Publications by authors named "Rong Fang"

103 Publications

Pulmonary coinfection of Mycobacterium tuberculosis and Tropheryma whipplei: a case report.

J Med Case Rep 2021 Jul 9;15(1):359. Epub 2021 Jul 9.

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.

Background: We diagnosed a clinical case of pulmonary infection involving Mycobacterium tuberculosis and Tropheryma whipplei in a patient with acute respiratory distress syndrome. The diagnosis was assisted by metagenomic next-generation sequencing of bronchoalveolar lavage fluid.

Case Presentation: A 44-year-old Han Chinese inmate was transferred to the emergency department because of dry cough, chest tightness, and shortness of breath. The patient's body temperature rose to 39.3 °C following empirical cephalosporin treatment for 1 week. The blood CD4+/CD8+ ratio was 0.7, suggesting immunodeficiency. Routine microbiological tests were performed, and tuberculosis interferon gamma release assays were positive. Mycobacterium tuberculosis polymerase chain reaction was also positive. Chest computed tomography scan revealed miliary nodules and ground-glass opacifications, which were in accordance with tuberculosis. To fully examine the etiology, we performed routine laboratory tests and metagenomic sequencing, the results of which indicated the presence of Mycobacterium tuberculosis and Tropheryma whipplei. We administered anti-tuberculosis regimen in combination with trimethoprim/sulfamethoxazole. The patient recovered, with chest computed tomography scan showing absorption of lesions.

Conclusions: Compared with traditional diagnostic methods such as culture and serology, metagenomic next-generation sequencing has the advantage of detecting a wide array of microorganisms in a single test and therefore can be used for clinical diagnosis of rare pathogens and microbial coinfections. It is particularly useful for immunocompromised patients as they are more prone to infection by opportunistic microorganisms.
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http://dx.doi.org/10.1186/s13256-021-02899-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269402PMC
July 2021

with a Genetically Disrupted Phage Integrase Gene Exhibits Attenuated Virulence and Induces Protective Immunity against Fatal Rickettsioses in Mice.

Pathogens 2021 Jun 30;10(7). Epub 2021 Jun 30.

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Although rickettsiae can cause life-threatening infections in humans worldwide, no licensed vaccine is currently available. To evaluate the suitability of live-attenuated vaccine candidates against rickettsioses, we generated a mutant RPATATE_0245::pLoxHimar (named 3A2) by insertion of a modified pLoxHimar transposon into the gene encoding a phage integrase protein. For visualization and selection, 3A2 expressed mCherry fluorescence and resistance to spectinomycin. Compared to the parent wild type (WT) , the virulence of 3A2 was significantly attenuated as demonstrated by significantly smaller size of plaque, failure to grow in human macrophage-like cells, rapid elimination of and ameliorated histopathological changes in tissues in intravenously infected mice. A single dose intradermal (i.d.) immunization of 3A2 conferred complete protection against both fatal and rickettsioses in mice, in association with a robust and durable rickettsiae-specific IgG antibody response. In summary, the disruption of RPATATE_0245 in resulted in a mutant with a significantly attenuated phenotype, potent immunogenicity and protective efficacy against two spotted fever group rickettsioses. Overall, this proof-of-concept study highlights the potential of mutants as a live-attenuated and multivalent vaccine platform in response to emergence of life-threatening spotted fever rickettsioses.
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http://dx.doi.org/10.3390/pathogens10070819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308654PMC
June 2021

Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway.

Biosci Rep 2021 Jun;41(6)

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Background: Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25-30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.

Methods: After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.

Results: Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC50 were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G2/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.

Conclusions: Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.
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http://dx.doi.org/10.1042/BSR20210093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202065PMC
June 2021

LncRNA NKILA knockdown promotes cell viability and represses cell apoptosis, autophagy and inflammation in lipopolysaccharide-induced sepsis model by regulating miR-140-5p/CLDN2 axis.

Biochem Biophys Res Commun 2021 Jun 28;559:8-14. Epub 2021 Apr 28.

Department of Emergency Internal Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai City, China. Electronic address:

Background: Long non-coding RNAs (lncRNAs) play vital roles in human diseases, including sepsis-induced acute kidney injury (AKI). Here, we aimed to investigate the functions of lncRNA NKILA in sepsis-engendered AKI.

Methods: HK2 cells stimulated with LPS were used to mimic sepsis-induced AKI in vitro. qRT-PCR was conducted for lncRNA NKILA and miR-140-5p levels. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to analyze cell viability and apoptosis. Western blot assay was utilized to measured protein levels. ELISA kits were used to examine the concentrations of IL-6, IL-1β and TNF-α. Dual-luciferase reporter assay was utilized to analyze the relationships among lncRNA NKILA, miR-140-5p and claudin 2 (CLDN2).

Results: LPS restrained HK2 cell viability and accelerated cell apoptosis and autophagy. LncRNA NKILA was increased in LPS-treated HK2 cells. LncRNA NKILA silencing reversed the promotional influence of LPS on cell progression in HK2 cells. miR-140-5p inhibition ameliorated lncRNA NKILA knockdown-mediated cell injury in LPS-mediated HK2 cells. CLDN2 was the target of miR-140-5p. MiR-140-5p elevation promoted cell viability and suppressed cell apoptosis, autophagy and inflammation in LPS-induced HK2 cells, with CLDN2 elevation overturned the effects.

