Yangyin Huayu Jiedu Preseription Regulates Autophagy and Apoptosis of Colon Cancer Cells in Hypoxic Environment Through PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of different oxygen concentration on the proliferation and autophagy of colon cancer cells and to explore the effect of Yangyin Huayu Jiedu Preseription （YHJP） on autophagy and apoptosis of colon cancer cells under hypoxia based on phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodHCT-116 cells were divided into normoxia group， 1% O2 group， and 5% O2 group. Cell viability was detected by cell proliferation assay （MTS）， and autophagy was observed based on monodansylcadaverine （MDC） staining. HCT-116 cells were treated with YHJP in 5% O2 microenvironment. The cells were divided into normal group， blank serum group， and low-， medium-， high-dose YHJP groups （5%， 15%， 25% serum containing YHJP）. Cell inhibition rate in each group was calculated by MTS， and changes in the rate of autophagy were detected based on MDC staining. Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide （PI） was employed to detect the apoptosis rate of each group. Western blotting was applied to measure the expression of autophagy proteins microtubule-associated protein 1 light chain 3 （LC3Ⅱ/Ⅰ）， yeast Atg6 homolog （Beclin-1）， ubiquitin-binding scaffold protein p62 （p62）， apoptosis-related proteins B-cell lymphoma-2 （Bcl-2）， Bcl-2/adenovirus E1B interacting protein 3 （BNIP-3）， and Bcl-2 associated X protein （Bax）， cleaved cysteine-aspartic acid protease-3 （Caspase-3）， hypoxia-inducible factor-1α （HIF-1α） and pathway proteins PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. ResultCell survival rates of the 1% O2 and 5% O2 groups were increased compared with that in the normoxia group， particularly the 5% O2 group （P<0.01）. The fluorescence intensity for autophagy in 1% O2 and 5% O2 groups was significantly increased compared with that in the normoxia group， especially the 5% O2 group. In the presence of 5% O2， compared with the blank serum group， medium-dose and high-dose YHJP groups showed high cell inhibition rate， low autophagy rate， high apoptosis rate （P<0.01）， and low expression of Beclin-1 protein （P<0.05）. Compared with low-dose YHJP group， high-dose YHJP group demonstrated low expression of Beclin-1 protein （P<0.05）. Compared with the blank serum group， the three YHJP groups had low expression of LC3Ⅱ/Ⅰ protein （P<0.05， P<0.01）. Compared with the blank serum group， medium-dose and high-dose YHJP groups showed high expression of p62 protein （P<0.01）. Compared with low-dose YHJP group， high-dose YHJP group showed high expression of p62 protein （P<0.05）. Compared with the blank serum group， high-dose YHJP increased the expression of BNIP-3 and Bax and decreased the expression of Bcl-2 （P<0.01）. The expression of Bax protein in the high-dose YHJP group was increased compared with that in the low-dose YHJP group （P<0.05）. The expression of HIF-1α in the medium-dose and high-dose YHJP groups was decreased （P<0.01） and the expression of p-PI3K/PI3K and p-Akt/Akt in the high-dose YHJP group was increased （P<0.05， P<0.01） compared with that in the blank serum group. The expression of p-Akt/Akt was higher in the high-dose YHJP group than in the medium-dose YHJP （P<0.05）. ConclusionHypoxic microenvironment can significantly promote autophagy and proliferation of colon cancer cells. YHJP can significantly inhibit autophagy and proliferation and promote apoptosis of colon cancer cells in 5% O2 environment by up-regulating the PI3K/Akt signaling pathway.

