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Meng-Yu Fu,1 Jie Hao,2 Lun-Hui Ye,3 Wei Jiang,2 Ying-Wen Lv,1 Jie-Liang Shen,2 Tao Fu1 1Department of Orthopaedics, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Anesthesiology, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of ChinaCorrespondence: Jie-Liang Shen; Tao Fu, Email 18996078008@qq.com; cqsdssrmyyft@163.comBackground: Since the application of ultrasound-guided erector spinae plane block (ESPB) in 2016, the approach has been gradually applied to perioperative analgesia in various surgeries. In recent years, more and more studies have focused on the effect of ESPB in perioperative analgesia of lumbar spinal surgery, but its clinical effect remains controversial.Objective: This systematic review and meta-analysis was designed to explore the efficacy and safety of ESPB used for perioperative pain management in lumbar spinal surgery.Methods: The Pubmed, Web of Science, Cochrane Library, and EMBASE databases were comprehensively searched for relevant articles from inception to March 2022. Randomized controlled trials (RCTs) comparing ESPB with placebo or without ESPB in lumbar spinal surgery were included. The Review Manager 5.3 software was employed for this meta-analysis.Results: Nineteen RCTs with 1381 participants were included for final analysis. ESPB group exhibited lower intraoperative consumption of sufentanil and remifentanil, lower total opioid consumption within 24 h and 48 h after surgery, lower incidence of rescue analgesia, longer time to first rescue analgesic and lower number of PCA button presses compared to the control group (P< 0.05). Moreover, the ESPB group had significantly lower pain scores at rest and on movement within 48 h after surgery compared with the control group (P< 0.05). In terms of opioid-related adverse reactions, ESPB reduced the incidence of postoperative nausea, vomitting, somnolence and itching in comparison to the control group (P< 0.05). ESPB-related serious complications were not reported in included studies.Conclusion: This meta-analysis demonstrated that ESPB used in lumbar spinal surgery was effective in relieving postoperative pain, decreasing the perioperative consumption of opioids, as well as decreasing the incidence of postoperative opioid-related adverse reactions.Keywords: erector spinae plane block, lumbar spinal surgery, perioperative analgesia, randomized controlled trial, meta-analysis

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: Disclosure This work was supported by the National Natural Science Foundation of China (82000611 to Jin-Huan Lin), and the Shanghai Pujiang Program (2020PJD061 to Jin-Huan Lin). All authors disclosed no financial relationships. Commentary Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a guideline-recommended approach for the management of pancreatic duct stones in the setting of painful chronic pancreatitis. In this case, the authors describe a suspected pancreaticobiliary fistula after P-ESWL. Previously described adverse events associated with P-ESWL include bleeding, perforation, pancreatitis, abdominal pain, and infection. Bile duct stricture can also occur as a consequence of pancreatic parenchymal edema after P-ESWL. Pancreaticobiliary fistulas, as seen in the current case, have been reported with endoscopic instrumentation and pancreatitis. Rarely, long-term stone formation can result in fistula as well. This case suggests multiple causes of a pancreaticobiliary fistula, and it is plausible that P-ESWL—associated injury is an additional factor. Early recognition and interpretation of pancreaticobiliary fistula on cholangiopancreatography is crucial to offer appropriate endoscopic therapy at an early stage of fistula formation for successful resolution. Shifa Umar, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Mohamed O. Othman, MD, GIE Senior Associate Editor

Toona ciliata is a deciduous or semi-deciduous tree species and belongs to the Toona genus of the Meliaceae family. Owing to low natural regeneration and over-exploitation, the species is listed as an endangered species at level II in China and its conservation has received increasing concern. Here, we sampled 447 individuals from 29 populations across the range-wide distribution of the T. ciliata complex in China and assessed their genetic variation using two chloroplast DNA markers. The results showed that the overall haplotype diversity and nucleotide diversity per site were high at h = 0.9767 and π = 0.0303 for the psb A- trn H fragment and h= 0.8999 and π = 0.0189 for the trn L- trn L fragment. Phylogenetic analysis supported the division of the natural distribution of T. ciliata complex into western and eastern regions. The genetic diversity was higher in the western region than in the eastern region, showing significant phylogeographic structure. Genetic differentiation among populations was moderate (Φst=42.87%), and the effects of isolation by distance (IBD) were significant. A neutrality test and mismatch distribution analysis indicated that the distribution of the T. ciliata complex generally did not expand, although a few local populations could likely expand after bottleneck effects. The overall results were complementary to and consolidated previous studies using mitochondrial and nuclear DNA markers. We finally discussed strategies for the genetic conservation of the T. ciliata complex.

As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Forest genetic conservation is typically species-specific and does not integrate interspecific interaction and community structure. It mainly focuses on the theories of population and quantitative genetics. This approach depicts the intraspecific patterns of population genetic structure derived from genetic markers and the genetic differentiation of adaptive quantitative traits in provenance trials. However, it neglects possible interspecific interaction in natural forests and overlooks natural hybridization or subspeciation. We propose that the genetic diversity of a given species in a forest community is shaped by both intraspecific population and interspecific community evolutionary processes, and expand the traditional forest genetic conservation concept under the community ecology framework. We show that a community-specific phylogeny derived from molecular markers would allow us to explore the genetic mechanisms of a tree species interacting with other resident species. It would also facilitate the exploration of a species' ecological role in forest community assembly and the taxonomic relationship of the species with other species specific to its resident forest community. Phylogenetic β-diversity would assess the similarities and differences of a tree species across communities regarding ecological function, the strength of selection pressure, and the nature and extent of its interaction with other species. Our forest genetic conservation proposal that integrates intraspecific population and interspecific community genetic variations is suitable for conserving a taxonomic species complex and maintaining its evolutionary potential in natural forests. This provides complementary information to conventional population and quantitative genetics-based conservation strategies.