Conclusion: LncRNA NKILA silencing protected HK2 cells from LPS-induced impairments by reducing CLDN2 through sponging miR-140-5p.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.074DOI Listing
June 2021

Subversion of Host Innate Immunity by a Modified Autophagic Response in Macrophages.

Front Immunol 2021 12;12:638469. Epub 2021 Apr 12.

Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, United States.

We recently reported that the and survivals of are -dependent, in association with an inhibited level of anti-rickettsial cytokine, IL-1β. In the present study, we sought to investigate how interacts with host innate immunity an -dependent autophagic response. We found that the serum levels of IFN-γ and G-CSF in -infected Lyz- mice were significantly less compared to mice, accompanied by significantly lower rickettsial loads in tissues with inflammatory cellular infiltrations including neutrophils. infection differentially regulated a significant number of genes in bone marrow-derived macrophages (BMMs) in an -depdent fashion as determined by RNA sequencing and Ingenuity Pathway Analysis, including genes in the molecular networks of IL-1 family cytokines and PI3K-Akt-mTOR. The secretion levels of inflammatory cytokines, such as IL-1α, IL-18, TNF-α, and IL-6, by infected Lyz- BMMs were significantly greater compared to infected BMMs. Interestingly significantly increased the levels of phosphorylated mTOR and P70S6K at a time when the autophagic response is induced. Rapamycin treatment nearly abolished the phosphorylated mTOR and P70S6K but did not promote significant autophagic flux during infection. These results highlight that modulates an -dependent autophagic response, which is not sensitive to regulation by mTORC1 signaling in macrophages. Overall, we demonstrate that counteracts host innate immunity including IL-1β-dependent inflammatory response to support the bacterial survival an mTORC1-resistant autophagic response in macrophages.
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http://dx.doi.org/10.3389/fimmu.2021.638469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071864PMC
April 2021

hsa‑miR‑5580‑3p inhibits oral cancer cell viability, proliferation and migration by suppressing LAMC2.

Mol Med Rep 2021 06 21;23(6). Epub 2021 Apr 21.

Department of Gastroenterology, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.

The present study aimed to explore whether and how microRNA‑5580‑3p (miR‑5580‑3p) affected oral cancer (OC) cell phenotypes via regulation of laminin subunit γ2 (LAMC2). Bioinformatics analysis was used to identify miR‑5580‑3p/LAMC2, a novel interactome that, to the best of our knowledge, has not been studied previously in OC. In the present study, the expression levels of miR‑5580‑3p and LAMC2 were detected by reverse transcription‑quantitative PCR, while the protein expression levels of LAMC2 were identified using western blotting. To determine the effects of miR‑5580‑3p and LAMC2 in OC, a number of experiments, including Cell Counting Kit‑8, 5‑bromo‑2'‑deoxyuridine cell proliferation and wound healing migration assays, were performed using OC SCC‑4 and Cal‑27 cell lines. Additionally, luciferase reporter assays were employed to examine the interaction between miR‑5580‑3p and LAMC2 mRNA. The results demonstrated that miR‑5580‑3p expression was downregulated, while LAMC2 expression was upregulated in OC tissues and cell lines. In addition to the observation that miR‑5580‑3p promoted the malignant phenotypes of OC, it was also revealed that miR‑5580‑3p inhibited OC cell viability, proliferation and migration by suppressing LAMC2. Therefore, the present study suggested that miR‑5580‑3p and LAMC2 may be potential biomarkers and therapeutic targets for OC diagnosis and therapies in the future.
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http://dx.doi.org/10.3892/mmr.2021.12092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072311PMC
June 2021

Usefulness of prenatal magnetic resonance imaging in differential diagnosis of fetal congenital cystic adenomatoid malformation and bronchopulmonary sequestration.

World J Clin Cases 2021 Feb;9(4):822-829

Department of Ultrasound, Huzhou Maternity & Child Health Care Hospital, Huzhou 313000, Zhejiang Province, China.

Background: Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are the most common lung diseases in fetuses. There are differences in the prognosis and treatment of CCAM and BPS, and the clinical diagnosis and treatment plan is usually prepared prior to birth. Therefore, it is quite necessary to make a clear diagnosis before delivery. CCAM and BPS have similar imaging features, and the differentiation mainly relies on the difference in supply vessels. However, it is hard to distinguish them due to invisible supplying vessels on some images.

Aim: To explore the application value of magnetic resonance imaging (MRI) in the differential diagnosis of fetal CCAM and BPS.

Methods: Data analysis for 32 fetuses with CCAM and 14 with BPS diagnosed by prenatal MRI at Huzhou Maternal and Child Health Care Hospital and Anhui Provincial Children's Hospital from January 2017 to January 2020 was performed to observe the source blood vessels of lesions and their direction. Pathological confirmation was completed through CT examination and/or operations after birth.