Mechanism of Yanghe Decoction against subcutaneous tumor in pulmonary metastasis from breast cancer through HIF-1α signaling pathway regulating glycolysis:based on network pharmacology and animal experiment / 中国中药杂志

This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis / 南方医科大学学报

OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

Relationships between lead-induced learning and memory impairments and gut microbiota disturbance in mice / 中华劳动卫生职业病杂志

Objective: To explore the effect of lead exposure on the neurobehavior and gut microbiota community structure in mice. Methods: In August 2019, 64 C57BL/6 mice were randomly divided into 4 groups: control group (0 ppm) , low lead exposure group (20 mg/l) , medium lead exposure group (100 mg/l) and high lead exposure group (500 mg/l) . During the experiment, they were free to eat and drink. The drinking water of the lead exposure group was mixed with lead acetate, and sodium acetate was added in the control group. After 10 weeks of exposure, the Morris water maze was used to test the learning and memory ability of each group of mice, and then they were sacrificed for sampling. ICP-MS was used to detect lead content in whole blood and brain tissue. ELISA was used to determine the level of IL-1β in mouse serum. 16S rRNA sequencing was used to detect the structural diversity of the intestinal flora in feces, and then the correlation between the flora and behavior indicators was analyzed. Results: In the Morris water maze experiment, compared with the control group, there was no significant difference in the body weight and swimming speed of the mice in the lead exposure groups. The escape latency of the mice in the 100 mg/l and 500 mg/l dose groups was prolonged, and the number of platform crossings decreased (P<0.05) ; meanwhile, the staying time of the mice in the 500 mg/l Pb-treated group in the target quadrant was lower than that of the control group, and the difference was statistically significant (P<0.05) . Compared with the control group, the blood lead content of the mice in each lead exposure group was significantly increased, and the brain lead content of mice in the 500 mg/l dose group was significantly elevated (P<0.05) . The serum IL-1β levels of mice in each lead exposure group were higher than those of the control group (P<0.05) . At the phylum level, the relative abundance of the Proteobacteria phylum in all of Pb-treated groups was significantly increased (P<0.05) ; at the genus level, Allobaculum, Desulfovibrio, Lachnospiraceae_NK4A136_group, Turicibacter and Ureaplasma were significantly increased (P<0.05) . Among them. The relative abundance of Desuffaoibrio, Turici bacter, and Ureaplasma was negatively correlated with the residence time of mice in the quadrant of the platform (r=-0.32, -0.29, -0.44, P<0.05) . Conclusion: Lead exposure induced learning and memory impairments in mice, which may be related to the disturbance of the gut microbiota.

Shanghai expert consensus on clinical protocol for traditional Chinese medicine treatment of COVID-19 among the elderly population (second edition) / 中西医结合学报

This document is the revised edition of the previously issued Shanghai Expert Consensus on Clinical Protocol for Traditional Chinese Medicine Treatment of COVID-19 among the Elderly Population. Based on the clinical experience and the Protocol for Diagnosis and Treatment of COVID-19 (Trial 9th Edition), this revised edition provides treatment approaches and recommendations to proactively cope with Omicron variant and increase the therapeutic efficacy for coronavirus disease 2019 among the elderly population in Shanghai, China.

Factors associated with failure of trial of labor in primiparae with preeclampsia and establishment of risk prediction model / 中华围产医学杂志

