Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

Banxia Xiexintang and Its Disassembled Prescriptions Regulate Colonic Mucosal Immunity in Young Rats with Flora Disorder / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and possible mechanism of Banxia Xiexintang and its disassembled prescriptions in regulating the flora disorder induced by mixed antibiotics in young rats. MethodSeventy male BALB/C young rats were randomly assigned into 7 groups： blank group， model group， Bifidobacterium tetralogy viable tablets （0.68 g·kg-1） group， Banxia Xiexintang （9.1 g·kg-1） group， Xinkai （3.19 g·kg-1） group， Kujiang （1.82 g·kg-1） group， and Ganbu （4.1 g·kg-1） group， with 10 rats in each group. Except the blank group， the other groups were given mixed antibiotics by gavage to induce intestinal flora disorder. After 14 days， the rats in different drug groups were administrated with corresponding drugs by gavage， and those in the blank group and model group with the same amount of normal saline once a day for 14 days. After that， fecal samples were collected aseptically for 16S rDNA sequencing of intestinal flora， and lipopolysaccharide （LPS， 10 mg·kg-1） was injected intraperitoneally to induce inflammatory reaction. The tissue morphology of colonic mucosa was observed via hematoxylin-eosin （HE） staining， and the macrophage infiltration of colonic mucosa was observed via toluidine blue staining and immunohistochemistry. The expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） mRNA were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the modeling changed the intestinal flora structure of the young rats （P<0.01）， damaged the colonic mucosa， reduced the macrophage infiltration， and down-regulated the mRNA levels of IL-1β， IL-6， IL-8， TNF-α， and IL-10 （P<0.01）. Compared with the model group， bifidobacterium quadruple viable tablets， Banxia Xiexintang and its disassembled prescriptions increased the diversity of intestinal flora and the relative abundance of beneficial bacteria such as Bacteroidetes and Firmicutes （P<0.01）. At the same time， they ameliorated colonic mucosal injury （P<0.05， P<0.01）， increased macrophage infiltration （P<0.05， P<0.01）， and up-regulated the mRNA levels of IL-6， IL-8， and TNF-α （P<0.01）. The mRNA level of IL-1β was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Kujiang， and Ganbu groups （P<0.01）， and that of IL-10 was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Xinkai， and Ganbu groups （P<0.01）. ConclusionBanxia Xiexintang and the disassembled prescriptions can adjust the intestinal flora of young rats exposed to antibiotics and protect the immune barrier of colonic mucosa after intestinal flora disorder. In particularly， the whole prescription of Banxia Xiexintang demonstrates the best performance.

Comparative analysis of pathological structure between acute closed and open Achilles tendon rupture / 中国骨伤