Toona ciliata is an endangered species due to over-cutting and low natural regeneration in China. Its genetic conservation is of an increasing concern. However, several varieties are recognized according to the leaf and flower traits, which complicates genetic conservation of T. ciliata . Here, we sequenced the whole chloroplast genome sequences of three samples for each of four varieties ( T. ciliata var. ciliata , T. ciliata var. yunnanensis , T. ciliata var. pubescens , and T. ciliata var. henryi ) in sympatry and assessed their phylogenetic relationship at a fine spatial scale. The four varieties had genome sizes ranged from 159,546 to 159,617 bp and had small variations in genome structure. Phylogenomic analysis indicated that the four varieties were genetically well-mixed in branch groups. Genetic diversity from the whole chloroplast genome sequences of 12 samples was low among varieties (average π  = 0.0003). Besides, we investigated genetic variation of 58 samples of the four varieties in sympatry using two markers ( psa A and trn L- trn F) and showed that genetic differentiation was generally insignificant among varieties ( Ф st  = 0%-5%). Purifying selection occurred in all protein-coding genes except for the ycf 2 gene that was under weak positive selection. Most amino acid sites in all protein-coding genes were under purifying selection except for a few sites that were under positive selection. The chloroplast genome-based phylogeny did not support the morphology-based classification. The overall results implicated that a conservation strategy based on the T. ciliata complex rather than on intraspecific taxon was more appropriate., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Nintedanib (Ninte) has been approved for the treatment of pulmonary fibrosis, and whether it can ameliorate chronic pancreatitis (CP) is unknown., Aims: This study was conducted to investigate the effect and molecular mechanism of Ninte on pancreatic fibrosis and inflammation in vivo and in vitro., Methods: The caerulein-induced CP model of murine was applied, and Ninte was orally administered. Pathological changes in pancreas were evaluated using hematoxylin & eosin, Sirius Red, Masson's trichrome, and anti-Ki-67 staining. For in vitro studies, the effects of Ninte on cell viability, apoptosis, and migration of pancreatic stellate cells (PSCs) were determined by CCK-8, flow cytometry, and wound healing assays, respectively. The potential molecular mechanisms of the effects of Ninte on PSCs were analyzed by RNA-Seq and verified at the gene expression and protein activity levels by qRT-PCR and Western Blot., Results: Ninte significantly alleviated the weight loss in mice with caerulein-induced CP and simultaneously attenuated the pancreatic damage, as evidenced by reduced acinar atrophy, collagen deposition, infiltration of inflammatory cells, and inhibited cell proliferation/regeneration. Besides, Ninte markedly suppressed the transcription of fibrogenic and proinflammatory genes in pancreatic tissues. Further in vitro studies showed that Ninte significantly inhibited the transcription and protein expression of genes corresponding to fibrogenesis and proliferation in PSCs. The results of RNA-Seq analysis and subsequent verification assays indicated that Ninte inhibited the activation and proliferation of PSCs via the JAK/STAT3 and ERK1/2 pathways., Conclusions: These findings indicate that Ninte may be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alternation of generations in plant life cycle provides a biological basis for natural selection occurring in either the gametophyte or the sporophyte phase or in both. Divergent biphasic selection could yield distinct evolutionary rates for phase-specific or pleiotropic genes. Here, we analyze models that deal with antagonistic and synergistic selection between alternative generations in terms of the ratio of nonsynonymous to synonymous divergence (Ka/Ks). Effects of biphasic selection are opposite under antagonistic selection but cumulative under synergistic selection for pleiotropic genes. Under the additive and comparable strengths of biphasic allelic selection, the absolute Ka/Ks for the gametophyte gene is equal to in outcrossing but smaller than, in a mixed mating system, that for the sporophyte gene under antagonistic selection. The same pattern is predicted for Ka/Ks under synergistic selection. Selfing reduces efficacy of gametophytic selection. Other processes, including pollen and seed flow and genetic drift, reduce selection efficacy. The polymorphism (πa) at a nonsynonymous site is affected by the joint effects of selfing with gametophytic or sporophytic selection. Likewise, the ratio of nonsynonymous to synonymous polymorphism (πa/πs) is also affected by the same joint effects. Gene flow and genetic drift have opposite effects on πa or πa/πs in interacting with gametophytic and sporophytic selection. We discuss implications of this theory for detecting natural selection in terms of Ka/Ks and for interpreting the evolutionary divergence among gametophyte-specific, sporophyte-specific, and pleiotropic genes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Neolamarckia cadamba (Roxb.) Bosser is a fast-growing deciduous tree species and belongs to the Neolamarckia genus of the Rubiaceae family. This species has great economic and medical values in addition to being an important timber species for multiple industrial purposes. However, few studies have examined the genetic diversity and population structure in the natural distribution of this species in China. Here, we applied both the haploid nrDNA ITS (619 bp for aligned sequences) and mtDNA (2 polymorphic loci) markers to investigate 10 natural populations (239 individuals in total) that covered most of the distribution of the species in China. The results showed that the nucleotide diversity was π = 0.1185 ± 0.0242 for the nrDNA ITS markers and π = 0.00038 ± 0.00052 for the mtDNA markers. The haplotype diversity for the mtDNA markers was h = 0.1952 ± 0.2532. The population genetic differentiation was small (Fstn = 0.0294) for the nrDNA ITS markers but large (Fstm = 0.6765) for the mtDNA markers. There were no significant effects of isolation by distance (IBD), by elevation, and by two climatic factors (annual average precipitation and tem perature). A geographic structure among populations (Nst