Objective:To investigate the risk factors associated with failure of trial of labor in primiparous women with preeclampsia (PE) and to establish a risk prediction model.Methods:Primiparae with PE who underwent trial of labor in the Department of Obstetrics of Suzhou Ninth People's Hospital from February 2018 to July 2020 were retrospectively selected as the modeling set, and divided into two groups: the success group and the failure group. Various parameters were compared between the two groups and those data with statistically significant difference were analyzed with multivariate logistic regression analysis. Those factors related to vaginal delivery failure in primiparous women with PE were identified. Based on the results, a risk prediction model was established using R language. Its performance was assessed with receiver operating characteristic (ROC) curve and goodness-of-fit test. This study also retrospectively enrolled primiparae with PE who underwent trial of labor in the same hospital from August 2020 to December 2021 as the validation set. Bootstrap method was used for verification and a calibration chart was created.Results:A total of 312 PE patients were selected as the modeling set with 89 in the failure group and 223 in the success group. Another 146 primiparae with PE were selected as the validation set. Logistic regression analysis showed that older age ( OR=1.609, 95% CI: 1.251-2.483), higher body fat rate in early pregnancy ( OR=1.456, 95% CI: 1.209-2.159) and higher ratio of umbilical artery systolic to diastolic flow velocity within a week before delivery ( OR=1.799, 95% CI: 1.372-2.794) were risk factors for vaginal delivery failure in primiparae with PE, while more maternal education during pregnancy ( OR=0.233, 95% CI: 0.054-0.672) and higher Bishop score ( OR=0.395, 95% CI: 0.258-0.756) were protective factors. A nomogram model to predict the risks of vaginal delivery failure was constructed based on the above five factors. The area under the ROC curve (AUC) of the modeling set was 0.921 (95% CI: 0.847-0.963) with the cut-off value of 0.213, and the corresponding sensitivity and specificity were 0.871 and 0.852, respectively;goodness-of-fit test showed that the observed values matched with those expected ( χ2=7.69, P=0.464); and the calibration curve indicated that the consistency of the prediction model was good. The AUC of the validation set was 0.903 (95% CI: 0.835-0.942) with the sensitivity and specificity of 0.892 and 0.796, respectively; the discrepancy between the observed values and those expected was not significant as indicated by goodness-of-fit test ( χ2=6.82, P=0.512); calibration curve of the validation set showed that the predicted values of the model was consistent with the actual values. Conclusions:The failure of vaginal delivery in primiparae with PE is associated with maternal age, prenatal body fat percentage, ratio of fetal umbilical artery systolic to diastolic flow velocity within a week before delivery, maternal education during pregnancy and Bishop score. The nomogram model based on these five risk factors for prediction of vaginal delivery failure performs well.

Case report of congenital disorder of glycosylation type Ia combined with dilated cardiomyopathy / 中华实用儿科临床杂志

Clinical data and follow-up of a case of congenital disorder of glycosylation type Ia (CDG-Ia) combined with dilated cardiomyopathy admitted to the Department of Cardiology, Children′s Hospital of Nanjing Medical University were analyzed retrospectively.The 5-year-old female patient was admitted in December 2016 due to recu-rrent shortness of breath for 2 months.Clinical symptoms and signs included repeated attacks of shortness of breath, physical retardation, malnutrition, binocular esotropia, multiple episodes of hypoglycemia, hepatosplenomegaly, hypotonia and other multi-system damages.Cardiac echocardiography suggested the feature of dilated cardiomyopathy, including the significant enlargement of the left ventricle, and decreased systolic function.Genetic testing revealed a compound heterozygous mutation in the PMM2 gene, and as a result, the patient was diagnosed as CDG-Ia.The patient′s condition improved after symptomatic treatments such as Cedilanid, Dopamine, Dobutamine, Furosemide, as well as support treatments like myocardium nutrition, blood sugar maintenance, liver protection, etc.After discharge, the patient was given oral Digoxin, Betaloc, Captopril and diuretics, and hypoglycemia-controlling agents.The patient was followed up every 3-6 months.After more than 2 years of follow-up, the heart function and heart enlargement gradually returned to normal.During the Corona Virus Disease 2019 outbreak, self-withdrawal continued for 2 months.Re-examinations showed decreased cardiac function and enlarged left ventricle again.Medications were resumed again, and the patient was followed up closely.This case report suggested that CDG-Ia may be associated with dilated cardiomyopathy, and the cardiac phenotype may be improved by symptomatic supportive treatment.

