To summarise Professor WANG Xixing's experience in treating brain tumour from emotions and minds. Professor WANG regarded abnormal emotions and minds as the key to the treatment of brain tumor. Emotions and minds internal damage lead to malfunction of the five zang organs， resulting in phlegm， stasis， dampness， toxicity and other pathogenic qi gathering in the brain and developing into brain tumour. The treatment advocated regulating qi of the five zang organs and dispelling phlegm， blood stasis， dampness and toxins at the same time. The brain tumour is classified into four syndromes： heart-spleen deficiency， liver depression and spleen deficiency， failure of the heart and kidney to interact， and liver-kidney yin deficiency， with Guipi Yangshen Decoction （归脾养神汤） to fortify the spleen and nourish the heart， Guishao Shunzhi Decoction （归芍顺志汤） to soothe the liver and fortify the spleen， Liangui Tongshen Decoction （连桂通神汤） to restore interaction between the heart and the kidney， and Zishui Qingmu Huashen Decoction （滋水清木化神汤） to nourish the kidney and clear liver. At the same time， it was emphasised that the patient's emotional changes should be paid attention to， and psychological guidance should be given at the right time， so as to overcome the disease with emotions and mind.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

【Objective】 To analyze the HIV-, HCV- and HBV- NAT yield rate in different areas of Henan province, so as to provide the basis for disease prevention and control as well as the establishment of a unified quality control standard for nucleic acid testing(NAT) in the Henan province. 【Methods】 The number and prevalence of NAT yielding samples with isolated infectious virus, namely HIV, HCV and HBV, in 18 blood stations in Henan province from 2017~2019, as well as the trends were analyzed. The NAT quality of each laboratory and each testing system was analyzed according to the ratio of reactive individual donation(ID) results to reactive minipools(MP). 【Results】 The HBV, HCV and HIV ID-NAT yield numbers in 3 501 251 blood donations were HBV 2 606(74/100 000), HCV 21 (0.63/100 000), and HIV 34(1.00/100 000). The HBV ID-NAT yield rate showed an upward trend in the whole province from 2017 to 2019, while the prevalence of HIV and HCV ID-NAT yield didn′t differ significantly during three years. 5 kinds of NAT detection systems were applied in 18 blood centers. among which Ⅰ, Ⅱ, Ⅳ and Ⅴ were triplex detection systems. 2661 ID-reactive samples were implicated in 5 595 MP-reactive samples, with a resolution rate of 47.56%. The resolution rate of triplex NAT system Ⅰ, Ⅱ, Ⅳ and Ⅳ was 39.63%~47.95%, 40.43%~54.36%, 51.61% and 70.00%~45.45%, respectively. An upward trend in triplex NAT resolution rate was observed in 8 laboratories, i. e.B, D, E, F, I, K, L and Q, and an descending trend in A and C. The NAT system Ⅲ, a ID-NAT system, was used only by laboratory C, presenting a NAT-yield rate of 0.19% (282/145 474) and resolution rate of 46.45% (131/282). 【Conclusion】 The majority of NAT-yield of one infectious virus in Henan province is HBV, presenting annual increasing trend. The quality management of NAT laboratories should be strengthened as the divergence was seen in the performance of different NAT laboratories.

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.
Escherichia coli ; Fibroblasts ; Humans ; Inflammation/drug therapy* ; Nanoparticles

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

BACKGROUND: Electromagnetic navigation bronchoscopy is a tool that can accurately navigation peripheral lung lesions. Because of electromagnetic navigation bronchoscopy (ENB) is too expensive, it has not been widely used in China. It is urgent for us to summarize experience in clinical application, especially in the diagnosis of pulmonary nodules. METHODS: The clinical data of patients with pulmonary peripheral lesions (PPLs) in our department undergoing ENB biopsy between July 2017 and December 2018 were retrospectively analyzed. RESULTS: There were 18 patients with 21 PPLs (10 males and 8 females). Among them, 11 patients got the final pathological diagnosis, 8 cases were diagnosed with adenocarcinoma lung cancer, 1 case was diagnosed with tuberculosis and 2 cases were diagnosed with small cell lung cancer. The positive rate of diagnosis was 61.1%. The sensitivity was 73.3%. The positive diagnosis rate is related to the size of the lesion, the positive diagnosis rate for lesions >2 cm is 100.0% (P=0.04). CONCLUSIONS Electromagnetic navigation bronchoscope is safe and effective in clinic. It has a high positive rate for the diagnosis of peripheral lung lesions larger than 2 cm, ENB has broad clinical application prospects.

