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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.
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【Objective】 To reduce the occurrence of adverse reactions to blood donation during platelet collection in female blood donors with low body weight and high platelet count, so as to improve the comfortableness during platelet collection and increase the proportion of repeated blood donors. 【Methods】 The control group and observation group were compared to explore the causes that may cause adverse reactions in the blood collection cycle using blood collection process program software in MCS+, and the incidence of blood donation reaction was compared and observed by increasing the times of oral administrations of calcium gluconate by 10%, increasing the number of collection cycles and reducing the peak plasma volume of the last cycle. 【Results】 After comparing the two groups, it was found that the incidence of adverse reactions in the observation group and the control group was 16.7%(3/18) and 81.2%(26/32), the proportion of repeated donors in the observation group and the control group was 77.7%(14/18) and 31.2%(10/32). 【Conclusion】 Female platelet donors with low body weight and high platelet count should be given more care during the collection process. It is suggested that giving more times of oral administrations of calcium gluconate by 10% and one more collection cycle to reduce the collection peak in each cycle, as well as the supplement of saline, which can effectively reduce the occurrence of adverse reactions to blood donation, thus improving blood donation satisfaction and increasing the proportion of repeated blood donors.
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【Objective】 To compare the platelet apheresis donation rate via telephone and WeChat appointment in Shijiazhuang area during the COVID-19 epidemic, so as to give suggestions for optimizing blood donation appointment in major public events. 【Methods】 The number and appointment type of apheresis donors from January to March 2019(the control) vs January to March 2020(study group 1) vs January to March 2021(study group2) in Shijiazhuang area were collected. A total of 1 204 and 1 305 questionnaires were distributed to two study groups to analyze their acceptance of telephone and WeChat appointment. 【Results】 More turnout donors preferred WeChat appointment, relative to telephone calls, during January to March 2020 and 2021. But some inactive donors preferred appointment given by telephone calls. 【Conclusion】 Different appointment methods should be adopted to recruit blood donors according to the targets of blood centers, in the event of national or local COVID-19 epidemic.
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Objective:To investigate the effects of highly active anti-retroviral therapy (HAART) on the activation of T lymphocytes and expression of CD4 + CD45RA + T cell subsets in HIV/AIDS patients. Methods:This study prospectively analyzed 105 HIV/AIDS patients undergoing HAART and 35 HIV-1-negative cases (healthy controls). Flow cytometry was used to detect the activation of T lymphocytes and the percentages of CD4 + CD45RA + T cell subsets in whole blood samples taken from healthy controls and HIV/AIDS patients before and after therapy. Results:The activation of T lymphocytes was significantly enhanced in the 105 HIV/AIDS patients than in the healthy controls before treatment ( P<0.01). The activated T lymphocytes gradually decreased after HAART. Firstly, CD4 + CD38 + HLA-DR + , CD8 + CD38 + and CD8 + HLA-DR + T lymphocytes decreased one month after therapy ( P<0.05). Then, four indicators of T lymphocyte activation including the expression of CD8 + CD38 + HLA-DR + T lymphocytes decreased significantly six months after therapy ( P<0.01). The percentage of CD8 + CD38 + HLA-DR + T lymphocytes detected 12 months after therapy was significantly lower than that analyzed six months after therapy ( P<0.01). No significant difference was found in the expression of the other three indicators for activation ( P>0.05). Twelve months after therapy, the four indicators for T lymphocyte activation in HIV/AIDS patients were still significantly higher than those of the control group ( P<0.01). The percentages of CD4 + CD45RA + T lymphocytes in HIV/AIDS patients were significantly lower than those in healthy controls before and 12 months after treatment ( P>0.05). Conclusions:HAART could reduce immune activation after six months of treatment, but could not reverse the activation nor restore the expression of CD4 + CD45RA + T lymphocytes in HIV/AIDS patients.