OBJECTIVE@#To investigate the morphological, histological and ultrastructural changes of acute closed rupture of Achilles tendon, in order to clarify the pathological basis of the injury and to explore the significance.@*METHODS@#From January 2015 to January 2019, 35 patients with acute Achilles tendon rupture who underwent the minimally invasive Achilles tendon suture technique were retrospectively analyzed. Among these patients, 12 cases in acute open Achilles tendon rupture group included 10 males and 2 females, with an average age of (35.1±9.7) years old ranging from 19 to 50, and the time from injury to operation was 2 to 8 hours with an average of(5.6±1.8);23 cases in acute closed Achilles tendon rupture group included 21 males and 2 females, with an average age of (35.5±6.6) years old ranging from 18 to 50, and the time from injury to operation was 3 to 15 hours with an average of (7.5±3.1). The gross appearance and imaging findings of the broken end of Achilles tendon tissue in the two groups were compared by naked eye observation and foot and ankle MRI at 4 to 6 hours before operation. HE staining, scanning and fluoroscopic electron microscopy, immunohistochemistry(Sirius red staining) were performed on the intraoperative Achilles tendon tissue specimens at 1 to 2 days after operation, the collagen fiber degeneration and local fat infiltration, collagen fiber shape, cell morphology and function, and the distribution of typeⅠand type Ⅲ collagen fibers in Achilles tendon were compared between the two groups.@*RESULTS@#Compared with the acute open Achilles tendon rupture group, the acute closed Achilles tendon rupture group had poor elasticity, hard texture, moderate edema, irregular shape of Achilles tendon broken end, horsetail shape, and more calcification around the broken end. HE staining results:the collagen fibers in the Achilles tendon of the acute open Achilles tendon rupture group were arranged irregularly, with hyaline degeneration and fat infiltration;The results of electron microscopy showed that collagen arranged disorderly and fibroblasts atrophied in the acute closed Achilles tendon rupture group. Immunohistochemical(Sirius staining) results:the proportion of collagenⅠin the acute open Achilles tendon rupture group and the acute closed Achilles tendon rupture group was(91.12±4.34)% and(54.71±17.78)% respectively, and the proportion of collagen Ⅲ was (8.88±4.34)% and (45.29±17.78)% respectively. The content of collagenⅠin the acute closed Achilles tendon rupture group was lower than that in the acute open Achilles tendon rupture group, and the content of collagen Ⅲ in the acute closed Achilles tendon rupture group was higher than that in the acute open Achilles tendon rupture group(P<0.05).@*CONCLUSION@#The morphology, histology and ultrastructure of the acute closed ruptured Achilles tendon are significantly altered compared with the normal Achilles tendon. The original fine and orderly spatial structure cannot be maintained, part of collagen Ⅰ is replaced by collagen Ⅲ, and the toughness and strength of the tendon tissue decreased, which may be the feature of degeneration of the Achilles tendon and an important pathological basis for closed Achilles tendon rupture.

Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patient's Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial / 中国医学科学杂志(英文版)

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Convolutional neural network based on temporal-spatial feature learning for motor imagery electroencephalogram signal decoding / 生物医学工程学杂志

With the advantage of providing more natural and flexible control manner, brain-computer interface systems based on motor imagery electroencephalogram (EEG) have been widely used in the field of human-machine interaction. However, due to the lower signal-noise ratio and poor spatial resolution of EEG signals, the decoding accuracy is relative low. To solve this problem, a novel convolutional neural network based on temporal-spatial feature learning (TSCNN) was proposed for motor imagery EEG decoding. Firstly, for the EEG signals preprocessed by band-pass filtering, a temporal-wise convolution layer and a spatial-wise convolution layer were respectively designed, and temporal-spatial features of motor imagery EEG were constructed. Then, 2-layer two-dimensional convolutional structures were adopted to learn abstract features from the raw temporal-spatial features. Finally, the softmax layer combined with the fully connected layer were used to perform decoding task from the extracted abstract features. The experimental results of the proposed method on the open dataset showed that the average decoding accuracy was 80.09%, which is approximately 13.75% and 10.99% higher than that of the state-of-the-art common spatial pattern (CSP) + support vector machine (SVM) and filter bank CSP (FBCSP) + SVM recognition methods, respectively. This demonstrates that the proposed method can significantly improve the reliability of motor imagery EEG decoding.

Analysis on Contents of Main Constituents in Prepared Morindae Officinalis Radix，Morindae Officinalis Radix Processed with Steaming and Salt / 中国实验方剂学杂志