Results: After birth, 31 cases after birth were confirmed to be CCAM, and 15 were confirmed to be BPS. The CCAM group consisted of 21 macrocystic cases and 10 microcystic cases. In 18 cases, blood vessels were visible in lesions. Blood supply of the pulmonary artery could be traced in eight cases, and in 10 cases, only vessels running from the midline to the lateral down direction were observed. No lesions were found in four macrocystic cases and one microcystic case with CCAM through CT after birth; two were misdiagnosed by MRI, and three were misdiagnosed by prenatal ultrasonography. The BPS group consisted of 12 intralobar cases and three extralobar cases. Blood vessels were visible in lesions of nine cases, in four of which, the systemic circulation blood supply could be traced, and in five of which, only vessels running from the midline to the lateral up direction were observed. Three were misdiagnosed by MRI, and four were misdiagnosed by prenatal ultrasonography.

Conclusion: CCAM and BPS can be clearly diagnosed based on the origin of blood vessels, and correct diagnosis can be made according to the difference in the direction of the blood vessels, but it is hard distinguish microcystic CCAM and BPS without supplying vessels. In some CCAM cases, mainly the macrocystic ones, the lesions may disappear after birth.
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http://dx.doi.org/10.12998/wjcc.v9.i4.822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852640PMC
February 2021

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction.

Front Cardiovasc Med 2020 26;7:582890. Epub 2020 Nov 26.

Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy . We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.
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http://dx.doi.org/10.3389/fcvm.2020.582890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726192PMC
November 2020

[Prenatal diagnosis of three fetuses with small supernumerary marker chromosomes].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Dec;37(12):1344-1348

Prenatal Diagnosis Center, Huzhou Women and Children's Health Care Hospital, Huzhou, Zhejiang 313000, China.

Objective: To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses.

Methods: The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs.

Results: In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother.

Conclusion: Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.
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http://dx.doi.org/10.3760/cma.j.cn511374-20190919-00481DOI Listing
December 2020

Video-Assisted Modified Ligation of the Intersphincteric Fistula Tract, an Integration of 2 Minimally Invasive Techniques for the Treatment of Parks Type II Anal Fistulas.

Surg Innov 2020 Dec 4:1553350620978026. Epub 2020 Dec 4.

Division of General Surgery, The Affiliated People' Hospital of Ningbo University, Ningbo, Zhejiang, China.

Complex anal fistula (CAF) is a challenging anorectal condition. Although numerous treatments for its management have been proposed, none is ideal. Herein, we investigated the clinical efficacy of video-assisted modified ligation of the intersphincteric fistula tract (LIFT) in comparison with the incision-thread-drawing procedure for Parks type II anal fistulas. Male and female adult patients with Parks type II anal fistula who were randomized to receive one of two procedures in the Anorectal Surgery Unit of the Affiliated People's Hospital of Ningbo University: video-assisted modified LIFT (test group, 30 cases) or incision thread drawing (control group, 30 cases). Healing and recurrence, postoperative pain, and postoperative autonomous anal control ability were compared. In the test group, the pain scores were significantly lower ( = .001) and wound healing was faster ( = .001). However, there were no marked differences between groups in operative efficacy or postoperative infection rate (all > .05). We followed all the patients for more than 18 months, with the test group having lower Jorge-Wexner incontinence ( = .005) and fecal incontinence (FI) severity index ( = .000) scores. No significant difference in recurrence ( = .351, = .554) or healing ( = 1.071, = .301) rate was found between the 2 groups. We established that video-assisted modified LIFT is superior in repairing Parks type II anal fistulas, with less trauma, quicker recovery, and better anal function.
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http://dx.doi.org/10.1177/1553350620978026DOI Listing
December 2020

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus.

Front Microbiol 2020 26;11:2069. Epub 2020 Aug 26.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Duck Tembusu virus (DTMUV) infection has caused great economic losses to the poultry industry in China, since its first discovery in 2010. Understanding of host anti-DTMUV responses, especially the innate immunity against DTMUV infection, would be essential for the prevention and control of this viral disease. In this study, transcriptomic analysis of duck embryonic fibroblasts (DEFs) infected with DTMUV reveals that several innate immunity-related pathways, including Toll-like, NOD-like, and retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways, are activated. Further verification by RT-qPCR confirmed that RIG-I, MAD5, TLR3, TLR7, IFN-α, IFN-β, MX, PKR, MHCI, MHCII, IL-1β, IL-6, (IFN-regulatory factor 1) IRF1, VIPERIN, IFIT5, and CMPK2 were up-regulated in cells infected with DTMUV. Through overexpression and knockdown/out of gene expression, we demonstrated that both VIPERIN and IRF1 played an important role in the regulation of DTMUV replication. Overexpression of either one significantly reduced viral replication as characterized by reduced viral RNA copy numbers and the envelope protein expression. Consistently, down-regulation of either one resulted in the enhanced replication of DTMUV in the knockdown/out cells. We further proved that IRF1 can up-regulate VIPERIN gene expression during DTMUV infection, through induction of type 1 IFNs as well as directly binding to and activation of the VIPERIN promoter. This study provides a genome-wide differential gene expression profile in cells infected with DTMUV and reveals an important function for IRF1 as well as several other interferon-stimulated genes in restricting DTMUV replication.
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http://dx.doi.org/10.3389/fmicb.2020.02069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480082PMC
August 2020

High-Fat Diet Affects Heavy Metal Accumulation and Toxicity to Mice Liver and Kidney Probably via Gut Microbiota.

