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Peng-Cheng Zhang,1,2 Yi Hong,3 Shi-Qin Zong,1,2 Long Chen,1,2 Chong Zhang,4 Dai-Zhi Tian,4 Dan Ke,5 Li-Ming Tian1,2,4 1Department of Dermatology, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Provincial Key Laboratory of Skin Infection and Immunity, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China; 3College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China; 4Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China; 5Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400000, People’s Republic of ChinaCorrespondence: Dan Ke, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, No. 40 of Daomenkou, Yuzhong District, Chongqing, 400000, People’s Republic of China, Tel +86 23 6390 1120, Fax +86 23 6373 1325, Email 2306896229@qq.com Li-Ming Tian, Department of Dermatology, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 215 of Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of China, Tel +86 27 8533 2606, Fax +86 27 8583 2563, Email jolly0731@126.comObjective: To investigate the variation of ferroptosis-related markers in HaCaT cell photoaging models induced by ultraviolet-B (UVB).Methods: UVB-treated HaCaT cells served as the model (UVB group) for cellular photoaging, whereas untreated HaCaT cells served as the control group. HaCaT cells were exposed to UVB and the ferroptosis inhibitor Ferrostatin-1 (Fer-1) as part of the UVB+Fer-1 group, and co-cultured with the ferroptosis inducer Erastin as part of the UVB+Erastin group. Reactive oxygen species (ROS) detection kit and senescence-related β galactosidase (SA-β-gal) staining were used to evaluate the senescence of HaCaT cells. Lipid reactive oxygen species were detected by C11 BODIPY581/591 probe and mitochondrial morphology was observed by transmission electron microscopy. The mRNA expressions of glutathione peroxidase 4 (GPX4) and ferroptosis-suppressor-protein 1 (FSP1) were detected by real-time reverse transcription-PCR (RT-RCP), and the level of GPX4 protein was measured by immunofluorescence assay.Results: The UVB group had considerably greater levels of ROS, SA-β-gal, and lipid reactive oxygen species than the control group. The UVB group’s mitochondrial volume was reduced, the membrane density increased, and the mitochondrial crest decreased or even disappeared. GPX4 and FSP1 expression levels were similarly found to be lower in the UVB group. Furthermore, the positive rate of SA-β-gal and lipid reactive oxygen species in the UVB+Fer-1 group was much lower than in the UVB group, but it was reverse in the UVB+Erastin group. This study showed that induced ferroptosis can aggravate aging, and vice versa.Conclusion: According to the findings, ferroptosis may be linked to UVB-induced skin photoaging, which could be attenuated by inhibition of ferroptosis.Keywords: skin aging, ferroptosis, oxidative stress

Miao Han,1,* Heng Li,2,* Dan Ke,3 Li-Ming Tian,4 Yi Hong,5 Chong Zhang,6 Dai-Zhi Tian,6 Long Chen,4 Li-Rui Zhan,4 Shi-Qin Zong4 1Department of Dermatology, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 2Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Hospital Affiliated to Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 3Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 4Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 6Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Ming Tian, Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Tongji Medicine College of Huazhong University of Science and Technology, No. 215 of Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of China, Tel +86 27 8533 2606, Fax +86 27 8583 2563, Email jolly0731@126.comPurpose: To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking.Methods: First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein–protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated.Results: A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, β-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB).Conclusion: Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.Keywords: Ba Zhen Tang, skin photoaging, network pharmacology, molecular docking, mechanism

Ting Yang,1,2 Wen-Juan Wu,1 Li-Ming Tian,3 Deng-Feng Zhang,4 Xiao-Yan Yang,1 Jue Qi,1 Ying Tu,1 Li He1 1Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650023, People’s Republic of China; 2Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, 435000, People’s Republic of China; 3Department of Dermatology, First Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 4Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, People’s Republic of ChinaCorrespondence: Li HeDepartment of Dermatology, First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, Yunnan, 650023, People’s Republic of ChinaTel/Fax +86 0871-65317895Email lihe_4785@163.comObjective: Androgens acting through the androgen receptor play a crucial role in the pathogenesis of acne. This study aimed to identify whether two key genes (CYP21A2 and CYP19A1) involved in the synthesis and metabolism of androgens were associated with Pillsbury III-IV severe acne vulgaris.Methods: We carried out a standard questionnaire survey about acne and enlisted 600 Pillsbury III-IV severe acne vulgaris patients and 652 healthy controls of Han Chinese descent from Yunnan, China in the study. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot assay and analyzed for association with severe acne.Results: There was no significant difference in gender between the two groups (P = 0.085), and the age of the acne case group was significantly lower than that of the control group (P < 0.001). Our results revealed that only two SNPs, rs6474 (p.Arg102Lys) (P = 0.001) and rs6465 (P = 0.025) of the CYP21A2 gene were significantly associated with severe acne among the Han Chinese. When subjects were divided into males and females, significant associations were observed only in male patients with severe acne vulgaris for four variants: CYP21A2 rs6474 (p.Arg102Lys) (P = 0.002); CYP21A2 rs6465 (P = 0.012); CYP19A1 rs8023263 (P = 0.037); and CYP19A1 rs2470152 (P = 0.007). Haplotype analyses showed that the distribution of CYP21A2 haplotypes was significantly associated with male patients, while no association of CYP19A1 haplotypes was observed. The structure of the human CYP21A2 consists of two substrate binding sites and one substrate access channel.Conclusion: This study shed a light on a potentially important effect of CYP21A2 and CYP19A1 genes in severe acne vulgaris in the Han Chinese, especially for male patients. Future studies using independently verified datasets from a broader geographical spectrum will be valuable in identifying the causal and functional variants responsible for severe acne vulgaris within the CYP19A1 and CYP21A2 genes.Keywords: androgen receptor, severe acne, synthesis, metabolism, genetic risk

Li-Ming Tian,1 Dan Ke2 1Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400000, People’s Republic of ChinaCorrespondence: Li-Ming TianDepartment of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Huazhong University of Science and Technology, No. 215 of Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of ChinaTel +86 27 8533 2606Fax +86 27 8583 2563Email tianlm632587@tom.comDan KeDepartment of Dermatology, Chongqing Traditional Chinese Medicine Hospital, No. 40 of Daomenkou, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 23 6390 1120Fax +86 23 6373 1325Email ked98527@163.comObjective: To study the relationship between the single nucleotide polymorphisms (SNPs) of the human β-defensin 1-gene (DEFB1) and the genetic susceptibility of acne vulgaris in the Han Chinese ethnic group.Methods: A total of 104 patients with acne vulgaris and 126 healthy participants were included in our study. We analyzed the association between acne vulgaris and the polymorphisms in the DEFB1 G-52A, C-44G, and G-20A gene. We then analyzed the relationship between the different genotypes and the susceptibility to acne vulgaris.Results: The frequency of DEFB1 C-44G genetic polymorphisms between the acne vulgaris group and the control group was significantly different (P < 0.05). The frequency of DEFB1 G-20A genetic polymorphisms between the acne vulgaris group and the control group was also significantly different (P < 0.05).Conclusion: The − 44G or − 20A allele showed a low expression in acne vulgaris, which has already been shown to correlate with the low risk of acne vulgaris among Chinese Han patients. This further supports the contribution of the DEFB1 gene to the pathogenesis of acne.Keywords: human β-defensin 1, genetic polymorphisms, acne vulgaris, Cutibacterium acnes, Han Chinese

