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Previously, we reported that HIV-1 patients infected with CRF07_BC had significantly lower viral loads than those infected with subtype B. Since HIV-1 viral load is associated with AIDS disease progression, the current study was to link multiple clinical and molecular databases, and compare clinical outcomes of HIV-1patients infected with CRF07_BC, CRF01_AE and subtype B in Taiwan. Molecular genotyping data of 2,982 HIV-1/AIDS patients were submitted to Taiwan CDC HIV-1/AIDS case management database. Then the database was linked to Taiwan National Health Insurance Research database and National Cause of Death database from 2000−2016. Subsequently, a subtype-based HIV/AIDS clinical database containing 1,605 patients including 858 (53.5%) subtype B, 690 (43.0%) CRF07_BC and 57 (3.5%) CRF01_AE patients was successfully established and the clinical outcomes and survival of these patients were analyzed. Analysis of transmission route showed this HIV-1/AIDS cohort consists of 761 (47.4%) men who have sex with men (MSM), 132 (8.2%) heterosexuals and 712 (44.4%) injection drug user (IDUs). Survival analysis showed subtype B patients had a significantly lower death rate (8.2%) than CRF07_BC and CRF01-AE patients (22.8% and 22.8%, respectively). The higher death rate for CRF07_BC versus subtype B patients could be largely influenced by transmission route (IDU: 95.7% vs. 3.9%; MSM: 85.8% vs. 2.0%), as well as lower ART uptake rates (69.9% vs. 96.3%). Indeed, subset analysis among IDU patients, CRF07_BC-infected patients had a better 16-year survival rate than patients infected with subtype B (74.3% vs. 45.7%, p < 0.05). Our findings suggest that the transmission route is one major factor influencing death rate, while ART treatment and HIV-1 subtypes may also play important roles. Our study is the largest long-term cohort study of patients infected with CRF07_BC and subtype B in the same geographic region.

Background Curculigoside is a natural phenolic glycoside compound produced by Curculigo orchioides Gaertn. This study aimed to explore the effects of curculigoside in promoting the osteogenic differentiation of adipose-derived stem cells (ADSCs) as well as the underlying mechanism. Methods ADSCs were treated with curculigoside at different concentrations (0 μmol/L, 1 μmol/L, 2.5 μmol/L, 5 μmol/L, 10 μmol/L, and 20 μmol/L), and cell viability was assessed by CCK-8 assay. Then, the alkaline phosphatase (ALP) activity was determined, and alizarin red S (ARS) staining was performed to measure the extracellular mineralization of curculigoside. Information about protein-chemical interactions is provided by the search tool for interactions of chemicals (STITCH) database. Then, LY294002 was administered to explore the mechanism by which curculigoside promotes the osteogenic differentiation of ADSCs. Western blot assays were performed to assess changes in the expression of osteogenic-related markers and the phosphorylation of PI3K and AKT. Finally, we established an ovariectomized (OVX)-induced osteoporosis mouse model and administered curculigoside to explore the effects of curculigoside in preventing bone loss in vivo. Results The CCK-8 assay indicated that curculigoside did not induce cytotoxicity at a concentration of 5 μmol/L after 48 h. The ALP and ARS results revealed that the induced group had higher ALP activity and calcium deposition than the control group. Moreover, the curculigoside group exhibited increased biomineralization, ALP activity, and ARS staining compared to the induced and control groups, and these effects were partially inhibited by LY294002. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the target genes of curculigoside were mainly involved in the PI3K-Akt signaling pathway. PCR and western blot analysis showed that the expression of RUNX2, ALP, and Osterix was upregulated in curculigoside-treated ADSCs, but this effect was partially reversed by the PI3K inhibitor LY294002. Moreover, the curculigoside-treated group exhibited significantly increased phosphorylation of AKT to P-AKT compared with the osteogenic induction group. After treatment with curculigoside, the mice had a higher bone volume than the OVX mice, suggesting partial protection from cancellous bone loss. In addition, when LY294002 was added, the protective effects of curculigoside could be neutralized. Conclusions Curculigoside could induce the osteogenic differentiation of ADSCs and prevent bone loss in an OVX model through the PI3K/Akt signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidities and mortality, and no effective drug treatment currently exists. We aimed to develop a novel treatment strategy to induce the expression of glycine N-methyltransferase (GNMT), which is an important enzyme regulating S-adenosylmethionine metabolism whose expression is downregulated in patients with NAFLD. Because 1,2,3,4,6-pentagalloyl glucose (PGG) is a GNMT inducer, and metformin was shown to upregulate liver mitochondrial GNMT protein expression, the effect of PGG and metformin was evaluated. Biochemical analysis, histopathological examination, immunohistochemical staining, reverse transcription-quantitative PCR (RT-qPCR), Western blotting (WB), proteomic analysis and Seahorse XF Cell Mito Stress Test were performed. The high-fat diet (HFD)-induced NAFLD mice were treated with PGG and metformin. Combination of PGG and metformin nearly completely reversed weight gain, elevation of serum aminotransferases, and hepatic steatosis and steatohepatitis. In addition, the downregulated GNMT expression in liver tissues of HFD-induced NAFLD mice was restored. The GNMT expression was further confirmed by RT-qPCR and WB analysis using both in vitro and in vivo systems. In addition, PGG treatment was shown to increase oxygen consumption rate (OCR) maximum capacity in a dose-dependent manner, and was capable of rescuing the suppression of mitochondrial OCR induced by metformin. Proteomic analysis identified increased expression of glutathione S-transferase mu 4 (GSTM4), heat shock protein 72 (HSP72), pyruvate carboxylase (PYC) and 40S ribosomal protein S28 (RS28) in the metformin plus PGG treatment group. Our findings show that GNMT expression plays an important role in the pathogenesis of NAFLD, and combination of an inducer of GNMT and metformin can be of therapeutic potential for patients with NAFLD.

