratio: 8.24±0.25 vs. 4.48±0.13, lung injury score: 0.60±0.03 vs. 0.12±0.02, both P < 0.01). It indicated that ARDS model was successfully reproduced. The arterial blood gas analysis and hemodynamic parameters of the ARDS model group were significantly worse than those of the control group. After 4-hour mechanical ventilation, the blood gas parameters of the LVT group were better than those of the ARDS model group and the HVT group [pH value: 7.36±0.02 vs. 7.24±0.02, 7.13±0.01; PaO 2 (mmHg): 92.4±2.1 vs. 61.8±2.3, 76.6±2.2; PaCO 2 (mmHg): 49.6±1.7 vs. 61.8±1.8, 33.6±1.3; PaO 2/FiO 2 (mmHg): 440.0±10.2 vs. 274.3±21.4, 364.7±10.5; all P < 0.05]. HR, BP and dp/dt max in the LVT group were significantly higher than those in the ARDS model group and the HVT group [HR (bpm): 346.9±5.4 vs. 302.3±10.1, 265.5±12.2; BP (mmHg): 125.4±2.2 vs. 110.0±2.5, 89.2±2.8; dp/dt max (mmHg/s): 1 393.3±30.3 vs. 1 236.4±20.5, 896.1±19.5; all P < 0.05], and RVSP was significantly lower than that in the ARDS model group and the HVT group (mmHg: 31.3±0.4 vs. 34.0±1.0, 38.8±0.9, both P < 0.05). Conclusion:Mechanical ventilation with low VT can improve the hemodynamic parameters of the right ventricle and protect the function of the right heart in ARDS rats.

Research progress of poly (β-amino ester)s-based gene vector / 药学学报

Poly (β-amino ester)s (PβAEs) contain tertiary amine backbones and biodegradable ester bonds, making them highly biocompatible and pH-responsive. Meanwhile, originated from combinatorial libraries, PβAEs are simple to synthesize, easy to obtain raw materials and can be easily adapted to meet the different performance needs of gene carriers by adjusting the monomer type, monomer ratio and reaction time. Therefore, PβAEs are promising material for non-viral gene carriers. This paper provides a comprehensive overview of the properties and synthesis of PβAEs gene carriers and summarizes the progress of research on the gene delivery of each type of PβAEs.

Identification of factors affecting Oncomelania hupensis density in Eastern Dongting Lake regions / 中国血吸虫病防治杂志

Objective To evaluate the impact of water pollutants, water levels and meteorological factors on the Oncomelania hupensis density in Eastern Dongting Lake regions, so as to provide insights into schistosomiasis control. Methods O. hupensis snails were surveyed using a systematic sampling method in snail-infested marshlands in Eastern Dongting Lake regions from 2007 to 2014, and data pertaining to water pollutants, water levels and meteorological factors were collected. The duration of submergence and the date of the start of submergence were calculated. The snail density and its influencing factors were descriptively analyzed, and a linear mixed model was generated to examine the impacts of variables on the snail density. In addition, smooth curves were fitted to investigate the relationship between snail density and variables. Results The snail density appeared a fluctuation in Eastern Dongting Lake regions during the period from 2007 to 2014, with the highest density on October, 2010 (52.79 snails/0.1 m2) and the lowest density on January 2009 (2.15 snails/0.1 m2). Linear mixed-model analysis showed that permanganate index, total phosphorus and the date of the start of submergence affected the snail density (t = 6.386, −2.920 and −3.892, all P values < 0.01). Smooth curve analysis revealed that the associations of the snail density with the permanganate index and total phosphorus appeared an approximately quadratic curve. After the end of April, the earlier date of the start of submergence resulted in a higher snail density. Conclusion Permenganate index, total phosphorus and the date of the start of submergence affect the O. hupensis snail density in Eastern Dongting Lake regions.

Associations of Sarcopenia, Handgrip Strength and Calf Circumference with Cognitive Impairment among Chinese Older Adults / 生物医学与环境科学（英文）

Objective@#To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults.@*Methods@#Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment.@*Results@#The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( @*Conclusion@#Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.

An acute schistosomiasis case in Wuhan City imported from another province of China in 2020 / 中国血吸虫病防治杂志

An imported case of acute schistosomiasis was reported in Wuhan City in 2020. The case was infected with Schistosoma by contact with the infested water due to playing water in the Yangtze River when working out of Hubei Province. The patient visited four medical institutions and the duration from onset to definitive diagnosis was 20 days. The patient’s low awareness of schistosomiasis prevention and control knowledge and lack of diagnosis and treatment awareness for schistosomiasis among medical institutions were considered as main causes of the development of acute schistosomiasis and progression to severe case. Intensifying schistosomiasis health education among mobile populations and improving the awareness and capability of early diagnosis of schistosomiasis among clinicians are recommended.

