Research progress of RNA drugs delivery / 药学学报

Ribonucleic acid (RNA) medicines have strong therapeutic potential for numerous rare genetic illnesses and malignancies because of its exact programmability based on Watson-Crick base pairing principle and unique ability to regulate gene expression. However, RNA medicines still have limitations in many areas, including stability, half-life time, immunogenicity, organ selectivity, cellular uptake and endosomal escape efficiency despite their great therapeutic potentials. This review briefly introduced numerous RNA medications [mostly messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotide (ASO)] that have intrigued of researchers in recent years, as well as their action mechanism in vivo. A number of delivery techniques, such as chemical modification, ligands coupling and nanocarriers have been proposed. The manufacture and applications of lipid nanoparticle, polymer nanoparticle and exosomes were discussed in depth. The goal of this work is to give a theoretical foundation and design concepts for the development of effective and safe RNA delivery technology, as well as to facilitate RNA therapeutic clinical translation.

Effect of Qigesan on Proliferation， Apoptosis and miR-133a/Akt/mTOR Signaling Pathway of Esophageal Cancer EC9706 Cells / 中国实验方剂学杂志

Objective:To observe the effect of Qigesan on the proliferation and apoptosis of the human esophageal cancer cell EC9706， and the effect on miR-133a/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method:The effective constituent of Qigesan was extracted by ethyl acetate. Thiazolyl blue tetrazolium bromide（MTT） colorimetric assay was used to determine the dosage of Qigesan on cells and to detect the effect of Qigesan on the proliferation of EC9706 cells. The effect of Qigesan on apoptosis of EC9706 cells was detected by flow cytometry. The effect of Qigesan on miR-133a and insulin-like growth factor 1 receptor（IGF-1R） mRNA expression was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） . The protein expression of Akt and mTOR in EC9706 cells was detected by Western blot. Result:Qigesan can inhibit the proliferation of EC9706 cells in a dose-dependent manner（<italic>P</italic><0.01）. Inhibitory concentrations 30% inhibition concentration（IC₃₀） 40 mg·L^-1 and median inhibition concentration（IC₅₀） 80 mg·L^-1 were selected for follow-up experiments. Compared with the blank group， both the inhibitor group and the combination drug group can inhibit the proliferation of EC9706 cells （<italic>P</italic><0.01）. The inhibitor at 0.25 μmol·L^-1 was selected for subsequent experiments. Compared with the blank group， Qigesan 80 mg·L^-1 dose group could significantly promote the late apoptosis rate and total apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， and the 40 mg·L^-1 dose group could significantly promote the late apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， which shows synergistic effect after concomitant use with Akt/mTOR inhibitor（<italic>P</italic><0.05）. Compared with the blank control group， each group can effectively increase expression of miR-133a（<italic>P</italic><0.05）. The combination of inhibitor and traditional Chinese medicine（TCM） has obvious promotion effect. Compared with blank control group， the expressions of Akt and mTOR were significantly decreased in each group（<italic>P</italic><0.05）. Compared with single medication， the expressions of Akt and mTOR were decreased in combination of inhibitor and TCM group. Conclusion:Qigesan can inhibit the growth of EC9706 cells and promote apoptosis， and its inhibitory mechanism may be related to the Akt/mTOR signaling pathway by regulating the expression of miR-133a.

The Liver Injury and Coagulation Dysfunction in the Patients with Severe/Critical COVID-19 / 中国实验血液学杂志

METHODS@#The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test.@*RESULTS@#Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27－80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05).@*CONCLUSION@#In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.

Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Esophageal cancer is one of the malignant tumors with a high morbidity and mortality in China. According to China's latest cancer report released by the National Cancer Center in 2019, the number of people suffering from esophageal cancer reached 246 000 in 2015, and the death toll reached 188 000. How to effectively treat esophageal cancer and improve the survival rate of patients is one of the most urgent problems in the field of medicine. Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most important signaling pathway for regulating cell survival, differentiation and apoptosis in the body. It also plays an important role in the occurrence and mechanism of various cancers. Recent studies have shown that the activation of PI3K/Akt signaling pathway is an important factor in regulating proliferation, apoptosis, cycle arrest, migration and invasion of esophageal cancer cells. The long-term clinical observation found that traditional Chinese medicine has a stable effect in the treatment of esophageal cancer and little side effects, especially in improving the quality of life of cancer patients and prolonging the survival period of patients. At present, it is a research hotspot to intervene this signal pathway with traditional Chinese medicine in the treatment of esophageal cancer, so as to explore its mechanism of action on esophageal cancer. This paper focused on literatures in CNKI and PubMed databases from 2009 to 2019, with PI3K/Akt signaling pathway, esophageal cancer and miRNA as the key words. A total of 226 literatures were retrieved, and 61 literatures relating to traditional Chinese medicine, esophageal cancer, miRNA and PI3K/Akt signaling pathway were sorted out and summarized. This paper reviewed the mechanism of PI3K/Akt signaling pathway in esophageal cancer, the relationship between miRNA and PI3K/Akt signaling pathway and esophageal cancer, and how traditional Chinese medicine can regulate the expressions of relevant proteins in PI3K/Akt signaling pathway to inhibit cell proliferation, affect cell growth cycle, induce cell apoptosis, inducing cell autophagy, inhibit tumor invasion and metastasis, inhibit angiogenesis. Finally, it can improve esophageal cancer to provide theoretical basis and scientific basis for the treatment of esophageal cancer with traditional Chinese medicine.

