Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections.

Ganodermataceae is one of the main families of macrofungi since species in the family are both ecologically and economically important. The double-walled basidiospores with ornamented endospore walls are the characteristic features of Ganodermataceae. It is a large and complex family; although many studies have focused on Ganodermataceae, the global diversity, geographic distribution, taxonomy and molecular phylogeny of Ganodermataceae still remained incompletely understood. In this work, taxonomic and phylogenetic studies on worldwide species of Ganodermataceae were carried out by morphological examination and molecular phylogenetic analyses inferred from six gene loci including the internal transcribed spacer regions (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), the second largest subunit of RNA polymerase II gene (rpb2), the translation elongation factor 1-α gene (tef1), the small subunit mitochondrial rRNA gene (mtSSU) and the small subunit nuclear ribosomal RNA gene (nSSU). A total of 1 382 sequences were used in the phylogenetic analyses, of which 817 were newly generated, including 132 sequences of ITS, 139 sequences of nLSU, 83 sequences of rpb2, 124 sequences of tef1, 150 sequences of mtSSU and 189 sequences of nSSU. The combined six-gene dataset included sequences from 391 specimens representing 146 taxa from Ganodermataceae. Based on morphological and phylogenetic analyses, 14 genera were confirmed in Ganodermataceae: Amauroderma, Amaurodermellus, Cristataspora, Foraminispora, Furtadoella, Ganoderma, Haddowia, Humphreya, Magoderna, Neoganoderma, Sanguinoderma, Sinoganoderma, Tomophagus and Trachydermella. Among these genera, Neoganoderma gen. nov. is proposed for Ganoderma neurosporum; Sinoganoderma gen. nov. is proposed for Ganoderma shandongense; Furtadoella gen. nov. is proposed to include taxa previously belonging to Furtadoa since Furtadoa is a homonym of a plant genus in the Araceae; Trachydermella gen. nov. is proposed to include Trachyderma tsunodae since Trachyderma is a homonym of a lichen genus in the Pannariaceae. Twenty-three new species, viz., Ganoderma acaciicola, G. acontextum, G. alpinum, G. bubalinomarginatum, G. castaneum, G. chuxiongense, G. cocoicola, G. fallax, G. guangxiense, G. puerense, G. subangustisporum, G. subellipsoideum, G. subflexipes, G. sublobatum, G. tongshanense, G. yunlingense, Haddowia macropora, Sanguinoderma guangdongense, Sa. infundibulare, Sa. longistipitum, Sa. melanocarpum, Sa. microsporum and Sa. tricolor are described. In addition, another 33 known species are also described in detail for comparison. Scanning electron micrographs of basidiospores of 10 genera in Ganodermataceae are provided. A key to the accepted genera of Ganodermataceae and keys to the accepted species of Ganoderma, Haddowia, Humphreya, Magoderna, Sanguinoderma and Tomophagus are also provided. In total, 278 species are accepted as members of Ganodermataceae including 59 species distributed in China. Taxonomic novelties: New genera: Furtadoella B.K. Cui & Y.F. Sun, Neoganoderma B.K. Cui & Y.F. Sun, Sinoganoderma B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella B.K. Cui & Y.F. Sun; New species: Ganoderma acaciicola B.K. Cui, J.H. Xing & Y.F. Sun, G. acontextum B.K. Cui, J.H. Xing & Vlasák, G. alpinum B.K. Cui, J.H. Xing & Y.F. Sun, G. bubalinomarginatum B.K. Cui, J.H. Xing & Y.F. Sun, G. castaneum B.K. Cui, J.H. Xing & Y.F. Sun, G. chuxiongense B.K. Cui, J.H. Xing & Y.F. Sun, G. cocoicola B.K. Cui, J.H. Xing & Y.F. Sun, G. fallax B.K. Cui, J.H. Xing & Vlasák, G. guangxiense B.K. Cui, J.H. Xing & Y.F. Sun, G. puerense B.K. Cui, J.H. Xing & Y.F. Sun, G. subangustisporum B.K. Cui, J.H. Xing & Y.F. Sun, G. subellipsoideum B.K. Cui, J.H. Xing & Y.F. Sun, G. subflexipes B.K. Cui, J.H. Xing & Y.F. Sun, G. sublobatum B.K. Cui, J.H. Xing & Y.F. Sun, G. tongshanense B.K. Cui, J.H. Xing & Y.F. Sun, G. yunlingense B.K. Cui, J.H. Xing & Y.F. Sun, Haddowia macropora B.K. Cui, Vlasák & Y.F. Sun, Sanguinoderma guangdongense B.K. Cui & Y.F. Sun, Sa. infundibulare B.K. Cui & Y.F. Sun, Sa. longistipitum B.K. Cui & Y.F. Sun, Sa. melanocarpum B.K. Cui & Y.F. Sun, Sa. microsporum B.K. Cui & Y.F. Sun and Sa. tricolor B.K. Cui & Y.F. Sun; New combinations: Furtadoella biseptata (Costa-Rezende et al.) B.K. Cui & Y.F. Sun, Fu. brasiliensis (Singer) B.K. Cui & Y.F. Sun, Fu. corneri (Gulaid & Ryvarden) B.K. Cui & Y.F. Sun, Neoganoderma neurosporum (J.S. Furtado) B.K. Cui & Y.F. Sun, Sinoganoderma shandongense (J.D. Zhao & L.W. Xu) B.K. Cui, J.H. Xing & Y.F. Sun and Trachydermella tsunodae (Yasuda ex Lloyd) B.K. Cui & Y.F. Sun. Citation: Sun Y-F, Xing J-H, He X-L, Wu D-M, Song C-G, Liu S, Vlasák J, Gates G, Gibertoni TB, Cui B-K (2022). Species diversity, systematic revision and molecular phylogeny of Ganodermataceae (Polyporales, Basidiomycota) with an emphasis on Chinese collections. Studies in Mycology 101: 287-415. doi: 10.3114/sim.2022.101.05.