Background: Acute lung injury (ALI) is associated with high morbidity and mortality and is partly driven promoted by ferroptosis. Proanthocyanidins (PAs) is a natural bioactive flavonoid with anti-inflammatory and antioxidant activities. PAs can also significantly protect against acute lung inflammation and ferroptosis in alveolar epithelial cells. However, it is unclear whether PAs can alleviate ALI by reducing ferroptosis. This study aimed to evaluate the protective effects of PAs and the potential mechanisms against Influenza A virus (IAV)-induced ALI., Methods: Mice were inoculated nasally with IAV to induce ALI. IAV-induced pulmonary inflammation and ferroptosis was tested by measuring the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and acyl-CoA synthetase long-chain family member (ACSL4) in lung tissue. The potential targets that PAs protect against IAV-induced ALI were determined via a systemic pharmacological analysis. The molecular mechanism of PAs in ALI treatment was investigated by assessing the level of inflammation and ferroptosis markers using Western Blot and quantitative real-time PCR., Results: Systemic pharmacological analysis suggested that PAs protect against IAV-induced pneumonia thorough TGF-β1 and its relative signaling pathway. PAs effectively alleviated histopathological lung injury, reduced inflammatory cytokines and chemokines secretion, which were increased in IAV-infected mice. Meanwhile, PAs further prevented mouse airway inflammation in ALI, concomitant with the decreased expression TGF-β1, smad2/3, p-Smad2, p-Smad3 and ferroptosis mediator IFN-γ. Furthermore，IFN-γ promotes cell lipid peroxidation and ferroptosis，PAs significantly reduced MDA and ACSL4 levels and upregulated GSH, GPX4, and SLC7A11., Conclusion: Overall, PAs can attenuate ferroptosis against IAV-induced ALI via the TGF-β1/Smad2/3 pathway and is a promising novel therapeutic candidate for ALI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Toona ciliata is an important timber species but is recognized as an endangered species at level II in China. Its genetic conservation is of increasing concern. Provenance trials and other breeding programs were conducted to develop seed transfer rules and multiplications. Here, we investigated twenty-nine populations sampled across the natural distribution of the T. ciliata complex using mtDNA and nrDNA ITS (ribosomal internal transcribed spacer) markers. Haplotype diversity was h = 0.190 ± 0.202 and nucleotide diversity was π = 0.000383 ± 0.000536 for mtDNA marker. Nucleotide diversity for ITS sequences was 0.00837 ± 0.000783. Haplotypes exhibited phylogeographic structure in spatial distribution. The extent of genetic differentiation was significant ( F st = 0.6994 ± 0.0079 for ITS and 0.8870 ± 0.0077 for mtDNA marker). Isolation by distance (IBD) and by elevation (IBE) occurred among populations. Phylogenetic relationships from mtDNA marker indicated three genetically distinct regions, each without IBD effects. Compared with pollen flow, seed flow was strongly impeded in the western region, but extensive in the central region, and less impeded in the eastern region. Most populations did not exhibit expansion, with only a few populations showing expansion after bottleneck effects. We discussed a strategy of region-based genetic conservation and proposed to conserve multiple populations in the western and eastern regions and a few populations in the central region.

Acute pancreatitis (AP) is a common digestive disease encountered in Emergency Departments that carries a heavy socioeconomic burden. This study was conducted to determine the global status of AP research. Articles related to AP published in 1999 to 2018 were retrieved from the Web of Science (WOS) database and the 20 highest-output countries or regions were determined based on the total number of publications. Correlation analysis of AP research output and the gross domestic product (GDP) of each country or region was conducted. The quantity and quality of research of these 20 highest-output countries were compared to the total output, outputs per capita, and average impact factor (IF). All annual data were analyzed using time-trend analysis. A keyword co-occurrence analysis was conducted to determine the highlights in AP research. In total, 17,698 publications were retrieved, and 16,461 papers (93.0%) of them were from the 20 highest-output countries. A significantly positive correlation was identified between AP research output and the GDP (R = 0.973, P < .001). The 5 highest-output countries were the USA (24.9%), China (12.3%), Germany (7.5%), Japan (6.7%), and the UK (6.1%). Finland ranked 1st in the number of publication per capita, the USA had the highest accumulated IF (25,432.758) and total citations (104,592), Switzerland had the highest average IF (6.723), and Netherland had the highest average citations (51.90). Genetic research and AP-related hyperglycemia were research highlights. Analysis of the global output of research of AP research showed signs of growth. Research output was positively correlated with GDP. For the most productive countries, research quality was stable. Although developing countries lagged behind in output per capita and quality, great progress has been made in the past 2 decades., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Toona ciliata and Toona sinensis belong to the Toona genus of the Meliaceae family and are important timber species in China. T. ciliata is an endangered species at level II due to overcutting and a low rate of natural regeneration. T. sinensis was cultivated as an economic and nutritious tree for more than 2000 years. The two species differ in flower and leaf morphological traits, reproductive systems, and range size of natural distribution. To reveal the potential molecular basis of these divergences, we examined the similarities and differences in their whole genome sequences. Results indicate that T. ciliata had a higher number of expanded gene families than T. sinensis . The whole genome duplication (WGD) occurred before their speciation. The long-terminal repeats (LTRs) insertion was earlier in the T. ciliata genome (3.2985 ± 2.5007 Mya) than in the T. sinensis genome (3.1516 ± 2.2097 Mya). Twenty-five gene families in the T. ciliata genome were detected to be under positive selection compared with background branches of ten different land species. The T. ciliata genome was highly collinear with the T. sinensis genome, but had low collinearity with the genomes of more distant species. These genomic and evolutionary divergences are potentially associated with the differences between T. ciliata and T. sinensis in terms of their reproductive systems and ecological adaptation.