Changes of microvascular diameter in non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the changes of microvascular diameter in non-proliferative diabetic retinopathy(NPDR)at different stages.<p>METHODS: Prospective case-control study. Patients with type 2 diabetes mellitus complicated with diabetic retinopathy(DR)who were hospitalized in the Endocrine Department of our hospital from September 2020 to March 2021 were selected and divided into diabetic non-retinopathy group(50 cases and 50 eyes), DR stage Ⅰ group(50 cases and 50 eyes), DR stage Ⅱ group(50 cases and 50 eyes), DR stage Ⅲ group(50 cases and 50 eyes)according to the “Clinical Diabetic Retinopathy Disease Severity Scale” formulated by the Chinese Medical Association in 1985. In addition, 50 cases and 50 eyes of a control group with normal physical examination were selected, totally 250 cases and 250 eyes. The fundus color photos were taken and entered into the ARIA1.0 automatic analysis software to record the diameters of arterio-venous and capillary vessels in different ranges, with 4 segments in each range and 200 segments in each group for statistical analysis.<p>RESULTS: There was no significant difference in the diameter of retinal artery between different stages of NPDR(<i>P</i>>0.05), and there was significant difference in the diameter of retinal vein and diameter of perimacular capillary amorg different stages of NPDR(<i>P</i><0.05). The multiple comparison of retinal vein diameter and perimacular capillary diameter in different groups was statistically significant(<i>P</i><0.01). The average score of retinal vein diameter in the range of 0-0.5PD was “stage Ⅲ course > stage Ⅱ course>stage Ⅰ course>normal group>control group”. The average score of retinal vein diameter group in the range of 0.5-1.0PD(including 0.5)was “stage Ⅲ course > stage Ⅱ course > stage Ⅰ course > normal group > control group”, the average score of perimacular capillary diameter group was “stage Ⅲ course > stage Ⅰ course > control group; Stage Ⅲ course > normal group; Stage Ⅱ course > stage Ⅰ course > control group; Stage Ⅱ course > normal group; The diseased normal group > the control group”, while there was no significant difference between the stage Ⅲ course and the stage Ⅱ course, the stage Ⅰ course and the diseased normal group(<i>P</i>>0.05).<p>CONCLUSION: Retinal artery diameter has no obvious change in NPDR stages. The retinal vein and perimacular capillary in diabetic patients are dilated. In different stages of NPDR, the diameter of the vein and perimacular capillary is gradually widened.

Analysis of Traditional Chinese Medicine prescriptions in 240 cases of COVID-19 / 中华全科医师杂志

Objective:To analyze Traditional Chinese Medicine(TCM) prescriptions in COVID-19 patients in Shanghai area.Methods:Two hundred and forty patients were enrolled in the study, including 19 mild cases, 199 moderate cases, 16 severe case and 6 critical cases. The COVID-19 formula in Shanghai area was extracted and input in TCM Inheritance platform. Data association method such as software association rules,improved mutual information method,complex system entropy clustering,unsupervised entropy hierarchical clustering were used to analyze the frequency,herb flavor and meridian, combination rule and core combination of different types of Chinese herbs in the treatment of COVID-19 in Shanghai area.Results:According to the frequency analysis of 240 prescriptions of Chinese medicine,194 herbs were found. The COVID-19 formula herbs were all "cold", the frequency of use in mild, moderate, severe and critical cases was [46.02%(104/226), 46.31%(1 230/2 656), 37.06%(146/394), 39.24%(31/79)]. The flavor was mainly "bitter" and the frequency of use in 4 types of disease were [36.53%(122/332), 37.33%(1 445/3 857), 35.96%(205/564), 33.62%(39/113)]. Scutellaria was the most frequently used TCM of "bitter and cold". The drugs used were mainly lung,stomach and spleen meridians. By comparing the formulas between mild and moderate cases,herb combinations with the highest frequency were all "scutellaria glycyrrhiza" and "tangerine glycyrrhiza". The formulas for 19 mild cases were collected,and 197 drug combinations were counted, and 125 Chinese medicine association rules,including 13 Chinese herbs. The formulas were extracted in 199 moderate cases of COVID-19, a total of 92 drug combinations and 38 Chinese medicine association rules were collected,including 19 Chinese herbs. In 16 severe cases, a total of 62 drug combination models and 46 Chinese medicine association rules were collected,including 17 Chinese herbs. For the 6 critical cases,80 Chinese medicine prescriptions were combined,and 10 Chinese medicine association rules, including 12 Chinese herbs.Conclusions:The herbal prescriptions of COVID-19 in Shanghai are characterized by clearing away heat and resolving dampness. By analyzing prescription rules with complex system entropy clustering, association compatibility ideas of different types of traditional Chinese medicine are found to be different among four types of COVID-19 cases. Analyzing the connection rules in formulas, by using the theory of TCM and pharmacology of traditional Chinese medical formula in different COVID-19 patients may be helpful for general practitioners.