[Therapeutic effect of different surgical methods for congenital small intestine atresia].

Objective: To compare and analyze the curative effect of three surgical methods in the treatment of small intestine atresia, and to provide evidence for individualized surgical treatment of children with small intestine atresia. Methods: The clinical diagnosis and treatment of 168 children with small intestine Ⅱ, Ⅲ, Ⅳ type atresia in our hospital from January 2008 to September 2017 were retrospectively analyzed and they were divided into different types according to the operation. The three groups were end-to-end anastomosis group (EEA, n=58), end oblique anastomosis group (EOA, n=68), and proximal end-end anastomosis group (PEA, n=42). The EEA group and the EOA group were further divided into group a (EEA-a/EOA-a) with a proximal intestinal tube diameter greater than 4.0 times the distal end and a group b ((EEA-b/EOA-b) with a diameter less than or equal to 4.0 times the distal intestinal tube diameter. The gender, gestational age, birth weight, type of atresia, and postoperative defecation time, postoperative feeding time, postoperative hospital stay and postoperative follow-up complications were compared. Results: There was no significant difference in gender, gestational age and birth weight between the groups (P>0.05). The PEA group was better than EEA-a group and EOA-a group in postoperative defecation time, postoperative feeding time, postoperative hospital stay and complications (P<0.05). The postoperative defecation time, postoperative feeding time, postoperative hospital stay and complications of the EOA-a group were better than those of the EEA-a group (P<0.05). There was no statistically significant difference in postoperative defecation time, postoperative feeding time, and complications between the EEA-b group and the EOA-b group (P>0.05), but the postoperative hospital stay in the EEA-b group was longer than that in the EOA-b group (P<0.05). Conclusion: PEA is recommended for children with a proximal intestinal canal diameter greater than 4.0 times greater than the distal end because of the rapid recovery and fewer complications; EOA is recommended for children with a proximal intestinal canal diameter of 4.0 or less because of its advantage of shorter hospital stay than EEA surgery. Congenital intestinal atresia has a better effect according to the specific conditions of the child.

Downregulation of hsa_circ_0000285 serves as a prognostic biomarker for bladder cancer and is involved in cisplatin resistance.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.

[Efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in the acute treatment of moderate and severe hypertension: a randomized, double-blind, positive-drug parallel-controlled, multi-center clinical study].