OBJECTIVE: The aim of our study was to validate association between -8 C/G variant of PSMA6 gene and T2DM in Chinese Dongxiang and Han populations. METHOD: We genotyped PSMA6 gene -8 C/G polymorphism in the control groups and T2DM groups in two populations from China using PCR-RFLP technique. Phenotypes and biochemical indicators were measured by biochemical technique. RESULT: The frequencies of CG+GG genotype were observably different from CC genotype in the T2DM groups and control groups (for Dongxiang population: OR=1.341, 95% CI: 1.101-1.632, P=0.004; for Han population: OR=1.313, 95% CI: 1.085-1.569, P=0.006 after adjusting for gender, age, and BMI, respectively). In the Dongxiang population, the FPG, HOMA-IR, SBP and TG levels of CG+GG genotype were markedly higher than those of the CC genotype in control group (all P<0.05). However, in the Han population, we only found that the FPI level of the CC genotype was significantly higher than that of the CG+GG genotype in control group (P<0.05). CONCLUSION: Our investigation suggests that -8 C/G variant of PSMA6 gene may be associated with T2DM and diabetes-related metabolic traits in Chinese Dongxiang and Han populations. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to use network pharmacology to explore the potential targets and mechanisms of action of Qibao Meiran Dan in relation to delaying skin aging., Methods: The traditional Chinese medicine systems pharmacology database and analysis platform, and the traditional Chinese medicine integrated database, were used to screen the active ingredients and targets of Qibao Meiran Dan. The human gene database GeneCards and the gene database of the National Center for Biotechnology Information were jointly adopted to obtain skin aging-related target genes. The search tool for the retrieval of interacting genes/proteins (STRING) database was used for core analysis of protein-protein interaction., Results: In total, 72 effective active ingredients, 273 action targets, 234 skin aging target genes, and 64 intersecting core targets were identified. GO enrichment analysis provided 393 biological process entries, and the KEGG analysis was represented by the tumor necrosis factor (TNF) signaling pathway, where the core targets of TNF-α and matrix metalloproteinase-1 (MMP-1) were enriched. The experimental results showed that cell morphology was clearer and more refractive in the Qibao Meiran Dan group than in the model group., Conclusion: Qibao Meiran Dan may regulate oxidative stress injury and collagen metabolism by downregulating the expression of TNF-α and MMP-1, thus slowing skin aging., (© 2022 Wiley Periodicals LLC.)

In the retina, signals originating from rod and cone photoreceptors can reach retinal ganglion cells (RGCs)-the output neurons-through different pathways. However, little is known about the exact sensitivities and operating ranges of these pathways. Previously, we created rod- or cone-specific Cx36 knockout (KO) mouse lines. Both lines are deficient in rod/cone electrical coupling and therefore provide a way to selectively remove the secondary rod pathway. We measured the threshold of the primary rod pathway in RGCs of wild-type mice. Under pharmacological blockade of the primary rod pathway, the threshold was elevated. This secondary component was removed in the Cx36 KOs to unmask the threshold of the third rod pathway, still below cone threshold. In turn, the cone threshold was estimated by several independent methods. Our work defines the functionality of the secondary rod pathway and describes an additive contribution of the different pathways to the retinal output.

Background: Tuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect., Methods: Multi-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data., Discussion: The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients., Trial Registration: This trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered)., (© 2021. The Author(s).)

Pyrus xerophila has strong resistance to drought, cold, salt, and rust. It is one of the main rootstock types of pear in Northwest China, with high production value. However, its habitat is seriously damaged. The prediction of the geographical distribution of P. xerophila under different climate scenarios will provide important scientific basis for rational development and utilization of resources and the protection of diversity. Based on MaxEnt model and ArcGIS spatial analysis, the potential spatial distribution pattern of P. xerophila in the current and future (2050, 2070) was constructed using comprehensive and accurate distribution records and high-resolution environmental data, and the relative importance of environmental factors was evaluated. The results showed that the suitable habitat area of P. xerophila was 3.32×10 5 km 2 , mainly located in eastern Qinghai, southern Gansu, southern Ningxia, central Shaanxi, southern Shanxi and western Henan. Mean UV-B of the month with lowest UV-B and altitude were identified as the critical factors shaping habitat availability for P. xerophila. Overall, with global warming, the potential habitat for P. xerophila might decrease in 2050 and 2070 under different CO 2 climate scenarios. Real-time monitoring of P. xerophila populations should be enhanced.

Obstructive sleep apnea syndrome (OSAS) can lead to alterations in right ventricular (RV) performance and pulmonary vascular haemodynamics. Additionally, altitude-related hypoxia is associated with pulmonary vasoconstriction, and the effect of high-altitude on the pulmonary circulation in OSAS patients can be further altered. We sought to assess alterations in RV morphology and function in OSAS patients living at high altitude by way of 2-dimensional speckle tracking echocardiography (2D-STE), real-time 3- dimensional echocardiography (RT-3DE) and cardiac biomarkers. We also evaluate the impact of continuous positive airway pressure (CPAP) treatment on RV performance. Seventy-one patients with newly diagnosed OSAS and thirty-one controls were included in this study. All individuals were assessed for cardiac biomarkers as well as underwent 2D-STE and RT-3DE. Forty-five OSAS patients underwent CPAP therapy for at least 24 weeks and were studied before and after CPAP treatment. RT-3DE was used to measure RV volume, and calculate RV 3D ejection fraction (3D RVEF). Peak systolic strain was determined. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide, and cardiac troponin T were also measured. Right atrium volume index, RV volume, RV volume index, systolic pulmonary artery pressure (sPAP), pulmonary vascular resistance (PVR) and level of serum CRP were significantly higher in OSAS group, while OSAS patients showed lower 3D RVEF and RV longitudinal strains. Compared to the patients with sPAP < 40 mmHg, RV longitudinal strains in patients with sPAP ≥ 40 mmHg were lower. Both RV global longitudinal strain and sPAP were associated with apnea-hypopnea index. Patients treated with 6 months of CPAP therapy had significant improvement in RV geometry and performance. RV structural abnormalities and RV function impairments were observed in OSAS patients living at moderate high altitude compared to control highlanders. The reversibility of these changes after application of CPAP were further confirmed.