Bibliometric analysis on the clinical researches of tumor treated with acupuncture-moxibustion on the base of PubMed database / 中国针灸

OBJECTIVE@#To analyze the literature characteristics of the clinical researches on tumor treatment with acupuncture-moxibustion in PubMed database so as to provide the references for the study of acupuncture-moxibusion in intervention of tumor.@*METHODS@#The articles on the clinical researches of acupuncture-moxibusion in treatment of tumor were retrieved from PubMed database listed till December 31, 2018. Using bibliometric methodology, the analysis was conducted on publication year, publication journal, author, country or region, research institution, disease spectrum and therapeutic regimen.@*RESULTS@#A total of 143 articles are included. The publications are increased steadily since 2004. The articles are published in 64 international journals, of which, @*CONCLUSION@#Acupuncture-moxibustion is quite extensively involved in the treatment of tumor in the field of nervous (mental) system and digestive system. But the regimen of acupuncture- moxibustion needs to be further optimized and promoted.

Wide Pulse Width Electroacupuncture Ameliorates Denervation-Induced Skeletal Muscle Atrophy in Rats via IGF-1/PI3K/Akt Pathway / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of the pulse width of electroacupuncture (EA) in the treatment of denervation-induced skeletal muscle atrophy in rats and examine the role of insulin-like growth factor 1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during EA.@*METHODS@#Sciatic nerve functional index (SFI), muscle wet weight and the cross-sectional area (CSA) of the gastrocnemius muscle were analyzed after treatment in model rats with EA of various pulse widths (0.5, 50, 100 and 200 ms). The apoptosis index (AI) and paired box (PAX)3 and PAX7 protein expression were also determined. Further, the mRNA and protein expressions of components of IGF-1/PI3K/Akt pathway and their downstream targets were determined, along with the inhibiting effect of the pathway with a PI3-specific inhibitor.@*RESULTS@#EA with a pulse width of 200 ms was found to have the best effect with regard to increasing SFI, CSA and muscle weight, decreasing AI, and increasing the expression of PAX3 and PAX7. The IGF-1/PI3K/Akt pathway was found to be activated by denervation, although the downstream forkhead box O (FoxO) pathway was not suppressed by its activation. The PI3K/Akt pathway and its downstream molecule mammalian target of rapamycin (mTOR) were up-regulated further by EA to promote muscle protein synthesis. Meanwhile, the expressions of downstream FoxO and F-box protein 32 (ATROGIN-1) were down-regulated to reduce protein degradation.@*CONCLUSIONS@#EA with 200-ms pulse width was found to have a more significant effect than 0.5-ms EA. The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway.

Clinical Efficacy of Modified Zengyetang Against Slow Transit Constipation Due to Qi-Yin Deficiency and Its Effect on Gastrointestinal Function / 中国实验方剂学杂志