Objective:To investigate the differences of main components of prepared Morindae Officinalis Radix，Morindae Officinalis Radix processed with steaming and salt. Method:A total of 83 batches samples were collected in the market， including 41 batches of prepared Morindae Officinalis Radix，32 batches of Morindae Officinalis Radix processed with steaming and 10 batches of Morindae Officinalis Radix processed with salt. The contents of main components were determined with high performance liquid chromatography coupled with four-pole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS），and the differences were analyzed. Result:The main components of prepared Morindae Officinalis Radix and Morindae Officinalis Radix processed with salt were fructo-oligosaccharides （GF<italic>n</italic>），monotropein. The main components of Morindae Officinalis Radix processed with steaming were fructose，glucose，sucrose，and monotropein. The main differences of prepared Morindae Officinalis Radix and<italic> </italic>Morindae Officinalis Radix processed with steaming and salt were the contents of fructose，glucose，sucrose and GF2-GF11. The contents of GF2-GF11 in Morindae Officinalis Radix processed with steaming and salt were all lower than those in prepared Morindae Officinalis Radix，with extremely significant differences（<italic>P</italic><0.01）. The contents of fructose，glucose and sucrose in<italic> </italic>Morindae Officinalis Radix processed with steaming were significantly higher than those in prepared Morindae Officinalis Radix. The content of GF3 in each batch was higher than 40.0 mg·g^-1 in prepared Morindae Officinalis Radix and Morindae Officinalis Radix processed with salt，and significantly higher than the limit in<italic> Chinese Pharmacopoeia</italic>. However，there were only a few batches of Morindae Officinalis Radix processed with steaming in line with the requirements of <italic>Chinese Pharmacopoeia</italic>. The contents of monotropein in processing Morindae Officinalis Radix and Morindae Officinalis Radix processed with steaming and salt were 42.6，39.8，32.3 mg·g^-1，respectively. The content of monotropein in prepared Morindae Officinalis Radix was higher than that in Morindae Officinalis Radix processed with steaming. The content of monotropein in Morindae Officinalis Radix processed with steaming was higher than that in Morindae Officinalis Radix<italic> </italic>processed with salt. Compared with the components of GF2-GF11，the effect of processing with steaming process and/or salt on monotropein content was relatively less. Conclusion:The contents of GF2-GF11 components in prepared Morindae Officinalis Radix were converted into fructose，glucose and sucrose after processing with steaming and/or salt. The results showed that the content limit of Morindae Officinalis Radix processed with steaming needs to be revised in line with the requirements of <italic>Chinese Pharmacopoeia </italic>for the quality control of Morindae Officinalis Radix. The results provide a reference basis for revising the quality standards and studying the pharmacodynamic material basis of prepared Morindae Officinalis Radix，Morindae Officinalis Radix processed with steaming and salt.

Effect of Banxia Xiexintang-containing Serum on Epithelial-mesenchymal Transition of Peritoneal Mesothelial Cells Induced by Gastric Cancer-derived Exosomes / 中国实验方剂学杂志

Objective:To investigate the effect of Banxia Xiexintang on the epithelial-mesenchymal transition （EMT） of human peritoneal mesothelial cell line （HMrSV5） induced by gastric cancer-derived exosomes （Exo）. Method:Banxia Xiexintang-containing serum was prepared and the human gastric cancer NCI-N87-derived exosomes （NCI-N87-Exo） were extracted， followed by their identification by transmission electron microscopy and Western blotting and labeling with 1，1-dioctadecyl-3，3，3，3- tetramethylindocarbocyanine perchlorate （Dil）. The cells were divided into the blank group， model group， and low-， medium-， and high-dose （13.5，27，54 g·kg^-1） Banxia Xiexintang groups. HMrSV5 cells in the blank group were cultured alone， the ones in the model group with 100 mg·L^-1 NCI-N87-Exo， and those in the low-， medium-， and high-dose Banxia Xiexintang groups with 100 mg·L^-1 NCI-N87-Exo plus low-， medium-， and high-dose 10% Banxia Xiexintang-containing serum， respectively. Confocal laser microscope was used to observe the uptake of NCI-N87-Exo by HMrSV5 cells at 24 h， 48 h and 72 h. Seventy-two hours later， the morphological changes in HMrSV5 cells were observed. The protein expression levels of E-cadherin， cytokeratin 19 （CK19）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， elastin， and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， Smad2/3， and p-Smad2/3 were assayed by Western blot. Result:It was observed under the transmission electron microscope that NCI-N87-Exo showed an oval or dish-shaped vesicle structure with a particle size ranging from 40 to 80 nm. Exo marker proteins CD9 and CD63 were highly expressed while calreticulin was not expressed， implying that the NCI-N87-Exo was confirmed. After 24 h， 48 h， 72 h of co-culture， it was observed under the fluorescence microscope that NCI-N87-Exo were taken up by HMrSV5 cells， which was positively correlated with time. Compared with the blank group， Banxia Xiexintang significantly inhibited the uptake of NCI-N87-Exo by HMrSV5 cells， with better effect noticed in the middle- and high-dose Banxia Xiexintang groups（<italic>P</italic><0.05，<italic>P</italic><0.01）. After intervention with Banxia Xiexintang-containing serum， the HMrSV5 cells were arranged densely， and the intercellular space was significantly reduced， with the most obvious changes present in the high-dose Banxia Xiexintang group. Western blot revealed that the protein expression levels of E-cadherin and CK19 in HMrSV5 cells after being intervened with the medium- and high-dose Banxia Xiexintang-containing serum were increased significantly as compared with those in the blank group， whereas the levels of <italic>α</italic>-SMA and Elastin were decreased significantly （<italic>P</italic><0.01）. Banxia Xiexintang-containing serum at the low， medium， and high doses remarkably down-regulated TGF-<italic>β</italic>₁ and p-Smad2/3 protein expression（<italic>P</italic><0.05，<italic>P</italic><0.01）. However， there was no significant change in Smad2/3. Conclusion:NCI-N87-Exo can be taken up by HMrSV5 cells to induce EMT. Banxia Xiexintang can inhibit the uptake of NCI-N87-Exo by HMrSV5 cells and the resulting EMT induced by NCI-N87-Exo， which is related to the regulation of TGF-<italic>β</italic>₁/Smads signaling pathway.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Effect of hypoxia on drug metabolizing enzymes and transporters and the role of microRNA / 药学学报