This aim of this study was to observe the effect of Yang Yan Qing E Wan (YYQEW) on senescent phenotypes and the expression of β-catenin and p16 INK4a in the hydrogen peroxide (H 2 O 2 )-induced premature senescence of normal human skin fibroblasts (NHSFs). Primary normal human skin fibroblasts were randomly divided into a normal group, a blank group, a model group, and a YYQEW group. The cells of the model group and the YYQEW group were exposed to 150 μmol/L H 2 O 2 for 2 h. The morphological changes of the cells were analyzed by microscopy and by kits used to estimate the activities of the senescence-associated β-galactosidase (SA-β-gal), reactive oxygen species (ROS), and superoxide dismutase (SOD). The outcomes revealed that dyeing rate proportion of SA-β-gal was 2.78% ± 0.22% in the normal group, 2.83% ± 0.29% in the blank group, 37.58% ± 2.56% in the model group, and 28.39% ± 0.93% in the YYQEW group. The number of SA-β-gal positive cells was thus significantly higher in the model group than in the normal or blank group. There were also fewer SA-β-gal positive cells in the YYQEW group compared with the model group. The expression of ROS and p16 INK4a in the model group increased significantly compared with that in the normal or blank groups, while the expression of ROS and p16 INK4a in the YYQEW group decreased significantly compared with that in the model group. The expression of SOD and β-catenin in the model group decreased significantly compared with that in the normal or blank group, and the expression of SOD and β-catenin in the YYQEW group increased significantly compared with that in the model group. Overall, it was found that YYQEW was able to delay the senescence of NHSFs induced by H 2 O 2 treatment by alleviating oxidative stress and regulating a number of senescence-related molecules, such as β-catenin and p16 INK4a ., (Copyright © 2020 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro . In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncoding RNAs (ncRNAs) that occupy over 90% of the human genome, and their main function is to directly or indirectly regulate messenger RNA (mRNA) expression and participate in the tumorigenesis and progression of malignances. In particular, some lncRNAs can interact with miRNAs as competing endogenous RNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNA molecules are interrelated and coordinate to form a dynamic lncRNA-mediated ceRNA regulatory network. Mounting evidence has revealed that lncRNAs that act as ceRNAs are closely related to tumorigenesis. To date, numerous studies have established many different regulatory networks in hepatocellular carcinoma (HCC), and perturbations in these ceRNA interactions may result in the initiation and progression of HCC. Herein, we emphasize recent advances concerning the biological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating the molecular mechanism underlying these HCC-related RNA molecules and providing novel insights into the diagnosis and treatment of HCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mouse photoreceptors are electrically coupled via gap junctions, but the relative importance of rod/rod, cone/cone, or rod/cone coupling is unknown. Furthermore, while connexin36 (Cx36) is expressed by cones, the identity of the rod connexin has been controversial. We report that FACS-sorted rods and cones both express Cx36 but no other connexins. We created rod- and cone-specific Cx36 knockout mice to dissect the photoreceptor network. In the wild type, Cx36 plaques at rod/cone contacts accounted for more than 95% of photoreceptor labeling and paired recordings showed the transjunctional conductance between rods and cones was ~300 pS. When Cx36 was eliminated on one side of the gap junction, in either conditional knockout, Cx36 labeling and rod/cone coupling were almost abolished. We could not detect direct rod/rod coupling, and cone/cone coupling was minor. Rod/cone coupling is so prevalent that indirect rod/cone/rod coupling via the network may account for previous reports of rod coupling., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-195 on myocardial infarction (MI) in rats via regulating the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. A total of 36 Sprague-Dawley rats were randomly divided into a normal group (n=12), a model group (n=12) and an miR-195 antagomir group (n=12). In the normal group, the heart was exposed only, and normal saline was intraperitoneally injected after operation. In the model group, the acute MI model was established. In the miR-195 antagomir group, the acute MI model was also established, and miR- 195 antagomir was intraperitoneally injected. The samples were collected at 2 weeks after surgery. Then cardiac function was detected via echocardiography, and the morphology of heart tissues was observed via hematoxylin and eosin (H&E) staining. Moreover, the expression of Collagen I was determined using immunohistochemistry, the protein expressions of TGF-β1, Smad3 and Smad7 were detected using Western blotting, and the expression of miR-195 was detected via quantitative polymerase chain reaction (qPCR). It was found by echocardiography that, compared with those in the normal group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) significantly declined, while left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) significantly rose in the other two groups (P<0.05). In comparison with the model group, the miR-195 antagomir group had significantly increased LVEF and LVFS, and significantly decreased LVDd and LVDs (P<0.05). The immunohistochemistry results showed that the mean optical density of tissues with positively expressed Collagen I was obviously higher in the other two groups than that in the normal group (P<0.05), while it was obviously lower in the miR-195 antagomir group than that in the model group (P<0.05). According to the results of Western blotting, the protein expressions of TGF-β1 and Smad3 were evidently increased, while the protein expression of Smad7 was evidently decreased in the other two groups compared with those in the normal group (P<0.05). The opposite results were found in the miR-195 antagomir group compared with those in the model group (P<0.05). The results of qPCR manifested that the expression of miR-195 was markedly higher in the other two groups than that in the normal group (P<0.05), while it was markedly lower in the miR-195 antagomir group than in the model group (P<0.05). Moreover, it was observed using H&E staining that the myocardial fibers in the normal group had normal arrangement and intact structure, without obvious morphological abnormalities. In the model group, the myocardial fibers were arranged disorderly, and there were massive proliferating fibrous tissues, with a high degree of fibrosis. In themiR-195 antagomir group, the myocardial fibers were damaged and arranged less disorderly, and proliferation and fibrosis could be seen in some fibrous tissues, but to a lesser extent than the model group. In conclusion, miR-195 promotes myocardial fibrosis in MI rats via up-regulating the TGF-β1/Smad signaling pathway., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

In this study, a novel ligand (HL) consisting of 2-methyl quinoline-4-carboxylic acid, rhodamine and naphthalene moiety, was designed and synthesized, it could be developed a ratiometric fluorescent sensor for selective detection of Al 3+ via fluorescence resonance energy transfer (FRET) from naphthalimide moiety to rhodamine moiety. The addition of Al 3+ trigger the significant fluorescence enhancement of HL at 550 nm at the expense of the fluorescent emission of HL centered at 524 nm., Competing Interests: Declaration of competing interest We declare that there is not conflict of interest for this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To clarify the expression pattern of miRNA-875-3p in CRC and its potential regulatory effect on the progression of CRC., Materials and Methods: MiRNA-875-3p level in 56 matched CRC tissues and adjacent normal tissues were determined. The correlation between the miRNA-875-3p level and pathological indexes of CRC patients was analyzed. Prognostic potential of miRNA-875-3p in CRC patients was assessed by introducing the Kaplan-Meier curves. Influences of miRNA-875-3p on viability, migration, and wound closure were assessed through a series of functional experiments. The interaction between miRNA-875-3p and PLK1 in regulating the progression of CRC was finally uncovered by Dual-Luciferase reporter gene and rescue experiments., Results: MiRNA-875-3p was downregulated in CRC tissues and cell lines. CRC patients with low level of miRNA-875-3p suffered a higher rate of distant metastasis and worse prognosis. Overexpression of miRNA-875-3p attenuated proliferative and migratory capacities of SW480 and HT29 cells. PLK1 was confirmed to be the target gene of miRNA-875-3p. PLK1 was upregulated in CRC tissues and cell lines, which was negatively regulated by miRNA-875-3p. MiRNA-875-3p alleviated the malignant progression of CRC via negatively regulating PLK1., Conclusions: MiRNA-875-3p is downregulated in CRC, which is closely related to distant metastasis and poor prognosis of CRC patients. MiRNA-875-3p alleviates the progression of CRC through targeting and downregulating PLK1.

