NRP1 contributes to stemness and potentiates radioresistance via WTAP-mediated m6A methylation of Bcl-2 mRNA in breast cancer.

NRP1 is a transmembrane glycoprotein that is highly expressed in a variety of tumors. There is evidence that NRP1 can enhance the stem cell properties of tumor cells, which are thought to be resistant to radiotherapy. This study aims to elucidate the potential mechanism of NRP1 in radiation resistance. We transfected NRP1 siRNA and plasmid in breast cancer cells to detect the expression of cancer stem cell markers by western blot and qRT-PCR. The effect of NRP1 on radiotherapy resistance was assesses by immunofluorescence and flow cytometry. In vivo, we established xenograft tumor model treating with shRNA-NRP1 to assess radiotherapy sensitivity. We found that NRP1 could enhance the stem cell properties and confer radioresistance of breast cancer cells. Mechanistically, we proved that NRP1 reduced IR-induced apoptosis by downregulation of Bcl-2 via methyltransferase WTAP in m6A-depentent way. It is suggested that these molecules may be the therapeutic targets for improving the efficacy of radiotherapy for breast cancer.

Comparative Phosphoproteomic Analysis of Sporulated Oocysts and Tachyzoites of Toxoplasma gondii Reveals Stage-Specific Patterns.

Toxoplasma gondii is an obligate intracellular protozoan of severe threat to humans and livestock, whose life history harbors both gamic and apogamic stages. Chinese 1 (ToxoDB#9) was a preponderant genotype epidemic in food-derived animals and humans in China, with a different pathogenesis from the strains from the other nations of the world. Posttranslational modifications (PTMs) of proteins were critical mediators of the biology, developmental transforms, and pathogenesis of protozoan parasites. The phosphoprotein profiling and the difference between the developmental phases of T. gondii, contributing to development and infectivity, remain unknown. A quantitative phosphoproteomic approach using IBT integrated with TiO2 affinity chromatography was applied to identify and analyze the difference in the phosphoproteomes between the sporulated oocysts and the tachyzoites of the virulent ToxoDB#9 (PYS) strain of T. gondii. A total of 4058 differential phosphopeptides, consisting of 2597 upregulated and 1461 downregulated phosphopeptides, were characterized between sporulated the oocysts and tachyzoites. Twenty-one motifs extracted from the upregulated phosphopeptides contained 19 serine motifs and 2 threonine motifs (GxxTP and TP), whereas 16 motifs identified from downregulated phosphopeptides included 13 serine motifs and 3 threonine motifs (KxxT, RxxT, and TP). Beyond the traditional kinases, some infrequent classes of kinases, including Ab1, EGFR, INSR, Jak, Src and Syk, were found to be corresponding to motifs from the upregulated and downregulated phosphopeptides. Remarkable functional properties of the differentially expressed phosphoproteins were discovered by GO analysis, KEGG pathway analysis, and STRING analysis. S8GFS8 (DNMT1-RFD domain-containing protein) and S8F5G5 (Histone kinase SNF1) were the two most connected peptides in the kinase-associated network. Out of these, phosphorylated modifications in histone kinase SNF1 have functioned in mitosis and interphase of T. gondii, as well as in the regulation of gene expression relevant to differentiation. Our study discovered a remarkable difference in the abundance of phosphopeptides between the sporulated oocysts and tachyzoites of the virulent ToxoDB#9 (PYS) strain of T. gondii, which may provide a new resource for understanding stage-specific differences in PTMs and may enhance the illustration of the regulatory mechanisms contributing to the development and infectivity of T. gondii.

Global phosphoproteome analysis reveals significant differences between sporulated oocysts of virulent and avirulent strains of Toxoplasma gondii.

