The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time.

Within-host HIV populations continually diversify during untreated infection, and this diversity persists within infected cell reservoirs during antiretroviral therapy (ART). Achieving a better understanding of on-ART proviral evolutionary dynamics, and a better appreciation of how the overall persisting pool of (largely genetically defective) proviruses differs from the much smaller replication-competent HIV reservoir, is critical to HIV cure efforts. We reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study who experienced HIV seroconversion, and used these data to characterize the diversity, lineage origins, and ages of proviral env-gp120 sequences sampled longitudinally up to 12 years on ART. We also studied HIV sequences emerging from the reservoir in two participants. We observed that proviral clonality generally increased over time on ART, with clones frequently persisting long term. While on-ART proviral integration dates generally spanned the duration of untreated infection, HIV emerging in plasma was exclusively younger (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained stable during ART in all but one participant, in whom there was evidence that younger proviruses had been preferentially eliminated after 12 years on ART. Analysis of the gag region in three participants corroborated our env-gp120-based observations, indicating that our observations are not influenced by the HIV region studied. Our results underscore the remarkable genetic stability of the distinct proviral sequences that persist in blood during ART. Our results also suggest that the replication-competent HIV reservoir is a genetically restricted, younger subset of this overall proviral pool.IMPORTANCECharacterizing the genetically diverse HIV sequences that persist in the reservoir despite antiretroviral therapy (ART) is critical to cure efforts. Our observations confirm that proviruses persisting in blood on ART, which are largely genetically defective, broadly reflect the extent of within-host HIV evolution pre-ART. Moreover, on-ART clonal expansion is not appreciably accompanied by the loss of distinct proviral lineages. In fact, on-ART proviral genetic composition remained stable in all but one participant, in whom, after 12 years on ART, proviruses dating to around near ART initiation had been preferentially eliminated. We also identified recombinant proviruses between parental sequence fragments of different ages. Though rare, such sequences suggest that reservoir cells can be superinfected with HIV from another infection era. Overall, our finding that the replication-competent reservoir in blood is a genetically restricted, younger subset of all persisting proviruses suggests that HIV cure strategies will need to eliminate a reservoir that differs in key respects from the overall proviral pool.

[Clinical therapy of Zisheng decoction recipe for chronic atrophic gastritis with intestinal metaplasia].

To explore the therapeutic effect and security of Zisheng decoction recipein treatment of the chronic atrophic gastritis (CAG) with intestinal metaplasia(IM). A total of 147 eligible cases were randomly divided into the traditional Chinese medicine group, Western medicine group and the combined group,47 cases in each group. Zisheng decoction recipe, famotidine, as well as Zisheng decoction recipe + famotidine were respectively given in the above three groups, with a treatment course of 30 d. The symptoms of traditional Chinese medicine, pathological score of gastric mucosa and the negative rate of Helicobacter pylori before and after treatment were observed in each group.The changes in pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (GAS-17) and endothelin-1 (ET-1)were also detected to compare the efficient and safety indexes in the three groups. The combined group was better than the traditional Chinese medicine groupand the Western medicine group in total effective rate (P<0.05), pathological score of gastric mucosa and the negative rate of Helicobacter pylori, and serum indexes improvement (P<0.05). The improvement in TCM symptom score was more obvious in traditional Chinese medicine group and combined group than the Western medicine group (P<0.05). In the comparison ofincidence of complications,heart, liver and renal dysfunction, the traditional Chinese medicine group (2 case,4.8%)< the combined group (7 case,15.2%)

Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time.

Within-host HIV populations continually diversify during untreated infection, and members of these diverse forms persist within infected cell reservoirs, even during antiretroviral therapy (ART). Characterizing the diverse viral sequences that persist during ART is critical to HIV cure efforts, but our knowledge of on-ART proviral evolutionary dynamics remains incomplete, as does our understanding of the differences between the overall pool of persisting proviral DNA (which is largely genetically defective) and the subset of intact HIV sequences capable of reactivating. Here, we reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study (WIHS) who experienced HIV seroconversion. We measured diversity, lineage origins and ages of proviral sequences (env-gp120) sampled up to four times, up to 12 years on ART. We used the same techniques to study HIV sequences emerging from the reservoir in two participants. Proviral clonality generally increased over time on ART, with clones frequently persisting across multiple time points. The integration dates of proviruses persisting on ART generally spanned the duration of untreated infection (though were often skewed towards years immediately pre-ART), while in contrast, reservoir-origin viremia emerging in plasma was exclusively "younger" (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained highly stable during ART in all but one participant in whom, after 12 years, there was evidence that "younger" proviruses had been preferentially eliminated. Analysis of within-host recombinant proviral sequences also suggested that HIV reservoirs can be superinfected with virus reactivated from an older era, yielding infectious viral progeny with mosaic genomes of sequences with different ages. Overall, results underscore the remarkable genetic stability of distinct proviral sequences that persist on ART, yet suggest that replication-competent HIV reservoir represents a genetically-restricted and overall "younger" subset of the overall persisting proviral pool in blood.

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.

Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods: The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches. Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment. Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

[Quantitative analysis of the concentration of Br-doping in micro-shell coating with XRF].