Purpose: Endoscopic retrograde cholangiopancreatography (ERCP) has been used in clinical practice for over 50 years. This study aims to investigate the current state of research in the field of ERCP., Methods: Web of Science database was searched using the term "ERCP" for articles published between 1994 and 2018. The total number of articles from the top 20 countries with the most published articles was determined. The top 5 countries were compared in terms of output per capita, number of articles published in top journals, cumulative impact factor (IF), and average IF. All annual data were subjected to time-trend analysis. The frequently used terms in the titles and abstracts of all articles were retrieved to conduct co-occurrence analysis to determine the research focus of ERCP., Results: A total of 9960 articles on ERCP were published between 1994 and 2018, of which 8778 articles were from the top 20 producing countries. There was a significant positive correlation between the output and GDP of each country (R = 0.870, P = .001). The United States of America (USA), Japan, Germany, Italy, and China were the top 5 producing countries with 3190 (32.0%), 868 (8.7%), 658 (6.6%), 512 (5.1%) and 488 (4.9%) articles published, respectively. The USA, Japan, Italy, and China were trending upwards in the total outputs and outputs per capita, while Germany were trending downwards. For average IF, Germany had a downwards trend, while the other 4 countries remained stable. Overall, the USA had the highest output per capita (97.5/10 million) and the highest average IF (6.454). China had the lowest output per capita (3.5/10 million) and average IF (3.125). The ERCP procedures for sphincter of Oddi dysfunction, the combination of ERCP, and laparoscopic cholecystectomy have been the research focus of ERCP., Conclusions: Except for Germany, research on ERCP will continue to increase in the top-producing countries. The outputs per capita and quality of articles from developed countries are higher than those from developing countries., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the clinical efficacy of a Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with different parameters in the treatment of chloasma. Methods: In this study, 30 patients with chloasma, symmetrically distributed on the left and right sides of the face and who were treated with a Fayton Q-switched 1064 nm Nd:YAG laser, were recruited. The patients were randomly selected for the treatment of facial lesions on the left and right sides of the face using a spot diameter of 9 mm and an energy density of 0.8 J/cm 2 on one side, and, on the opposite side, a spot diameter of 6 mm with an energy density of 1.2 J/cm 2 . The laser frequency was 5 Hz and treatment was conducted once every 7-10 days and repeated eight times as a course of treatment. At the end of the course of treatment, as well as 1, 3, and 6 months after treatment, front-facing images and 45° left- and right-side images were taken, respectively. The curative effect of the treatment was evaluated using the Melasma Area Severity Index (MASI) score. Results: The results of this study showed that the total effective rate of a Fayton Q-switched 1064 nm Nd:YAG laser in the treatment of chloasma was 60%. Conclusions: Using a Q-switched 1064 nm Nd:YAG laser represents a safe and effective approach for the treatment of chloasma. The therapeutic effects of the parameter sets, that is, a spot diameter of 9 mm and an energy density of 0.8 J/cm 2 , and a spot diameter of 6 mm with an energy density of 1.2 J/cm 2 , were similar. The treatment time and average effective times of the latter were relatively shortened. Clinical Trial Registration number researchregistry6799.