Development of practical liberal courses for students with non-biology majors under the "Double First-class" background / 生物工程学报

Life sciences are the disciplines most closely related with human beings. As experimental disciplines, life sciences develop rapidly and highly intersect in many scientific fields. Under the "double first-class" initiative, the comprehensive development-oriented talent training system has put forward an urgent need for life sciences literacy and comprehensive ability training of college students. Taking the reform of liberal education curriculum system as an opportunity, we developed a series of eight life sciences practical liberal courses for students with non-biology majors. The courses cover all sub-disciplines or directions of life sciences, and aim to foster interdisciplinary talents with life sciences knowledge and literacy, as well as practical and innovative abilities. These courses could serve as references for experimental teaching centers in colleges and universities to set up practical liberal and experimental courses.

Analysis on acupoint selection rules for impotence treated with acupuncture and moxibustion in ancient based on data mining technology / 中国针灸

Based on the data mining technology, the rules of acupoint selection and prescription were analyzed for impotence treated with acupuncture and moxibustion in ancient recorded in

Effects of overexpression of human vascular endothelial growth factor 165 and human tissue inhibitor of metalloproteinase 1 on rats with myocardial infarction / 中华急诊医学杂志

Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGF 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism. Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGF 165 group, Ad-hTIMP-1 group and Ad-hVEGF 165+Ad-hTIMP-1 group (hVEGF 165+hTIMP-1) ( n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference t-test. Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGF 165-hTIMP-1 group were significantly increased (both P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both P<0.05). LVEF and LVFS in the hVEGF 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGF 165 group (64.65±4.00) %, (30.95±2.57) % (both P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-Track group ( P<0.01 or P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGF 165-hTIMP-1 group were increased than those in the Ad-Track group ( P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-hVEGF 165 group (both P<0.05). There was no statistically difference in the mRNA expression of Bax, Caspase-3, Bad, and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). The protein expression of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.01), and the protein expression of Bcl-2 in the hVEGF 165-hTIMP-1 group was increased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.05). There were no statistically differences in the protein expression of Bax, Caspase-3 and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). Conclusions:Ad-hVEGF 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGF 165 and hTIMP-1 may have a synergistic effect on MI.

Study on pharmacokinetic and gastrointestinal distribution study of mesalazine enteric-coated sustained-release granules in rats / 药学实践杂志

Objective To evaluate the pharmacokinetics of the new mesalazine enteric-coated sustained-release granules in SD rats and their distribution in the gastrointestinal tract, and to understand the preclinical pharmacokinetics and gastrointestinal distribution characteristics of the preparation. Methods Rats were administered orally to determine the drug concentrations in plasma samples and in the gastrointestinal tract. The commercially available mesalazine sustained-release granule was used as a reference to self-developed one to evaluate the process of absorption and elimination in vivo, relative bioavailability, and distribution in the gastrointestinal tract. Results The relative bioavailability of mesalazine enteric-coated sustained-release granule and non-enteric-coated one characterized by mesalazine was 89.62% ± 9.36%. After oral administration of mesalazine enteric-coated sustained-release granules, the drug has a high concentration distribution in the stomach within 2-8 hours, and gradually enters and remains in the jejunum, ileum and colon over time for 6-12 hours and then reaching a high concentration distribution in the colon. This help for the absorption of mesalazine, as well as the fixed-point release of the drug to produce a therapeutic effect. Conclusion The absorption and elimination process of mesalazine enteric sustained-release granule showed linear kinetic characteristics. There was no significant difference in pharmacokinetic parameters from the commercially available formulations, and it had a certain fluidity in the gastrointestinal tract. Good gastrointestinal distribution characteristics help the absorption of drugs in the body and the targeted release of the site of action

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis

@#The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

The effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA, salvianolic acid B and ginsenoside Rg / 中国天然药物

