Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway.

CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

[Effects of thunder-fire moxibustion on the motor function in the patients of osteoporosis with low skeletal muscle mass： a randomized controlled trial].

OBJECTIVE: To observe the effects of thunder-fire moxibustion on the visual analogue scale (VAS) score, Young's modulus of multifidus and 6 m walking speed in the patients of osteoporosis with low skeletal muscle mass. METHODS: Sixty patients of osteoporosis with low skeletal muscle mass were randomly divided into a medication group (30 cases) and a medication+thunder-fire moxibustion group (30 cases). In the medication group, caltrate was prescribed for oral administration, 2 tablets/day （600 mg/tablet）, for 4 weeks. In the medication+thunder-fire moxibustion group, on the base of oral administration with caltrate, thunder-fire moxibustion was exerted at Mingmen (GV4), Yaoyangguan(GV3), and bilateral Shenshu (BL23), Ganshu (BL18) and Dachangshu (BL25), 30 minutes at GV4, GV3 and BL18, and another 30 minutes at BL23 and BL25, once every other day, 3 times a week for 4 weeks. Before and after the treatment, VAS score, Young's modulus of the 4th lumbar multifidus and the average speed of 6 m walking were assessed. RESULTS: After the treatment, the VAS score was decreased (P<0.05, P<0.01) and the speed of 6 m walking was increased (P<0.05, P<0.01) in both groups in comparison with their own pre-treatment. Compared with the medication group, VAS score was decreased remarkably (P<0.05) and the speed of 6 m walking remarkably increased (P<0.01) in the medication+thunder-fire moxibustion group after the treatment. Self-comparison showed that, compared with the same side before the treatment, the value of Young's modulus after the treatment was decreased on both sides in the medication+thunder-fire moxibustion group (P<0.01). After the treatment, compared with the medication group on the same side, the value of Young's modulus was decreased on both sides (P<0.01) in the medication+thunder-fire moxibustion group. CONCLUSION: Thunder-fire moxibustion can relieve pain intensity, decrease the tension of the multifidus, and increase the walking speed.

[Effect of moxibustion of "Ganshu"(BL18) and "Shenshu" (BL23) on musculoskeletal interaction in osteoporosis rats].

OBJECTIVE: To observe the effect of moxibustion of "Ganshu" (BL18)and "Shenshu" (BL23) on bone mineral density (BMD), biomechanics, bone metabolism and musculoskeletal morphology of osteoporosis (OP) rats, so as to explore its mechanism underlying treatment of OP via bone-muscle interaction. METHODS: Thirty-two female SD rats were randomly divided into sham operation, OP model, moxibustion and medication (nilestriol) groups, with 8 rats in each group. For rats of the sham operation group, a small amount of fat around the ovaries was removed, and those of the other 3 groups received removal of bila-teral ovaries for establishing OP model. Moxibustion was applied to bilateral BL18 and BL23 for 30 min, once every other day, 3 times a week for 12 weeks. Rats of the medication group received gavage of nilestriol (1 mg/kg) once a week for 12 weeks.After the interventions, a dual-energy absorptiometry was used to determine the BMD and bone mineral content of the rats' right femur and the fourth lumbar vertebrae under anesthesia, and three-point bending test used to detect the biomechanical properties (including load, displacement, stiffness) of the right femur. The levels of serum type I collagen C-terminal peptide (CTX-I), acid-resis-tant tartrate phosphatase (TRACP) and estradiol (E2) were determined using enzyme-linked immunosorbent assay, and histopathological changes of the left femur and the quadriceps observed after hematoxylin-eosin (H.E.) staining. RESULTS: Compared with the sham operation group, the BMD and bone mineral contents of the right femur and the fourth lumbar vertebra, the load and stiffness of the right femur, and concentration of serum E2 were significantly decreased (P<0.01, P<0.05), and the displacement of the right femur, and concentrations of serum CTX-Ⅰ and TRACP notably increased in the model group (P<0.01). After the interventions, the decreased levels of BMD and bone mineral contents, the load and stiffness and concentration of serum E2, and the increased levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP were all reversed by both moxibustion (except the bone mineral content of the fourth lumbar vertebra) and medication (P<0.01,P<0.05). No signi-ficant differences were found between moxibustion and medication in up-regulating the levels of BMD and bone mineral contents, the load and stiffness (except serum E2) and down-regulating the levels of the displacement, and concentrations of serum CTX-Ⅰ and TRACP (P>0.05). H.E. staining revealed that rats in the sham operation group showed mild thinness of the bone cortex, uneven thickness of trabecular bone, with distortion, fracture and osteoporosis of the left femur, and different size of rhabdomyocytes in the right quadriceps femoris muscle, with obvious proliferation of interstitial fibrous tissue and inflammatory cell infiltration, which were relatively and clearly milder in both moxibustion and medication groups. CONCLUSION: Moxibustion of BL18 and BL23 can increase the BMD and bone mineral content, improve biomechanical performance, adjust bone metabolism, and mitigate bone and the attached muscle histopathological changes in OP rats, suggesting that modulating interaction between bones and muscles is probably one of the ideas in the treatment of OP.

