Research of pharmacokinetics of thalidomide in SD rats with inflammatory bowel disease / 中国药理学通报

Aim To investigate the absorption of thalidomide in inflammatory bowel disease(IBD)SD rats compared with healthy rats to provide a basis for the safety and efficacy of thalidomide in clinical practice. Method The IBD rat model was induced by the 2, 4, 6-trinitrobenzene sulfonic acid, by which the rats were continuously intervened for six days. The general state and disease activity index of the rats were recorded every day. The rats in IBD group after modeling and control group were administered with thalidomide at a dose of 10 mg·kg-1. The blood sample of the rats was collected at different time points. After a comprehensive evaluation of morphological and histopathological results, the samples of rats with IBD were determined by proven high performance liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated and compared with the healthy rats. Results The body weight of rats in IBD group was obviously lower than that in control group and the disease activity index, score of colonic macroscopic morphous and histopathology were obviously higher than those in control group. The success rate of modeling was 62.5%. The pharmacokinetic results showed that the Cmax(P<0.05)and AUC(P<0.01)of the IBD group both increased by 2 to 3 times, but there was no significant difference in t1/2,Tmax,MRT and other parameters. Conclusions The rate and extent of oral thalidomide absorption of rats in the model of inflammatory bowel disease significantly increase compared to those of healthy rats, which may provide new considerations for clinical practice of thalidomide in the treatment of IBD.

Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation / 国际口腔科学杂志·英文版

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i-/- odontoblasts. Through treating pulp precursor cells with Atp6i-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.

Spike-specific CXCR3+ TFH cells play a dominant functional role in supporting antibody responses in SARS-CoV-2 infection and vaccination

CD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3- TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3- TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3- TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory. HighlightsO_LISARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, which persisted for at least two years in the majority of symptomatic COVID-19 convalescent patients. C_LIO_LIInactivated vaccine immunization also elicited spike-specific TFH cell and antibody responses, which rapidly declined over time, and a third dose significantly promoted antibody maturation and potency. C_LIO_LISpike-specific CXCR3+ TFH cells exhibited more durable responses than spike-specific CXCR3- TFH cells, correlated with antibody responses and showed superior capacity in supporting ASC differentiation and antibody production than spike-specific CXCR3- TFH cells. C_LI

Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451 / 中国结合医学杂志

OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

Improvement on compactibility of the alcoholic extract of Zingiberis Rhizoma by co-spray drying with HPMC / 中国中药杂志

Aiming to solve the poor compactibility of the alcoholic extract of Zingiberis Rhizoma(ZR), this study explored the feasibility of its physical modification using co-spray drying with a small amount of hydroxypropyl methyl cellulose(HPMC). Based on the univariate analysis, the influence of two independent variables(the HPMC content in the product and the solid content of spray material) on the powder properties and tablet properties of the dried product was investigated by the central composite design. With the tensile strength and disintegration time of the tablets as the evaluation indexes, the optimal prescription was determined as follows: the HPMC content was 15% and the solid content of spray material was 25.6%. The accuracy of the regression model established for predicting tensile strength and disintegration time of tablets was verified, and the results revealed that the measured values were close to the predicted ones with deviations of 0.47% and-8.2%, indicating good prediction and reproducibility of the model. The tensile strength(4.24 MPa) of tablets prepared with the optimal prescription was 3.59 times that(1.18 MPa, far lower than the baseline of 2 MPa for qualified tablets) with the spray-dried powder of the ZR. On the other hand, due to the addition of HPMC, the disintegration time of tablets increased from 7.3 min to 24.6 min. On the whole, this study provided a new strategy to solve the common problem of poor compactibility of raw Chinese medicinal materials, which facilitated the successful preparation of Chinese medicinal tablets with high drug loads.