Background: Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract in which excessive activation of inflammatory response is correlated. Cyanidin-3-O-glucoside (C3G) is a powerful anti-inflammatory agent, widely existing in fruits and vegetables. However, the role of C3G has rarely been investigated in dextran sulfate sodium (DSS)-induced colitis., Methods: In an attempt to elucidate the possible mechanism of IBD and develop new efficient therapeutic methods for colitis, we evaluated the effects of C3G on DSS-induced colitis. DSS-induced colitic C57BL/6 mice were intraperitoneal injected with 1ug C3G or phosphate buffer every 2 days, a total of 3 times; the changes in macrophages and regular T cells were analyzed by flow cytometry and immunofluorescence. Cytokines and chemokines were measured by real-time quantitative polymerase chain reaction., Results: The results showed that C3G treatment did not cause changes in body weight and colon length as much as those of DSS-treated mice only. Cytokine expression levels such as interleukin (IL)- 6, IL-1β, IL-18, tumor necrosis factor α, interferon γ (IFN γ) in colons and mesenteric lymph nodes (mLNs) from C3G-treated mice were lower than those from colitic mice. Meanwhile, C3G injection inhibited the decrease in CCL22 levels and Tregs induction in colitic mice. Furthermore, the activation of macrophages by LPS and increase of CD169+ cells induced by type I IFN could be inhibited by C3G directly in vitro., Conclusions: The study is the first to demonstrate strong effects of C3G to alleviate DSS-induced colonic damage in mice. The effect of C3G on DSS-induced colitis clearly showed a decrease of CD169+ macrophages in both the colon and mLNs. An increase of CD169+ cells induced by type I IFN could be inhibited by C3G. All these data suggest that the role of C3G in colitic inflammation was mediated at least partially by CD169+ cells and the type I IFN pathway., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Understanding the interaction between large herbivores and pasture production, especially with respect to the grazing optimization hypothesis, is critical for pasture management and generating theoretical and testable predictions. However, the optimization hypothesis remains contradictory in alpine meadows on the Qinghai-Tibet Plateau (QTP). In this study, we tested the grazing optimization hypothesis using four yak-grazing intensities (no grazing, light grazing, moderate grazing and heavy grazing) in alpine meadow habitats from 2015 to 2017. The results indicated that species diversity did not differ significantly among grazing regimes during the experimental period. However, the aboveground net primary production (ANPP) under moderate grazing consistently significantly exceeded that in control enclosures over 3 years, confirming the grazing optimization hypothesis. Levels of overcompensation varied among grazing intensities and years, and grazing-induced plant compensation may only occur in the short term. The enhanced regrowth of Poaceae and Cyperaceae induced by yak grazing might contribute to the overall level of overcompensation by plant community. Our results strongly support the grazing optimization hypothesis in the context of alpine meadows grazed by yaks, emphasizing the complex interactions between ANPP, herbivores and other ecological factors in alpine meadows on the QTP. These findings provide new insights for the development of an ecological conservation strategy that will help restore this fragile ecosystem and balance the seemingly incompatible requirements of animal husbandry.

Cadmium (Cd) is a poisonous metal that is toxic for male reproduction. Cyanidin-3-O-glucoside (C3G) as typical anthocyanin benefits many organs. In this study, we investigated the protective effects and associated underlying mechanisms of C3G against the toxicity of Cd on male reproduction in rat Leydig cell line R2C cells. Cells were pre-protected with C3G (5-160 μmol/L) for 2 h and then treated with cadmium sulfate (CdSO 4 ) (10-160 μmol/L) for 24 h. The results showed that cytotoxicity, mitochondrial damage, superoxide dismutase 2 (SOD2), and overproduction of reactive oxygen species (ROS) in CdSO 4 -treated R2C cells were significantly reduced with C3G pre-treatment. Moreover, C3G pre-treatment led to upregulated expression of steroidogenic acute regulatory (StAR) protein and progesterone production. Our study suggests that C3G may be a potential therapeutic agent against Cd-induced reproductive toxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To resovle the problems of in-situ conservation and resource utilization of Pyrus caller-yana, maximum entropy model (MaxEnt) and geographic information system (GIS) were used to predict the global ecological suitable region of P. calleryana in different climate scenarios based on 236 distribution data and 19 ecological factors. The results showed that the ecological suitable regions of P. calleryana were mainly concentrated in North America, Asia and other regions, with a total area of 1.6×10 7 km 2 . In China, the regions with high ecological suitability were Hunan, Hubei, Anhui, Jiangxi, Jiangsu, Zhejiang and Fujian provinces. The main factors affecting the geographical distribution of P. calleryana were mean annual temperature and mean annual precipitation, followed by the seasonality of temperature. The model simulations indicated that P. calleryana would have different suitable habitat areas and marginally suitable habitat areas in different climate scenarios. In terms of the spatial distribution of the potential habitat area, both the distributional range and the center of distribution of suitable and marginally suitable habitat area would shift from east to west. The suitable habitat area in North America and marginally suitable habitat areas in Europe would increase rapidly.

The wild Ussurian pear was the most important wild pear resource in northern China, belonging to the most hardiness species. Taking 48 accessions of wild Ussurian pear and 2 accessions of cultivated Ussurian pear as test materials, this paper studied the morphology of leaves, chlorophyll content, and photosynthetic characteristics. We compared the difference between the wild and cultivated Ussurian pear, analyzed the photosynthetic characteristics of wild Ussurian pear, clarified the interrelationships between the indices, and established significant linear equations of photosynthesis and water-related physiological indices. The results showed that the leaf morphological index, chlorophyll content and photosynthetic indices for cultivated Ussurian pear were significantly lower than their average values for wild Ussurian pear. The specific leaf area (SLA), leaf dry matter content ( LDMC) , and intercellular CO2 concentration had low coefficients of variation, and the other 8 indices had variation coefficient indices between 0.12-0.41. So, the level of diversity was high, indicating obvious difference in photosynthetic characteristic of wild pear resources in China. The photosynthetic indices were significantly correlated with chlorophyll composition (Chl a/b) and LDMC. The photosynthetic rate had significant exponential correlation with the intercellular CO2 concentration, transpiration rate, and stomatal conductance. The photosynthetic rate was mainly affected by stomatal limitation. The wild variety 'Jinzhoushanli' was selected as high photosynthetic genetic resource.