Practice and experience of regional medical center entrance linkage and closed-loop management under the wartime situation of the COVID-19 in China.

On 28 July 2021, the first indigenous case of novel coronavirus pneumonia (COVID-19) emerged in Yangzhou, marking the beginning of a public health crisis caused by the new coronavirus pneumonia. It is a significant challenge for hospitals to carry out prevention and control measures to ensure the safety of medical professionals and patients when facing the changes in an epidemic situation. Subei People's Hospital, as one of the first group of "Grade III-class A" hospitals in Jiangsu Province and the Yangzhou Regional Medical Centre, responded quickly and scientifically to prevent and control the disease. A closed-loop management system was implemented at the hospital entrance (consisting of the outpatient clinic, emergency clinic, fever clinic, and buffer ward) and an epidemic prevention and control group was established with the assistance of multiple departments. This group optimized the pre-screening and triage system, standardized the fever clinic consultation process, and improved the construction of an information-based prevention and control network so that patients were detected, diagnosed, isolated, and treated early. The emergency management capability was improved to achieve zero missed consultations of patients attending for COVID-19 and to effectively maintain medical order during this critical period. This current report systematically summarizes the operational practices and the effectiveness achieved by implementation of the entrance closed-loop management in the hospital and analyzed the key operational issues for future reference by medical institutions and management departments.

[Electroacupuncture on motor function in patients with primary osteoporosis: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture on motor function and muscle state in patients with primary osteoporosis (POP). METHODS: A total of 60 female patients with POP were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case dropped off). On the basis of adjusting lifestyle, caltrate was given orally in the control group, 2 pills a day for 4 weeks. On the basis of the treatment in the control group, electroacupuncture was applied at Zusanli (ST 36), Yanglingquan (GB 34), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), etc. in the observation group, with disperse-dense wave of 2 Hz/10 Hz in frequency, once every other day, 3 times a week for 4 weeks. The time of timed up-and-go test (TUGT) and the value of 10 m maximal walking speed (10 m MWS) before and after treatment were compared in the two groups, and the Young's modulus values of bilateral multifidus muscles in prone position and sitting position before and after treatment were compared by real-time shear wave elastography (SWE) in the two groups. RESULTS: After treatment, the TUGT time was decreased compared before treatment in the observation group (P<0.01), and that in the observation group was shorter than the control group (P<0.01). After treatment, the value of 10 m MWS test was increased compared before treatment in the observation group (P<0.05). After treatment, the Young's modulus values of bilateral multifidus muscles in prone position and sitting position were increased compared before treatment in the observation group (P<0.01); except for the left side in sitting position, the Young's modulus values of multifidus muscles in the observation group were higher than those in the control group (P<0.01, P<0.05). CONCLUSION: On the basis of oral caltrate, electroacupuncture can improve the motor function and muscle state in patients with POP.

Norepinephrine modulates wakefulness via α1 adrenoceptors in paraventricular thalamic nucleus.