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ(2)=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ(2)=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ(2)=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ(2)=15.611, P<0.001). Conclusions: In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

[Meta analysis of clinical safety and efficacy evaluation of peripheral arterial disease patients with critical limb ischemia who accepted bypass surgery or endovascular therapy].

Objective: To evaluate the safety and efficacy of peripheral arterial disease patients with critical limb ischemia who accepted BSX or EVT. Methods: According to the requirements of systematic review, we searched MEDLINE (1980-2014), Emabse (1980-2014), Journals @ Ovid Full Text (1980-2014) databases, selected literature and extracted data, meta-analysis was performed through STATA11.2. Results: A total of 17 studies (3 RCTs, 14 non-randomized studies) and 5 515 patients (BSX group: 2 454, EVT group: 2 769) were deemed eligible. Meta-analysis showed there were no differences between the two groups in 30-day mortality (OR=1.110, P=0.523). However, BSX was significantly associated with increasing overall complications (OR=2.456, P=0.003), infections (OR=3.163, P<0.001) and thrombosis (OR=3.069, P=0.002), but showed a reduction in dissection and pseudoaneurysm (OR=0.537, P=0.012). During the follow-up, BSX had significant advantages. The 1-year and 3-year primary patency of BSX patients were higher than EVT group (1 year, OR=1.415, P=0.008; 3 years, OR=1.619, P<0.001); so were in secondary patency( 1 year, OR=2.156, P<0.001; 3 years, OR=2.547, P<0.001). Meanwhile, the 5-year overall survival rate was also higher in BSX group (OR=1.243, P=0.007). Conclusions: EVT has potential advantages in reducing surgical trauma and early postoperative complications, shortening hospital stay and so on. Concerning long-term results, BSX is better in reducing long-term mortality and improving long-term patencies than EVT group.

[The diagnostic value of plasma fibrin related markers in perioperation of femoral fracture].

Objective: To investigate potential value of fibrin related markers in patients with femoral fracture during perioperative period. Methods: Ninety-five patients were enrolled, including 39 males with (53±24) years old and 56 females with (73±13) years old, of which 44 fracture on caput femoris, 34 collum femoris and 17 shaft of femur. Sampling on the day before operation and 1(st,) 3(rd,) 5(th) days after operation, fibrin monomer (FM), D-dimer(DD), fibrinogen degradation product (FDP) and other coagulation assays were detected by reagents from Stago. Difference in day-to-day and between surgical sites were analyzed with general linear model (repeated measures). Results: FDP level on pre-operation, 1(st,) 3(rd,) 5(th) day after operation were 7.88(5.19, 12.12), 15.68(9.84, 29.48), 8.44 (6.27, 12.49) and 10.28 (7.56, 14.00) mg/L, the value of fibrin monomer were 5.00 (5.00, 6.03), 9.89(5.04, 30.12), 5.00 (5.00, 6.04) and 5.02(5.00, 5.76) mg/L. The value of D-Dimer were 2.24(1.41, 3.60), 4.78(2.74, 9.18), 2.60(1.79, 3.88) and 2.91(2.20, 3.85) mg/L, respectively, each parameter changs statistically during observation (Z=4.758, 6.027, 3.238 respectively, P<0.05). On the 5th day after surgery, fibrin monomer in patients with venous thrombus embolism (VTE) were higher than that in patients without VTE, 10.18(7.24, 28.11) mg/L vs 5.10(5.00, 6.73) mg/L (Z=-1.580, P<0.05), which showed potential value evaluating of post-operative VTE. No statistical changes were found in prothrombin time or thrombin time (TT) (P>0.05), but activated partial thromboplastin time (APTT) varied from day to day in (38.1±4.9), (40.8±5.2), (45.1±6.2) and (41.9±6.3)s with statistically difference (F=7.127, P<0.05). Similarly, fibrinogen changed statistically in (5.01±0.94), (4.99±1.35), (6.00±1.75), (5.81±1.38)g/L (F=8.927, P<0.05). Conclusion: Fibrin monomer, additional to markers as D-dimer, shows its value on activated coagulation associated to post-operative thromboembolism for patients receiving femoral surgery.