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Objectives To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM).Methods A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion.Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection.Results A total number of 4 305 MSM were followed during 2013-2015.Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms.HIV incidence among followed MSM during the study period appeared as 4.3/100 person years,with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95％ CI:1.49-3.24) times than that of insertion anal intercourse group.Those who used rush-poppers (aRR=1.55,95％CI:1.10-2.17),unprotected anal intercourse (aRR=2.24,95％ CI:1.62-3.08),and those with syphilis infection (aRR=2.95,95％ CI:2.00-4.35) were also risk factors for HIV new infections.After controlling other factors,the relationship between the ways of seeking partners and HIV new infection was not statistical significant.Conclusion Risk factors for HIV new infection among MSM appeared complex and interactive,suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.
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Cholesteatoma is an abnormal formation of benign cystic lesions from the squamous epithelium of the temporal bone, and the local invasive growth could damage the structures of middle ear. Cholesteatoma has been the research focus in otorhinolaryngology, however the pathogenesis of it is still unclear. From the previous studies we found that the epidermal proliferation was one of the important factors in the pathogenesis of the cholesteatoma, which was also involved in multiple proliferation pathways. In this paper, we briefly reviewed the progress and the mechanisms of the actions of cholesteatoma in these pathways.
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Objective: To study the clinical efficacy of Sini-Moxibustion in the treatment of cancer-induced fatigue in patients with yang- deficiency gastrointestinal cancer. Methods: A total of 120 patients with gastrointestinal cancer treated in our department from January 2017 to January 2018 were randomly divided into 2 groups: the fire moxibustion group and the conventional group. The conventional group and the fire therapy group were treated with basic treatments such as anti-cancer and nutritional support. The conventional group added Sini-Moxibustion to the basic treatment, and the fire therapy group added"Sini-Moxibustion"therapy for a period of 1 month. Tthe indicators of the 2 groups of patients with Piper fatigue scale and grade, quality of life, symptoms of yang deficiency symptoms, clinical efficacy and blood tests of patients with chemotherapy were evaluated. Results: After the treatment, the degrees of fatigue in the fire moxibustion group was lower than that in the conventional group with statistically significant difference ( χ2 =4.24, P =0.037 ＜ 0.05). The scores of improvement in the quality of life scale and five subscales in the fire moxibustion were higher than those in the conventional group with statistically significant difference (P ＜ 0.01), and the improvement score of the body yang deficiency in the fire moxibustion group was greater than that of the conventional group (P ＜ 0.01). The scores of fatigue, nausea and vomiting, insomnia, anorexia, and diarrhea in the fire moxibustion group were higher than those in the conventional group with statistically significant difference (P ＜ 0.05 or P ＜ 0.01). After treatment, the total effective rate was 76.67％ in the fire moxibustion treatment group, which was higher than the conventional group 91.53％ with statistically significant difference ( χ2 =5.64, P =0.012 ＜ 0.01). Hemoglobin improvement value of 3.92 ± 1.18 in the fire moxibustion group was higher than that of the conventional group 1.02 ± 0.52 with statistically significant difference (t =7.212, P =0.003 ＜ 0.01). Conclusion: Sini-moxibustion can improve the CRF of patients with yangdeficiency gastrointestinal cancer, reduce the symptoms of yang deficiency, improve the quality of life, and increase the hemoglobin content in patients with chemotherapy.
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Objectives To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM).Methods A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion.Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection.Results A total number of 4 305 MSM were followed during 2013-2015.Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms.HIV incidence among followed MSM during the study period appeared as 4.3/100 person years,with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95％ CI:1.49-3.24) times than that of insertion anal intercourse group.Those who used rush-poppers (aRR=1.55,95％CI:1.10-2.17),unprotected anal intercourse (aRR=2.24,95％ CI:1.62-3.08),and those with syphilis infection (aRR=2.95,95％ CI:2.00-4.35) were also risk factors for HIV new infections.After controlling other factors,the relationship between the ways of seeking partners and HIV new infection was not statistical significant.Conclusion Risk factors for HIV new infection among MSM appeared complex and interactive,suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.