In this study, the differences in the phosphoproteomic landscape of sporulated oocysts between virulent and avirulent strains of Toxoplasma gondii were examined using a global phosphoproteomics approach. Phosphopeptides from sporulated oocysts of the virulent PYS strain (Chinese ToxoDB#9) and the avirulent PRU strain (type II) were enriched by titanium dioxide (TiO2) affinity chromatography and quantified using IBT approach. A total of 10,645 unique phosphopeptides, 8181 nonredundant phosphorylation sites and 2792 phosphoproteins were identified. We also detected 4129 differentially expressed phosphopeptides (DEPs) between sporulated oocysts of PYS strain and PRU strain (|log1.5 fold change| > 1 and p < 0.05), including 2485 upregulated and 1644 downregulated phosphopeptides. Motif analysis identified 24 motifs from the upregulated phosphorylated peptides including 22 serine motifs and two threonine motifs (TPE and TP), and 15 motifs from the downregulated phosphorylated peptides including 12 serine motifs and three threonine motifs (TP, RxxT and KxxT) in PYS strain when comparing PYS strain to PRU strain. Several kinases were consistent with motifs of overrepresented phosphopeptides, such as PKA, PKG, CKII, IKK, MAPK, EGFR, INSR, Jak, Syk, Src, Ab1. GO enrichment, KEGG pathway analysis and STRING analysis revealed DEPs significantly enriched in many biological processes and pathways. Kinase related network analysis showed that AGC kinase was the most connected kinase peptide. Our findings reveal significant difference in phosphopeptide profiles of sporulated oocysts between virulent and avirulent T. gondii strains, providing new resources for further elucidation of the mechanisms underpinning the virulence of T. gondii.

First report of the prevalence and genetic characterization of Giardia duodenalis and Cryptosporidium spp. in Yunling cattle in Yunnan Province, southwestern China.

Yunling cattle is an unique cattle breed distributed in Yunnan Province, southwestern China. It is yet to know whether Yunling cattle are infected with Giardia duodenalis and Cryptosporidium spp.. The objectives of the present study were to investigate the prevalence and characterize the assemblages of G. duodenalis and species of Cryptosporidium spp. in Yunling cattle in Yunnan province. The overall prevalence of G. duodenalis and Cryptosporidium spp. were 10.49% (41/391) and 0.77% (3/391), respectively. The age was considered as the risk factor for Yunling cattle infection with G. duodenalis (χ2 = 8.082, OR = 2.56, P = 0.004). Two assemblages of G. duodenalis, assemblage A (n = 1) and assemblage E (n = 40), were identified by amplification of the ß-giardin (bg) and glutamate dehydrogenase (gdh) gene loci using the nested PCR methods. Furthermore, Cryptosporidium andersoni (n = 1) and Cryptosporidium ryanae (n = 2) were detected by nested PCR targeting the small subunit (SSU) rRNA gene. This is the first report of G. duodenalis and Cryptosporidium spp. in Yunling cattle in China, which provided baseline date for further studies of the prevalence, genetic identity, and public health potential of these parasites in Yunling cattle.

Generation and application of a monoclonal antibody against the 18-kDa oncosphere antigen of Taenia pisiformis.

Taenia pisiformis is a parasite that causes cysticercosis pisiformis, which has acquired economic relevance because of its effects on animal welfare and production. A useful assay for the detection of T. pisiformis is needed for the prevention of cysticercosis pisiformis and control of the parasite. The 18-kDa oncosphere antigen is expressed in the oncosphere of several cysticerci in species of the genus Taenia, including T. pisiformis. This protein plays an important role in tissue invasion and has extensive applications in diagnosis. In this study, the T. pisiformis 18-kDa oncosphere antigen (TPO18) was expressed in soluble form and successfully purified for use in the production of monoclonal antibodies (MAbs) against TPO18. Twenty hybridomas were obtained using ELISA, and the subcloning process identified three positive hybridoma cell lines, which were designated as 4E8, 5G5, and 7E8. MAb 7E8 exhibited the highest titer and had an IgG2b heavy chain and a kappa light chain. Western blot analysis demonstrated that MAb 7E8 reacted with GST-TPO18. Immunohistochemistry showed that TPO18 was widely distributed in the drape and wall of uteri in adults of T. pisiformis adults and in the fibrous layer of the sucker and cyst cavity of T. pisiformis cysticerci. This research will provide a foundation for the development of diagnostic tools and will contribute to a better understanding of the functions of TPO18.

Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle.

Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.

Molecular characterization of Eimeria spp. and Blastocystis in rabbits in Shandong Province, China.