The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA (miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.

A preliminary study on the surgical timing of spinal tuberculosis / 中国骨伤

OBJECTIVE@#To observe the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and nerve function in patients with spinal tuberculosis before and after surgery, explore the timing of surgical intervention, and evaluate its influence on surgical safety.@*METHODS@#A retrospective analysis was conducted on 387 patients with spinal tuberculosis who received surgical treatment from March 2012 to March 2017, including 278 males and 109 females, aged 12 to 86 years old with an average of (49.9±19.1) years. There were 64 cases of cervical tuberculosis, 86 cases of thoracic tuberculosis, 76 cases of thoracolumbar tuberculosis and 161 cases of lumbar tuberculosis. There were 297 patients with single segmental involvementand 90 patients with multiple segmental involvement. Among them, 62 cases presented neurological damage, and preoperative spinal cord neurological function depended on ASIA grade, 5 cases of grade A, 8 cases of grade B, 39 cases of grade C, and 10 cases of grade D. According to the duration of preoperative antituberculosis treatment, the patients were divided into group A (256 cases, receiving conventional quadruple antituberculosis treatment for 2-4 weeks before surgery) and group B (131 cases, receiving conventional quadruple antituberculosis treatment for more than 4 weeks before surgery). The two groups were compared in terms of gender, age, preoperative complicated pulmonary tuberculosis, lesion site, lesion scope, surgical approach, drug resistance and other general clinical characteristics. ESR, CRP, visual analogue scale(VAS), Oswestry Disability Index (ODI), Frankel grade and postoperative complications were observed.@*RESULTS@#All 387 patients were followed up for 12 to 36 (18.3±4.5) months. There were no significant differences in gender, age, preoperative pulmonary tuberculosis, lesion site, lesion range, surgical approach, preoperative drug resistance and other characteristics between two groups. A total of 32 patients in two groups did not heal after surgery, with an incidence rate of 8.27%. The VAS and spinal cord dysfunction index of the two groups were significantly improved after surgery (@*CONCLUSION@#After 2-4 weeks of anti tuberculosis treatment before operation, patients with spinal tuberculosis could be operated upon with ESR and CRP in a descending or stable period. In principle, patients with spinal tuberculosis and paraplegia should be treated as soon as possible after active preoperative management of the complication without emergency surgery.