Fufang Danshen preparation (FDP) is consisted of Salviae Miltiorrhizar Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi) and Borneolum Syntheticum (borneol). FDP is usually used to treat myocardial ischemia hypoxia, cerebral ischemia and alzheimer's disease, etc. In the treatment of cerebrovascular diseases, borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs, especially to the brain. The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA (TS IIA), salvianolic acid B (SAB) and ginsenoside Rg1 in FDP. Male healthy Sprague-Dawley (SD) rats were given Danshen extracts, Sanqi extracts (Panax notoginsengsaponins) or simultaneously administered Danshenextracts, Sanqi extracts and borneol. Plasma and brain samples were collected at different points in time. The concentration of TS IIA, SAB and Rg1 was determined by UPLC-MS/MS method. The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software. In comparison with Danshen and Sanqi alone, there were significant differences in pharmacokinetic parameters of TS IIA, SAB and Rg1, and the brain distribution of SAB and TS IIA when Danshen, Sanqi and borneol were administrated together. Borneol statistically significant shortened t

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

A new non-invasive liver disease model to judge the prognosis of patients with acute upper gastrointestinal hemorrhage due to cirrhosis / 中国医师杂志

Objective@#To evaluate the accuracy of the new non-invasive liver disease model platelet-albumin-bilirubin index (PALBI) in the diagnosis of patients with acute upper gastrointestinal hemorrhage (AUGIB) due to cirrhosis.@*Methods@#277 patients with AUGIB due to cirrhosis were analyzed retrospectively. The data of platelet, total bilirubin, albumin, creatinine, international standardized ratio and etiology of cirrhosis were collected. Univariate and multivariate logistic regression analysis was used to identify independent risk factors for death in patients with cirrhosis complicated by AUGIB. Analysis of variance was used to compare the differences between the model for end-stage liver disease (MELD) and PALBI grades. Pearson correlation analysis was used to assess the association between MELD and PALBI. The operating characteristic curve (ROC) was used to compare the predictive power of both for short-term and long-term mortality in patients with cirrhosis complicated by AUGIB.@*Results@#The short-term and long-term mortality rates of patients with cirrhosis complicated by AUGIB were 13.7% and 23.5%, respectively. The average hospital stay was (9.1±3.9)days. The high MELD score and high PALBI index were confirmed as independent risk factors of death by single factor and multiple factors [odds ratio (OR)=1.17, 4.43; P<0.05]; the Pearson correlation analysis showed there was a positive correlation between MELD score and PALBI index (r=0.735, P<0.05). The PALBI score was scored in MELD-a patients, further subdivided into PALBI-1a and PALBI-1b. There were statistical difference in the 1-year mortality rate between the two groups (7.0% vs 17.8%, χ2=4.033, P<0.05). The ROC curve was used to compare the predictive power of MELD and PALBI for short-term mortality. The area under curve (AUC) of PALBI was 0.767 (95% CI: 0.712-0.815), while the AUC of the MELD score was 0.651 (95% CI: 0.591-0.707), with statistically significant difference (Z=2.328, P<0.05). The predictive power of PALBI and MELD for long-term mortality were 0.731(95% CI: 0.674-0.782), 0.754 (95% CI: 0.699-0.804), but the difference was not statistically significant (Z=0.828, P>0.05).@*Conclusions@#PALBI has a better predictive effect on patients with cirrhosis complicated by AUGIB than MELD scores. PALBI can achieve a more precise prognosis classification for patients with MELD-a, and maintain a good prediction ability on the short-term (within 30 days of hospitalization and discharge) and long-term (within 1 year after discharge) mortality of patients. As a new liver disease model, PALBI can be used as an effective non-invasive means to judge the prognosis of patients with liver cirrhosis complicated by AUGIB .

Two cases of familial benign pemphigus treated with botulinum toxin type A / 中华皮肤科杂志

Botulinum toxin type A was firstly used to treat two patients with familial benign pemphigus, who showed poor response to conventional therapies. Case 1, a 64-year-old male patient, presented with erythema and erosions on bilateral axillary and inguinal regions for 2 years, and was injected with botulinum toxin type A at a dose of 50 U in the right axillary fossa and right groin separately. Case 2, a 33-year-old female patient, presented with erythema and blisters on bilateral axillary and inguinal regions and the right waist for 9 years, and was injected with botulinum toxin type A at a dose of 25 U in the left axillary fossa, right waist and bilateral groins separately. After the injection of botulinum toxin type A, sweating was inhibited in the 2 patients within 1 week, and skin lesions were gradually attenuated within 2 weeks. One month after the injection, erythema and erosions on bilateral axillary and inguinal regions mostly regressed in the case 1, and no recurrence was observed during 18-month follow-up. Six weeks after the injection, most of the skin lesions regressed in the case 2, only patchy hyperpigmentation was observed, and no obvious new lesions occurred. A few lesions recurred in the case 2 during 10-month follow-up, but were attenuated after the treatment with topical glucocorticoids.