Objective:To observe the clinical effect of modified Zengyetang in treating slow transit constipation （STC） due to Qi-Yin deficiency and its effect on gastrointestinal function. Method:One hundred and thirty eligible patients were randomly divided into a control group （<italic>n</italic>=65， 6 cases dropped out or were lost to follow-up and 59 completed the trial） and a treatment group （<italic>n</italic>=65， 3 cases dropped out or were lost to follow-up and 62 completed the trial）. Patients in the control group received oral mosapride citrate dispersible tablets， 5 mg per time， three times per day， while those in the treatment group were treated with modified Zengye Tang， one bag per day， for four successive weeks. The main symptom constipation， the Patient Assessment of Constipation Symptoms （PAC-SYM）， and traditional Chinese medicine （TCM） syndrome scores， colonic transit， as well as motilin （MTL）， vasoactive intestinal peptide （VIP）， and substance P （SP） levels before and after treatment were recorded， together with the frequency of spontaneous complete bowel movements （SCBMs） per week and STC recurrence during treatment. Result:The clinical efficacy （95.16%） of the treatment group was higher than that （81.36%） of the control group （<italic>χ</italic>²=5.631 4， <italic>P</italic><0.05）， whereas the recurrence rate （30.65%） of the treatment group was significantly lower than that （57.63%） of the control group （<italic>χ</italic>²=8.941 1， <italic>P</italic><0.01）. After treatment， the main symptom constipation， three sub-scale and total PAC-SYM， and TCM syndrome scores in the treatment group were obviously decreased as compared with those in the control group （<italic>P</italic><0.01）. The proportions of residual markers at 24， 48， and 72 h in the treatment group declined in contrast to those in the control group （<italic>P</italic><0.01）. The frequency of SCBMs per week in the 2^nd， 3^rd， and 4^th weeks of the treatment group was higher than that in the control group （<italic>P</italic><0.01）. Compared with the control group after treatment， the treatment group exhibited significantly elevated MTL and SP but lowered VIP （<italic>P</italic><0.01）. Conclusion:Modified Zengyetang relieves the clinical symptoms， regulates gastrointestinal hormone secretion， increases the frequency of SCBMs， enhances colonic transit， and decreases the recurrence of patients with STC due to Qi-Yin deficiency.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action.@*METHODS@#A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups.@*RESULTS@#The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044).@*CONCLUSION@#In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.@*METHODS@#A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.@*RESULTS@#COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3@*CONCLUSION@#Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3

Research of Disposable Respiratory Filter to the Measurement of Impulse Oscillometery / 中国医疗器械杂志

OBJECTIVE@#To study the influence of disposable respiratory filter on the results of impulse oscillometery.@*METHODS@#90 healthy subjects were randomly selected and impulse oscillometery results were taken repeatedly through disposable respiratory filter and control device. All results were statistically analyzed.@*RESULTS@#When using the disposable respiratory filter, respiratory impedance (Zrs) and resistance at all frequency (R5Hz-R35Hz) were significantly increased compared with the control device (P<0.01). The two measurements had a significant linear correlation (P<0.01) and a regression equation was established. The disposable respiratory filter did not exist in statistic difference to response frequency (Fres) and the elastic resistance (X5Hz-X15Hz) at all frequency(P>0.05).@*CONCLUSIONS@#The disposable respiratory filter can be used when testing pulmonary compliance, chest wall disease and obstruction outside the airway in impulse oscillometery system to avoid infection and ensure quality.

Effect of melatonin on oligodendrocyte maturation and differentiation in corpus callosum of septic neonatal rats / 中华急诊医学杂志

Objective:To investigate the effect of melatonin on oligodendrocyte maturation and differentiation in corpus callosum of septic neonatal rats induced by systemic lipopolysaccharide (LPS) injection.Methods:Sprague-Dawley rats were randomly allocated into the control group, septic experimental group, and melatonin group. In the septic experimental group, rats were intraperitoneally administrated with lipopolysaccharide (LPS) (1 mg/kg). In the melatonin group, melatonin was intraperitoneally administered (10 mg/kg) at 0.5 h after LPS injection. The expression level of IL-6, olig1, olig2, and the MAG protein were detected by Western blot at different time points in the three groups. BV-2 cells were used in vitro. For drug administration, the effect of LPS, melatonin and melatonin receptor antagonist, luzindole, on IL-6 expression in BV-2 microglia cell was determined by Western blot. The medium of BV2 cell were collected to treat primary OPCs. The expression level of olig1, olig2 and MAG protein in primary OPCs were detected by Western blot. SPSS 20.0 statistical software was used for analysis, and the data were analyzed by one-way ANOVA and two-way ANOVA. Differences were considered to be statistically significantly if P<0.05. Result:Compared with the LPS group, the expression of IL-6 was significantly decreased in the corpus callosum at 6 h, l d, and 3 d in the melatonin group ( P<0.05). The expression of olig1, olig2 and MAG protein were increased at day 7, 14, and 28 in the melatonin group compared with the LPS group ( P<0.05). In vitro the expressions of IL-6 was significantly increased after LPS treatment ( P<0.05), but was decreased in the LPS+melatonin treatment group ( P<0.05). After treatment with melatonin receptor inhibitor, luzindole, the expressions level of IL-6 was increased ( P<0.05). The expression of olig1, olig2 and MAG protein were decreased with conditioned medium in the LPS BV2 cell group than the control group in the primary OPCs ( P<0.05). However, those were increased with conditioned medium in the LPS+melatonin BV2 cell group than the LPS group ( P<0.05). Conclusions:Melatonin may inhibit the inflammation response in the corpus callosum through its receptor, and may promote the maturation and differentiation of oligodendrocyte, suggesting that melatonin may have therapeutic effect on neuroinflammation and axonal hypomyelination on PWM in septic neonatal rats.