Eimeria spp. and Blastocystis are the common parasites that parasitize the intestinal tract of rabbits, which can seriously threaten the health of rabbits and lead to economic losses to the rabbit industry. However, information about the prevalence and transmission of these two parasites in rabbits is limited in China. The objective of this study was to survey the prevalence of Eimeria spp. and Blastocystis in rabbits in Shandong Province. A total of 616 rabbit fecal samples were collected from two cities (Rizhao and Weihai) in Shandong Province, eastern China, and Eimeria spp. and Blastocystis were identified by polymerase chain reaction based on species-specific markers. The prevalence of Eimeria spp. was 20% (123/616) and the Blastocystis prevalence was 0.97% (6/616). Five different Eimeria species (Eimeria intestinalis, E. perforans, E. magna, E. media, and E. irresidua) and the ST4 subtype of Blastocystis were identified in rabbits by sequence analysis. This is the first report of Blastocystis prevalence and subtype ST4 in rabbits in Shandong Province. The findings provide baseline data for the prevention and control of Eimeria spp. and Blastocystis in rabbits in Shandong Province, China.

Protective efficacy of pVAX-RON5p against acute and chronic infections of Toxoplasma gondii in BALB/c mice.

Toxoplasma gondii can infect all the warm-blooded animals and humans and causes serious diseases especially in immuno-compromised patients and pregnant women. Rhoptry neck proteins (RONs) play an important role in the formation of moving junction, which mediates the invasion of this parasite. A recombinant plasmid pVAX-RON5p, which can express part of RON5 protein in the eukaryocyte, was generated and used to immune BALB/c mice for evaluating the protective efficacy against the acute and chronic infections of T. gondii. Both humoral and cellular immune responses were evoked in mice by pVAX-RON5p immunization, and a slightly prolonged survival period was detected in the immunized group (7.6 ± 3.31 days) compared to the blank control (4.9 ± 0.32 days) after acute T. gondii infection (P < 0.05). For chronic infection of T. gondii, the number of cysts in the brain of pVAX-RON5p-immunized mice decreased 25.8% compared to blank control (P < 0.05). Our data suggested that RON5p DNA vaccine can induce partial protective immunity against acute and chronic T. gondii infections.

Uncontrolled blood pressure as an independent risk factor of early impaired left ventricular systolic function in treated hypertension.

BACKGROUND: Uncontrolled blood pressure (BP) is commonly observed in patients receiving antihypertensive agents. However, its relationship with early left ventricular (LV) dysfunction has not been elucidated. METHODS: This study enrolled 276 patients with treated hypertension and 85 healthy controls. The 140/90 mm Hg was used to define controlled (HT1 group, n=145) or uncontrolled BP (HT2 group, n=131) according to the concurrent guidelines. LV myocardial function was assessed by two-dimensional speckle tracking imaging, and the circumferential end-systolic wall stress (cESS)-corrected mid-wall fraction shortening (MWFS), systolic longitudinal (εLs-18), circumferential (εCs-18), and radial (εRs-18) strain were measured. RESULTS: Despite similar ejection fraction, the HT1 and HT2 groups displayed an overall reduction in the cESS-corrected MWFS (13.4±2.7 vs 11.7±1.7 vs 15.5±1.2), εLs-18 (15.6±2.8 vs 13.0±2.2 vs 17.4±2.8), εCs-18 (17.3±3.4 vs 14.1±2.7 vs 18.9±3.3), and εRs-18 (18.4±4.0 vs 14.8±3.1 vs 20.5±4.5) %·cm2 /kdyne·10-2 when compared with the control group (all P<.001). The changes were more obvious in the HT2 group, regardless of LV hypertrophy. Reductions in the cESS-corrected MWFS and εLs-18 were seen in 68 (25%) and 52 (19%) patients, respectively. Uncontrolled BP were 4.365 times (95% CI 2.203-8.648, P<.001) and 3.928 times (1.851-8.337, P<.001) more likely to be associated with the changes. CONCLUSIONS: Uncontrolled BP in hypertensive patients is associated with further reduction in LV myocardial function detected by advanced echocardiographic techniques, which cannot be explained by the increase in afterload. It might be regarded as a composite risk factor for earlier and faster development of clinical heart failure, therefore, a simplified treatment target.

A Unique Case of a 12-Year-Old Boy With Noonan Syndrome Combined With Noncompaction of the Ventricular Myocardium.