[Evaluation between bypass surgery and endovascular therapy to peripheral arterial disease patients with critical limb ischemia].

Bypass surgery(BSX) and endovascular therapy(EVT) are the most important therapeutic method to critical limb ischemia.EVT has potential advantages in reducing surgical trauma and early postoperative complications, shortening hospital stay and so on. Concerning long-term results, BSX is better in reducing long-term mortality and improving long-term patency than EVT group. Therefore, control indications reasonably and select individualized methods, avoid the abuse of EVT are more meaningful for patients.

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity.

AIMS/HYPOTHESIS: Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. METHODS: Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. RESULTS: miR-181a targets the 3' untranslated region (3'UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR-181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. CONCLUSIONS/INTERPRETATION: miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes.

Nutritional Status and Renal Function in Relation to Frailty among the Community-Dwelling Elderly Taiwanese Population.

OBJECTIVES: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese. DESIGN: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. MEASUREMENTS: We measured nutritional status (including serum albumin and total protein levels), renal function (including serum blood urea nitrogen, creatinine, urine protein, and urine creatinine levels), hand grip strength (GS) and calculated appendicular muscle mass (AMM). RESULTS: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs). For the men with normal and weak GS, serum albumin levels were 4.15 ± 0.2 and 4.10 ± 0.2 g/dL (p < 0.01), and UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2 (p < 0.001), respectively. GS was positively correlated with serum albumin and urine creatinine levels (r = 0.136 and 0.177, both p < 0.001). AMM was also positively correlated with serum albumin and urine creatinine levels (r = 0.078 and 0.091, both p < 0.001). In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p < 0.05 and p < 0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR (urine creatinine for women) which presented a variance of 22.1% and 13.8%, respectively. CONCLUSION: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among elder population in Taiwan.

Combined effect of C-reactive protein gene SNP +2147 A/G and interleukin-6 receptor gene SNP rs2229238 C/T on anthropometric characteristics among school children in Taiwan.

OBJECTIVE: The purpose of this study was to explore the combined effect of the C-reactive protein (CRP) +2147 A/G (rs1205) and interleukin (IL)-6R rs2229238 C/T single-nucleotide polymorphisms (SNPs) on the anthropometric variables of school children in Taiwan. SUBJECTS AND DESIGN: Cross-sectional analyses were performed using the data from the Taipei Children Heart Study-II. After multi-stage sampling, we selected 430 boys and 463 girls with an average age of 13.1 years. We genotyped these individuals for the CRP +2147 A/G and IL-6R rs2229238 C/T SNPs using a TaqMan 5' nuclease assay. Anthropometric characteristics, which included body height, body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), body fat percentage (BF), and waist circumference to height ratio (WHtR), were measured/calculated. RESULTS: When considering the CRP +2147 A/G polymorphism, GG genotype boys were heavier and had larger BMI, WC, HC, BF and WHtR than A allele carriers. The odds ratio (OR) of larger WHtR in GG genotype boys was 2.14 (95% CI: 1.09-4.21). For the IL-6R rs2229238 C/T polymorphism, T allele carrier girls had larger WC and WHtR than those carrying the CC genotype. The OR of a larger HC for T allele carrier boys was 2.33 (95% CI: 1.16-4.68). Boys with the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T had higher OR for BW, BMI, WC, HC, BF and WHtR than boys who were carriers of the A allele of CRP +2147 A/G and had the CC genotype of IL-6R rs2229238 C/T (OR range=3.86-8.04, all P<0.05). CONCLUSION: Boys who carry the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T have a greater risk of having abnormal BW, BMI, WC, HC, BF and WHtR and of developing obesity than individuals who do not have these genotypes.

Vitamin D receptor alleviates hepatic ischemia and reperfucion injury by mediating endoplasmic reticulum stress through autophagy.