Front Microbiol 2020 28;11:1604. Epub 2020 Jul 28.

Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Previous studies proved that heavy metals could increase the risk of disease by acting on the gut microbiota. Meanwhile, gut microbiota played important roles in detoxifying heavy metals. However, the response of gut microbiota to heavy metals and which microbes dominated this detoxification processes are still unclear. This study investigated the difference of high-fat-diet (HFD) and normal-diet (ND) gut microbiota and their response to and detoxification effects on arsenic (As), cadmium (Cd), and lead (Pb) exposure. Results showed that gut microbiota of ND and HFD was significantly different and responded to As, Pb, and Cd exposure differently, too. When exposed to 100 ppm As, Cd, or Pb, HFD-fed mice accumulated more heavy metals in the liver and kidney along with more severe functional damage than ND-fed mice, indicated by a more dramatic increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and urinary total protein (TPU), urinary uric acid (UUA), and urinary creatinine (Ucrea) content. Among ND gut microbiota, relative abundance of , , , and was significantly increased by arsenic (As) exposure; relative abundance of and was significantly increased by Cd exposure; relative abundance of , , and were significantly increased by Pb exposure. However, among HFD gut microbiota, those microbes were not significantly changed. Bivariate association analysis found weak positive correlations between content of fecal excreted heavy metals and richness of total fecal microbiota as well as abundance of some of the heavy metal-enriched microbes. Our study concluded that HFD increased disease risk of heavy metal exposure probably via its gut microbiota which excreted less heavy metal through feces.
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http://dx.doi.org/10.3389/fmicb.2020.01604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399142PMC
July 2020

miRNA-338-3p/CAMK IIα signaling pathway prevents acetaminophen-induced acute liver inflammation in vivo.

Ann Hepatol 2021 Mar-Apr;21:100191. Epub 2020 Mar 20.

Department of Infectious Diseases, The Hospital of Yan 'an People, Shaanxi 716000, China. Electronic address:

Introduction And Objectives: N-acetyl-p-aminophenol (APAP)-induced liver injury is a major clinical challenge worldwide. The present study investigated the molecular role of microRNA (miR)-338-3p in the development of APAP-induced acute liver injury.

Materials And Methods: B6 mice were treated with an miR-338-3p agomir, antagomir, and intraperitoneally injected with APAP 24h later to induce acute liver injury. Histological analysis was performed to evaluate the degree of liver injury. The gene expression of miR-338-3p and its downstream regulators was measured by reverse transcription-quantitative PCR and western blot. The miR target was validated using a luciferase reporter assay.

Results: The results revealed that miR-338-3p was significantly upregulated following the intraperitoneal administration of APAP. Augmenting miR-338-3p alleviated acute liver injury caused by APAP overdose, while silencing of miR-338-3p exhibited a detrimental effect. Moreover, miR-338-3p inhibited the expression of pro-inflammatory cytokines by preventing the aberrant activation of inflammatory signaling pathways, including the nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CAMK IIα) was identified as a direct target of miR-338-3p.

Conclusion: The present study demonstrated that miR-338-3p inhibited inflammation in APAP-induced acute liver injury.
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http://dx.doi.org/10.1016/j.aohep.2020.03.003DOI Listing
March 2020

Activation of ASC Inflammasome Driven by Toll-Like Receptor 4 Contributes to Host Immunity against Rickettsial Infection.

Infect Immun 2020 03 23;88(4). Epub 2020 Mar 23.

Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA

Rickettsiae are cytosolically replicating, obligately intracellular bacteria causing human infections worldwide with potentially fatal outcomes. We previously showed that activates ASC inflammasome in macrophages. In the present study, host susceptibility of ASC inflammasome-deficient mice to was significantly greater than that of C57BL/6 (B6) controls and was accompanied by increased rickettsial loads in various organs. Impaired host control of in ASC mice was associated with dramatically reduced levels of interleukin 1β (IL-1β), IL-18, and gamma interferon (IFN-γ) in sera. The intracellular concentrations of in bone marrow-derived macrophages (BMMs) of TLR4 and ASC mice were significantly greater than those in BMMs of B6 controls, highlighting the important role of inflammasome and these molecules in controlling rickettsiae in macrophages. Compared to B6 BMMs, TLR4 BMMs failed to secrete a significant level of IL-1β and had reduced expression levels of pro-IL-1β in response to infection with , suggesting that rickettsiae activate ASC inflammasome via a Toll-like receptor 4 (TLR4)-dependent mechanism. Further mechanistic studies suggest that the lipopolysaccharide (LPS) purified from together with ATP stimulation led to cleavage of pro-caspase-1 and pro-IL-1β, resulting in TLR4-dependent secretion of IL-1β. Taken together, these observations indicate that activation of ASC inflammasome, most likely driven by interaction of TLR4 with rickettsial LPS, contributes to host protective immunity against These findings provide key insights into defining the interactions of rickettsiae with the host innate immune system.
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http://dx.doi.org/10.1128/IAI.00886-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093143PMC
March 2020

Quantitative Proteomics of the Endothelial Secretome Identifies RC0497 as Diagnostic of Acute Rickettsial Spotted Fever Infections.