Norepinephrine (NE) neurons in the locus coeruleus (LC) play key roles in modulating sleep and wakefulness. Recent studies have revealed that the paraventricular thalamic nucleus (PVT) is a critical wakefulness-controlling nucleus in mice. However, the effects of NE on PVT neurons remain largely unknown. Here, we investigated the mechanisms of NE modulating wakefulness in the PVT by using viral tracing, behavioral tests, slice electrophysiology, and optogenetics techniques. We found that the PVT-projecting LC neurons had few collateral projections to other brain nuclei. Behavioral tests showed that specific activation of the LC-PVT projections or microinjection of NE into the PVT accelerated emergence from general anesthesia and enhanced locomotion activity. Moreover, brain slice recording results indicated that NE increased the activity of the PVT neurons mainly by increasing the frequency of spontaneous excitatory postsynaptic currents via α1 adrenoceptors. Thus, our results demonstrate that NE modulates wakefulness via α1 adrenoceptors in the PVT.

Long Noncoding RNA FENDRR Inhibits Lung Fibroblast Proliferation via a Reduction of ß-Catenin.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and usually lethal lung disease and it has been widely accepted that fibroblast proliferation is one of the key characteristics of IPF. Long noncoding RNAs (lncRNAs) play vital roles in the pathogenesis of many diseases. In this study, we investigated the role of lncRNA FENDRR on fibroblast proliferation. Human lung fibroblasts stably overexpressing FENDRR showed a reduced cell proliferation compared to those expressing the control vector. On the other hand, FENDRR silencing increased fibroblast proliferation. FENDRR bound serine-arginine rich splicing factor 9 (SRSF9) and inhibited the phosphorylation of p70 ribosomal S6 kinase 1 (PS6K), a downstream protein of the mammalian target of rapamycin (mTOR) signaling. Silencing SRSF9 reduced fibroblast proliferation. FENDRR reduced ß-catenin protein, but not mRNA levels. The reduction of ß-catenin protein levels in lung fibroblasts by gene silencing or chemical inhibitor decreased fibroblast proliferation. Adenovirus-mediated FENDRR transfer to the lungs of mice reduced asbestos-induced fibrotic lesions and collagen deposition. RNA sequencing of lung tissues identified 7 cell proliferation-related genes that were up-regulated by asbestos but reversed by FENDRR. In conclusion, FENDRR inhibits fibroblast proliferation and functions as an anti-fibrotic lncRNA.

miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor.

Influenza A virus (IAV) infections result in a large number of deaths and substantial economic losses each year. MicroRNAs repress gene expression and are involved in virus-host interactions. miR-29a is known to have anti-tumor and anti-fibrotic effects. However, the role of miR-29a in IAV infection is unclear. In the present study, we investigated the effect of miR-29a on IAV infection and the mechanisms by which it functions. IAV infection was found to cause decreased miR-29a expression in lung epithelial A549 cells and mouse lungs. Overexpression of miR-29a reduced IAV mRNA and protein levels and progeny virus production in HEK293 and A549 cells. Inhibition of IAV infection by miR-29a was observed with different strains of IAV, including A/PR/8/34, A/WSN/1933, and clinical isolates A/OK/3052/09 and A/OK/309/06 H3N2. Knockout of miR-29a using CRISPR/Cas9 resulted in an increase in viral mRNA and protein levels, confirming that miR-29a suppresses IAV infection. A 3' untranslated region (3'-UTR) reporter assay showed that miR-29a had binding sites in the 3'-UTR of the Wnt-Ca2+ signaling receptor frizzled 5 gene, and overexpression of miR-29a reduced the level of the endogenous frizzled 5 protein. Wnt5a treatment of HEK293 and A549 cells enhanced IAV infection. Our results suggest that miR-29a inhibits IAV infection, probably via the frizzled 5 receptor.

Synthesis, binding, and functional properties of tetrahydroisoquinolino-2-alkyl phenones as selective σ2R/TMEM97 ligands.

Sigma-2 receptor (σ2R/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ2 ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ2 ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σ2R/TMEM97. Especially, 4 analogs showed Ki values ranging from 0.38 to 5.1 nM for σ2R/TMEM97 with no or low affinity for sigma-1 receptor (σ1R). Functional assays indicated that these 4 most potent analogs had no effects on intracellular calcium concentration and were classified as putative σ2R/TMEM97 antagonists according to current understanding. The σ2R/TMEM97 has been suggested to play important roles in the central nervous system. Based on published pharmacological and clinical results from several regarded σ2R/TMEM97 antagonists, these analogs may potentially be useful for the treatment of various neurodegenerative diseases.