Hepatic ischemia and reperfusion (IR) injury is a common complication in clinical practice. Endoplasmic reticulum (ER) stress and autophagy are the key factors in the process of hepatic IR injury. The vitamin D receptor (VDR) can mediate ER stress and autophagy; however, it can also mitigate IR injury. The relationship between VDR, ER stress, and autophagy in hepatic IR injury is unknown. VDR knockout mice and wild-type littermates underwent 70% liver ischemia (90 min) and reperfusion (6 h). To observe the effect of autophagy in the relationship with VDR and ER stress in hepatic IR injury, the autophagy agonist rapamycin and its inhibitor chloroquine were used in the study. Meanwhile, RAW264.7 cells were studied in vitro to verify the relationship between VDR, autophagy, and ER stress. VDR was involved in hepatic IR injury and its activation reduced liver injury and inhibited an inflammatory response. ER stress took part in the liver injury during the process of IR. Meanwhile, VDR activation was found to inhibit inflammation by ER stress, and vice versa. Furthermore, autophagy was the connection between VDR and ER stress. After treatment with rapamycin or chloroquine, the effect of VDR activation or VDR silencing in ER stress was partially reversed. The same tendency was observed in vitro. ER stress and autophagy are important mechanisms of hepatic IR injury. VDR can regulate ER stress through autophagy and then protect the liver from IR injury.

The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells.

The Notch ligand, Jagged-1, plays an essential role in tissue formation during embryonic development of primitive organisms. However, little is known regarding the role of Jagged-1 in the regulation of tissue-specific stem cells or its function in humans. Here, we show that uncommitted human hematopoietic cells and cells that comprise the putative blood stem cell microenvironment express Jagged-1 and the Notch receptors. Addition of a soluble form of human Jagged-1 to cultures of purified primitive human blood cells had modest effects in augmenting cytokine-induced proliferation of progenitors. However, intravenous transplantation of cultured cells into immunodeficient mice revealed that human (h)Jagged-1 induces the survival and expansion of human stem cells capable of pluripotent repopulating capacity. Our findings demonstrate that hJagged-1 represents a novel growth factor of human stem cells, thereby providing an opportunity for the clinical utility of Notch ligands in the expansion of primitive cells capable of hematopoietic reconstitution.

Expression of T follicular helper lymphocytes with different subsets and analysis of serum IL-6, IL-17, TGF-ß and MMP-3 contents in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the expression levels of T follicular helper (Tfh) with different subsets in patients with rheumatoid arthritis (RA) and their serum interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-ß (TGF-ß) and matrix metalloproteinase 3 (MMP-3) contents. PATIENTS AND METHODS: The medical records of 45 RA patients in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Chengdu Medical College from January 2016 to April 2018 were retrospectively analyzed. They were divided into the RA high activity group (24 cases, group A) (DAS28 score ≥ 5.0) and RA low activity group (21 cases, group B) (3.2 < DAS28 score < 5.0). At the same time, 20 healthy subjects were selected as a control group. Flow cytometry was used to detect the expression levels of Tfh1, Tfh2 and Tfh17, enzyme-linked immunosorbent assay to detect serum IL-6, IL-17, IL-21 and MMP-3 concentrations. The correlation of Tfh cells with IL-6, IL-17, IL-21 and MMP-3 was analyzed. RESULTS: Those of peripheral blood mononuclear cell (PBMC) Tfh2 and Tfh17 cells were significantly higher in group A than those in group B (p < 0.05). Compared with the control group, the concentrations of serum IL-6, IL-17 and MMP-3 significantly increased (p < 0.001), but that of serum TGF-ß markedly decreased in group A and group B (p < 0.01). The concentrations of serum IL-6, IL-17 and MMP-3 were remarkably higher in group A than those in group B (p < 0.001), but that of serum TGF-ß was significantly lower in group A than that in group B (p < 0.001). The expression level of PBMC Tfh2 cells, PBMC Tfh17 cells was positively correlated with serum IL-6, IL-17 and MMP-3. The expression levels of Tfh2 and Tfh17 cells are positively correlated with serum IL-6, IL-17 and MMP-3 concentrations, negatively correlated with serum TGF-ß concentration. CONCLUSIONS: Tfh2 and Tfh17 are expected to be new targets for immunotherapy in RA patients.

Synthesis and Characterization of SiO2@Y2MoO6:Eu3+ Core-Shell Structured Spherical Phosphors by Sol-Gel Process.