Non‑small cell lung cancer (NSCLC) cells harboring mutations in the epidermal growth factor receptor (EGFR) gene initially respond well to EGFR tyrosine kinase inhibitors (TKI), including gefitinib. However the tumor cells will invariably develop acquired resistance to the drug. The EGFR T790M mutation is generally considered to be the molecular genetic basis of acquired TKI resistance. The present study aimed to explore how the T790M mutation induces tumor cells to escape inhibition by TKI treatment. An acquired gefitinib‑resistant cell line (NCI‑H1975/GR) was generated from the NCI‑H1975 human NSCLC cell line, which harbors the sensitive L858R and resistant T790M mutations of EGFR. The resistant cell line was established by exposing the cells intermittently to increasing concentrations of gefitinib. The mechanisms by which NSCLC acquires resistance to TKIs based on the T790M mutation, were investigated by detecting the protein expression levels of the EGFR/Kirsten rat sarcoma viral oncogene homolog (KRAS)/v‑Raf murine sarcoma viral oncogene homolog B (BRAF) transduction pathway, and epithelial‑mesenchymal transition (EMT) with immunocytochemistry. The resistance of the NCI‑H1975/GR cells to gefitinib was 2.009‑fold, as compared with the parent cells; however, the protein expression levels of EGFR, KRAS and BRAF were lower in the resistant cells. Some mesenchymal morphology was observed in the NCI‑H1975/GR cells, alongside a decreasing E‑cadherin expression and increasing vimentin expression. These results suggest that the reactivation of the EGFR/KRAS/BRAF transduction pathway was not detected in the NCI‑H1975/GR cells. EMT may have an important role in the development of acquired resistance to EGFR‑TKIs in NSCLC cells with sensitivity and resistance mutations.

The aim of our study was to assess the potential role of thyroid-stimulating hormone (TSH) in the risk of developing atherosclerosis in subclinical hypothyroidism (SCH). A cohort of 240 SCH patients and 150 euthyroid volunteers were recruited for the study. SCH patients were stratified into 2 groups according to TSH levels (group A: TSH<10 mIU/l; group B: TSH>10 mIU/l). All subjects were examined for clinical and biochemical parameters. Visfatin, omentin-1, and circulating endothelial biomarkers were measured. Patients in group B received l-thyroxine replacement to achieve euthyroidism; after 6 months of euthyroidism all measurements were repeated. Patients with SCH had higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and C-reactive protein (CRP) levels and lower nitric oxide (NO) and omentin-1 levels compared to euthyroid subjects (all p<0.05). TC, LDL-C, and CRP decreased significantly, while NO and omentin-1 levels increased significantly after l-thyroxine replacement. Based on multivariate liner stepwise regression analysis, omentin-1 was independently correlated with BMI and TSH; NO was independently correlated with age, TSH, LDL-C, and omentin-1. High TSH level contributes to endothelial dysfunction in SCH, while TSH-induced decrease of omentin-1 provides a new link between SCH and atherogenic risk., (© Georg Thieme Verlag KG Stuttgart · New York.)

In mammalian retinae, the first steps in the process of discrimination of color are mediated by color-opponent neurons that respond with opposite polarity to signals from short (S, blue) and longer wavelength (M, green or L, red) cones. Primates also contain a second system that is different from M and L cones. Although pathways responding to the onset of S-cone stimulation (S-ON) are well known, the existence of bipolar cells and retinal ganglion cells that respond to the offset of S-cone stimulation (S-OFF) has been controversial. We have recorded from and stained three different types of S/M color-opponent ganglion cells in the rabbit retina that are distinguished by the polarity of their responses to S-cone stimulation, the stratification pattern of their dendrites, and the distinct mechanisms underlying their color-opponent responses. We describe an S-ON and an S-OFF pathway formed by amacrine cells inverting the S-ON signal. Most importantly, we also provide both anatomical and physiological evidence for a direct S-OFF pathway dependent on an S-OFF cone bipolar cell. The results indicate a greater diversity of pathways for processing of signals from S-cones than previously suspected.

The identity of the types of different neurons in mammalian retinae is now close to being completely known for a few mammalian species; comparison reveals strong homologies for many neurons across the order. Still, there remain some cell types rarely encountered and inadequately described, despite not being rare in relative frequency. Here we describe in detail an additional ganglion cell type in rabbit that is bistratified with dendrites in both sublaminae, yet spikes only at light onset and has no response bias to the direction of moving bars. This ON bistratified ganglion cell type is most easily distinguished by the unusual behavior of its dendritic arbors. While dendrites that arborize in sublamina b terminate at that level, those that ascend to arborize in sublamina a do not normally terminate there. Instead, when they reach the approximate radius of the dendrites in sublamina b, they dive sharply back down to ramify in sublamina b. Here they continue to course even further away from the soma at the same level as the branches wholly contained in sublamina b, thereby forming an annulus of secondary ON dendrites in sublamina b. This pattern of branching creates a bistratified dendritic field of approximately equal area in the two sublaminae initially, to which is then added an external annulus of dendrites only in sublamina b whose origin is entirely from processes descending from sublamina a. It is coupled to a population of wide-field amacrine cells upon which the dendrites of the ganglion cell often terminate., (Copyright © 2012 Wiley Periodicals, Inc.)

In the nudibranch mollusk Hermissenda, ciliary locomotion contributes to the generation of two tactic behaviors. Light elicits a positive phototaxis, and graviceptive stimulation evokes a negative gravitaxis. Two classes of light-responsive premotor interneurons in the network contributing to ciliary locomotion have been recently identified in the cerebropleural ganglia. Aggregates of type I interneurons receive monosynaptic excitatory (I(e)) or inhibitory (I(i)) input from identified photoreceptors. Type II interneurons receive polysynaptic excitatory (II(e)) or inhibitory (II(i)) input from photoreceptors. The ciliary network also includes type III inhibitory (III(i)) interneurons, which form monosynaptic inhibitory connections with ciliary efferent neurons (CENs). Illumination of the eyes evokes a complex inhibitory postsynaptic potential, a decrease of I(i) spike activity, a complex excitatory postsynaptic potential, and an increase of I(e) spike activity. Here, we characterized the contribution of identified I, II, and III(i) interneurons to the neural network supporting visually guided locomotion. In dark-adapted preparations, light elicited an increase in the tonic spike activity of II(e) interneurons and a decrease in the tonic spike activity of II(i) interneurons. Fluorescent dye-labeled type II interneurons exhibited diverse projections within the circumesophageal nervous system. However, a subclass of type II interneurons, II(e(cp)) and II(i(cp)) interneurons, were shown to terminate within the ipsilateral cerebropleural ganglia and indirectly modulate the activity of CENs. Type II interneurons form monosynaptic or polysynaptic connections with previously identified components of the ciliary network. The identification of a monosynaptic connection between I(e) and III(i) interneurons shown here suggest that they provide a major role in the light-dependent modulation of CEN spike activity underlying ciliary locomotion.