Effect of Ranae Oviductus Protein Hydrolysate on Ethanol-induced L-02 Cell Injury / 中国实验方剂学杂志

Objective:To study the protective effect and mechanism of Ranae Oviductus protein hydrolysate （ROPH） on the expression of pathway-related proteins in ethanol-induced L-02 cell injury. Method:The ROPH was prepared by compound enzymatic hydrolysis. L-02 cell injury model was induced with 400 mmol·L^-1ethanol. Cell viability was detected by cell counting kit-8 （CCK-8） assay. Cell cycle and apoptosis were examined by flow cytometry. JC-1/Hochest staining was employed for qualitative investigation. The expression of related proteins in apoptosis， mitogen-activated protein kinase （MAPK） signaling pathway， and pyroptosis in L-02 cells was detected by Western blot. Result:The results of the CCK-8 assay showed that 400 mmol·L^-1ethanol could induce L-02 cell injury within 12 hours. Compared with the blank group， the model group showed decreased viability of L-02 cells （<italic>P</italic><0.01）， elevated percentage of the cell cycle in the G₀/G₁ phase （<italic>P</italic><0.01）， increased total cell apoptosis rate （<italic>P</italic><0.01）， reduced mitochondrial membrane potential （<italic>P</italic><0.01）， up-regulated expression of apoptosis-related proteins ［B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Cytochrome C （Cyt C）， and cysteine-dependent aspartate specific protease-3 （Caspase-3）］ （<italic>P</italic><0.05， <italic>P</italic><0.01） and MAPK signaling pathway-related proteins ［C-Jun amino-terminal kinase （JNK） and p38 MAPK］ （<italic>P</italic><0.05， <italic>P</italic><0.01）， and potentiated expression of pyrolysis-related proteins Caspase-1 and interleukin-1<italic>β </italic>（IL-1<italic>β</italic>） （<italic>P</italic><0.05）. Compared with the model group， the ROPH treatment group exhibited improved cell cycle arrest （<italic>P</italic><0.05， <italic>P</italic><0.01）， diminished total cell apoptosis rate （<italic>P</italic><0.01）， elevated mitochondrial membrane potential in a dose-dependent manner， down-regulated expression of Bax， Cyt C， and Caspase-3 proteins （<italic>P</italic><0.05， <italic>P</italic><0.01）， up-regulated expression of Bcl-2 protein （<italic>P</italic><0.05， <italic>P</italic><0.01）， and a downward trend in expression of proteins related to MAPK signaling pathway and pyrolysis （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:ROPH could inhibit oxidative stress-triggered liver injury in ethanol-induced cells by improving mitochondrial membrane potential， reducing the expression of proteins in the mitochondria-mediated apoptosis pathway， and inhibiting the expression of proteins related to the MAPK signaling pathway and pyrolysis pathway to reduce the mitochondrial dysfunction and inflammatory response in ethanol-induced L-02 liver cells and inhibit oxidative stress， thereby exerting a therapeutic role in alcoholic liver injury.

Quality value transmitting of volatile components in personalized preparations:a case study of Menthae Haplocalycis Herba / 中国中药杂志

Considering the characteristic chromatograms and quality value transmitting of three volatile components, this study investigated the changes in volatile components of Menthae Haplocalycis Herba in each heating process of personalized preparations and identified the critical control points for the application of volatile components from traditional Chinese medicine in such preparations. The characteristic chromatograms of volatile components in Menthae Haplocalycis Herba were established by gas chromatography, followed by the quantitative determination of three volatile components menthone, menthol, and piperitone and the comparison of retention rates of volatile components during the crushing, extraction, concentration and drying of preparation products and their change rules in characteristic peaks. The results showed that the volatile components of Menthae Haplocalycis Herba were reduced in each process. The loss rate was low in the crushing process when the volatile component peaks were present, but high in the extraction and concentration processes, manifested as the absence of partial component peaks and the presence of new component peaks. The changes in volatile components of Chuanxiong Chatiao Granule in the drying process were compared with those in Chuanxiong Chatiao Pill, both of which were prepared from the raw Menthae Haplocalycis Herba powder, and the findings demonstrated that Chuanxiong Chatiao Pill was superior to Chuanxiong Chatiao Granule. This study confirmed that the retention rates of volatile components in Menthae Haplocalycis Herba were mostly affected by the extraction and concentration processes, and the packing of preparations helped to reduce the loss of volatile components in Menthae Haplocalycis Herba powder, which has provided reference for the application of Chinese medicinal materials containing volatile components in the personalized preparations.