SiO2@Y2MoO6:Eu3+ core-shell phosphors were prepared by the sol-gel process. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectra (EDS), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as kinetic decays were used to characterize the resulting SiO2@Y2MoO6:Eu3+ core-shell phosphors. The XRD results demonstrated that the Y2MoO6:Eu3+ layers on the SiO2 spheres crystallized after being annealed at 700 °C and the crystallinity increased with raising the annealing temperature. The obtained core-shell phosphors have spherical shape with narrow size distribution (average size ca. 640 nm), non-agglomeration, and smooth surface. The thickness of the Y2MoO6:Eu3+ shells on the SiO2 cores could be easily tailored by varying the number of deposition cycles (70 nm for four deposition cycles). The Eul+ shows a strong PL emission (dominated by 5D0-7F2 red emission at 614 nm) under the excitation of 347 nm UV light. The PL intensity of Eu3+ increases with increasing the annealing temperature and the number of coating cycles.

Cones regenerate from retinal stem cells sequestered in the inner nuclear layer of adult goldfish retina.

PURPOSE: To determine whether retinal progenitor cells in the inner nuclear layer give rise to regenerated cones after laser ablation of photoreceptors in adult goldfish retina. METHODS: Using a technique developed previously in this laboratory, photoreceptors in the retina of adult goldfish were ablated with an argon laser. The mitotic marker, bromodeoxyuridine, was used to label proliferating and regenerated cells, which were identified with cell-specific markers. RESULTS: Cells proliferating locally within lesion included microglia, Müller glia, and retinal progenitors in the inner nuclear layer (INL). The nuclei of both Müller glia and associated retinal progenitors migrated from the inner to the outer nuclear layer. The proliferating retinal progenitors, which express Notch-3 and N-cadherin, regenerated cone photoreceptors and then rod photoreceptors. CONCLUSIONS: Previous work has demonstrated that photoreceptors in the goldfish retina regenerate selectively after laser ablation, but the source of regenerated cones has not been identified. The results reported here provide support for the existence of retinal stem cells within the adult fish retina that are capable of regenerating cone photoreceptors. The data also support the involvement of Müller glia in the production of regenerated cones.

Lipotropes alter casein gene expression in bovine mammary acinar culture.

Lipotropes (methyl group containing nutrients, including methionine and choline, folic acid, and vitamin B(12)) are essential for cell proliferation and differentiation of mammary tissues. Lipotropes interact in the supply and regulation of intracellular methyl group pools, thereby affecting synthesis and methylation of DNA. To determine the effect of lipotropes on milk protein gene expression, acini isolated from mammary tissues of lactating cows were cultured in one of three treatment media: (1) control, (2) lipotrope deficient, and (3) lipotrope supplemented. beta-Casein mRNA was determined by Northern blotting, and milk protein secretion was measured by a pulse-chase method. The level of beta-casein mRNA was lower in cells grown in lipotrope-deficient medium than in cells grown in the lipotrope-supplemented and control media. Acinar cells cultured in lipotrope-deficient medium also had approximately threefold less milk protein secretion than that of cells in either control or lipotrope-supplemented media. Protein secretion did not differ in the control and lipotrope-supplemented groups. The present study indicates that lipotrope deficiency suppresses total protein secretion and beta-casein gene expression in bovine mammary alveolar epithelial cells in culture.

Underregistration of neonatal deaths: an empirical study of the accuracy of infantile vital statistics in Taiwan.

STUDY OBJECTIVE: The accuracy of the official statistic on infant deaths in Taiwan has been questioned. This study aimed to survey infant deaths nationwide, to measure associated vital statistics, and compare them with the official statistics to assess accuracy. DESIGN AND PARTICIPANTS: A nationwide survey of all gestational outcomes occurring at > or = 20 weeks' gestation over a three day study period (15-17 May 1989) was conducted to collect data from 23 counties and cities nationwide using a two stage data collection procedure. MAIN RESULTS: The survey derived infant death rate was 9.72 per 1000 live births, which was higher than the reported official statistic of 5.71 per 1000 live births. A more detailed examination of data on infant deaths showed that the estimated neonatal death rate of 6.68 per 1000 live births (95% confidence intervals: 3.33, 11.96 per 1000 live births) was significantly higher than the published official statistic of 1.94 per 1000 live births, while the postneonatal mortality of 3.04 per 1000 live births was comparable to the reported statistic of 3.37 per 1000 live births. CONCLUSIONS: This study empirically documented the underregistration of infant deaths in Taiwan, particularly those occurring during the first 27 days of life.

Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions.

OBJECTIVES: This case-control study was conducted to investigate the role of viral load of high-risk human papillomaviruses (HPVs) in the development of cervical squamous intraepithelial lesions (SILs) and invasive cancers. METHODS: A total of 30 female cases who had histological evidence of low-grade SIL (n=10) or high-grade SIL and above (n=20) were identified as the case group at the Tri-Service General Hospital, Taipei between September 1998 and March 1999. In addition, 80 female controls who had normal cervical cytology were enrolled and individually matched on age (+/-5 years) and date of recruitment to each case. Cervical swabs collected from study subjects were tested for the positivity and viral load of high-risk HPVs by Hybrid Capture II assay. Additionally, subjects completed a risk factor questionnaire. RESULTS: Among sex behavioral factors studied, younger age at first intercourse was associated with a significantly elevated risk of cervical SIL and invasive cancers. With respect to HPV infection, high-risk HPV DNA was present in 70% (21/30) of case and 21% (17/80) of control subjects, resulting in an odds ratio (OR) of 6.6 [95% confidence interval (C.I.)=2.6-17.0]. Moreover, women who had a high viral load were at significantly greater risk for cervical SIL and invasive cancers than those who were infected with a low viral load (OR=18.0, 95% C.I.=3.0-108.5). CONCLUSIONS: Among the variables tested, infection with a high viral load of high-risk HPVs is the strongest determinant for cervical SIL and cervical cancers in Taiwan.

Na+/Ca2+ exchange current in myocytes isolated from rat hypertrophied heart.

Effects of myocardial hypertrophy on the Na+/Ca2+ exchange current in isolated rat cardiac myocytes were investigated, using whole cell patch techniques. Goldblatt 2-kidney, one-clip technique was used to induce cardiomyocyte hypertrophy. The results demonstrated that the Ni(2+)-sensitive Na+/Ca2+ exchange current density was larger in hypertrophied cells than that in normal cells. At a holding potential of mV, the outward current densities were 1.53 +/- 0.31 pA/pF in normal cells and 2.62 +/- 0.53 pA/pF in hypertrophied cells (P < 0.01). At a holding potential of -100 mV, the inward current densities were 0.42 +/- 0.14 pA/pF in normal cells and 1.12 +/- 0.33 pA/pF in hypertrophied cells (P < 0.001). The results suggest that during myocardial hypertrophy the Na+/Ca2+ exchange current is significantly increased.

[Inhibition of Na+/Ca2+ exchange by tetrapeptide FMRFa in intact rat ventricular myocytes].

AIM: To study the effects of Phe-Met-Arg-Phe-NH2(FMRFa) on Na+/Ca2+ exchange and its specificity for Na+/Ca2+ exchange in rat ventricular myocytes. METHODS: Na+/Ca2+ exchange current and other currents of ion channels were measured using whole cell voltage clamp techniques. RESULTS: A dose-related inhibition of tetrapeptide FMRFa on Na+/Ca2+ exchange was observed in rat ventricular myocytes. Inward and outward INa+/Ca2+ were inhibited by 60.1% and 56.5%, respectively, at highest concentration (100 mumol.L-1) and its IC50 were 20 mumol.L-1 and 34 mumol.L-1 in inward and outward INa+/Ca2+, respectively. Inward and outward INa+/Ca2+ were inhibited 38.7% and 34.9%, respectively, at FMRFa 5 mumol.L-1. FMRFa 5 mumol.L-1 and 20 mumol.L-1 did not affect L-type calcium current, sodium current, transient outward current and inward rectifier potassium current. CONCLUSION: These data indicate that FMRFa is a specific inhibitor of Na+/Ca2+ exchange in intact rat ventricular myocytes.