Aims: L-selectin belongs to selectin family of adhesion molecule and participates in the generation and development of type 2 diabetes (T2D). In this study, we evaluated the relationship between the P213S polymorphism of L-selectin gene and T2D and insulin resistance in the Chinese population., Methods: We genotyped P213S polymorphism in 801 patients with T2D and 834 healthy controls in the Chinese population using polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Plasma glucose, insulin, lipid, blood urea nitrogen, creatinine and uric acid levels were measured by biochemical technique., Results: The frequency of 213PP genotype and P allele of the L-selectin gene in patients with T2D was significantly higher than that in controls (P=0.007; P=0.019, respectively). The relative risk of allele P suffered from T2D was 1.191 times higher than that of allele S. Moreover, the levels of FPG and HOMA-IR of PP and PS genotype carriers were significantly higher than those of SS genotype carriers in the T2D group (P<0.05)., Conclusion: These findings indicated that the P213S polymorphism of L-selectin gene may contribute to susceptibility to T2D and insulin resistance in the Chinese population, and P allele appears to be a risk factor for T2D., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes., Objective: To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population., Methods: We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory., Results: No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (P<0.05). In the control group, the subjects with variant genotypes had significantly increased levels of FINS, HOMA-IR compared with Leu72Leu genotype (P<0.05)., Conclusion: The Leu72Met polymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To study the toll-like receptor 2 (TLR2) Arg753Gln gene polymorphisms of acne patients of Gan-depression induced qi stagnation syndrome and damp-heat in the interior syndrome, thus laying the foundation for genetics studies on its occurrence., Methods: The distribution and the frequency of allelic genes were studied in 75 acne patients of damp-heat in the interior syndrome, and 87 acne patients with Gan-depression induced qi stagnation syndrome, as well as 70 healthy subjects (as the normal control group) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique., Results: There was significant difference in the frequency of the genotype Arg/Gln + Gln/Gln in the TLR2 Arg753Gln genetic polymorphisms [26. 44% (23/87) in Gan-depression induced qi stagnation syndrome, 41.33% (31/75) in damp-heat in the interior syndrome, and 12.86% (9/70) in the normal control group] (P < 0.05)., Conclusion: The existence of 753Gln allele in the Arg753Gln of TLR2 increased the onset risk of acne patients of Gan-depression induced qi stagnation syndrome and damp-heat in the interior syndrome.

Mammalian retinas contain about 20 types of ganglion cells that respond to different aspects of the visual scene, including the direction of motion of objects in the visual field. The rabbit retina has long been thought to contain two distinct types of directionally selective (DS) ganglion cell: a bistratified ON-OFF DS ganglion cell that responds to onset and termination of light, and an ON DS ganglion cell, which stratifies only in the ON layer and responds only to light onset. This division is challenged by targeted recordings from rabbit retina, which indicate that ON DS ganglion cells occur in two discriminably different types. One of these is strongly tracer-coupled to amacrine cells; the other is never tracer-coupled. These two types also differ in branching pattern, stratification depth, relative latency, and transience of spiking. The sustained, uncoupled ON DS cell ramifies completely within the lower cholinergic band and responds to nicotine with continuous firing. In contrast, the transient, coupled ON DS ganglion cell stratifies above the cholinergic band and is not positioned to receive major input from cholinergic amacrine cells, consistent with its modest response to the cholinergic agonist nicotine. Much data have accrued that directional responses in the mammalian retina originate via gamma-aminobutyric acid (GABA) release from the dendrites of starburst amacrine cells (Euler et al., 2002). If there is an ON DS ganglion cell that does not stratify in the starburst band, this suggests that its GABA-dependent directional signals may be generated by a mechanism independent of starburst amacrine cells., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To investigate cause of chronic wounds and related status of patients so as to provide strategy for study and treatment of chronic wounds and establishment of health policy., Methods: A total of twelve thousand one hundred and sixty-one cases hospitalized in our hospital in 2008 were enrolled in the study. A chronic wound was defined as skin tissue defect which could not heal after one month of treatment. Medical records were thus screened. Then a retrospective study was performed on patients with chronic wounds with analysis of age, gender, injury cause, therapy, and average length of hospital stay. Data were processed with chi-square test and one-way analysis of variance., Results: Investigation showed: 397 out of 12 161 cases (accounting for 3.3%) were recognized as having chronic wounds. (1) The main causes for chronic wound were burn, diabetes, and pressure ulcer, accounting for 59.9% (238/397), 15.6% (62/397), 10.8% (43/397), respectively. The other causes were operative injury, infection, varicosity, etc. There was statistical difference among the numbers of patients with chronic wounds with regard to various causes of injury (χ(2) = 136.21, P = 0.001). (2) Among patients with chronic wound, the ratio of male and female was 2.0:1.0 with mean age of (44 ± 23) years, and the highest ratio occurred in patients older than 70 years. There was significant difference in the numbers of patients with chronic wound among different age groups (χ(2) = 24.12, P = 0.025). There was statistical difference among the numbers of patients with chronic wound in different age groups with each cause of injury (with χ(2) values from 7.86 to 28.31, P values all below 0.05). (3) All patients with chronic wounds received traditional dressing. In 60.5% (240/397) and 86.4% (343/397) of patients, operative treatment or antibiotics were given. (4) The average length of hospital stay in patients with chronic wound [(38 ± 27) d] was longer as compared with that of all the inpatients in the same period [(15 ± 7) d, F = 22.82, P = 0.012]. There was obvious difference in the average length of hospital stay among patients with chronic wound caused by different reasons (F = 24.06, P = 0.036), in which burn injury resulted in the longest length of hospital stay [(47 ± 27) d]., Conclusions: Chronic wounds are mainly caused by diabetes and burn, and characterized by old age and longer length of hospital stay. It is necessary to strengthen translational research and related policy making, so that more rational treatment can be applied for patients with chronic wounds.

The antioxidative capacity of endomorphins (EMs), endogenous μ-opioid receptor agonists, has been demonstrated by IN VIVO assays. In this study, we attempt to evaluate the effects of endomorphin 1 (EM1) and endomorphin 2 (EM2) on pancreatic islet injuries induced by streptozotocin (STZ), alloxan (ALX) and H(2)O(2), respectively. Wistar rats' islets were isolated and purified. The function of the islet cells, the insulin response to glucose stimulation was examined by insulin Radio Immuno Assay and the cell viability was measured by MTT assay. DNA fragments were performed to evaluate the apoptosis, while the cell cycle distribution was analyzed by PI staining flow cytometric analysis. Furthermore, the islet were treated with EM1, EM2 or ALX for 24 h, and the expression of p53 and p21 protein were determined by Western blot. The results showed that STZ, ALX, and H(2)O(2) displayed clear concentration-dependent inhibitory effects on the pancreatic islet cells. While EMs improved the viability of islet induced by STZ, ALX or H(2)O(2), and EMs enhanced insulin accumulation of the cell supernatant after ALX and STZ stimulation. Our data also showed both that EMs inhibited cell apoptosis and cell cycle G1 arrest induced by STZ and ALX through down-regulaing p53 and p21 expression. Taken together, these results demonstrate that EMs can protect islet cells from STZ, ALX and H(2)O(2) induced injuries. Our observations imply that the endomorphins may have protective effects on islet cells oxidative injury., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To explore the correlation between androgen-related CYP17 gene polymorphisms and female post adolescent acne in Han population in Hunan Province., Methods: The female patients with post adolescent acne and high levels of androgen (A group), those without high levels of androgen (B group) and healthy subjects (C group) were enrolled. The CYP17 gene polymorphism was investigated by PCR using DNA samples from peripheral blood lymphocytes. The T-->C transition in the risk allele (A2) produced a new recognition site for the restriction endonuclease MspA1 I. Three genotypes of androgen-related CYP17 gene (A1A1, A1A2, and A2A2) were determined and confirmed by sequencing., Results: The frequency of the A1A2 gene was similar in the cases and controls (P>0.05). The frequency of A2A2 gene was not significantly different between groups A and C (P>0.05). The frequency of A2A2 gene was significantly different between groups A and B and between groups B and C (P<0.05)., Conclusion: The presence of base substitution in androgen-related CYP17 gene at -34 bp (T-->C) increases the risk of post adolescent acne in female subjects with increased androgen levels.