Research progress in immunotherapy for glioblastoma / 药学学报

Glioma is the most common primary intracranial tumor, among which glioblastoma (GBM) is the most malignant subtype. Because of its high heterogeneity and invasiveness, GBM can't be completely removed by surgical resection and is also resistance to chemotherapy and radiotherapy. Even after a standard therapy, the median survival time is only 14.6 months, the five-year survival rate is less than 10%, and the relapse of GBM is common. Immunotherapy, a new treatment paradigm, treats cancer through regulating the autologous immune system and the tumor microenvironment. As a promising method to improve the prognosis of GBM, immunotherapy has attracted more and more attention. This paper gives a review to the difficulty, the mainly existing strategies and the bottlenecks in GBM immunotherapy, aiming at providing new direction to improve the prognosis of GBM patients.

Bone Metabolic Markers in Patients with Obstructive Sleep Apnea Syndrome / 中华医学杂志(英文版)

Background@#Obstructive sleep apnea syndrome (OSAS) is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers.@*Methods@#A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density (BMD) and the serum levels of total procollagen type 1 N-terminal propeptide (t-P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), vitamin D (VD), and parathyroid hormone (PTH) were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses.@*Results@#No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels of t-P1NP and β-CTX in the severe OSAS group were significantly higher than those in the obesity group (48.42 ± 23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P < 0.001; 0.53 ± 0.24 ng/ml vs. 0.41 ± 0.13 ng/ml, P = 0.011, respectively). The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups (both P < 0.001), and decreased as the severity of OSAS increased (P < 0.001). The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups (both P < 0.001). The results of correlation analysis indicated that the level of apnea-hypopnea index (AHI) was correlated with the levels of t-P1NP (r = 0.396, P < 0.001), VD (r = -0.404, P < 0.001), and PTH (r = 0.400, P < 0.001), whereas the level of minimum Osaturation (SaOmin) was correlated with the levels of VD (r = 0.258, P = 0.016) and PTH (r = -0.376, P < 0.001).@*Conclusions@#The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.

Genetic polymorphism of CYP-1A1, CYP2D6 and risks of chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of CYP-1A1 and CYP2D6 and risks of chronic benzene poisoning (BP).</p><p><b>METHODS</b>A case control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technology was used for detecting the single nucleotide polymorphisms (SNPs) of MspI in the non-coding region of CYP-1A1 gene and c.188, g.212 position in the first extron of CYP2D6 gene.</p><p><b>RESULTS</b>The individuals with CYP1A1 MspI T/T genotype had a 1.32 times (95% CI: 1.05 approximately 1.65, P = 0.02) increased risk of BP compared with those carrying T/C and C/C genotypes. In no-smoking population, there was a 1.56 times (95% CI: 1.15 approximately 2.12, P = 0.003) increased risk of BP for subjects carrying CYP1A1 MspIT/T genotype compared with those carrying T/C and C/C genotypes. The individuals carrying CYP2D6 c.188 C/C or C/T genotype had a 1.23 times (95% CI: 1.05 approximately 1.42, P = 0.01) increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23 times (95% CI: 1.04 approximately 1.47, P = 0.01) increased risk of BP for subjects carrying CYP2D6 c.188 C/C or C/T genotypes compared with those carrying T/T genotype. The single nucleotide polymorphism of g.212 position in the first extron of CYP2D6 gene had not been validated.</p><p><b>CONCLUSION</b>The individuals with CYP2D6 c.188 C/C, CYP2D6 c.188 C/T and CYP1A1 MspIT/T genotypes tend to be more susceptible to benzene toxicity.</p>