Evaluation of the exposure risk of SARS-CoV-2 in different hospital environment.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs.

The acromion-greater tuberosity impingement index: A new radiographic measurement and its association with rotator cuff pathology.

PURPOSE: Several radiographic parameters describe humeral head coverage by the acromion. We describe a new radiographic measurement, the acromion-greater tuberosity impingement index (ATI), and its ability to predict rotator cuff pathology. METHODS: The ATI was measured with magnetic resonance imaging (MRI) and X-ray analysis in 83 patients with rotator cuff pathology and 76 patients with acute rotator cuff tears. The lateral acromial angle (LAA), acromion type, the acromion index (AI) and the critical shoulder angle (CSA) were measured to assess their correlations with the ATI. Receiver operating characteristic (ROC) curves were used to predict degenerative rotator cuff pathology. The change in the ATI after acromion surgery was evaluated in both groups. RESULTS: According to the ROC curves, the ATI is a good predictor of degenerative rotator cuff pathology on both X-ray (cut-off, 0.865) and MRI (cut-off, 0.965). Patients with degenerative rotator cuff pathology had a significantly higher average ATI compared to the trauma group (p = 0.001 for X-ray and MRI). The degenerative group had a significantly lower LAA (p = 0.001) and a higher ratio of type III acromion (p = 0.035) than the trauma group. The ATI on X-ray was negatively related to the LAA and positively related to the AI, the CSA and acromion type (each p < 0.05). The ATI on MRI was negatively related to the LAA and positively related to the AI and acromion type (each p <0.05). More patients in the degenerative group than the trauma group needed acromioplasty or acromion decompression (p < 0.05). The ATI on MRI was significantly lower after acromion surgery compared to before surgery in both groups (p < 0.05). CONCLUSION: The ATI is a good predictor of degenerative supraspinatus tendon tears or subacromial impingement syndrome. The ATI on MRI is more accurate and can precisely guide acromion surgery.

[Effect of thunder-fire moxibustion combined with vibration training on low back pain of primary osteoporosis].

OBJECTIVE: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young's modulus of ultrasonic wave, and seek an objective evaluating method. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone (Young's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment. RESULTS: Compared before treatment, the VAS scores, Young's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P<0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P<0.05). In the observation group, the VAS scores, Young's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P<0.05). CONCLUSION: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

Hypoxia and transforming growth factor ß1 regulation of long non-coding RNA transcriptomes in human pulmonary fibroblasts.

One of the key characteristics of idiopathic pulmonary fibrosis (IPF) is accumulation of excess fibrous tissue in the lung, which leads to hypoxic conditions. Transforming growth factor (TGF) ß is a major mediator that promotes the differentiation of fibroblasts to myofibroblasts. However, how hypoxia and TGFß together contribute the pathogenesis of IPF is poorly understood. Long non-coding RNAs (lncRNAs) have regulatory effects on certain genes and are involved in many diseases. In this study, we determined the effects of hypoxia and/or TGFß on mRNA and lncRNA transcriptomes in pulmonary fibroblasts. Hypoxia and TGFß1 synergistically increased myofibroblast marker expression. RNA sequencing revealed that hypoxia and TGFß1 treatment resulted in significant changes in 669 lncRNAs and 2,676 mRNAs compared to 150 lncRNAs and 858 mRNAs in TGFß1 alone group and 222 lncRNAs and 785 mRNAs in hypoxia alone group. TGFß1 induced the protein expression of HIF-1α, but not HIF-2α. On the other hand, hypoxia enhanced the TGFß1-induced phosphorylation of Smad3, suggesting a cross-talk between these two signaling pathways. In all, 10 selected lncRNAs (five-up and five-down) in RNA sequencing data were validated using real-time PCR. Two lncRNAs were primarily located in cytoplasm, three in nuclei and five in both nuclei and cytoplasm. The silencing of HIF-1α and Smad3, but not Smad2 and HIF-2α rescued the downregulation of FENDRR by hypoxia and TGFß1. In conclusion, hypoxia and TGFß1 synergistically regulate mRNAs and lncRNAs involved in several cellular processes, which may contribute to the pathogenesis of IPF.