Purpose: Only few studies have analyzed the global distribution of anesthesia research. This study was designed to reveal the current global research status of anesthesiology., Methods: Articles published between 1999 and 2018 in international journals in the field of anesthesiology were retrieved from the PubMed database. The top 20 ranked countries were identified. The gross domestic product (GDP) of each country was also retrieved to reveal the correlation between research outputs and the economy. The total outputs and outputs per 10 million inhabitants in each country were calculated and compared. To analyze the quality of publications among the top 10 ranked countries, the impact factor (IF), article influence score (AIS), and immediacy index (ImI) were calculated and analyzed. In addition, the keywords of publications were retrieved to conduct co-occurrence analysis in order to determine the research focus in anesthesiology., Results: A total of 112,918 articles were published in 30 selected journals from 1999 to 2018. There was a positive correlation between research outputs and GDP of 10 countries (p < 0.001, r = 0.825). The USA ranked 1st with 21,703 articles, followed by the UK (8393 articles) and Germany (6504 articles). Canada had the highest number of publications per 10 million inhabitants in 2018. The UK had the highest average IF (4.70), average AIS (1.16), and average ImI (1.64) among the 10 countries. The research highlights in the field of anesthesiology included "mechanism and management of pain", "cardiac anesthesia", "pediatric anesthesia and airway management", "analgesia" and "anesthetic agents"., Conclusion: Regarding quantity trend, the output of global production in anesthesiology increased continuously as the number of articles from the high-output countries showed an increasing trend; however, there was still a gap between developing and developed countries in research quality. High-quality research should be encouraged in developing countries., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Developing high-performance electrocatalysts for urea oxidation reaction (UOR) can not only solve the problem of environmental pollution, but also solve the problem of the energy crisis by producing hydrogen for electrodes. The preparation of porous three-dimensional nanostructures as efficient electrocatalysts has become important work. Here, we developed a novel three-dimensional (3D) nanostructure of NiFe(OH) X nanoparticles/nickel foam with a high active area by a simple electroplating method and a subsequent treatment with ferric ion solution. This structure shows much greater UOR activity than the control sample (Ni/Ni foam) with the potential of 1.395 V ( vs. RHE) (with an overpotential of 1.025 V) for driving the current density of 100 mA cm -2 in 1.0 M KOH electrolyte with 0.33 M urea. This work not only provides rapid and large-scale preparation of a three-dimensional nanostructure, but also gives a new way to design and obtain high-performance electrocatalysts., Competing Interests: There are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Ethnopharmacological Relevance: Carvacrol, a monoterpene phenol from Mosla chinensis Maxim, which is a commonly Chinese herbal medicine. The most important pharmacology of it is dispelling exogenous evils by increasing perspiration. And it is the gentleman medicine in the Chinese herbal compound prescription of Xin-Jia-Xiang-Ru-Yin, mainly for the treatment of summer colds with dampness including influenza virus A infection., Aim of the Study: Our preliminary study verified that the Xin-Jia-Xiang-Ru-Yin could inhibit acute lung injury of mice with influenza virus A infection. And there have been some reports implicating the high antimicrobial activity of carvacrol for a wide range of product preservation, but little research including the effects of it on viral infection. The aim of this study was to reveal the antiviral effects of carvacrol, the main constituent in Mosla chinensis Maxim., Materials and Methods: Initially, C57BL/6 mice were grouped and intranasally administered FM1 virus to construct viral infection models. After treatment with ribavirin and carvacrol for 5 days, all mice were euthanized, and specimens were immediately obtained. Histology, flow cytometry and Meso Scale Discovery (MSD) analysis were used to analyze pathological changes in lung tissue, the expression levels of cytokines and the differentiation and proportion of CD4 + T cells subsets, while Western blot and qRT-PCR were used to detect the expression of related proteins and mRNA., Results: Carvacrol attenuated lung tissue damage, the proportions of Th1, Th2, Th17 and Treg in CD4 + T cells and the relative proportions of Th1/Th2 and Th17/Treg cells. Carvacrol inhibited the expression of inflammation-associated cytokines including IFN-γ, IL-2, IL-4, IL-5, IL-12 and TNF-ɑ, IL-1, IL-10, IL-6. Decreased levels of TLR7, MyD88, IRAK4, TRAK6, NF-κB, RIG-I, IPS-I and IRF mRNA in carvacrol-treated mice were observed comparing to the mice in VC group. Further, the total expression of RIG-I, MyD88 and NF-κB proteins had increased significantly in the VC group but reduced obviously in the group treated with ribavirin or carvacrol., Conclusions: These results indicate that carvacrol is a potential alternative treatment for the excessive immune response induced by influenza virus A infection, the cold-fighting effect of Mosla chinensis Maxim may depend on the anti-virus of carvacrol., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Metabolic syndrome (MS) is one of the major causes of coronary artery diseases (CAD). Gut microbiome diversity and its natural fermentation products are not only correlated with MS and CAD, but their correlations also appear to be stronger than the associations with traditional risk factors. Therefore, the aim of this study was to provide a new potential pathway for the natural fermentation product butyrate to improve MS and to examine whether it is associated with serum metabolic profiles and gut flora composition. Methods: C57BL/6J mice fed a high-fat diet (HFD) were treated with 400 mg/kg of sodium butyrate for 16 weeks. Blood and fecal samples were collected, and the metabolite concentrations and 16s rRNA were measured with liquid chromatography-MS and Illumina platform, respectively. The plasma differential metabolites and gut microbiome composition were analyzed with XCMS online and QIIME 2, respectively. Results: Gut microbiome-derived butyrate reduced glucose intolerance and insulin resistance, resisting HFD-induced increase in the relative abundance of f&#95; Lachnospiraceae , f&#95; Rikenellaceae , and f&#95; Paraprevotellaceae . Meanwhile, sodium butyrate increased the levels of α-linolenate, all-trans-retinal, resolvin E1, and leukotriene in the plasma, and the differential pathways showed enrichment in mainly resolvin E biosynthesis, histidine degradation, lipoxin biosynthesis, and leukotriene biosynthesis. Moreover, sodium butyrate increased the levels of phosphorylated-adenosine 5'-monophosphate-activated protein kinase (p-AMPK) and facilitated glucose transporter member 4 (GLUT4) in the adipose tissue. Conclusion: Butyrate can induce AMPK activation and GLUT4 expression in the adipose tissue, improving cardiovascular disease (CVD)-related metabolic disorder, resisting HFD-induced gut microbiome dysbiosis, and promoting resolvin E1 and lipoxin biosynthesis. Oral supplement of the natural fermentation product butyrate can be a potential strategy for preventing CVD., (Copyright © 2019 Gao, Lv, Long, Chen, He, Ruan and Zhu.)

Colorectal cancer (CRC) is one of the most difficult cancers to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidences show that Evodiamine (EVO) exerts an inhibitory effect on cancer cell apoptosis, migration, and invasion. In this study, we investigated the effects of EVO on the metastasis of CRC cells in vitro and in vivo. In vitro, wound-healing and transwell assay showed that migration and invasion of HT-29 and HCT-116 CRC cells were inhibited significantly by EVO. Western blot and RT-PCR showed that EVO reduced the expression of matrix metalloproteinase-9 in a dose-dependent manner. In EVO-induced cells, the intracellular NAD+/NADH ratio was increased, the level of Sirt1 was increased, and acetyl-NF-κB P65 was decreased. This process was inhibited by nicotinamide, an inhibitor of Sirt1. In vivo, EVO reduced tumor metastasis markedly. These findings provide evidences that EVO suppresses the migration and invasion of CRC cells by inhibiting the acetyl-NF-κB p65 by Sirt1, resulting in suppression of metalloproteinase-9 expression in vitro and in vivo.