Genetic diversity and genetic structures of original plants of Viticis Fructus:an SSR markers-based analysis / 中国中药杂志

The present study aimed to provide the protection strategies for wild germplasm resources of original plants of Viticis Fructus and a theoretical basis for the sustainable use of Viticis Fructus. The genetic diversity and genetic structures of the 232 indivi-duals in 19 populations of Vitex rotundifolia and V. trifolia were analyzed by eight SSR markers with tools such as Popgene32, GenAlex 6.502, and STRUCTURE. Bottleneck effect was detected for the population with more than 10 individuals. The results indicated that 42 and 26 alleles were detected from the populations of V. rotundifolia and V. trifolia, respectively, with average expected heterozygo-sities of 0.448 6 and 0.583 9, which are indicative of low genetic diversity. AMOVA revealed the obvious genetic variation of V. rotundifolia and V. trifolia within population(84.43%, P<0.01; 60.37%, P<0.01). Furthermore, in eight SSR loci, six from V. rotundifolia populations and two from V. trifolia populations failed to meet Hardy-Weinberg equilibrium expectations(P<0.05), which confirmed that the populations experienced bottleneck effect. As assessed by Mantel test, geographical distance posed slight impacts on the genetic variation between the populations of V. rotundifolia and V. trifolia. Principal component analysis(PCA) and STRUCTURE analysis demonstrated evident introgression of genes among various populations. The original plants of Viticis Fructus were confirmed low in genetic diversity and genetic differentiation level. Therefore, the protection of wild resources of original plants of Viticis Fructus should be strengthened to ensure its sustainable use.

Changes in the intestinal flora of rats under high altitude hypoxia / 药学学报

The structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia was investigated. Animal experiments strictly follow the regulations of Medical Laboratory Animal Ethics Committee of Qinghai University, School of Medicine. SD rats were randomly divided into a control group, a moderate altitude hypoxia group, and a high altitude hypoxia group. The pH value of the feces was measured and histopathological changes in the small intestine were determined by HE staining, and the intestinal flora were characterized by 16S rDNA high throughput sequencing technology on the 3rd, 7th, 15th, and 30th day of hypoxia exposure. Compared with the control group, the fecal pH value of rats in the moderate altitude hypoxia group and the high altitude hypoxia group was decreased significantly. The lamina propria and submucosa capillaries were slightly dilated and congested on the 3rd day in the moderate altitude hypoxia group. In the high altitude hypoxia group the submembrane capillaries were dilated and congested, the lamina propria of the mucosa showed mild edema, and the lymphatic vessels were dilated on the 7th day. The composition and diversity of intestinal flora in these rats changed significantly with prolonged exposure to the high altitude hypoxic environment. A total of 35 phyla, 87 classes, 205 orders, 337 families, 638 genera, and 256 species were annotated in the three groups of rats, including Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Akkermansia, and Lactobacillus_murinus. Compared with the control group, the intestinal flora of the hypoxic groups showed the most significant changes by the 15th day. There were 9 microbiota of gut microorganisms with relative abundance in the moderate altitude hypoxia group, of which Rikenellaceae_RC9_gut_group bacteria was the most common, there were 19 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group, of which Ruminococcaceae bacteria was the most common. The results of this study indicate significant changes in the intestinal flora with high altitude hypoxia, and establish a foundation for further research on the initiation and development of diseases and drug metabolism in high altitude hypoxia.

Determination of harpagide and harpagoside contents in Scrophularia ningpoensis from 15 origins / 药学实践杂志

Objective To establish an HPLC method for the simultaneous determination of harpagide and harpagoside content in Scrophularia ningpoensis (SN). Methods An Eclipse C18 column was used for determination of methanol extract of S. ningpoensis with a HPLC-PDA method and mobile phase of acetonitrile-0.03% phosphate solution in a gradient elution manner. The flow rate of mobile phase was 1.0 ml/min, and the detection wavelengths were 210 nm and 280 nm. Results Harpagide and harpagoside contents in SN showed good linear relationships within 0.1020-0.5100 mg/ml (r=0.9999) and 0.0340-0.1700 mg/ml (r=0.9999). Their average recovery rates were 97.44% and 97.08%.The RSDs were 0.93% and 1.24%.. There were significant differences in the contents of harpagide and harpagoside in SN from 15 origins (P<0.01). The content of harpagoside in Sichuan Long-dong, Zhejiang Lin-an, Zhejiang Pan-an and Henan Nan-feng is higher. Conclusion This method is stable, accurate and reproducible and can be used for the quality control of SN.

Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. Bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased β-cell compensation (i.e., oral disposition index (DI

Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Observational study of the implementation of medical emergency team in hospital / 中华危重病急救医学

Objective:To analyze the implementation of medical emergency team (MET) in Fuxing Hospital of Capital Medical University, and to investigate the characteristics such as the time, department, disease, cause of the MET calls, in order to provide a basis for the improvement of MET's implementation.Methods:A retrospective study was conducted. MET calls that received between January 1st, 2015 and December 31st, 2018 at Fuxing Hospital were collected. The calls' information included the quarter, time, and the patients' gender, age, admission time, department, admission diagnosis, the reason for the calls, the operation and outcome of the MET upon arrival.Results:A total of 846 MET calls were occurred during 4 years from 2015 to 2018. The frequencies of the first and third quarter were relatively high with 28.0% (237/846) and 26.5% (224/846), respectively. The events mainly occurred during the day (08:00-19:59) with 611 calls (72.2%). There were more men [64.3% (544/846)] than women [35.7% (302/846)]. The calls were mainly from the elderly over 60 years old, and gradually increased with age, which distributed the most in patients aging 80-89 years old, accounting for 51.5% of all calls (436/846). Among all the MET events, 80.5% (681/846) were from department of internal medicine, 18.8% (159/846) were from department of surgery, and 0.7% (6/846) were from department of gynecology and obstetrics. The top 3 diseases reported in the calls were respiratory diseases [31.6% (267/846)], nervous system diseases [20.8% (176/846)] and circulatory diseases [9.9% (84/846)]. The reason of MET calls showed that abnormal pulse oxygen saturation [SpO 2, 27.8% (235/846)] were the most among 4 vital signs. After MET rescue, 7.3% (62/846) of the patients died, 48.7% (412/846) were transferred to intensive care unit (ICU) for further treatment, and 41.9% (354/846) remained under observation. Conclusions:The frequency of MET calls in Fuxing Hospital of Capital Medical University was relatively stable over the years, mostly received in the daytime (08:00-19:59) of the first and third quarter. Most of the patients were male aged 80-89 years old. The most MET calls were from department of internal medicine and due to respiratory disease. SpO 2 was the most common abnormal indicator. According to the above characteristics, MET can focus on them in the future.

A randomized controlled study of roxatidine in the prevention of stress related mucosal disease / 中华急诊医学杂志

Objective:To evaluate the efficacy of roxatidine and omeprazolein on preventing gastrointestinal bleeding in critically ill patients.Methods:A prospective cohort study was conducted in adult patients admitted to an intensive care unit (ICU), who had risk factors for stress related mucosal disease (SRMD), and had an estimated stay of no less than 5 days and mechanical ventilation for more than 48 h. Patients were randomized into the experiment group (Roxatidine 75 mg IV Q12 h) and control group (Omeprazole 40 mg IV Q12 h). Demographic data, acute physiology and chronic health score (APACHEⅡ) and SOFA score on day 1 were collected, intragastric pH values were tested every 2 hours for the first 5 days, the daily average of pH and proportion of patients with average pH≥4 were calculated. Stool occult blood were detected at day 1 and bacterial culture of gastric juice were performed before medication administration and on day 5 after medication administration. The implementation of enteral nutrition support, situation of gastrointestinal hemorrhage and adverse effects were analyzed. Furthermore, length of hospital stay and mortality in ICU and on the 28th day were acquired. SPSS 22.0 software was used for data analysis. Consecutive data were expressed as mean and standard deviation, categorical data were expressed as frequencies (percentage). Comparison of measurement data between groups was performed by analysis of variance or rank sum test. Comparison of count data between groups was performed by the Chi-square test. P<0.05 was regarded as statistically significant. Results:A total of 91 patients were recruited and randomly separated into experimental group ( n=46) and control group ( n=45) from October 2017 to March 2018. There were no statistical differences in gender, age, body mass index (BMI), enteral nutrition status, APACHEⅡ and SOFA score on day 1 between the two groups (all P>0.05). Roxatidine in the experiment group rapidly increased the intragastric pH to ≥4.0 and continued to stabilize at pH ≥4.0 during the monitoring period. Omeprazole increased and maintained intragastric pH≥5.0. The proportion of patients with average pH≥4.0 was 82.5% in the second 24 hours in the experiment group, and stably increased to 90% on day 5. There were no significant differences between groups in gastrointestinal bleeding, length of hospital stay, and mortality in ICU and on 28th day(all P> 0.05). No drug related adverse effects occurred during the study period. Logistic-regression analysis did not screen for risk factors of SRMD. Conclusions:Roxatidine acetate hydrochloride can rapidly elevate and maintain the gastric pH above 4.0, and has similar efficacy and safety as omeprazole in inhibiting gastric acid secretion and preventing SRMD with gastrointestinal bleeding.

Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2019 version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Rubus chingii Hu: an overview of botany, traditional uses, phytochemistry, and pharmacology / 中国天然药物

Rubus chingii Hu, a member of the rosaceae family, is extensively distributed in China and Japan. Its unripe fruits (Fupenzi in Chinese) have a long history of use as an herbal tonic in traditional Chinese medicine for treating various diseases commonly associated with kidney deficiency, and they are still in use today. Phytochemical investigations on the fruits and leaves of R. chingii indicate the presence of terpenoids, flavonoids, steroids, alkaloids, phenylpropanoids, phenolics, and organic acids. Extracts or active substances from this plant are reported to have various pharmacological properties, including antioxidant, anti-inflammatory, antitumor, antifungal, antithrombotic, antiosteoporotic, hypoglycemic, and central nervous system-regulating effects. This review provides up-to-date information on the botanical characterizations, traditional usages, chemical constituents, pharmacological activities, toxicity, and quality control of R. chingii. Possible directions for future research are also briefly proposed. This review aims to supply fundamental data for the further study of R. chingii and contribute to the development of its clinical use.

Effect of Yanghetang on Apoptosis of Triple Negative Breast Cancer Cell Line MDA-MB-231 Based on Egr1/p21 Signaling Pathway / 中国实验方剂学杂志

Objective::To investigate the effect of ancient recipe Yanghetang and its drug-contained serum on apoptosis of triple negative breast cancer cell line MDA-MB-231 based on the signal pathway of early growth response gene 1 (Egr1)/cyclin dependent inhibitor (p21). Method::The drug-containing serum of Yanghetang was prepared from rats, and MDA-MB-231 cells were cultured in vitro. The blank control group was set, and MDA-MB-231 cells in Yanghetang high, middle, and low dose groups (23.4, 11.7, 5.85 g·kg-1) were intervened for 24, 48, 72 h, respectively. After that, the cell counting kit-8(CCK-8) method was used to detect the cell proliferation of each group. The blank control group was set, while MDA-MB-231 cells in Yanghetang high, middle, and low dose groups (23.4, 11.7, 5.85 g·kg-1) were treated for 48 h, and then flow cytometry was used to detect the apoptosis of each group and the distribution of cell cycle. The expression of Egr1 and p21 mRNA in each group was detected by quantificational Real-time polymerase chain reaction (Real-time PCR), while the expression of Egr1 and p21 protein in each group was detected by Western blot. Result::After MDA-MB-231 cells were intervened by Yanghetang for 24, 48, 72 h, MDA-MB-231 cell proliferation was significantly inhibited in Yanghetang high and middle dose groups as compared with the blank control group (P<0.01). After MDA-MB-231 cells were intervened by Yanghetang for 48 h, the apoptosis was significantly increased in Yanghetang high and middle dose groups as compared with the blank control group (P<0.05, P<0.01). In the Yanghetang high, middle dose groups, the proportion of cell cycle G0/G1 phase decreased, and the proportion of G2/M phase increased (P<0.05, P<0.01). The mRNA and protein expressions of Egr1, p21 were increased in Yanghetang high and middle groups (P<0.05, P<0.01). Conclusion::Yanghetang can activate Egr1/p21 signaling pathway in MDA-MB-231 cells, increase the expression of Egr1 and p21, and cause G2/M cell cycle arrest, thereby inducing apoptosis of MDA-MB-231 cells.