Long Noncoding RNA FENDRR Exhibits Antifibrotic Activity in Pulmonary Fibrosis.

Abnormal activation of lung fibroblasts contributes to the initiation and progression of idiopathic pulmonary fibrosis (IPF). The objective of the present study was to investigate the role of fetal-lethal noncoding developmental regulatory RNA (FENDRR) in the activation of lung fibroblasts. Dysregulated long noncoding RNAs in IPF lungs were identified by next-generation sequencing analysis from the two online datasets. FENDRR expression in lung tissues from patients with IPF and mice with bleomycin-induced pulmonary fibrosis was determined by quantitative real-time PCR. IRP1 (iron-responsive element-binding protein 1), a protein partner of FENDRR, was identified by RNA pulldown-coupled mass spectrometric analysis and confirmed by RNA immunoprecipitation. The interaction region between FENDRR and IRP1 was determined by cross-linking immunoprecipitation. The in vivo role of FENDRR in pulmonary fibrosis was studied using adenovirus-mediated gene transfer in mice. The expression of FENDRR was downregulated in fibrotic human and mouse lungs as well as in primary lung fibroblasts isolated from bleomycin-treated mice. TGF-ß1 (transforming growth factor-ß1)-SMAD3 signaling inhibited FENDRR expression in lung fibroblasts. FENDRR was preferentially localized in the cytoplasm of adult lung fibroblasts and bound IRP1, suggesting its role in iron metabolism. FENDRR reduced pulmonary fibrosis by inhibiting fibroblast activation by reducing iron concentration and acting as a competing endogenous RNA of the profibrotic microRNA-214. Adenovirus-mediated FENDRR gene transfer in the mouse lung attenuated bleomycin-induced lung fibrosis and improved lung function. Our data suggest that FENDRR is an antifibrotic long noncoding RNA and a potential therapeutic target for pulmonary fibrosis.

[Systematic review of Shenqi Fuzheng Injection combined with chemotherapy for treatment of breast cancer].

Databases including China Biological Medicine database(CBM), Chinese scientific journals full-text database(VIP), China National Knowledge Infrastructure database(CNKI), WanFang Data, PubMed, and EMbase were searched from inception to March 2018 to collect the randomized controlled trials(RCTs) on Shenqi Fuzheng Injection combined with chemotherapy for the treatment of breast cancer. All included studies were critically appraised by two independent reviewers by following the cochrane systematic review method and using Revman 5.3 software and State 12.0 for data analysis. After screening, 20 RCTs involving 2 095 patients were included in the study. Meta-analysis showed that as compared with control group of chemotherapy alone, Shenqi Fuzheng Injection combined with chemotherapy could improve the clinical curative efficiency, the KPS score, and immune function indexes such as total T cells, Th cells and Ts cells; inhibit the decline of white blood cells(WBC), platelets in blood system, T-lymphocyte subsets such as CD3~+, CD4~+, CD4~+/CD8~+, alleviate myelosuppression and reduce the incidence of side effects such as gastrointestinal adverse reaction, liver and kidney dysfunction and abnormal electrocardiogram. The results revealed that for clinical breast cancer patients, Shenqi Fuzheng Injection combined with chemotherapy could significantly improve its clinical efficacy and reduce adverse reactions. However, the conclusions still need to be verified by high-quality, multi-center, large-sample, prospective, randomized and double-blind clinical trials. In conclusion, this study has systemically evaluated the efficacy and safety of Shenqi Fuzheng Injection combined with chemotherapy in treatment of breast cancer and provided the reference of evidence-based medicine for safe and effective clinical application of medicines.

miR-193b represses influenza A virus infection by inhibiting Wnt/ß-catenin signalling.