Background: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD)., Methods: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively., Results: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group., Conclusion: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Introduction: We aimed to characterize postpartum disease flares among treatment-naive mothers with chronic hepatitis B (CHB). CHB mothers were enrolled and compared with non-infected mothers in terms of postpartum alanine aminotransferase (ALT) abnormalities., Methods: Demographic, virological, and biochemical parameters were collected up to postpartum week 16, with flares and exacerbations defined as ALT levels 5-10 and >10 times the upper limit of normal, respectively. Outcome assessments included ALT flares or exacerbation and their predictive parameters., Results: Among 4236 patients enrolled, 869 and 3367 had no infection (group A) and had CHB (group B), respectively. Infected mothers were further stratified into two subgroups by the presence (B1, n = 1928) or absence (B2, n = 1439) of detectable serum levels of hepatitis B virus (HBV) DNA (lowest level of quantitation, 100 IU/mL). A significantly higher frequency of abnormal ALT levels was observed in group B vs. group A (28.27 vs. 20.37%, p < 0.001). ALT events mainly occurred in group B1 (flares, 115/1928, 5.96%; exacerbations, 57/1928, 2.96%). The ALT levels had a bimodal pattern, with peaks at postpartum weeks 3-4 and 9-12. On multivariate analysis, elevated ALT levels and detectable levels of HBV DNA at delivery were independent risk factors for postpartum disease flares. Further subgroup analysis in group B1 demonstrated that a cut-off HBV DNA level of 5 log 10 IU/mL at delivery predicted ALT events (positive predictive value, 14.4%; negative predictive value, 98.2%)., Conclusions: Postpartum ALT level elevation is common in CHB patients. ALT flares or exacerbations are mainly observed in mothers with elevated ALT or HBV DNA levels ≥5 log 10 IU/mL at delivery.

A series of novel quinolone derivatives (8a-j) were synthesized, and their anticancer activities were tested in human cancer cell lines, human lung carcinoma cell (A549), human promyelocytic leukemia cell (HL-60), and human cervical cancer cell (Hela). Compound 8i was found to be 5-times more potent in cell-killing activity for cell lines A549, HL-60, and Hela than the positive control irinotecan or cisplatin, with IC 50 of 0.009, 0.008 and 0.010 µM, respectively. The docking study revealed that compound 8i might have strong interactions with the active site of DNA-topoisomerase I.

Objective: To explore the role of miR-133b in ovarian cancer and to preliminarily elucidate the mechanism of miR-133b in epithelial-mesenchymal transition (EMT) of ovarian cancer., Patients and Methods: MiR-133b was detected in ovarian cancer specimens, and the relationship of miR-133b with each pathological index and clinical index of ovarian cancer was analyzed. The action targets of miR-133b in ovarian cancer were analyzed systematically and studied deeply via the target validation and cell function validation. Finally, the possible reasons of ovarian cancer metastasis were analyzed through the molecular regulation mechanism in EMT of ovarian cancer., Results: The miR-133b level in ovarian cancer was significantly lower than in normal ovarian tissues and benign ovarian tumors (p<0.05). The level of miR-133b in ovarian cancer was related to differentiated degree and lymphatic metastasis. Dual-luciferase assay indicated that connective tissue growth factor (CTGF) was the target gene regulated by miR-133b. Reverse transcriptase-polymerase chain reaction (RT-PCR) as well as Western blot results proved that the expression level of E-cadherin representing the epithelial cell phenotype was increased, while the expression level of vimentin representing the mesenchymal cell phenotype was decreased. Transwell assay confirmed that the migration and invasion abilities of ovarian cancer cells declined after transfection with miR-133b plasmid. After co-transfection with miR-133b and CTGF overexpression plasmids, RT-PCR and Western blotting proved that the expression level of E-cadherin representing the epithelial cell phenotype was decreased, while the expression level of vimentin representing the mesenchymal cell phenotype was increased; transwell assay confirmed that the cell migration and invasion abilities were increased after co-transfection., Conclusions: The results of this study showed that miR-133b may serve as a new molecular marker of EMT of ovarian cancer, and act as a molecular marker of differentiated degree and lymphatic metastasis of ovarian cancer.

Objective: The effects of DNA methyltransferase (DNMT) inhibitor RG108 on the proliferation and apoptosis of endometrial cancer was investigated, and whether its mechanism was related to the inhibition of DNMT3B, thereby affecting the human mutL homolog 1 (hMLH1) methylation status and its expression, was further studied., Materials and Methods: Culture of human endometrial cancer Ishikawa cell lines: cells grew adhering to the wall in Roswell Park Memorial Institute-1640 (RPMI-1640) medium (supplemented with 10% fetal bovine serum (FBS) and 2 mM L-glutamic acid). After the cells were treated with RG108, the changes in cell viability were detected via methyl thiazolyl tetrazolium (MTT) assay. The effect of RG108 on cell cycle was detected via flow cytometry, and its effect on cell apoptosis was detected via flow cytometry and TUNEL. Moreover, the methylation status of hMLH1gene in endometrial cancer cells was detected via methylation specific-PCR (MSP), and the changes in DNMT3Band hMLH1 expressions were detected via RT-PCR and Western blotting, respectively., Results: MTT results showed that RG108 inhibited the cell viability in a dose-dependent and time-dependent manner. Flow cytometry revealed that RG108 blocked the cell cycle in G2/M phase and promoted the apoptosis, and TUNEL assay further proved that RG108 promoted the apoptosis. It was found in the detection via MSP that the methylated hMLH1 gene was significantly reduced after 72 h of treatment with RG108. Besides, RT-PCR and Western blotting showed that RG108 inhibited the DNMT3B expression and activated the hMLH1 expression., Conclusions: The demethylation drug RG108 can significantly inhibit the proliferation of endometrial cancer cells, block the cell cycle in the G2/M phase and induce the cell apoptosis, which is a new candidate drug in the treatment of endometrial cancer. RG108 realizes the hMLH1 demethylation and increases the hMLH1 expression through inhibiting the expression of DNMT3B.