A new HPLC-UV technique for the separation and analysis of 10 monosaccharides achieved within 13.5 min using 1-phenyl-3-methyl-5-pyrazolone (PMP) as the labelling molecule of the reductive monosaccharides has been established by combining common high performance liquid chromatography-UV and C18 column. The established technique was applied to the quantification of the monosaccharide components in extract of Silybum marianum. The results showed that the tested 10 monosaccharides as PMP derivatives were baseline separated under the HPLC conditions proposed. It was confirmed that Silybum marianum extract was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, xylose, galactose and arabinose with the molar ratio of 0.66:0.84:0.58:1.0:1.6:0.69:2.7:4.8. Quantitative recoveries of the compositional monosaccharides separated from the extract were in the range of 92.4%-104.0%, and the RSD values fell within 0.68%-3.81%. The results demonstrated that the proposed HPLC method was simple, rapid, convenient, and precise, and it was applicable to the analysis of the compositional monosaccharides of Silybum marianum extract.

Background: Inflammatory cytokines such as tumor necrosis factor receptor 2 (TNFR2) and Toll-like receptor 2 (TLR2) are the main responsible mediators of inflammatory acne. Factors affecting their production may possibly influence the degree of inflammatory response and hence may account for the clinical severity of acne. However, the roles of TNFR2 and TLR2 in the pathophysiology of acne vulgaris are poorly understood. We therefore investigated the relationship between acne vulgaris susceptibility and the polymorphisms in the TNFR2 M196R as well as TLR2 Arg753Gln gene., Methods: A total of 93 acne vulgaris patients and 90 healthy subjects from the Chinese Han ethnic group were enrolled in the study. The polymerase chain reaction restriction fragment length polymorphism technique was adopted to analyze the single-nucleotide polymorphisms of the TNFR2 M196R and TLR2 Arg753Gln gene, and to examine the association between acne vulgaris and the polymorphisms in the TNFR2 M196R as well as TLR2 Arg753Gln gene. The relationship between different genotypes and the susceptibility to acne vulgaris was analyzed., Results: There is a significant difference in the frequency of TNFR2 M196R genetic polymorphisms between the moderate-acne to severe-acne subgroups and the control group (p < 0.05), and there is also a significant difference in the frequency of TLR2 Arg753Gln genetic polymorphisms between the severe-acne subgroup and control group (p < 0.05)., Conclusion: The 196R allele of TNFR2 M196R as well as the 753Gln allele of TLR2 Arg753Gln are risk factors for acne vulgaris in Chinese Han patients, further supporting the contribution of inflammatory cytokines to the pathogenesis of acne.

The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and gamma-aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here we show that 5-HT increased the peak amplitude of light-evoked complex excitatory postsynaptic potentials (EPSPs), enhanced intrinsic excitability, and increased spike activity of identified type I(e(A)) interneurons. In contrast, 5-HT decreased spike activity and intrinsic excitability of type I(e(B)) interneurons. The classification of two categories of type I(e) interneurons was also supported by the observation that 5-HT produced opposite effects on whole cell steady-state outward currents in type I(e) interneurons. Serotonin produced a reduction in the amplitude of light-evoked complex inhibitory PSPs (IPSPs), increased spontaneous spike activity, decreased intrinsic excitability, and depolarized the resting membrane potential of identified type I(i) interneurons. In contrast to the effects of 5-HT, GABA produced inhibition in both types of I(e) interneurons and type I(i) interneurons. These results show that 5-HT and GABA can modulate the intrinsic excitability of type I interneurons independent of the presynaptic effects of the same transmitters on excitability and synaptic efficacy of photoreceptors.

The function of thyrotropin (TSH) in the thyroid gland is mediated by thyrotropin receptor (TSHR). In addition to the thyroid, TSHR expression has been described in some non-thyroidal tissues, although it is uncertain whether TSHR is present in hepatocytes. One study has reported hepatic expression of TSHR mRNA, but this was considered to be because of illegitimate transcription, and there has not been a study investigating its protein expression and function in hepatocytes. Here, we examined the expression of TSHR in human and rat liver tissues, as well as human normal hepatocyte cell line L-02. Our results demonstrated that hepatic TSHR mRNA could be detected and had the same sequence as that of thyroid-derived mRNA. TSHR protein was also expressed and mainly located in the hepatocyte cell membrane. Moreover, bovine TSH and immunoglobulin from sera of patients with Graves' disease stimulated cAMP production in these cells. Taken together, these data show that TSHR is present and functional in hepatocytes, and this expression is not a case of illegitimate transcription. Given the pivotal role of the liver in body metabolism and many human diseases, our findings provide important implications for a potentially novel physiopathological role of TSH via acting on the TSHR in hepatocytes besides its classical role in regulating the thyroid function.

A Pavlovian-conditioning procedure may produce modifications in multiple behavioral responses. As an example, conditioning may result in the elicitation of a specific somatomotor conditioned response (CR) and, in addition, other motor and visceral CRs. In the mollusk Hermissenda conditioning produces two conditioned responses: foot-shortening and decreased locomotion. The neural circuitry supporting ciliary locomotion is well characterized, although the neural circuit underlying foot-shortening is poorly understood. Here we describe efferent neurons in the pedal ganglion that produce contraction or extension of specific regions of the foot in semi-intact preparations. Synaptic connections between polysensory type Ib and type Is interneurons and identified foot contractile efferent neurons were examined. Type Ib and type Is interneurons receive synaptic input from the visual, graviceptive, and somatosensory systems. Depolarization of type Ib interneurons evoked spikes in identified tail and lateral foot contractile efferent neurons. Mechanical displacement of the statocyst evoked complex excitatory postsynaptic potentials (EPSPs) and spikes recorded from type Ib and type Is interneurons and complex EPSPs and spikes in identified foot contractile efferent neurons. Depolarization of type Ib interneurons in semi-intact preparations produced contraction and shortening along the rostrocaudal axis of the foot. Depolarization of Is interneurons in semi-intact preparations produced contraction of the anterior region of the foot. Taken collectively, the results suggest that type Ib and type Is polysensory interneurons may contribute to the neural circuit underlying the foot-shortening CR in Hermissenda.

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type I(i) (off-cell) spike activity, excitation of type I(e) (on-cell) spike activity, decreased spike activity in type III(i) inhibitory interneurons, and increased spike activity of ciliary efferent neurons. Here we show that pairs of type I(i) interneurons and pairs of type I(e) interneurons are electrically coupled. Neither electrical coupling or synaptic connections were observed between I(e) and I(i) interneurons. Coupling is effective in synchronizing dark-adapted spontaneous firing between pairs of I(e) and pairs of I(i) interneurons. Out-of-phase burst activity, occasionally observed in dark-adapted and light-adapted pairs of I(e) and I(i) interneurons, suggests that they receive synaptic input from a common presynaptic source or sources. Rhythmic activity is typically not a characteristic of dark-adapted, light-adapted, or light-evoked firing of type I interneurons. However, burst activity in I(e) and I(i) interneurons may be elicited by electrical stimulation of pedal nerves or generated at the offset of light. Our results indicate that type I interneurons can support the generation of both rhythmic activity and changes in tonic firing depending on sensory input. This suggests that the neural network supporting ciliary locomotion may be multifunctional. However, consistent with the nonmuscular and nonrhythmic characteristics of visually modulated ciliary locomotion, type I interneurons exhibit changes in tonic activity evoked by illumination.