Characteristics and development assumptions of personalized traditional Chinese medicine granules / 中国中药杂志

Personalized traditional Chinese medicine(TCM) granules are positioned as a solid dosage form of TCM decoctions, boasting strong applicability and wide application range. The market prospect of personalized TCM granules is promising in that their preparation by mixed decoction makes up for the shortcoming of formula granules like the Chinese patent medicine granules and classical TCM prescription granules whose components cannot be changed flexibly. However, such factors as insufficient basic research, equipment mismatch, and low process commonality have limited their clinical application. After analyzing the characteristics of perso-nalized TCM granules, their production status, and the bottlenecks restricting their development, this paper pointed out the meaning and key points of developing a generalized preparation process for personalized TCM granules and affirmed the vital roles of the preparation and process prediction system and the on-line detection technology in improving the productivity of granulation. Finally, some assumptions on technology development for solving the specific problems of personalized TCM granules were shared to provide some ideas for the application and development of personalized TCM granules in clinical practice.

Evaluation of effect of oral health intervention on children in Shaoshan area of Hunan province / 北京大学学报(医学版)

OBJECTIVE@#To understand the oral health status of children aged 3-12 in Shaoshan area of Hunan province and to evaluate the role of oral health educations based on community such as fluoride varnish, oral hygiene introduction in improving the oral health of children in the area so as to gain expe-rience.@*METHODS@#The study used cluster sampling to select 3 kindergartens and 2 primary schools in different economic development areas of Shaoshan. Oral health status survey and interventions were conducted in December 2014 and September 2016, respectively. The average debris index, decayed missing filled teeth (deciduous teeth: dmft; permanent teeth: DMFT), and caries prevalence rate of children aged 3-6 years and 6-12 years were compared. At the same time, children aged 5 and 12 were used as representative populations to compare the indices as listed before and the caries prevalence rate of the first permanent molar in 12-year-old children was compared as well. Finally, health economic analysis was carried out based on the 2 years' result.@*RESULTS@#In this study, 992 children and 896 children in 2014 and 2016 were included respectively. As for children aged 3-6 years, the average debris index and dmft in 2016 were significantly less than that in 2014 (P < 0.001, P < 0.001), and the difference of DMFT was not significant (P=0.419). Children aged 6-12 years showed the same result, the average debris index and dmft in 2016 were significantly less than those in 2014 (P < 0.001, P=0.013), and the difference in DMFT was not significant (P=0.674). 173 and 179 5-year-old children were included in 2014 and 2016 respectively, and the dmft showed significant difference (P=0.038); the caries prevalence rate was 75.7% and 71.5%, respectively, which was also not significant (P=0.370). With respect to the 12-year-old children, 65 and 104 children were included and the differences in dmft and DMFT were not significant (P=0.133, P=0.171). The caries prevalence of the first permanent molar in the 12-year-old children was 36.9% and 26.9%, whose difference was not significant (P=0.171).@*CONCLUSION@#The application of fluoride varnish and oral health education can significantly reduce the dmft of children aged 3-12 years in Shaoshan area and significantly improve the oral hygiene status. DMFT, the caries prevalence rate of 5-year-old children's deciduous teeth and 12-year-old children's first permanent molar showed a decline.