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Objective To investigate the changes in the percentages of CD4+T lymphocyte subsets and the homeostasis of T lymphocytes among MSM ( men who have sex with men) population with different stages of HIV-1 infection. Methods A total of 166 untreated MSM with HIV infection were enrolled and di-vided into three groups including early HIV infection (EHI, n=38) , HIV (n=94) and AIDS (n=34) groups. Sixty-two MSM negative for anti-HIV antibody were selected as healthy controls. Blood samples were collected into EDTA tubes and detected to analyze the changes in the distribution of CD4+ T cells and CD8+T lymphocyte subsets ( CD4+ CD45RA+, CD8+ CD28+, CD4+ CD25+ CD127-) and the percentages of activated (CD38, HLA-DR) and apoptotic cells (CD95) with disease progression by flow cytometry. Re-sults The expression of CD4+CD45RA+ T lymphocytes gradually decreased with the progression of AIDS. The percentage of CD4+CD45RA+ T lymphocytes in HIV group was lower than that of the control group, but higher than that of the AIDS group (P=0. 015, P=0. 000). No significant difference was found between the EHI and the control groups (P>0. 05). CD8+CD28+T cells were significantly reduced in the EHI group and remained at a low level with disease progression. No significant difference in the proportion of CD4+CD25+CD127- T cells was observed among all groups (P>0. 05). The percentage of CD4+CD38+HLA-DR+T cells increased gradually and the highest level was detected in the AIDS group, followed by those in the HIV, EHI and control groups (P<0. 01). The percentages of CD8+CD38+, CD8+HLA-DR+, CD8+ CD38+HLA-DR+and CD8+CD95+T cells in the EHI, HIV and AIDS groups were significantly higher than those in the control group (P<0. 01), but there was no significant difference among the former three groups (P>0. 05). Con-clusion HIV infection caused the changes in the numbers and functions of T lymphocyte subsets and accel-erated the activation and apoptosis of T lymphocytes, which aggravated the T lymphocyte immune dysfunction even further. A comprehensive analysis of the alterations in different T cell subsets would be conducive to re-flect the immune deficiency and the severity of disease. CD4+ and CD8+ T cells were activated in the early stage of HIV infection, which indicated that studying the immune response during that stage might help to understand their roles in disease progression.
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Chemotherapy is one of the primary treatment for malignant tumors.Platinum drugs as the most commonly used cycle non-specific clinical antitumor drugs show good curative effect in the clinical treatment of solid tumors,however,resistance or cross-resistance of theplatinum analogous has become one of the main obstacles for platinum and its analogous,which limits their clinical applications.miRNAs play an important role in biology,including cell proliferation,differentiation,apoptosis,stress tolerance,and physiological metabolism.There is a close relationship between miRNAs target gene regulation and tumor drug-resistance.This article is mainly about the role of miRNAs in tumor of platinum resistance.
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Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.
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Objective To investigate the chemokine 12 (CXCL12) and chemokine receptor 4 (CXCR4) expressions in hypopharyngeal carcinoma and its place in the disease development,invasion and metastasis of significance.Methods Immunohistochemistry was used to detect the expressions of CXCL12 and CXCR4 in 35 cases of hypopharyngeal cancer tissues and in 28 cases of tumor-adjacent non-tumor tissues.Results The expressions of CXCL12 and CXCR4 in the hypopharynx carcinomas were significantly higher (P ＜ 0.05).Both expressed in hypopharyngeal carcinomas was significantly positively correlated (P ＜ 0.01).Both hypopharynx cancer in lymph node metastasis group were significantly higher than the expression of cervical lymph node metastasis group,the difference was significant (P ＜ 0.05).Conclusions CXCL12 and CXCR4 are involved in hypopharynx cancer development,invasion and metastasis,and there is a positive feedback regulation mechanism between two factors.Moreover,CXCL12 and CXCR4 have synergistic effect in development,invasion and metastasis of hypopharynx cancers.