Anti-HBV effect of fusion protein (TA1-IFN) in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the anti-HBV effect of fusion protein thymosin alpha1-interferon alpha (TA1-IFN) in vitro and to compare its effect with a combination of interferon alpha and thymosin alpha1.</p><p><b>METHODS</b>After 2.2.15 cells were seeded for 24 hours, drugs of five serial concentrations (8000, 4000, 2000, 1000, 500 U/ml) were added to the wells, then the medium was changed every three days. After 2.2.15 cells were treated with drugs for 6 days, the medium was collected. The inhibitory rates on HBsAg and HBeAg were determined using Abbot kit, and the cytotoxicity of different drugs by means of MTT colorimetric assays was also observed.</p><p><b>RESULTS</b>The inhibitory rate of fusion protein on HBsAg, HBeAg was dose-dependent and reached the maximum at 8000 U/ml concentration. In the meantime, the inhibitory rates of fusion protein on HBsAg and HBeAg were 72.2% +/- 0.8% and 60.4% +/- 1.1% respectively, and the cell survival rate was 85.2% +/- 2.0%; In the corresponding concentration, the inhibitory rates of combination thymosin alpha 1 and interferon alpha on HBsAg and HBeAg were 40.0% +/- 0.7%, 34.5% +/- 3.2% respectively. The results showed significant statistical differences between them; cell survival rate 70.0% +/- 1.9%, and the difference of the results was also significant. Cytotoxicity of fusion protein was weaker than a combination of thymosin alpha 1 and interferon alpha.</p><p><b>CONCLUSION</b>Fusion protein TA1-IFN exerted stronger anti-HBV effects in vitro. Its anti-HBV effects in vitro were stronger than the combination of thymosin alpha and interferon alpha, and its cytotoxicity was weaker than the combination of thymosin alpha and interferon alpha. Our studies provided important evidence for clinical research on TA1-IFN, and also brought new hope for hepatitis B therapy.</p>

Toxoplasma infection in males with sterility in Shenyang, China / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the Toxoplasma gondii (TOX) infection in males with sterility and the effect of the infection on the reproductive function of males.</p><p><b>METHODS</b>Enzyme linked immunoabsorbent assay (ELISA) was used to detect TOX-CAg, TOX-IgG and TOX-IgM in the peripheral blood of male patients with sterility.</p><p><b>RESULTS</b>Among 100 cases of male sterility, 7 were TOX-IgG positive (7%), 16 TOX-IgM positive (16%) and 13 TOX-CAg positive (13%). Among 100 normal males, 7 were TOX-IgG positive (7%), 3 TOX-IgM positive (3%) and 1 TOX-CAg positive (1%).</p><p><b>CONCLUSION</b>TOX infection may affect the fertility of males and cause male sterility. For this reason, males should prevent themselves from TOX infection.</p>

Study on relationship among thyroid hormone relativity and Syndrome Differentiation-types of TCM in patients with congestive heart failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the relationship between the TCM Syndrome Differentiation-types of congestive heart failure (CHF) and thyroid hormones, including triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), and atrial natriuretic peptide (ANP), as well as cardiac function parameters, including left ventricular ejection fraction (LVEF), mean velocity of circumferentid fiber shortening (mVcf) and A peak/E peak (A/E).</p><p><b>METHODS</b>One hundred patients with CHF were divided into 4 Syndrome Differentiation-type groups, their cardiac function parameters, ANP and thyroid hormones were determined and compared with those in the 23 subjects in the control group.</p><p><b>RESULTS</b>In CHF patients with edema and blood stasis Syndrome type, the level of plasma ANP was significantly higher than that in the control group (P < 0.05); level of T3 was significantly lower than that in the control group and in CHF patients of other three (Xin-qi deficiency, Yin-deficiency and blood stasis) Syndrome groups (P < 0.01, P < 0.01, P < 0.05 and P < 0.01); levels of LVEF and mVcf were significantly lower than those in the other three Syndrome groups (all P < 0.01). Level of T4 in other three Syndrome groups significantly increased than that in the edema and blood stasis Syndrome type. A/E value showed a higher level in patients of all TCM type than that in the control (P < 0.01). Correlation analysis showed that T3 was positively correlated with LVEF and T4 (r = 0.200, P < 0.05, and r = 0.293, P < 0.01), and negatively correlated with ANP (r = -0.263, P < 0.01); T4 was negatively correlated with A/E (r = -0.226, P < 0.05).</p><p><b>CONCLUSION</b>The lowering of T3 and T4 and increasing of ANP may be one of the important reasons for lowering of LVEF in CHF patients with edema and blood stasis Syndrome-type. The decrease of T4 may be one of the important reasons for elevation of A/E and aggravation of left ventricular diastolic dysfunction in CHF patients of all the 4 TCM Syndrome-types.</p>

Clinical application of MR diffusion tensor imaging in lumbar disc annulus fibrosus / 中华放射学杂志

0.05).Seven cases in LDH group and 9 cases in HID group were found in FT picture.The mean DCavg value in annulus fibrosus disruption was significantly larger (1.01?0.10)?10~(-9)mm~2/s and the mean FA value(0.15?0.03)was significantly smaller than those in normal place(P