LncRNA LINC00313 Knockdown InhibitsTumorigenesis and Metastasis in HumanOsteosarcoma by Upregulating FOSL2through Sponging miR-342-3p

Purpose@#Osteosarcoma (OS) is the most common primary bone tumor, with high morbidity in infants and adolescents. Long noncodingRNA LINC00313 has been found to modulate papillary thyroid cancer tumorigenesis and to be dysregulate in lung cancer.However, the role of LINC00313 in OS has not yet been addressed. @*Materials and Methods@#We evaluated mRNA and protein expression using real-time quantitative PCR and Western blotting. Cellproliferation was evaluated using MTT; apoptosis and autophagy were assessed with flow cytometry, Western blotting, and/orGFP-LC3 assay. Transwell assay was conducted to measure cell migration and invasion. Potential target sites for LINC00313 andmiR-342-3p were predicted with starBase v.2.0 and TargetScan Human, and verified using luciferase reporter assay, RNA immunoprecipitation,and RNA pull-down assay. In vivo, xenogeneic tumors were induced with U2OS and MG-63 cells, separately. @*Results@#LINC00313 was upregulated and miR-342-3p was downregulated in OS tissues and cells. High expression of LINC00313was associated with shorter overall survival. FOSL2 downregulation and miR-342-3p overexpression suppressed cell proliferationand migratory and invasive abilities while promoting apoptosis and autophagy, all of which were consistent with the effects ofLINC00313 knockdown. miR-342-3p, sponged by LINC00313, inversely modulated FOSL2 by targeting MG-63 cells, and FOSL2expression was positively controlled by LINC00313. LINC00313 knockdown suppressed tumor growth in vivo. @*Conclusion@#LINC00313 is upregulated in OS, and LINC00313 knockdown plays a vital anti-tumor role in OS cell progressionthrough a miR-342-3p/FOSL2 axis. Our study suggests that LINC00313 may be a novel, promising biomarker for diagnosis andprognosis of OS.

Exploration on mechanisms of Salvia miltiorrhiza in treating cirrhosis based on network pharmacology / 中草药

Objective: Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Salvia miltiorrhiza for cirrhosis. Methods: TCMSP database was utilized to obtain the active components of S. miltiorrhiza. Through GeneCards, OMIM and DRAR-CPI, the potential targets of S. miltiorrhiza for the treatment of cirrhosis were screened. Cytoscape 3.6.0 software was established to construct the active components-targets network of S. miltiorrhiza. STRING database and Generate style from statistics of Cytoscape 3.6.0 software were conducted to draw a graph of protein interaction network. Molecular docking was carried out through Systems Dock Web Site with the active components of S. miltiorrhiza. The GO classified enrichment analysis and the KEGG pathway enrichment analysis were performed by using DAVID database. Results: Selecting the OB ≥ 30% and DL ≥ 0.18 as filter condition, 65 active components and 75 targets of S. miltiorrhiza were involved. S. miltiorrhiza exerted its effects on treating cirrhosis mainly by regulating signaling pathways including MAPK, Toll-like receptor, Gap junction, PI3K/AKT, Natural killer cell mediated cytotoxicity signaling pathway and so on. Conclusion: This study preliminarily predicted the major targets and pathways of S. miltiorrhiza acting on cirrhosis, which provided new ideas and clues for its further research.

Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis / 中国医学科学院学报

To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (=0.020,<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.