Mechanistic target of rapamycin kinase (Mtor) is required for spermatogonial proliferation and differentiation in mice / 亚洲男科学杂志(英文版)

Spermatogonial development is a vital prerequisite for spermatogenesis and male fertility. However, the exact mechanisms underlying the behavior of spermatogonia, including spermatogonial stem cell (SSC) self-renewal and spermatogonial proliferation and differentiation, are not fully understood. Recent studies demonstrated that the mTOR complex 1 (mTORC1) signaling pathway plays a crucial role in spermatogonial development, but whether MTOR itself was also involved in any specific process of spermatogonial development remained undetermined. In this study, we specifically deleted Mtor in male germ cells of mice using Stra8-Cre and assessed its effect on the function of spermatogonia. The Mtor knockout (KO) mice exhibited an age-dependent perturbation of testicular development and progressively lost germ cells and fertility with age. These age-related phenotypes were likely caused by a delayed initiation of Mtor deletion driven by Stra8-Cre. Further examination revealed a reduction of differentiating spermatogonia in Mtor KO mice, suggesting that spermatogonial differentiation was inhibited. Spermatogonial proliferation was also impaired in Mtor KO mice, leading to a diminished spermatogonial pool and total germ cell population. Our results show that MTOR plays a pivotal role in male fertility and is required for spermatogonial proliferation and differentiation.

Comparative analysis of clinical effects according to syndrome differentiation of Qili Qiangxin Capsules on ischemic heart failure: Meta-analysis / 中国中药杂志

Databases including CNKI,Wan Fang,CBM,VIP,PubMed and Cochrane Library were searched to collect qualified researches,and the quality of articles was evaluated according to scales. Meta-analysis including subgroup analysis was performed by using Rev Man 5. 3 software and Meta-regression test was performed by using Stata 12. 0 software. All of these methods were used to systematically evaluate the safety and clinical efficacy of Qili Qiangxin Capsules in treatment of ischemic heart failure under two circumstances( with or without syndrome differentiation). A total of 22 randomized controlled trials( RCTs) involving 1 942 patients were included,with generally low quality. RESULTS: of Meta-analysis showed that as compared with the routine Western treatment alone,additional use of Qili Qiangxin Capsules could improve the clinical efficacy( RR = 1. 21,95%CI[1. 16,1. 27],P<0. 000 01) in treatment of ischemic heart failure,with its combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 03,I~2= 78. 9%),Meta-regression( sig = 0. 9,P = 0. 057); left ventricular ejection fraction( WMD = 7. 28,95% CI[5. 18,9. 38],P<0. 000 01),with combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 01,I2= 83. 2%),Meta-regression( I~2= 81. 09%,R2= 29. 08%,sig = 0. 47,P = 0. 029); 6-minute walk test( WMD = 33. 20,95%CI[24. 70,41. 70 ],P < 0. 000 01); left ventricular end diastolic diameter( WMD =-4. 61,95% CI[-5. 38,-3. 84 ],P <0. 000 01); left ventricular end diastolic volume( WMD =-34. 43,95%CI[-38. 81,-30. 05],P< 0. 000 01); and left ventricular end systolic volume( WMD =-9. 60,95% CI[-13. 16,-6. 05],P < 0. 000 01). Adverse effects were reported in 11 patients taking Qili Qiangxin Capsules and in 20 patients with routine treatment group,tolerable in both groups. None of the patients had obvious abnormality in liver and kidney function. Qili Qiangxin Capsules were effective and safe in the treatment of ischemic heart failure,which can further improve clinical efficacy as compared with routine treatment alone. Qili Qiangxin Capsules with syndrome differentiation showed more significant effects than those without syndrome differentiation,indicating better efficacy of clinical syndrome differentiation. However,these conclusions still need to be verified with more high-quality and large-sample literature.

A hiddenly high hepatitis C virus related liver disease burden among Chinese patients with non-liver disease complaints: A hospital based study from 2013 to 2017

Objective:To determine the frequency of anti-HCV antibody positivity in patients with non-liver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status.Methods:A hospital based survey of non-liver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1. were the patients adequately advised of the implication of anti-HCV positive finding; 2. to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists.Results:A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive (0.94%). However, only 45.10% (1 253/2 778) of the anti-HCV antibody (+) patients were referred to hepatologists and received HCV RNA test. In addition, 34.10% (312/915) and 1.42% (13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma (HCC), respectively. Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases. Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines. Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection.Conclusions:Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.