Am J Pathol 2020 02 16;190(2):306-322. Epub 2020 Jan 16.

Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas. Electronic address:

Mediterranean spotted fever is a reemerging acute tick-borne infection produced by the α-proteobacterium, Rickettsia conorii. Rickettsia conorii infects vascular endothelial cells producing disseminated plasma leakage, manifesting as nonspecific fever, headache, and maculopapular rash. Because there are no available tests of early infection, Mediterranean spotted fever is often undiagnosed and untreated, resulting in significant mortality. To address this critical need, we have applied a quantitative proteomics pipeline for analyzing the secretome of primary human umbilical vein endothelial cells. Of the 104 proteins whose abundance changed significantly in the R. conorii-infected human umbilical vein endothelial cells' secretome, 46 proteins were up-regulated: 45 were host secreted proteins (including cytokines), and 1 was a rickettsial protein, the putative N-acetylmuramoyl-l-alanine amidase RC0497. Proteins with sequence highly homologous to RC0497 were found to be shared by many species of the spotted fever group rickettsiae, but not typhus group rickettsiae. Quantitative targeted proteomics studies of plasma from a mouse model of sublethal and lethal R. conorii identified RC0497 in the blood, and its circulating levels were proportionally associated with infection outcome. Finally, the presence of RC0497 in the serum samples from a cohort of humans presenting with acute rickettsioses was confirmed. The detection of RC0497 has the potential to be a sensitive and specific marker for acute rickettsial spotted rickettsioses.
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http://dx.doi.org/10.1016/j.ajpath.2019.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983917PMC
February 2020

Transcribed Ultraconserved Regions, Uc.323, Ameliorates Cardiac Hypertrophy by Regulating the Transcription of CPT1b (Carnitine Palmitoyl transferase 1b).

Hypertension 2020 01 18;75(1):79-90. Epub 2019 Nov 18.

From the Department of Cardiology (Y.S., W.F., R.X., B.D., Z.L., C.C., J.L., Y.W., J.Z., H.H., J.J., Z.W., G.D., R.F., Z.-p.H., Y.D., C.L.), the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Transcribed ultraconserved regions (T-UCRs) are a novel class of long noncoding RNAs transcribed from UCRs, which exhibit 100% DNA sequence conservation among humans, mice, and rats. However, whether T-UCRs regulate cardiac hypertrophy remains unclear. We aimed to explore the effects of T-UCRs on cardiac hypertrophy. First, we performed long noncoding RNA microarray analysis on hearts of mice subjected to sham surgery or aortic banding and found that the T-UCR uc.323 was decreased significantly in mice with aortic banding-induced cardiac hypertrophy. In vitro loss- and gain-of-function experiments demonstrated that uc.323 protected cardiomyocytes against hypertrophy induced by phenylephrine. Additionally, we discovered that mammalian target of rapamycin 1 contributed to phenylephrine-induced uc.323 downregulation and uc.323-mediated cardiomyocyte hypertrophy. We further mapped the possible target genes of uc.323 through global microarray mRNA expression analysis after uc.323 knockdown and found that uc.323 regulated the expression of cardiac hypertrophy-related genes such as (Carnitine Palmitoyl transferase 1b). Then, chromatin immunoprecipitation proved that EZH2 (enhancer of zeste homolog 2) bound to the promoter of CPT1b via H3K27me3 (trimethylation of lysine 27 of histone H3) to induce CPT1b downregulation. And overexpression of CPT1b could block uc.323-mediated cardiomyocyte hypertrophy. Finally, we found that uc.323 deficiency induced cardiac hypertrophy. Our results reveal that uc.323 is a conserved T-UCR that inhibits cardiac hypertrophy, potentially by regulating the transcription of CPT1b via interaction with EZH2.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13173DOI Listing
January 2020

Maf1 ameliorates cardiac hypertrophy by inhibiting RNA polymerase III through ERK1/2.

Theranostics 2019 25;9(24):7268-7281. Epub 2019 Sep 25.

Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China, 510080.

: An imbalance between protein synthesis and degradation is one of the mechanisms of cardiac hypertrophy. Increased transcription in cardiomyocytes can lead to excessive protein synthesis and cardiac hypertrophy. Maf1 is an RNA polymerase III (RNA pol III) inhibitor that plays a pivotal role in regulating transcription. However, whether Maf1 regulates of cardiac hypertrophy remains unclear. : Cardiac hypertrophy was induced by thoracic aortic banding (AB) surgery. Both the and gain- and loss-of-function experiments by Maf1 knockout (KO) mice and adenoviral transfection were used to verify the role of Maf1 in cardiac hypertrophy. RNA pol III and ERK1/2 inhibitor were utilized to identify the effects of RNA pol III and ERK1/2. The possible interaction between Maf1 and ERK1/2 was clarified by immunoprecipitation (IP) analysis. : Four weeks after surgery, Maf1 KO mice exhibited significantly exacerbated AB-induced cardiac hypertrophy characterized by increased heart size, cardiomyocyte surface area, and atrial natriuretic peptide (ANP) expression and by exacerbated pulmonary edema. Also, the deficiency of Maf1 causes more severe cardiac dilation and dysfunction than wild type (WT) mice after pressure overload. In contrast, compared with adenoviral-GFP injected mice, mice injected with adenoviral-Maf1 showed significantly ameliorated AB-induced cardiac hypertrophy. study has demonstrated that Maf1 could significantly block phenylephrine (PE)-induced cardiomyocyte hypertrophy by inhibiting RNA pol III transcription. However, application of an RNA pol III inhibitor markedly improved Maf1 knockdown-promoted cardiac hypertrophy. Moreover, ERK1/2 was identified as a regulator of RNA pol III, and ERK1/2 inhibition by U0126 significantly repressed Maf1 knockdown-promoted cardiac hypertrophy accompanied by suppressed RNA pol III transcription. Additionally, IP analysis demonstrated that Maf1 could directly bind ERK1/2, suggesting Maf1 could interact with ERK1/2 and then inhibit RNA pol III transcription so as to attenuate the development of cardiac hypertrophy. : Maf1 ameliorates PE- and AB-induced cardiac hypertrophy by inhibiting RNA pol III transcription via ERK1/2 signaling suppression.
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http://dx.doi.org/10.7150/thno.33006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831308PMC
September 2020

Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain.

Br J Nutr 2019 12;122(12):1359-1367

Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, USA.

Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
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http://dx.doi.org/10.1017/S0007114519002472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908754PMC
December 2019

Inhibition of the transcriptional kinase CDK7 overcomes therapeutic resistance in HER2-positive breast cancers.

Oncogene 2020 01 28;39(1):50-63. Epub 2019 Aug 28.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.

Resistance of breast cancer to human epidermal growth factor receptor 2 (HER2) inhibitors involves reprogramming of the kinome through HER2/HER3 signaling via the activation of multiple tyrosine kinases and transcriptional upregulation. The heterogeneity of induced kinases prevents kinase targeting by a single kinase inhibitor and presents a major challenge to the treatment of therapeutically recalcitrant HER2-positive breast cancers (HER2+ BCs). As a result, there is a critical need for effective treatment that attacks the aberrant kinome activation associated with resistance to HER2-targeted therapy. Here, we describe a novel treatment strategy that targets cyclin-dependent kinase 7 (CDK7) in HER2 inhibitor-resistant (HER2iR) breast cancer. We show that both HER2 inhibitor-sensitive (HER2iS) and HER2iR breast cancer cell lines exhibit high sensitivity to THZ1, a newly identified covalent inhibitor of the transcription regulatory kinase CDK7. CDK7 promotes cell cycle progression through inhibition of transcription, rather than via direct phosphorylation of classical CDK targets. The transcriptional kinase activity of CDK7 is regulated by HER2, and by the receptor tyrosine kinases activated in response to HER2 inhibition, as well as by the downstream SHP2 and PI3K/AKT pathways. A low dose of THZ1 displayed potent synergy with the HER2 inhibitor lapatinib in HER2iR BC cells in vitro. Dual HER2 and CDK7 inhibition induced tumor regression in two HER2iR BC xenograft models in vivo. Our data support the utilization of CDK7 inhibition as an additional therapeutic avenue that blocks the activation of genes engaged by multiple HER2iR kinases.
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http://dx.doi.org/10.1038/s41388-019-0953-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937212PMC
January 2020

Severe acute pancreatitis with blood infection by Candida glabrata complicated severe agranulocytosis: a case report.

BMC Infect Dis 2018 Dec 29;18(1):706. Epub 2018 Dec 29.

Department of Emergency Internal Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, People's Republic of China.

Background: Blood infection with Candida glabrata often occurs in during severe acute pancreatitis (SAP). It complicate severe agranulocytosis has not been reported.

Case Presentation: We present a case where a SAP patient presenting with a sudden hyperpyrexia was treated for 19 days. We monitored her routine blood panel and CRP levels once or twice daily. The results showed that WBC count decreased gradually. And the lowest level of WBC was appeared at the 21st day of treatment. WBC 0.58 × 10/L(4.0-10.0 × 10/L), neutrophils 0.1 × 10/L [2.20%] (2.5-7.5 × 10/L). During treatment, Candida glabrata was identified as the infecting agent through blood culture, drainage tubes culture and gene detection. During anti-infection therapy, the patient had severe agranulocytosis. With control of the infection, her WBC and granulocyte counts gradually returned to the normal range.

Conclusions: Blood infection with Candida glabrata can complicate severe agranulocytosis.
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http://dx.doi.org/10.1186/s12879-018-3623-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310945PMC
December 2018

Clinical value of prenatal MRI for diagnosis of isolated ventriculomegaly and prediction of early postnatal developmental outcomes.

Prenat Diagn 2019 01 13;39(2):124-129. Epub 2019 Jan 13.

Department of Ultrasound, Maternity and Child Care Hospital, Huzhou, China.

Objective: To investigate the relationship of ventriculomegaly (VM) with postnatal neurological development.

Methods: Fetuses with isolated VM on MRI (n = 160; VM group) were separated into three subgroups according to lateral ventricle width: subgroup A (10.0-12.0 mm; n = 113), subgroup B (12.1-15.0 mm; n = 37), and subgroup C (>15.0 mm; n = 10). Fifty normal fetuses formed a control group. Post-delivery changes in ventricular width and neurological development were assessed with MRI/ultrasonography and the Gesell Development Schedules (GDS), respectively, at 3, 6, 12, and 18 months.