Due to an increasing emergence of new and drug-resistant strains of the influenza A virus (IAV), developing novel measures to combat influenza is necessary. We have previously shown that inhibiting Wnt/ß-catenin pathway reduces IAV infection. In this study, we aimed to identify antiviral human microRNAs (miRNAs) that target the Wnt/ß-catenin signalling pathway. Using a miRNA expression library, we identified 85 miRNAs that up-regulated and 20 miRNAs that down-regulated the Wnt/ß-catenin signalling pathway. Fifteen miRNAs were validated to up-regulate and five miRNAs to down-regulate the pathway. Overexpression of four selected miRNAs (miR-193b, miR-548f-1, miR-1-1, and miR-509-1) that down-regulated the Wnt/ß-catenin signalling pathway reduced viral mRNA, protein levels in A/PR/8/34-infected HEK293 cells, and progeny virus production. Overexpression of miR-193b in lung epithelial A549 cells also resulted in decreases of A/PR/8/34 infection. Furthermore, miR-193b inhibited the replication of various strains, including H1N1 (A/PR/8/34, A/WSN/33, A/Oklahoma/3052/09) and H3N2 (A/Oklahoma/309/2006), as determined by a viral reporter luciferase assay. Further studies revealed that ß-catenin was a target of miR-193b, and ß-catenin rescued miR-193b-mediated suppression of IAV infection. miR-193b induced G0/G1 cell cycle arrest and delayed vRNP nuclear import. Finally, adenovirus-mediated gene transfer of miR-193b to the lung reduced viral load in mice challenged by a sublethal dose of A/PR/8/34. Collectively, our findings suggest that miR-193b represses IAV infection by inhibiting Wnt/ß-catenin signalling.

Isolation, synthesis, and cytotoxicity evaluation of two impurities in nomegestrol acetate.

Nomegestrol acetate (NOMAc) is a synthetic progesterone analog and classified as a fourth-generation progestin. It has been approved in many countries for oral contraception, hormonal replacement therapy (HRT), and treatment of various gynecological disorders. There are several synthetic routes reported for the synthesis of NOMAc and they all share the very similar last three to five steps toward the conversion of 6-methylene to 6-methyl-6,7-unsaturated structure. Therefore the final product from different processing routes may have similar impurity profiles. In the analysis of NOMAc, we identified two impurities, impurity A (listed in EP 8.0) and impurity B (not specified in EP 8.0). Both impurities were further confirmed by synthesis. In addition, both impurities and NOMAc were evaluated for their in vitro cytotoxicities against L02 liver cells, mesenchymal stem cells, MCF-7 breast cancer cells, and C33A cervical cancer cells. These three analogs are not cytotoxic to the four cell lines at low concentrations (<20 µM). NOMAc and impurity A showed cytotoxicity to L02, MCF-7, and C33A cells at high concentrations, while impurity B did not show significant cytotoxicity to any of the cell lines tested.

[Systematic review on efficacy and safety of Danshen Chuanxiongqin Injection in treatment of acute cerebral infarction].

To systemically evaluate the therapeutic efficacy and safety of Danshen Chuanxiongqin Injection in treatment of acute cerebral infarction and provide the reference of evidence-based medicine for its clinical safety and effective drug use. Databases including CNKI, WanFang Data, SinoMed, the Cochrane Library, EMbase and PubMed were searched from inception to April 2018 to collect the randomized controlled trials (RCTs) on Danshen Chuanxiongqin Injection in the treatment of acute cerebral infarction. The quality of all included studies was evaluated by two independent reviewers following the cochrane systematic review method and using Revman5.3 software and State13.0 for Meta-analysis. A total of 30 RCTs involving 3 233 patients with acute cerebral infarction were included in the study after literature quality evaluation. Meta-analysis showed that as compared with the control group of conventional western medicine alone, Danshen Chuanxiongqin Injection combined with conventional western medicine can achieve better efficacy in treatment of acute cerebral infarction, increase the clinical total effective rate (RR=1.22, 95% CI [1.18, 1.27], P<0.000 01) and activities of daily living (MD=9.42, 95% CI [8.12, 10.72], P<0.000 01), and improve the degree of neurological impairment (MD=-3.99, 95% CI [-4.89, -3.07], P<0.000 01). Furthermore, the result showed that Danshen Chuanxiongqin Injection in the treatment of acute cerebral infarction can significantly decrease the whole blood high-shear viscosity, whole blood low-shear viscosity, plasma viscosity, fibrinogen level and other hemorheological indexes (P<0.01). This Meta-analysis demonstrated that Danshen Chuan xiongqin injection in the treatment of acute cerebral infarction is safe and effective, but lacks the large multicenter clinical randomized trials to support the treatment outcome.