Expression of Notch signaling pathway in cultured human osteoarthritic articular chondrocytes / 局解手术学杂志

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.

The Role of Fibrocyte in the Pathogenesis of Silicosis / 生物医学与环境科学（英文）

Exposure to free silica induces silicosis and myofibroblasts are regarded as primary effector cells. Fibrocytes can differentiate into myofibroblast. Therefore, the present study was designed to investigate whether fibrocytes participate in silicosis. The rat model of silicosis was established. Hematoxylin-eosin stainings and Masson stainings were used to evaluate the histopathology and collagen deposition. Flow cytometry and immunofluorescence were performed to detect the number of fibrocytes and their contribution to myofibroblasts. Results showed that fibrocytes participate in silicosis. Trend analysis of different sources of myofibroblasts during silicosis indicated that fibrocytes and lung type II epithelial cell-derived myofibroblasts play an important role in the early stage of silicosis, while resident lung fibroblast-derived myofibroblasts play a predominant role during the fibrosis formative period.

A hiddenly high hepatitis C virus related liver disease burden among Chinese patients with non-liver disease complaints: A hospital based study from 2013 to 2017

Objective: To determine the frequency of anti-HCV antibody positivity in patients with non-liver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status. Methods: A hospital based survey of non-liver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1. were the patients adequately advised of the implication of anti-HCV positive finding; 2. to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists. Results: A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive (0.94%). However, only 45.10% (1 253/2 778) of the anti-HCV antibody (+) patients were referred to hepatologists and received HCV RNA test. In addition, 34.10% (312/915) and 1.42% (13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma (HCC), respectively. Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases. Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines. Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection. Conclusions: Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.

Crystalline Silica Promotes Rat Fibrocyte Differentiation in Vitro, and Fibrocytes Participate in Silicosis in Vivo / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to investigate the effects of SiO2 on fibrocytes and whether fibrocytes participate in silicosis in vivo.</p><p><b>METHODS</b>A macrophagocyte (AM)/fibrocyte coculture system was established, and AMs were treated with 100 μg/mL SiO2. Flow cytometry was used to detect the number of fibrocytes. Real-time PCR was performed to measure the expression of collagen I, collagen III, and α-SMA mRNA. The levels of collagen I, collagen III, and TGF-β1 protein were determined by ELISA. Immunohistochemical staining was performed to measure α-SMA protein expression. A rat silicosis model was induced by intratracheal instillation of SiO2. Lung histopathological evaluation was conducted using HE and Masson's trichrome staining after 1 and 9 weeks. The number of fibrocytes in peripheral blood or lung tissue of rat was detected by flow cytometry. Double-color immunofluorescence was applied to identify fibrocytes in the lung tissue.</p><p><b>RESULTS</b>Peripheral blood monocytes were found to differentiate into fibrocytes in vitro in a time-dependent manner, and exposure to crystalline silica might potentiate fibrocyte differentiation. In addition, fibrocytes were able to migrate from peripheral blood to the lung tissue, and the number of fibrocytes was increased after SiO2 exposure.</p><p><b>CONCLUSION</b>Silica exposure potentiates fibrocyte differentiation, and fibrocytes may participate in silicosis in vivo.</p>

Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells.

BACKGROUND: Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells. METHODS: SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool. RESULTS: LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC. CONCLUSIONS: LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589.