A 12-year-old Chinese boy was admitted with dyspnea after exercise. Based on his clinical features, echocardiography tests, and family history, he was diagnosed with Noonan syndrome (NS) combined with noncompaction of the ventricular myocardium (NVM). Noonan syndrome (NS) is a common syndrome, but to the best of our knowledge, our case is the first reported case of NS combined with NVM. In our case, the detected mutated genes may be inherited and unreported genes caused NS or NVM. Our research may enrich our knowledge about NS and contribute to furthering our understanding of the pathogenesis and treatment. In summary, we present a unique case of NS combined with NVM.

[Screening and Applications of qPCR Primers for apomucin Gene of Echinococcus multilocularis].

Objective: To screen for the optimal qPCR primers for Echinococcus multilocularis apomucin gene (Em-apo) and analyze Em-apo expression. Methods: Primers were designed based on 4 Em-apo sequences from GeneDB. Primer specificity and PCR efficiency were determined, based on which the optimal primer pairs were selected. Alterations of Em-apo expression in 1 000 E. multilocularis protoscoleces treated with albendazole（5 µg/ml） and insulin（100 ng/ml） were separately assessed using the selected primers. DMSO used in albendazole dilution and in PBS insulin dilution were used as the control. Results: Specific primers for Em-apo-1, Em-apo-2/3, Em-apo-4 and actin were selected. qPCR melting curves revealed a single peak for each primer pair and an amplification efficiency from 95% to 101%. The qPCR showed increased expression of Em-apo-1（1.51±0.27）, Em-apo-2/3 （1.39±0.30） and Em-apo-4（1.14±0.18） after albendazole treatment in comparison to the DMSO control（1.00）（P>0.05 among the three genes）; and an unaltered Em-apo-1 expression, slightly decreased Em-apo-4 expression, and significantly decreased Em-apo-2/3 expression（0.73±0.09） after insulin treatment in comparison to the PBS control (P>0.05 among the three genes）. Conclusion: The selected specific primers for Em-apo genes can be used to analyze the gene expression by qPCR. Treatment with albendazole and insulin show certain effects on the expression of Em-apo genes in E. multilocularis protoscoleces.

Seroprevalence of Encephalitozoon cuniculi and Toxoplasma gondii in domestic rabbits (Oryctolagus cuniculus) in China.

The breeding of domestic rabbits (Oryctolagus cuniculus) for human consumption has a long tradition in China. Infections that can affect the production of meat or even be transmitted from animals to humans are important to monitor, especially for public health reasons as well as for their impact on animal health. Thus, a total of 1,132 domestic rabbit sera from 4 regions in China were collected for serological screening for Encephalitozoon cuniculi and for Toxoplasma gondii by ELISA and modified agglutination test (MAT), respectively. Antibodies to E. cuniculi were detected in 248/1,132 (21.9%) sera tested while antibodies against T. gondii revealed a seroprevalence of 51/1,132 (4.5%). We believe that the present results are of epidemiological implications and public health importance due to the acknowledged susceptibility of humans to E. cuniculi and T. gondii infections. Therefore, routine screening tests of domestic rabbits are proposed considering the zoonotic potential of these parasites.

Higher blood pressure control rate in a real life management program provided by the community health service center in China.

BACKGROUND: Community health service center (CHSC) in China is always regarded as a good facility of primary care, which plays an important role in chronic non-communicable disease management. This study aimed to investigate the blood pressure (BP) control rate in a real life CHSC-based management program and its determinants. METHODS: The study enrolled 3191 patients (mean age of 70 ± 10 years, 43% males) in a hypertension management program provided by the Yulin CHSC (Chengdu, China), which had been running for 9 years. Uncontrolled BP was defined as the systolic BP of ≥140 mmHg and/or the diastolic BP of ≥90 mmHg, and its associated factors were analyzed by using logistic regression. RESULTS: The duration of stay in the program was 33 ± 25 months. When compared with the BP at entry, the recent BP was significantly lowered (147 ± 17 vs. 133 ± 8 mmHg; 83 ± 11 vs. 75 ± 6 mmHg) and the BP control rate was dramatically increased (32 vs. 85%) (all p < 0.001). The age of >70 years [1.40 (odds ratio), 1.15-1.71 (95% confidence interval)], female gender (0.76, 0.63-0.93), longer stay of >33 months (0.77, 0.63-0.94), doctor in charge (0.97, 0.95-0.99), and the use of calcium channel blocker (1.35, 1.09-1.67) were significantly related to uncontrolled BP at the recent follow up (all p < 0.05). CONCLUSIONS: This CHSC-run hypertension program provides an ideal platform of multi-intervention management, which is effective in achieving higher BP control rate in community patient population. However, the BP control status could be affected by age, gender and adherence of the patients, as well as practice behavior of the doctors.