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Gastric cancer is a malignant disease with high incidence and mortality. The therapeutic methods for advanced gastric cancer, including chemotherapy and targeted therapy are very limited. Immunotherapy is a new method for cancer treatment. The immune checkpoint inhibitors developed for cancer treatment mainly target the CTLA-4 and PD-1/PD-L pathways. There have already been several inhibitors approved for the treatment of melanoma and non-small cell lung cancer by the FDA, including Ipilimumab (fully human antibody against CTLA-4), Pembrolizumab (fully human antibody against PD-1) and Nivolumab (fully human antibody against PD-1). There are also many on-going clinical trials investigating the value of immune checkpoint inhibitors in treating various malignancies, including advanced gastric cancer. In KEYNOTE-012 trial, for advanced gastric and esophagogastric junction cancer anti-PD-1 therapy seemed to be safe and effective for advanced gastric cancer with PD-L1 positivity. Moreover, studies of adoptive cell therapy and tumor vaccine in gastric cancer are underway. Here the latest developments in immunotherapy for gastric cancer will be illustrated.
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Humans , Antibodies, Monoclonal , Therapeutic Uses , Antibodies, Monoclonal, Humanized , Therapeutic Uses , B7-H1 Antigen , Metabolism , CTLA-4 Antigen , Metabolism , Disease Progression , Immunotherapy , Ipilimumab , Programmed Cell Death 1 Receptor , Metabolism , Stomach Neoplasms , TherapeuticsABSTRACT
Objective To explore the feasibility of adding a flexible linker between two-pore-domain potassium channel TREK-1 (TWIK related K + channel 1)monomers to construct a tandem-linked dimer.Methods PCR was used to add a flexible linker between the two TREK-1 monomers.The cRNA obtained from in vitro transcription using the above vector was injected into Xenopus oocytes.After 24 -48 h,currents were recorded from these oocytes using a two-electrode voltage clamp.The effects of extracellular Ba2 + and pH on TdTREK-1 were observed and compared with those of native dimeric TREK-1.Results The tandem-linked dimeric TdTREK-1 was highly expressed in Xenopus oocytes.The currents through these channels were inhibited by extracellular Ba2 +and acidification.Furthermore,the responsiveness of the concatenated dimers to these extracellular stimuli was similar to that of native dimers.Conclusion Adding a flexible linker between the two monomers to construct the tandem-linked dimer does not affect the expression and gating properties of TREK-1, suggesting that the method be feasible.Such a method will allow the manipulation of a single subunit,which will help basis study the structure and function of TREK-1.
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OBJECTIVE To investigate the effect of clopidogrel(Clog),a platelet aggregation inhibitor,on the development of colitis-associated colon cancer(CAC)and its possible mechanism. METHODS To establish a CAC model,male BALB/c mice were treated with single azoxymethane(AOM) 10 mg · kg-1 by ip. One week later,the mice drank 2.5% dextran sulfate sodium(DSS)for one week and water for two weeks,which lasted three cycles. From the first day mice received 2.5%DSS water, Clog 12.5,25.0 and 50.0 mg · kg-1 was ig administered once a day. Body mass,clinical symptoms,the number of colon tumor and tumor size in colon tissue were recorded. Hyperplasia of tumors was analyzed by HE staining. In the early inflammatory phase of the CAC model,the length of colons was measured, histological structure and epithelium cell proliferation of colon tissues were evaluated by HE staining and Ki67 staining,respectively. In the tumorigenesis and progression phase of the CAC model,epithe?lium cell proliferation of colon tissues was evaluated by Ki67 staining. The mRNA expression of tumor necrosis factor-α(TNF-α)was detected by real-time quantitative PCR. The expression of chemokine(C-X-C motif)ligand 2(CXCL2)and its receptor 2(CXCR2)in colon tissues was detected by PCR and immu?nohistochemistry. RESULTS Compared with model group,clinical symptoms of mice in Clog 12.5 mg · kg-1 group were alleviated,the size of colon tumors was decreased(P<0.05),and hyperplasia of tumors was reduced(P<0.05). During the inflammatory phase,the clinical symptoms of mice in Clog 12.5 mg·kg-1 group were significantly alleviated(P<0.05),the decrease of body mass was reduced(P<0.01),the colon shrinkage was ameliorated(P<0.01),the inflammatory injury and epithelium cell proliferation in colon tissues were reduced(P<0.05). During the tumorigenesis and progression phase,epithelium cell prolif?eration in colon tissues in Clog 12.5 mg·kg-1 group was reduced(P<0.01),and the mRNA and protein expression of TNF-α,CXCL2 and CXCR2 of colon tissues was decreased(P<0.05). CONCLUSION Clog can alleviate inflammation during the CAC early inflammatory phase and inhibit the formation of CAC. The antitumor effect of Clog may be related to the decrease in expression of CXCL2 and CXCR2.