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4- O -β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate., Competing Interests: The authors declare no conflict of interest.

The main aim of this retrospective cross-sectional study was to examine the relationship between vertebral compression fracture and thoracolumbar Cobb angles. Fracture prevalence was found to be significantly higher for patients with moderate [odds ratio (OR) = 4.78 (2.88-7.95)] or severe kyphosis [OR = 10.7 (5.11-22.40)] than for patients with mild kyphosis. The relationship between degree of thoracolumbar kyphosis and vertebral compression fracture was analyzed., Introduction: The hypothesis that vertebral compression fracture in women is related to thoracolumbar kyphosis severity was tested, and a clinically important cutoff degree of sagittal thoracolumbar Cobb angle (TLCobb) was determined., Methods: Demographic data, clinical data, and quantitative computed tomography (QCT) findings were compiled for 212 postmenopausal women with thoracolumbar fracture (study group) and 150 postmenopausal women with degenerative lumbar disease (control group). Group proportions and characteristics were compared with chi-squared tests and unpaired t tests, respectively., Results: In this retrospective cross-sectional study cohort, 17 patients had T11 fractures, 79 had T12 fractures, 89 had L1 fractures, and 27 had L2 fractures. QCT findings and TLCobb differed between the study and control groups (both p < 0.001). No significant differences were found in body mass index (BMI), disk height, or coronal TLCobb. After adjustment for age, BMI, and QCT findings, fracture prevalence was found to be higher in the thoracolumbar kyphosis study group than in the control group [OR = 6.16, 95% confidence interval (CI) 3.88-9.78]. Sagittal TLCobbs of 7.5-15° and >15° were associated with an increased fracture prevalence, with ORs of 4.78 (2.88-7.95) and 10.7 (5.11-22.40), respectively., Conclusion: Vertebral fracture prevalence in postmenopausal women was found to be associated with thoracolumbar kyphosis. A TLCobb sagittal angle >15° should be considered an indicator for vertebral fracture assessment.

This study aims to analyze the postsurgical health-related quality of life (HRQOL) and quality of voice (QOV) of patients with laryngeal carcinoma with an expectation of improving the treatment and HRQOL of these patients. Based on the collection of information of patients with laryngeal carcinoma regarding clinical characteristics (age, TNM stage, with or without laryngeal preservation and/or neck dissection, with or without postoperative irradiation and/or chemotherapy, etc.), QOV using Voice Handicap Index (VIH) scale and HRQOL using EORTC QLQ-C30 and EORTCQLQ-H&N35 scales, the differences of postsurgical HRQOL related to their clinical characteristics were analyzed using univariate nonparametric tests, the main factors impacting the postsurgical HRQOL were analyzed using regression analyses (generalized linear models) and the correlation between QOV and HRQOL analyzed using spearman correlation analysis. A total of 92 patients were enrolled in this study, on whom the use of EORTC QLQ-C30, EORTC QLQ-H&N35 and VHI scales revealed that: the differences of HRQOL were significant among patients with different ages, TNM stages, and treatment modalities; the main factors impacting the postsurgical HRQOL were pain, speech disorder, and dry mouth; and QOV was significantly correlated with HRQOL. For the patients with laryngeal carcinoma included in our study, the quality of life after open surgeries were impacted by many factors predominated by pain, speech disorder, and dry mouth. It is suggested that doctors in China do more efforts on the patients' postoperative pain and xerostomia management and speech rehabilitation with the hope of improving the patients' quality of life.

We examined the serum concentration of human epididymis protein (HE4) in patients with benign gynecological diseases complicated with chronic renal deficiency and its significance in the differential diagnosis of benign and malignant gynecological diseases. Serum HE4 and cancer antigen 125 concentrations were detected by chemiluminescence. Clinically or pathologically confirmed gynecological diseases were grouped and retrospectively analyzed, including 50 cases of gynecological benign diseases, 35 cases of non-mucinous epithelial ovarian carcinoma, 36 cases of endometrial adenocarcinoma, 15 cases of gynecological benign diseases patients complicated with chronic renal deficiency, 15 cases of gynecological diseases without chronic renal deficiency, and 30 normal controls. Serum HE4 values in the ovarian cancer group, endometrial cancer group, gynecological benign diseases with chronic renal deficiency group, and chronic renal deficiency group were significantly increased compared with the benign gynecological diseases and normal control groups, showing a significant difference (P < 0.001). A comparison of 4 groups with high HE4 showed that the HE4 level in the 2 groups with renal deficiency were higher than those in the ovarian cancer and endometrial cancer groups, but the difference was not significant (P > 0.05); there was no significant difference between 2 groups with renal deficiency (P > 0.05). Serum concentration of HE4 was high in patients with chronic renal deficiency, which should be distinguished during differential diagnosis of gynecological benign and malignant tumors in patients with chronic renal deficiency to avoid misdiagnosis.