Men who have sex with men (MSM) is the major risk population of HIV-1 infection in Taiwan, and its surveillance has become critical in HIV-1 prevention. We recruited MSM subjects from 17 high-risk venues and 4 community centers in northern and southern Taiwan for anonymous HIV-1 screening during 2013-2015. Blood samples were obtained for genotyping and phylogenetic analysis, and a questionnaire survey covering demographic variables and social behavior was conducted. In total, 4,675 subjects were enrolled, yielding a HIV-1 prevalence rate of 4.3% (201/4675). Eight risk factors including subjects who did not always use condoms (OR = 1.509, p = 0.0123), those who used oil-based lubricants (OR = 1.413, p = 0.0409), and those who used recreational drugs (OR = 2.182, p = < .0001) had a higher risk of HIV-1 infection. The annual prevalence and incidence of HIV-1 showed a downward trend from 2013 to 2015 (6.56%, 5.97 per 100 person-years in 2013; 4.53%, 3.97 per 100 person-years in 2014; 1.84%, 2.08 per 100 person-years in 2015). Factors such as always using condoms, water-based lubricant use, correct knowledge of lubricating substitutes, and recreational drug use were significantly associated with the trend of incidence. Phylogenetic tree analysis showed that the cross-regional and international interaction of the local MSM population may have facilitated transmission of HIV. This survey of high-risk venues showed decreased prevalence and incidence of HIV-1 infection in Taiwan from 2013 to 2015, and this may be related to changes in behavioral patterns. Moreover, cross-regional interaction and recreational drug use need to be considered in future surveillance.

The epigenetic factors causing competence differences between SN (surrounded nucleolus) and NSN (non-surrounded nucleolus) oocytes, the significance for the increased histone acetylation and methylation in SN oocytes, and whether chromatin configuration or histone modification determines oocyte competence, are unclear. This study has addressed these issues by using the ovary-holding (OH) stress models where oocyte SN configuration was uncoupled from histone modifications and developmental potential. Prepubertal mouse ovaries containing high percentages of NSN oocytes were preserved at 37 or 39 °C for 1 or 2 h before examination for oocyte chromatin configuration, developmental competence, histone modification and apoptosis. Whereas 1-h OH at 37 °C caused a moderate apoptosis with increased oocyte competence, improved histone modification and a normal NSN-to-SN transition, harsher OH conditions induced a severe apoptosis with decreased oocyte competence, impaired histone modification and a pseudo (premature) NSN-to-SN transition. Observations on Fas/FasL expression and using the gld (generalized lymphoproliferative disorder) mice harboring FasL mutations indicated that OH triggered oocyte apoptosis with activation of the Fas signaling. It was concluded that OH stress caused oocyte apoptosis with activation of the Fas/FasL system and that oocyte competence was more closely correlated with histone modification than with chromatin configuration.