Molecular characterization of Taenia multiceps isolates from Gansu Province, China by sequencing of mitochondrial cytochrome C oxidase subunit 1.

A total of 16 Taenia multiceps isolates collected from naturally infected sheep or goats in Gansu Province, China were characterized by sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. The complete cox1 gene was amplified for individual T. multiceps isolates by PCR, ligated to pMD18T vector, and sequenced. Sequence analysis indicated that out of 16 T. multiceps isolates 10 unique cox1 gene sequences of 1,623 bp were obtained with sequence variation of 0.12-0.68%. The results showed that the cox1 gene sequences were highly conserved among the examined T. multiceps isolates. However, they were quite different from those of the other Taenia species. Phylogenetic analysis based on complete cox1 gene sequences revealed that T. multiceps isolates were composed of 3 genotypes and distinguished from the other Taenia species.

[Significance of anti-citrullinated human papilloma virus-47 E2(345-362) peptide antibodies in diagnosis of early-stage rheumatoid arthritis].

OBJECTIVE: To investigate the prevalence and the diagnostic values of antibodies to the citrullinated HPVP in early-stage rheumatoid arthritis. METHODS: Antibodies against HPVP and citrullinated HPVP were detected by ELISA in the sera of 101 patients with early-stage RA, 149 patients with other rheumatic diseases and 40 healthy controls. The prevalence and diagnostic values of these antibodies for early-stage RA were analyzed by statistical software. RESULTS: (1)The prevalence of IgG, IgM antibodies to citrullinated HPVP in early-stage RA were significantly higher than that in the patients with other rheumatic diseases as well as in the healthy individuals.(2)The diagnostic sensitivity of IgG and IgM citrullinated HPVP antibodies in early-stage RA were 62.4% and 66.3% respectively and the specificity value of the two antibody isotypes were 88.7% and 89.6%,similar to that of the anti-CCP antibody. (3)The positivity rates of IgG and IgM antibodies against citrullinated HPVP were 59.4% and 71.9% in IgM-RF negative early-stage RA patients, and 39.4% and 51.5% in anti-CCP antibody negative early-stage RA patients. (4) The DAS28 score [ IgG (6.3±1.0) vs. (5.6±0.9), P=0.002; IgM (6.2±1.1) vs. (5.6±0.8), P=0.008] , X-ray stages (IgG 56.1% vs. 21.2%, P=0.001;IgM 50.9% vs. 29.4%, P=0.036),anti-CCP antibodies(IgG 96.8% vs. 55.3%, P=0.001; IgM 89.6% vs. 64.7%, P=0.023) in citrullinated HPVPP positive patients were higher than those of citrullinated HPVP negative patients. Additionally, the levels of ESR[IgG(70.3±32.4)vs.(51.9±27.8), P=0.004; IgM (67.4±31.5)vs.(53.8±27.7), P=0.035] in citrullinated HPVP positive patients were higher than those of negative patients (P<0.05). CONCLUSION: IgG and IgM antibodies to citrullinated HPVP are highly sensitive and specific novel biomarkers for early-stage RA diagnosis, and are related to disease activity and joint damage.

[Prevalence and significance of antibodies to citrullinated human fibrinogen ß67-77 peptide in rheumatoid arthritis].