PURPOSE: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) was implicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-induced liver injury. MATERIALS AND METHODS: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-time quantitative PCR and western blot. Liver injury was determined by levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory cytokines, numbers of infiltrating mononuclear cells using AST/ALT assay kit, enzyme-linked immunosorbent assay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 was predicted on targetScan software, and confirmed by luciferase reporter assay. RESULTS: SEB induced liver injury in D-galactosamine (D-gal)-sensitized mice, as demonstrated by increased serum levels of AST and ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, and promoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulated in SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviated liver injury accompanied with SOCS1 upregulation. Besides, splenocytes under SEB challenge released less INF-γ, TNF-α, IL-6, and IL-2 during miR-222-3p knockdown. Mechanically, SOCS1 was targeted and downregulated by miR-222-3p. Upregulation of SOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block the suppressive role of miR-222-3p knockdown in SEB-induced splenocytes. CONCLUSION: Inhibition of miR-222-3p relieves SEB-induced liver inflammatory injury by upregulating SOCS1, thereby providing the first evidence of miR-222-3p in SEB-induced liver injury.
Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Blotting, Western ; Cytokines ; Down-Regulation ; Enterotoxins ; Enzyme-Linked Immunosorbent Assay ; Interferon-gamma ; Interleukin-2 ; Interleukin-6 ; Liver ; Luciferases ; Lung Injury ; Mice ; Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; Up-Regulation

Objective To investigate the relationship between corneal basal nerve change and type 2 diabetic retinopathy based on confocal laser microscopy.Methods Together 118 patients with type 2 diabetes (T2D) were collected in our hospital from February 2016 to February 2017,including 57 patients with diabetic retinopathy (DR group) and 61 patients without DR (NDR group).For comparison,60 healthy volunteers were selected as the control group.And all the subjects were examined by corneal confocal laser microscopy to analyze the relationship between the morphological parameters of the corneal nerve and clinical variables.Results Corneal nerve fiber density,corneal nerve branch density and corneal nerve branch length in DR group were (20.03 ±4.22) · mm-2,(22.01 ± 7.05) · mm-2 and (9.50 ± 1.76) mm ·mm-2,significantly less than those of the control group and NDR group (all P ＜ 0.05);and corneal nerve fiber curvature was (0.30 ± 0.03),significantly higher than that of the control group and NDR group (all P ＜ 0.05);In DR patients,phase Ⅲ patients had smaller the corneal nerve fiber density,corneal nerve branch density and corneal nerve branch length,but the larger corneal nerve fiber curvature than the phase Ⅰ and Ⅱ patients (all P ＜ 0.05);course of disease of DR group was (12.04 ± 2.48) years,which was significantly higher than that of NDR group (P ＜ 0.05),while fasting C peptide and fasting insulin were (1.41 ± 0.58) μg · L-1 and (20.05 ± 7.91) mU · L-1,respectively,significantly lower than those of NDR group (all P ＜ 0.05);The duration of T2D was negatively correlated with the corneal nerve branch density and corneal nerve branch length (r =-0.322,-0.317,all P ＜0.05);Fasting C peptide was positively correlated with the corneal nerve branch density (r =0.298,P ＜ 0.05),and negatively correlated with the corneal nerve curvature (r =-0.311,P ＜ 0.05).Conclusion Patients with T2D retinopathy have abnormal morphology of corneal nerve.And confocal laser scanning microscopy is conducive to the early detection of microvascular disease in T2D patients with a longer course of disease or a low level of fasting C peptide.

[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.