The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4-47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.

To systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making. PubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software. A total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96-1.08), = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58-0.76), < 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26-1.40), < 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28-1.80), < 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13-0.62), = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04-0.77), = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9-6.11), < 0.00001]. While NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies. 10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.

Objective: To investigate the application of artificial tiger bone powder on fracture healing time, wrist functional recovery and quality of life (QOL) in elderly patients with distal radius fracture. Methods: The study was a randomised controlled trials performed from January 2015 to December 2016 in a hospital. Elderly patients with distal radius fracture were divided into the treatment and the control groups by the random sealed envelope method. All patients were given splint or plaster fixation after manipulative reduction, and functional exercise, the treatment group was also given artificial tiger bone powder orally (trade name: Jintiange capsule), the control group was given an oral placebo in their appearance and usage identical with the treatment group. Prior to treatment and 6, 12 months after treatment, the wrist function was assessed by range of motion, including flexion-extension, radial-ulnar and pronation-supination, and the QOL was assessed by the Mos 36-item Short Form Health Survey. Each patient's fracture healing time was recorded. Results: Before treatment, there were no significant differences in wrist function and QOL between the two groups. At 6 and 12 months after treatment, the wrist function and QOL in the treatment group were better than those in the control group, the differences were statistically significant (P< 0.05). The fracture healing time in the treatment group was shorter than that of the control group, and the difference was statistically significant (P< 0.05). Conclusion: The early usage of artificial tiger bone powder for elderly patients with distal radius fracture can promote the healing of fracture, recovery of wrist joint function, and ultimately improve the QOL for elderly patients.

BACKGROUND:Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa.This study aimed to investigate the effects of periplaneta americana extract on immune function,nutrition status and gastrointestinal complications of early enteral nutrition patients with systemic inflammatory response syndrome(SIRS).METHODS:Patients with SIRS were randomly divided into two groups:treatment and control groups.All patients in the two groups received conventional therapy including enteral nutrition,but periplaneta americana extract,an additional Chinese medicine,was given to the patients in the treatment group.At the beginning of treatment(0 day)and 1,3,and 7 days after treatment,the levels of immunoglobulin(Ig A),total lymphocyte count(TLC),total protein(TP)and prealbumin(PA)were respectively tested in patients’venous blood.The incidences of bloating,diarrhea,aspiration pneumonia and high blood sugar at 7 days after treatment were recorded.The mortality of the patients in 28 days was recorded.RESULTS:At 3 and 7 days after treatment,the levels of Ig A and TLC in the treatment group were higher than those in the control group(P<0.05).At 7 days after treatment,the levels of TP and PA in the treatment group were higher than those in the control group(P<0.05).The incidences of bloating and diarrhea in the treatment group were lower than those in the control group,the differences were significant(P<0.05).The mortality of treatment group was lower than that of the control group(P>0.05).CONCLUSION:Periplaneta americana extract could reduce gastrointestinal complications and improve immune function and nutritional status in patients with systemic inflammatory response syndrome.

The mechanisms for the transition from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) chromatin configuration during oocyte growth/maturation are unclear. By manipulating enzyme activities and measuring important molecules using small-follicle pig oocytes with a high proportion of NSN configuration and an extended germinal vesicle stage in vitro , this study has the first time up-to-date established the essential role for intra-oocyte mitogen-activated protein kinase (MAPK) in the NSN-to-SN transition. Within the oocyte in 1–2 mm follicles, a cAMP decline activates MAPK, which prevents the NSN-to-SN transition by activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while inhibiting histone deacetylase (HDAC). In cumulus cells of 1–2 mm follicles, a lower level of estradiol and oocyte-derived paracrine factor (ODPF) reduces natriuretic peptide receptor 2 (NPR2) while enhancing FSH and cAMP actions. FSH elevates cAMP levels, which decreases NPR2 while activating MAPK. MAPK closes the gap junctions, which, together with the NPR2 decrease, reduces cyclic guanosine monophosphate (cGMP) delivery leading to the cAMP decline within oocytes. In 3–6 mm follicles, a higher level of estradiol and ODPF and a FSH shortage initiate a reversion of the above events leading to MAPK inactivation and NSN-to-SN transition within oocytes.