OBJECTIVE: To detect the antibodies against human fibrinogen (FIB) ß67-77 peptide and citrullinated human FIB ß67-77 peptide in rheumatoid arthritis (RA) and examine their diagnostic values in RA. METHODS: The antibodies against FIB ß67-77 peptide and citrullinated FIB ß67-77 peptide were detected by enzyme-linked immunosorbent assay (ELISA) in 227 RA patients, 188 other connective tissue disease and 100 healthy controls. And their clinical applications were analyzed in the diagnosis of RA. RESULTS: (1) The prevalence and titer of IgG, IgA and IgM isotypes of anti-citrullinated FIB ß67-77 peptide antibodies in RA were significantly higher than those with other rheumatic diseases and healthy individuals. However, the prevalence of anti-FIB ß67-77 peptide antibodies in RA patients was similar to those with other rheumatic diseases and healthy individuals (P > 0.05). (2) The diagnostic sensitivity of IgG, IgA and IgM of anti-FIB ß67-77 peptide antibodies for RA were 50.7%, 48.5% and 55.1% and the specificity 94.8%, 92.7% and 92.4% respectively. The sensitivity of combined detection of 3 subtypes was up to 87.7% and the specificity 78.5%. (3) No significant correlations existed between anti-citrullinated FIB ß67-77 peptide antibodies, RF, anti-CCP antibody, AKA and APF respectively. Moreover, the seropositive rates of IgG, IgM and IgA of anti-citrullinated FIB ß67-77 peptide were 52.9%, 39.2% and 54.9% in IgM-RF negative patients Versus 48.5%, 53.1% and 37.5% in anti-CCP antibody, AKA and APF negative patients respectively. CONCLUSION: IgG, IgM and IgA antibodies to citrullinated FIB ß67-77 peptide are sensitive and specific in the diagnosis of RA. And the test of anti-citrullinated FIB ß67-77 peptide antibodies is especially useful in diagnosing RA with other negative autoantibodies.

Takayasu arteritis and hyperthyroidism: A secondary hypertension case report.

INTRODUCTION: Renovascular disease and hyperthyroidism are secondary hypertension. Takayasu arteritis (TAK) is a chronic, progressive, nonspecific great vasculitis involving the aorta and its major branches. It is one of the causes of renal artery stenosis. Hyperthyroidism is an endocrine disease caused by improper continuous synthesis and secretion of excessive thyroid hormone by the thyroid gland. Both diseases can raise blood pressure (BP). CASE PRESENTATION: we present a case of 18-year-old. Female, after exercise, fatigue palpitations. The maximum BP was 190/87 mm Hg, ankle-brachial index was <0.9. C-reactive protein and erythrocyte sedimentation rate were elevated. Imaging revealed multiple vascular stenosis. Triiodothyronine, tetraiodothyroxine, serum-free triiodothyronine, serum-free thyroxine, thyroid peroxidase antibody and thyroid stimulating receptor antibody were elevated. TSH reduced. She was diagnosed with TAK and hyperthyroidism. After treatment, the BP was normal, the thyroid function gradually returned to normal, and the symptoms improved. CONCLUSION: It is suggested that the BP of both upper limbs should be measured in newly diagnostic hypertension. If BP is not measured in both upper limbs, it is likely to be missed diagnosis. The cause of vascular stenosis needs to be identified, otherwise interventional treatment may lead to aggravation of the condition. Few cases of TAK complicated with hyperthyroidism have been reported. Both diseases are related to the immune system, whether there is any correlation between the 2 diseases, further research is needed. Early diagnosis, early treatment, the earlier intervention, the better prognosis.

Anti-carbonic anhydrase II antibody reflects urinary acidification defect especially in proximal renal tubules in patients with primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is a systemic autoimmue disease featured by excessive autoantibody production. It has been demonstrated that anti-carbonic anhydrase II (anti-CA II) antibody is correlated with renal tubular acidosis in pSS; however, no further details about urinary acidification defect have been reported, and the antibody's relationship with other organ impairments remains unknown. This case-control study aimed to examine anti-CA II antibody levels in relation to various systemic complications in pSS, and evaluate its potential role as a organ-specific biomarker in a Chinese cohort. Serum anti-CA II antibody levels were determined using ELISA in 123 patients with pSS and 72 healthy controls. The medical records of the patients were collected, and the correlation between serum anti-CA II antibody and clinical/immunological parameters was investigated. Serum anti-CA II antibody level and its positive rate were significantly increased in pSS patients compared with controls, and ANA-positive patients presented even higher titers of the antibody. In anti-CA II positive group, remarkably higher urine pH and bicarbonate, as well as lower urine titratable acid and serum potassium were observed, which indicated renal tubular acidification dysfunction both involving bicarbonate reabsorption and acid secretion. In addition, platelet count and complement 3, complement 4 levels decreased, whereas serum IgG, IgA and γ-globulin levels increased notably in accord with a higher EULAR SS disease activity index score in these patients. Further analysis showed that anti-CA II antibody was most elevated in patients with defect in bicarbonate reabsorption, reflecting proximal renal tubular injury, rather than in patients with distal renal tubular acidosis as previously reported. In conclusion, anti-CA II antibody reflects renal (especially proximal renal tubular) and hematologic impairment as well as increased disease activity in pSS. It may act as a serum biomarker of systemic damage of pSS.