Results: GDS scores of subgroup A and subgroup B did not differ from that of the controls at 3 and 6 months. Subgroup B scores differed significantly from the control scores at 12 and 18 months. Subgroup C scores differed from the control scores at all-time points (all P < 0.05). In the VM group, GDS scores at 12 and 18 months were significantly different from the scores at 3 months, and the score at 18 months was significantly different from the score at 6 months (P < 0.05 for all).

Conclusion: The milder the VM, the more likely it was to disappear or improve in the postnatal period. However, specific postnatal rehabilitation should be considered when fetal ventricular width is greater than 12.1 mm.
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http://dx.doi.org/10.1002/pd.5399DOI Listing
January 2019

Supports Infection in Macrophages and .

Infect Immun 2019 01 19;87(1). Epub 2018 Dec 19.

Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA

Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of was significantly greater in infected tissues of mice than in the counterparts of Lyz- mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of in bone marrow-derived macrophages (BMMs) than in Lyz- BMMs was abolished by exogenous treatment with recombinant IL-1β. induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in -competent BMMs but not in -deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of and -containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that favors infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of in macrophages to the pathogenesis of rickettsial diseases.
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http://dx.doi.org/10.1128/IAI.00651-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300621PMC
January 2019

Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection.

Annu Rev Pathol 2019 01 27;14:127-152. Epub 2018 Aug 27.

The University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0609, USA; email: , , ,

Obligately intracytosolic rickettsiae that cycle between arthropod and vertebrate hosts cause human diseases with a spectrum of severity, primarily by targeting microvascular endothelial cells, resulting in endothelial dysfunction. Endothelial cells and mononuclear phagocytes have important roles in the intracellular killing of rickettsiae upon activation by the effector molecules of innate and adaptive immunity. In overwhelming infection, immunosuppressive effects contribute to the severity of illness. Rickettsia-host cell interactions involve host cell receptors for rickettsial ligands that mediate cell adhesion and, in some instances, trigger induced phagocytosis. Rickettsiae interact with host cell actin to effect both cellular entry and intracellular actin-based mobility. The interaction of rickettsiae with the host cell also involves rickettsial evasion of host defense mechanisms and exploitation of the intracellular environment. Signal transduction events exemplify these effects. An intriguing frontier is the array of rickettsial noncoding RNA molecules and their potential effects on the pathogenesis and transmission of rickettsial diseases.
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505701PMC
January 2019

The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia.

Aging Dis 2018 Aug 1;9(4):696-705. Epub 2018 Aug 1.

1Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Our study aimed to identify the underlying causes in patients with early onset dementia by clinical and genetic exploration. We recruited a group of 38 patients with early-onset dementia. Firstly, hexanucleotide repeat expansions in gene were screened in all subjects to exclude the possibility of copy number variation. Then, the whole exome sequencing (WES) was conducted, and the data were analyzed focusing on 89 dementia-related causing and susceptible genes. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. There were no pathogenic expansions in detected. According to the ACMG standards and guidelines, we identified five known pathogenic mutations, P284L, c.857-1G>A, I143T, G209E and G389R, and one novel pathogenic mutation K687N. All these mutations caused dementia with the mean onset age of 38.3 (range from 27 to 51) and rapid progression. Eleven variants with uncertain significance were also detected and needed further verification. The clinical phenotypes of dementia are heterogeneous, with both onset ages and clinical features being influenced by mutation position as well as the causative gene. WES can serve as efficient diagnostic tools for different heterogeneous dementia.
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http://dx.doi.org/10.14336/AD.2018.0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065298PMC
August 2018

[Runoff and nitrogen loss characteristics in soil-epikarst system on a karst shrub hillslope].

Ying Yong Sheng Tai Xue Bao 2017 Jul;28(7):2197-2206

College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541006, Guangxi, China.

With the development of the binary structure of karst landforms, surface water is largely drained with rapid loss of nutrients. However, the pathway and mechanism of nutrient loss remain elusive. From a three-dimensional (vegetation-soil-epikarst system) perspective of a critical zone in karst area, this study conducted rainfall induced runoff and nitrogen loss monitoring during monsoon in karst shrub slopes. Isotope-based (D and O) hydrograph separation method was applied to partition the ratio of 'old' and 'new' water in main hydrological path. The main results were summarized as follows. Deep percolation and interflow were the dominant hydrological pathways, accoun-ting for 71% and 9% of total rainfall amount, respectively. In contrast, surface runoff occupied less than 2%. Both deep percolation and interflow were dominated with 85% and 61% of old water, respectively. The highest nitrate concentration occurred in deep percolation (1.97 mg·L), while the highest ammonium nitrogen concentration occurred in interflow (1.18 mg·L). Deep percolation contributed 89.4% of total nitrogen loss, which was significantly higher than that of surface runoff and interflow. Old water ratio showed a significant positive correlation with nitrate nitrogen concentration, ammonium nitrogen concentration, and total nitrogen loss, suggesting it might be the main agent driving nitrogen migration for the whole soil-epikarst system in karst hillslopes. The results would provide scientific basis for rational allocating water resources and developing nutrient loss control technology in karst region of southwestern China.
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http://dx.doi.org/10.13287/j.1001-9332.201707.029DOI Listing
July 2017

[Epidemiological characteristics of malaria in Leshan City, 1950-2015].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2017 May;29(5):629-631

Leshan Center for Disease Control and Prevention, Sichuan Province, Leshan 614000, China.