Aims: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid., Methods: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed., Results: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05)., Conclusions: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.

Serotonin immunoreactive (5-HT-IR) neurons identified as cerebropleural ganglion triplets (CPTs) in Hermissenda may be homologues of 5-HT-IR neurons identified in other opisthobranch molluscs. In studies of isolated nervous systems and semi-intact preparations we used a combination of immunohistochemical techniques and fluorescent labeling with Lucifer yellow to identify 5-HT-IR CPT neurons after investigating sensory inputs and motor neuron projections. Here we show that identified 5-HT-IR CPT interneurons receive sensory input from mechanoreceptors and photoreceptors. In semi-intact preparations with intact pedal nerves P1 and P2, cutaneous stimulation of the middle or tail regions of the foot with calibrated von Frey hairs elicited spikes recorded from identified CPT interneurons. Illumination of the eyes evoked a small complex excitatory postsynaptic potential (EPSP) and resulted in a modest increase in the spike discharge of CPT interneurons. Immunostaining of Lucifer yellow-labeled neurons revealed that CPT interneurons projected an axonal process to the contralateral pedal ganglion. Depolarization of CPT interneurons with extrinsic current evoked EPSPs and spikes recorded from identified VP2 pedal neurons, motor neurons previously shown to elicit movement of the anterior foot. Extrinsic current stimulation of CPT interneurons in semi-intact preparations evoked movement of the anterior foot but did not facilitate ciliary activity or evoke PSPs recorded in identified VP1 ciliary motor neurons. Our results show that CPT neurons are polysensory interneurons that contribute to reflexive foot contractions in Hermissenda.

An understanding of associative learning requires (1) an adequate description of the experimental conditions under which learning is produced, (2) a knowledge of what is learned or the determination of the content of learning, and (3) an explanation of how learning generates changes in behavior (Rescorla, 1980). These basic issues are being addressed at both the behavioral and cellular/molecular levels by the analysis of associative learning in animals with relatively uncomplex nervous systems. Use of Pavlovian conditioning of invertebrates as a model for associative learning has led to the identification of cellular and synaptic mechanisms underlying the formation of basic associations. However, an understanding of the associative processes that form the basis for Pavlovian conditioning requires an explanation not only of the mechanisms of temporal contiguity or predictability between the conditioned stimulus (CS) and the unconditioned stimulus (US), but also of how changes produced in the nervous system by conditioning are expressed in behavior. Studies with invertebrates have provided the opportunity to examine how associative learning is expressed in the neural circuitry that supports the generation of learned behavior.

Rho GTPases acting through effector proteins regulate actin dynamics and cytoskeletal structure. In Hermissenda Csp24 is a cytoskeletal-related protein that contributes to the development of intermediate-term memory, and is homologous to other beta-thymosin-like repeat proteins containing multiple actin-binding domains. We have examined the role of Rho GTPase activity and its downstream target ROCK, and cyclin-dependent kinase 5 (Cdk5) on the phosphorylation of Csp24 using 32PO4 labeling of proteins separated with 2-D PAGE. The ROCK inhibitor Y-27632 significantly increased Csp24 phosphorylation, and the Rho activator lysophosphatidic acid (LPA) or the Cdk5 inhibitor butyrolactone significantly decreased Csp24 phosphorylation. Pretreatment with Y-27632 before LPA application significantly reduced the decreased phosphorylation of Csp24 normally detected in nervous systems exposed to LPA. Using a pull-down assay we found that LPA treatments activated Rho and exposure to 5-HT decreased Rho activity. Our results indicate that the Rho/ROCK and Cdk5 signaling pathways contribute to the regulation of Csp24 phosphorylation., (Copyright 2004 Elsevier Inc.)

Objective: To study the prevalence and determinants of Helicobacter pylori (H. pylori) infection among coal miners and to seek for competent preventive measures., Methods: 425 coal miners from three coal mines, Tangshan, Daxing, and baodian were chosen under stratified random cluster sampling. Face to face interview was conducted to fill the unified questionnaires by trained interviewers. 306 subjects underwent gastroenduoscopy to detect the situation of the gastroenduodenal diseases, according to the Sydney System of diagnosis. Mucosa biopsies were also undertaken according to the regulated location for culture of H. pylori and for pathological examination. Blood samples were obtained to detect the anti-HpU-IgG by enzyme-linked immunosorbent assay (ELISA). H. pylori infection was determined through culture and ELISA but confirmed under the standards set at the National Congress on Gastroduodenal Diseases in 1999., Results: Among 425 eligible coal miners being tested, 297 (69.9%) were H. pylori positive and the rate for those working underground (74.0%) was higher than that of those working on ground (P=0.004). No difference was found among coal miners between the three mines (P >0.05). Age, living conditions in childhood, number of current family members, the amount of alcohol intake and ways of eating at home were strongly associated with the status of H. pylori infection., Conclusions: Difference of H. pylori infection prevalences between the underground and the aboveground coal miners was noticed. Determinants that influencing the H. pylori infection would include socioeconomic factors, individual habits and ways of eating at home.

Pavlovian conditioning of Hermissenda produces both light-elicited inhibition of normal positive phototactic behavior and conditioned stimulus (CS)-elicited foot-shortening. Rotation, the unconditioned stimulus (US) elicits foot-shortening and reduced forward ciliary locomotion. The neural circuit supporting ciliary locomotion and its modulation by light is known in some detail. However, the neural circuits responsible for rotation-elicited foot-shortening and reduced forward ciliary locomotion are not known. Here we describe components of the neural circuit in Hermissenda that produce anterior foot contraction and ciliary activation mediated by statocyst hair cells. We have characterized in semi-intact preparations newly identified pedal ventral contraction motor neurons (VCMNs) and interneurons (I(b)). Type I(b) interneurons receive polysynaptic input from statocyst hair cells and project directly to VCMNs and cilia-activating motor neurons. Depolarization of VCMNs with extrinsic current in normal artificial seawater (ASW) and high-divalent cation ASW, and under conditions where central synaptic transmission was suppressed with 5 mM Ni(2+) ASW, elicited a contraction of the ipsilateral anterior foot measured from videotape recordings. Mechanical displacement of the statocyst or depolarization of identified statocyst hair cells with extrinsic current elicited spikes and complex excitatory postsynaptic potentials (EPSPs) in type I(b) interneurons and complex EPSPs and spikes recorded in VCMNs. Type I(b) interneurons are electrically coupled and project to VCMNs and VP1 cilia-activating motor neurons located in the contralateral pedal ganglia. The results indicate that statocyst hair-cell-mediated anterior foot contraction and graviceptive ciliary locomotion involve different interneuronal circuit components from the circuit previously identified as supporting light modulated ciliary locomotion.