Clinical and angiographic predictors of major side branch occlusion after main vessel stenting in coronary bifurcation lesions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Major side branch (SB) occlusion is one of the most serious complications during percutaneous coronary intervention (PCI) for bifurcation lesions. We aimed to characterize the incidence and predictors of major SB occlusion during coronary bifurcation intervention.</p><p><b>METHODS</b>We selected consecutive patients undergoing PCI (using one stent or provisional two stent strategy) for bifurcation lesions with major SB. All clinical characteristics, coronary angiography findings, PCI procedural factors and quantitative coronary angiographic analysis data were collected. Multivariate logistic regression analysis was performed to identify independent predictors of SB occlusion. SB occlusion after main vessel (MV) stenting was defined as no blood flow or any thrombolysis in myocardial infarction (TIMI) flow grade decrease in SB after MV stenting.</p><p><b>RESULTS</b>Among all 652 bifurcation lesions, 32 (4.91%) SBs occluded. No blood flow occurred in 18 lesions and TIMI flow grade decreasing occurred in 14 lesions. In multivariate analysis, diameter ratio between MV/SB (odds ratio [OR]: 7.71, 95% confidence interval [CI]: 1.53-38.85, P = 0.01), bifurcation angle (OR: 1.03, 95% CI: 1.02-1.05, P < 0.01), diameter stenosis of SB before MV stenting (OR: 1.05, 95% CI: 1.03-1.07, P < 0.01), TIMI flow grade of SB before MV stenting (OR: 3.59, 95% CI: 1.48-8.72, P < 0.01) and left ventricular eject fraction (LVEF) (OR: 1.06, 95% CI: 1.02-1.11, P < 0.01) were independent predictors of SB occlusion.</p><p><b>CONCLUSIONS</b>Among clinical and angiographic findings, diameter ratio between MV/SB, bifurcation angle, diameter stenosis of SB before MV stenting, TIMI flow grade of SB before MV stenting and LVEF were predictive of major SB occlusion after MV stenting.</p>

Comparison of clinical features of purulent meningitis between small-for-gestational-age and appropriate-for-gestational-age infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the differences in the clinical features of purulent meningitis (PM) between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants.</p><p><b>METHODS</b>The clinical data of 58 full-term infants with PM were analyzed retrospectively. The infants were classified into a SGA group (13 cases) and an AGA group (45 cases) according to their birth weight and gestational age. Clinical manifestations, laboratory results, and outcomes were compared between the two groups.</p><p><b>RESULTS</b>The incidence of decreased muscle tone in the SGA group was significantly higher than that in the AGA group (P<0.05); the positive rate in the Pandy's test for cerebrospinal fluid in the SGA group was significantly higher than that in the SGA group (P<0.05). Brain imaging examination showed that the incidence of brain injuries in the SGA group was significantly higher than that in the AGA group (P<0.05).</p><p><b>CONCLUSIONS</b>SGA infants with PM display a higher risk of brain injury, suggesting a poorer outcome, compared with AGA infants.</p>

Analysis of genetic diversity and amino acid sequence of HIV-1tat in CNS and peripheral tissue of a patient with ADC and a patient with non-ADC / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the diversity of HIV-1 tat gene in CNS and peripheral tissue of a patient with ADC and a patient with non-ADC, so as to research HIV evolution, the mechanism of CNS invasion and the pathogenesis of ADC.</p><p><b>METHODS</b>The tat gene was amplified with nested PCR from genomic DNA which was extracted from spleen and basal ganglia of one non-ADC patient with a wide range of cerebral artery atherosclerosis and one ADC patient. PCR products were cloned into the PGEM-T vector, after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced. HIV-1 tat sequences were processed with BioEdit and MEGA4. With the softwares, neighbor-joining tree, p-distances, values of ds/dn, and analysis of amino acid motifs were all done, so as to research the diversity of HIV-1 tat gene in CNS and peripheral tissue.</p><p><b>RESULTS</b>Gene mutation of HIV-1 tat exist in the two patients, the mutation process of tat isolated from ADC patient suffered more compartmentalization than tat isolated from non-ADC patient, the differences of tat genes between CNS and peripheral tissue in ADC patient were greater than the non-ADC patient. Ds/dn showed that the virus gene mutation played a major role, the body intend to remove harmful non-synonymous mutations.</p><p><b>CONCLUSIONS</b>The compartmentation of tat gene in CNS and peripheral tissue of the two patients was different, the reason may be related to the pathway of HIV into the CNS, the relationship between HIV gene mutation in CNS and ADC still need more investigation.</p>