Objective: To analyze the epidemiological characteristics of malaria in Leshan City, so as to provide the evidence for formulating the strategy and measures for consolidating the achievements of malaria elimination.

Methods: The data of epidemiological characteristics of malaria in Leshan City from 1950 to 2015 were collected and analyzed with the descriptive epidemiology method.

Results: There were four larger scale epidemics of malaria in Leshan City from 1950 to 2015. The order of malaria in infectious diseases dropped from the first to the twentieth. The peak season for malaria epidemics ceased. The Plasmodium species, patient age, occupation and sex distribution of malaria were different in the different periods. In November 2016, the whole city achieved the national standard for malaria elimination.

Conclusions: After years of prevention and control, the epidemiological characteristics of malaria have changed significantly in Leshan City, and the effect of anti-malarial measures is significant. In the future, we should strengthen the monitoring, and prevention and control of imported malaria.
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http://dx.doi.org/10.16250/j.32.1374.2017038DOI Listing
May 2017

[Prenatal genetic analysis of a fetus with Wolf-Hirschhorn syndrome and Edward syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Oct;34(5):714-717

Huzhou Women and Children's Health Care Hospital, Huzhou, Zhejiang 313000, China.

Objective: To screen for genomic copy number variants (CNVs) in a fetus with cardiac abnormalities and intrauterine growth retardation through single nucleotide polymorphism microarray (SNP array) and karyotyping analysis.

Methods: The fetus and its parents were subjected to conventional G banding and SNP-array analysis. The results were confirmed with fluorescence in situ hybridization (FISH).

Results: G-banding analysis showed that the fetus has a karyotype of 47,XX,+mar. The father has a karyotype of 46,XY,t(4;18) (p15.2q11.2), while the mother showed a normal karyotype. SNP-array detected two microduplications at 18p11.32q11.2 (20.5 Mb) and 4p16.3p15.2 (24.7 Mb) in the fetus. The supernumerary marker chromosome carried by the fetus has derived from the balanced translocation carried by its father. The result was confirmed by FISH.

Conclusion: Based on the two microduplications, the fetus was diagnosed as Wolf-Hirschhorn syndrome in conjunction with Edward syndrome. Verification of the origin of the supernumerary marker chromosome by SNP-array has provided a basis for prenatal genetic diagnosis.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2017.05.021DOI Listing
October 2017

[Genetic analysis of two cases with Dandy-Walker deformed fetus].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Oct;34(5):666-670

Center for Prenatal Diagnosis, the Mother and Child Health Care Hospital of Huzhou, Huzhou, Zhejiang 313000, China.

Objective: To explore the genetic etiology of two fetuses with Dandy-Walker malformation using single nucleotide polymorphism microarray (SNP-array).

Methods: The fetuses and their parents were subjected to G banding karyotype analysis. The fetuses were also subjected to SNP-array analysis.

Results: The parents of both fetuses showed a normal karyotype. One fetus has a 46,X,?i(X)(q10), while for another conventional cell culture has failed. SNP-array showed that one fetus carried a 6p25.3p25.2 microdeletion, and another carried a Xp22.33p22.2 deletion and a Yq11.221q11 duplication. The abnormal fragments have involved FOXC1, SHOX and STS genes, which are associated with Dandy-Walker malformation.

Conclusion: Alteration of 6p25.3p25.2, Xp22.33p22.2 copy numbers probably underlies the Dandy-Walker syndrome in the fetuses. The disorder may be attributed to abnormal expression of FOXC1, SHOX, and STS genes. SNP-array can provide an important supplement for prenatal diagnosis.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2017.05.010DOI Listing
October 2017

[Prenatal diagnosis of a fetus with 5p15.33 microdeletion].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Jun;34(3):416-418

Huzhou Maternity and Child Care Hospital, Huzhou, Zhejiang 313000, China.

Objective: To screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.

Methods: The fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.

Results: A 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.

Conclusion: This study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2017.03.023DOI Listing
June 2017

Rickettsiae as Emerging Infectious Agents.

Clin Lab Med 2017 06;37(2):383-400

Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, 301 University Boulevard, Keiller Building, Galveston, TX 77555-0609, USA. Electronic address:

With advances in molecular genetics, more pathogenic rickettsial species have been identified. Pathogenic rickettsiae are transmitted by vectors, such as arthropods, into the patient's skin and then spread into the microvascular endothelial cells. Clinical manifestations are characterized by fever with headache and myalgias, followed by rash 3 to 5 days later. The undifferentiated nature of clinical symptoms, knowledge of the epidemiology, and the patient's history of travel and exposure to arthropod vectors are critical to the empiric administration of antimicrobial therapy. Doxycycline is currently the most effective antibiotic for treatment of all spotted fever group and typhus group rickettsioses.
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http://dx.doi.org/10.1016/j.cll.2017.01.009DOI Listing
June 2017
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