Bone marrow mesenchymal stem cell transplantation alleviates radiation-induced myocardial fibrosis through inhibition of the TGF-ß1/Smad2/3 signaling pathway in rabbit model.

Background: and purpose: Radiotherapy (RT) is an effective treatment for most malignant chest tumors. However, radiation-induced myocardial fibrosis (RIMF) is a serious side effect of RT. Currently, due to the mechanism of RIMF has not been fully elucidated, there is a lack of effective therapeutic approach. In this study, we aimed to investigate the role and possible mechanisms of bone marrow mesenchymal stem cells (BMSCs) in the therapy of RIMF. Materials and methods: Twenty-four New Zealand white rabbits were allotted into four groups (n = 6). Rabbits in the Control group received neither irradiation nor treatment. A single dose of 20 Gy heart X-irradiation was applied to the RT group, RT + PBS group and RT + BMSCs group. Rabbits in the RT + PBS group and RT + BMSCs group were injected with 200 µL PBS or 2 × 106 cells via pericardium puncture 24 h following irradiation, respectively. Echocardiography was used to test the cardiac function; Then the heart samples were collected, and processed for histopathological, Western blot and immunohistochemistry investigations. Results: It was observed that BMSCs have therapeutic effect on RIMF. Compared with the Control group, inflammatory mediators, oxidative stress and apoptosis were significantly increased, meanwhile, cardiac function was remarkably decreased in the RT group and RT + PBS group. However, in the BMSCs group, BMSCs significantly improved cardiac function, decreased inflammatory mediators, oxidative stress and apoptosis. Furthermore, BMSCs remarkably reduced the expression level of TGF-ß1 and the phosphorylated-Smad2/3. Conclusions: In conclusion, our research indicates BMSCs have the potential to alleviate RIMF through TGF-ß1/Smad2/3 and would be a new therapeutic approach for patients with myocardial fibrosis.

Subtyping of Nonhuman Primate-Adapted Cryptosporidium hominis in Macaca Fascicularis and Macaca mulatta in Yunnan Province, Southwestern China.

Background: Cryptosporidium spp. are a type of protozoan parasite responsible for causing diarrheal illness worldwide. They infect a broad range of vertebrate hosts, including both non-human primates (NHPs) and humans. In fact, zoonotic transmission of cryptosporidiosis from NHPs to humans is frequently facilitated by direct contact between the two groups. However, there is a need to enhance the information available on the subtyping of Cryptosporidium spp. in NHPs in the Yunnan province of China. Materials and Methods: Thus, the study investigated the molecular prevalence and species of Cryptosporidium spp. from 392 stool samples of Macaca fascicularis (n = 335) and Macaca mulatta (n = 57) by using nested PCR targeting the large subunit of nuclear ribosomal RNA (LSU) gene. Of the 392 samples, 42 (10.71%) were tested Cryptosporidium-positive. Results: All the samples were identified as Cryptosporidium hominis. Further, the statistical analysis revealed that age is a risk factor for the infection of C. hominis. The probability of detecting C. hominis was found to be higher (odds ratio = 6.23, 95% confidence interval 1.73-22.38) in NHPs aged between 2 and 3 years, as compared with those younger than 2 years. Sequence analysis of the 60 kDa glycoprotein (gp60) identified six (IbA9 n = 4, IiA17 n = 5, InA23 n = 1, InA24 n = 2, InA25 n = 3, and InA26 n = 18) C. hominis subtypes with "TCA" repeats. Among these subtypes, it has been previously reported that the Ib family subtypes are also capable of infecting humans. Conclusion: The findings of this study highlight the genetic diversity of C. hominis infection among M. fascicularis and M. mulatta in Yunnan province. Further, the results confirm that both these NHPs are susceptible to C. hominis infection, posing a potential threat to humans.