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The combined teaching method of case-based learning and W2 H2 thinking-type learning was used in the comparative morphology experiment teaching.The teaching method can further strengthen the reform of the compar-ative morphology experiment teaching, and improve the quality of practice teaching.
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Aim To investigate the roles of FFJ-5 in human breast cancer MCF7 cells and drug-resistant MCF7/DOX cells and to explore its mechanisms. Methods MTT assay was used to detect the effect of FFJ-5 on MCF7 and MCF7/DOX cell proliferation and sensitivity of doxorubicin in MCF7/DOX cells.West-ern blot was used to investigate the effect of FFJ-5 on expression of EGFR,p-EGFR,Akt,p-Akt,PKM2, cleaved caspase-3,cleaved PARP and P-gp.DNA lad-der analysis was performed to determine the effect of FFJ-5 on genomic DNA.RT-PCR was performed to de-tect the influence of FFJ-5 on multidrug resistance gene MDR1 mRNA levels.Results The results showed that FFJ-5 inhibited the growth of MCF7 ,inhibited the expression and activity of EGFR and Akt,and conse-quently reduced the expression of PKM2 in MCF7 cells;FFJ-5 activated caspase-3 and induced genomic DNA fragmentation;FFJ-5 also inhibited the growth of MCF7/DOX cells and enhanced the anti-tumor activity of doxorubicin in MCF7/DOX cells.Conclusion The results suggest that FFJ-5 could inhibit MCF7 cell growth and induce MCF7 cell apoptosis through inhibi-tion of EGFR-Akt-PKM2 pathway and activation of ap-optosis-related factors caspase-3 , meanwhile FFJ-5 could also reverse the resistance of MCF7/DOX.
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Objective To investigate the correlation between toll-like receptor 9 (TLR9) gene 2848G/A polymorphism and primary antineutrophil cytoplasmic antibodies (ANCA) associated small vasculitis (AAV). Methods A case-control study was performed among 135 patients diagnosed with AAV and 140 disease-free control and we test the serum biochemical parameter. Polymorphism was analyzed by polymerase chain restricted fragments length polymorphism. As for statistic method, according to the character of data, we performed t-test, chi-square test, Spearman grade related analysis and one-way ANOVA. Results ① The frequencies of AA, GG, GA genotype of TLR9 2848 in AAV patients were 14.07%, 38.52%, and 47.71%, respectively; ② Significant increase in IgM was observed in AA genotype than GG+GA genotype in AAV patients (F=4.561, P0.05). Conclusion AA, GA and GG genotypes are detected in TLR9 2848G/A in patients with AAV in Guangxi, without significant correlation with susceptibility to primary AAV in Guangxi.
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Objective To investigate the subtype distribution of HIV-1 infection among men having sex with men (MSM) in Xi' an city.Methods 5 ml anti-coagulating blood samples were collected from MSM who had been reported during 2010-2012 in Xi'an.Both gag and env genes were amplified by nested RT-PCR from the extracted RNA and then sequenced.The acquired sequences were compared with international subtype references,and then the genetic distances were calculated and phylogenetic trees were constructed by Mega 5.2.Epidemiological information including sexual behavior characteristics,history of drug use,blood donation,etc.were gathered.Results 168 samples were successfully amplified and sequenced.Results from Phylogenic analysis showed that the gag and env sequences of 165 samples shared the same subtypes,of which 79 (47.0％) were CRF01_AE,74 (44.0％) were CRF07_BC and 12 (7.1％) belonged to subtype B.There were 3 samples with gag and env sequences classified into different subtypes,of which 2 (1.2％) were CRF01_AE/A1,and the other 1 was CRF07_BC/CRF01_AE.Conclusion At least three HIV-1 subtypes including CRF01_AE,CRF07_BC were identified among MSM population in Xi'an city.
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Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood-brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.