Background: The prevalence of diabetes is increasing in China. Glucose control is very important in diabetic patients. The aim of this study was to compare the accuracy of five glucose meters used in Chinese hospitals with a reference method, in the absence and presence of various factors that may interfere with the meters., Methods: Within-run precision of the meters was evaluated include Roche Accu-Chek Inform®, Abbott Precision PCx FreeStyle®, Bayer Contour®, J&J LifeScan SureStep Flexx®, and Nova Biomedical StatStrip®. The interference of hematocrit level, maltose, ascorbic acid, acetaminophen, galactose, dopamine, and uric acid were tested in three levels of blood glucose, namely low, medium, and high concentrations. Accuracy (bias) of the meters and analytical interference by various factors were evaluated by comparing results obtained in whole blood specimens with those in plasma samples of the whole blood specimens run on the reference method. Impact of oxygen tension on above five blood glucose meters was detected., Results: Precision was acceptable and slightly different between meters. There were no significant differences in the measurements between the meters and the reference method. The hematocrit level significantly interfered with all meters, except StatStrip. Measurements were affected to varying degrees by different substances at different glucose levels, e.g. acetaminophen and ascorbic acid (Freestyle), maltose and galactose (FreeStyle, Accu-Chek), uric acid (FreeStyle, Bayer Contour), and dopamine (Bayer Contour)., Conclusions: The measurements with the five meters showed a good correlation with the plasma hexokinase reference method, but most were affected by the hematocrit level. Some meters also showed marked interference by other substances., (© 2013 Wiley Periodicals, Inc.)

A novel series of quinolone derivatives (6a-n) were designed and synthesized, and their biological activities were evaluated as potential antitumor topoisomerase I (Top I) inhibitors. Among these compounds, 6j exhibited the most potent antitumor activities against multiple cancer cell lines. Docking simulation was performed to insert compound 6j into the crystal structure of DNA-Top I to determine the probable binding model.

Kawasaki disease (KD) is a complex disease, leading to the damage of multisystems. The pathogen that triggers this sophisticated disease is still unknown since it was first reported in 1967. To increase our knowledge on the effects of genes in KD, we extracted statistically significant genes so far associated with this mysterious illness from candidate gene studies and genome-wide association studies. These genes contributed to susceptibility to KD, coronary artery lesions, resistance to initial IVIG treatment, incomplete KD, and so on. Gene ontology category and pathways were analyzed for relationships among these statistically significant genes. These genes were represented in a variety of functional categories, including immune response, inflammatory response, and cellular calcium ion homeostasis. They were mainly enriched in the pathway of immune response. We further highlighted the compelling immune pathway of NF-AT signal and leukocyte interactions combined with another transcription factor NF- κ B in the pathogenesis of KD. STRING analysis, a network analysis focusing on protein interactions, validated close contact between these genes and implied the importance of this pathway. This data will contribute to understanding pathogenesis of KD.

A method for the analysis of flavonoids in Astragali Radix by high-performance liquid chromatography (HPLC) combined with photodiode-array detection (DAD) and an electrospray ionization (ESI)--mass spectrometry (MS) was developed. After the samples were extracted with ethanol, the optimum separation conditions for these analytes were achieved using a gradient elution system and a 2.0 x 150 mm Shimadzu VP-ODS column. Eight flavonoids were identified to exist in Astragali Radix based on their characteristic UV data and mass spectra. The concentrations of three major components in this herb--ononin, calycosin and formononetin--were determined by LC/ESI-MS in positive selective ion monitoring (SIM) mode. The calibration curves were linear in the range of 0.9~180.0 μg·mL⁻¹ for ononin, 1.8~360.0 μg·mL⁻¹ for calycosin and 1.4~280 μg·mL⁻¹ for formononetin, respectively. The limits of quantification (LOQ) and detection (LOD) were 0.9 μg· mL⁻¹ and 0.2 μg mL⁻¹ for ononin, 1.8 μg mL⁻¹ and 0.5 μg·mL-1 for calycosin, 1.4 μg mL⁻¹ and 0.5 μg·mL⁻¹ for formononetin, respectively. The standard recoveries were between 95.4~104.7%. The developed method was proven to be useful for the quantitative and qualitative analysis of flavonoid constituents in various resources of Astragali Radix.

The possible involvement of the nitric oxide (NO)-cyclic GMP (cGMP)-protein kinase G (PKG) pathway on bovine lactoferrin (BLF)-induced spinal antihyperalgesic activity was elucidated in sciatic nerve injured rats. Intrathecal BLF reduced thermal hyperalgesia in a dose-dependent manner. Pretreatment with NG-L-nitro-arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase), 7-nitroindazole (7-NI, neuronal NO synthase inhibitor), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl-cyclase inhibitor), (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2, 9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo-[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor) or glybenclamide (ATP-sensitive K+ channel blocker), but not NG-D-nitro-arginine methyl ester (D-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2 (CTOP, selective mu-opioid receptor antagonist) or naloxone (nonselective opioid receptor antagonist) prevented BLF-induced antihyperalgesia. Data suggest that BLF-induced spinal antihyperalgesia could be due to activation of the NO-cGMP-PKG-K+ channel pathway and it is not mediated by mu-opioid receptor in a model of neuropathic pain.

Male rats were immunized with prostate tissue homogenate supernate (PTHS) of male rats with complete Freund's adjuvant (CFA) intra dermal in the multiple points and simultaneously immunized with 0.5 ml Pertussis-Diphtheria-Tetanus (PDT) vaccine intra peritonea on 0 and 30th day. At the 45th day after first immunization, animals were sacrificed and a series of examinations such as HE stain, assay of TNF-alpha by ELISA and assay of inducible nitric oxide synthase (iNOS) mRNA by in-situ hybridization (ISH) were taken. We observed that there was a remarkable up-regulation of TNF-alpha expression in the high dosage model group. The results of macropathology, histopathology and iNOS ISH also revealed the same tendency. This experimental procedure is effective to induce chronic abacterial prostatitis (CAP).