Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

The study aims at predicting ecological suitability of Ephedra intermedia in China by using maximum entropy Maxent model combined with GIS, and finding the main ecological factors affecting the distribution of E. intermedia suitability in appropriate growth area. Thirty-eight collected samples of E. intermedia and E. intermedia and 116 distribution information from CVH information using ArcGIS technology were analyzed. MaxEnt model was applied to forecast the E. intermedia in our country's ecology. E. intermedia MaxEnt ROC curve model training data and testing data sets the AUC value was 0.986 and 0.958, respectively, which were greater than 0.9, tending to be 1.The calculated E. intermedia habitat suitability by the model showed a high accuracy and credibility, which indicated that MaxEnt model could well predict the potential distribution area of E. intermedia in China.

Objective To investigate the expressions of Wnt-1 and FZD-1 in small cell lung cancer(SCLC) patients and their relations with chemotherapy resistance,clinical feature and prognosis.Methods Peripheral blood specimens were collected from 41 SCLC patients.The expression of Wnt-1 and FZD-1 in peripheral blood monouclear cells (PBMC) were detected.The relationship among the expression of Wnt-1 and FZD-1,clinicopathologic feature and prognosis was analyzed.Results The relative expression of Wnt-1 and FZD-1 in chemotherapy resistant group was significantly higher than that in chemotherapy sensitive group (all P ＜ 0.05).The expression of Wnt-1was positively correlated with that of FZD-1 (r =0.186,P ＜ 0.05).The FZD-1expression level was not correlated with patients' age,sex and smoking history (all P ＞ 0.05),but closely with clinic-staging (P =0.008).The Wnt-1 expression level was not correlated with patients' clinical features (all P ＞ 0.05).There was statistical difference in median survival time between Wnt-1 and FZD-1 high-expression group and low-expression group.Conclusions Wnt-1 and FZD-1relationships with chemotherapy resistance and prognosis.Wnt-1 and FZD-1 may act as an important role in chemotherapy resistance of SCLC and could be served as indicators for the chemotherapy resistance and outcome assessment of SCLC.

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3β, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1β-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

Synthetic biology research methods which design and build a new artificial biological systems (medicinal plants or microorganisms system) with specific physiological functions through clarifying and simulating the basic law of the biosynthesis of active components of traditional Chinese medicine, is considered to be a potential method to produce an abundant resources of bioactive components. Tanshinones is a kind of diterpene quinone compounds with important pharmacological activities from traditional Chinese medicine Salvia miltiorrhiza. This article systematically introduced the research progress of the synthetic biology of S. miltiorrhiza, in order to provide references for studies on other terpenoid bioactive components of traditional Chinese medicines, and give new research strategies for the sustainable development of traditional Chinese medicine resources.
Diterpenes, Abietane ; biosynthesis ; Medicine, Chinese Traditional ; Salvia miltiorrhiza ; metabolism ; Synthetic Biology

OBJECTIVETo evaluate the efficiency of one-step multiplex RT-PCR for identifying four common fusion transcripts (TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL) in children with acute lymphoblastic leukemia (ALL).

METHODSTotal RNA was extracted from bone marrow samples of 76 children who were newly diagnosed with ALL between January 2003 and December 2010. These RNAs were analyzed for TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL by one-step multiplex RT-PCR or common nested-multiplex PCR. The PCR products were confirmed by DNA sequencing.

RESULTSTEL/AML1 was found in 12 cases (the length of products was 298 bp in 9 cases and 259 bp in 3 cases), E2A/PBX1 was found in 3 cases (the length of products was 373 bp), BCR/ABL was found in 1 case (the length of products was 2 124 bp), and MLL/AF4 was found in 7 cases (the length of products was 427 bp in 1 case and 673 bp in 6 cases) using one-step multiplex RT-PCR combined with DNA sequencing. The results were consistent with those using common nested-multiplex PCR.

CONCLUSIONSOne-step multiplex RT-PCR may be another alternative for detection of common fusion transcripts in children with ALL.

Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Infant ; Male ; Multiplex Polymerase Chain Reaction ; methods ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA

Objective To investigate the effects of knee replacement postoperative on reducing hemoglobin by the different doses of tranexamic acid application.Methods A total of 116 knee replacement patients were enrolled and divided into the treatment group and the control group , 58 cases in each group .The surgical procedures and methods of the two groups were same , as patients in the control group were given intrave-nously before incision tranexamic acid 50 mg? kg -1 , and those in the treatment group received tranexamic acid 100 mg? kg -1 . During the peri-operative phase , the index of operation time , incision size , blood loss during operation , post -surgery drainage and the total number of blood transfusion , as well as hemoglobin were observed . Results Patients in two groups were all discharged after successful com-pletion surgery .The blood loss , postoperative drainage , the total amount of blood transfusion of the treatment group were significantly less than those of control group ( P<0.05 ) .The postoperative values in the two groups were showed significantly decreased ( P<0.05 ) , but preoperative hemoglobin values of the treatment group were significantly higher (P<0.05).The data of preoperative and postoperative coagulation indicators compared between two groups showed no significant difference .Patients were followed up for 3 months.The incidence of complications of deep vein thrombosis (1 case), acute myocardial infarction ( 0 case), transient neuro-logical symptom (1 case) in the treatment group were significantly lower than that in control group (5, 3, 4 cases) (P<0.05).Conclusion High dose of tranexamic acid applications can reduce blood loss and transfusion knee re -placement volume , and relieve the postoperative decrease of hemoglobin , meanwhile , it has no obvious effect on coagu-lation function with defined security .