In inertial confinement fusion (ICF) physics experiment, the micro-shell that contains Br-doped CH coating must be characterized for doping Br concentration level. X-ray fluorescence (XRF), with its unique capability to quantitatively determine concentrations of most elements simultaneously and non-destructively, is generally the method of choice for total dopant (Z > 11) concentration. In the present paper, a method to determine the dopant concentration in ICF micro-shell coating with X-ray fluorescence spectrometry is described, and the calibration model is founded by the calculation of fluorescence intensity of film and micro-shell sample. Based on the calibration model, the fluorescence intensity vs concentration of Br-doped CH coating of micro-shell was obtained. The experiment result shows that X-ray fluorescence spectrometry is a nondestructive and accurate method of measurement of coating dopant in the inertial confinement fusion micro-shell sample, and the measuring error is about 5% for Br doped CH coating of micro-shells with 10 micron thickness coating.

Challenges with accessing health care for young children presumed to have malaria in the rural district of Butaleja, Uganda: a qualitative study.

OBJECTIVE: A qualitative study was conducted to gain insight into challenges reported by Butaleja households during a previous household survey. Specifically, this paper discusses heads of households' and caregivers' perceptions of challenges they face when seeking care for their very young children with fever presumed to be malaria. METHODS: Eleven focus groups (FGs) were carried out with household members (five with heads of households and six with household caregivers) residing in five sub-counties located across the district. Purposive sampling was used to ensure the sample represented the religious diversity and geographical distance from the peri-urban center of the district. Each FG consisted of five to six participants. The FGs were conducted at a community centre by two pairs of researchers residing in the district and who were fluent in both English and the local dialect of Lunyole. The discussions were recorded, translated, and transcribed. Transcripts were reviewed and coded with the assistance of QDA Miner (version 4.0) qualitative data management software, and analyzed using thematic content analysis. RESULTS: The FG discussions identified four major areas of challenges when managing acute febrile illness in their child under the age of five with presumed malaria (1) difficulties with getting to public health facilities due to long geographical distances and lack of affordable transportation; (2) poor service once at a public health facility, including denial of care, delay in treatment, and negative experiences with the staff; (3) difficulties with managing the child's illness at home, including challenges with keeping home-stock medicines and administering medicines as prescribed; and (4) constrained to use private outlets despite their shortcomings. CONCLUSIONS: Future interventions may need to look beyond the public health system to improve case management of childhood malaria at the community level in rural districts such as Butaleja. Given the difficulties with accessing quality private health outlets, there is a need to partner with the private sector to explore feasible models of community-based health insurance programs and expand the role of informal private providers.

N'-(2-Hydroxy-benzyl-idene)-2-methoxy-benzohydrazide monohydrate.

In the title compound, C(15)H(14)N(2)O(3)·H(2)O, the Schiff base mol-ecule is approximately planar, with a dihedral angle between the two aromatic rings of 10.2 (3)°. The mol-ecular structure is stabilized by O-H⋯N and N-H⋯O hydrogen bonds. In the crystal structure, the Schiff base and water mol-ecules are linked together by inter-molecular O-H⋯O hydrogen bonds, forming chains parallel to the a axis.

4-Chloro-N'-(2-hydroxy-benzyl-idene)benzohydrazide monohydrate.

The asymmetric unit of the title compound, C(14)H(11)ClN(2)O(2)·H(2)O, contains a Schiff base mol-ecule and a water mol-ecule of crystallization. The dihedral angle between the two aromatic rings is 27.3 (4)°. In the crystal structure, mol-ecules are linked into a two-dimensional network parallel to the bc plane by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds involving the water mol-ecules.

2-Meth-oxy-N'-(2-methoxy-benzyl-idene)benzohydrazide.

The title Schiff base compound, C(16)H(16)N(2)O(3), was derived from the condensation of 2-methoxy-benzaldehyde with 2-methoxy-benzohydrazide in an ethanol solution. The dihedral angle between the two aromatic rings is 87.5 (3)°. In the crystal structure, the mol-ecules are linked into chains running parallel to the a axis by inter-molecular N-H⋯O hydrogen bonds.

Challenges with accessing health care for young children presumed to have malaria in the rural district of Butaleja, Uganda: a qualitative study

OBJECTIVE: A qualitative study was conducted to gain insight into challenges reported by Butaleja households during a previous household survey. Specifically, this paper discusses heads of households' and caregivers' perceptions of challenges they face when seeking care for their very young children with fever presumed to be malaria. METHODS: Eleven focus groups (FGs) were carried out with household members (five with heads of households and six with household caregivers) residing in five sub-counties located across the district. Purposive sampling was used to ensure the sample represented the religious diversity and geographical distance from the peri-urban center of the district. Each FG consisted of five to six participants. The FGs were conducted at a community centre by two pairs of researchers residing in the district and who were fluent in both English and the local dialect of Lunyole. The discussions were recorded, translated, and transcribed. Transcripts were reviewed and coded with the assistance of QDA Miner (version 4.0) qualitative data management software, and analyzed using thematic content analysis. RESULTS: The FG discussions identified four major areas of challenges when managing acute febrile illness in their child under the age of five with presumed malaria: (1) difficulties with getting to public health facilities due to long geographical distances and lack of affordable transportation; (2) poor service once at a public health facility, including denial of care, delay in treatment, and negative experiences with the staff; (3) difficulties with managing the child's illness at home, including challenges with keeping home-stock medicines and administering medicines as prescribed; and (4) constrained to use private outlets despite their shortcomings. CONCLUSIONS: Future interventions may need to look beyond the public health system to improve case management of childhood malaria at the community level in rural districts such as Butaleja. Given the difficulties with accessing quality private health outlets, there is a need to partner with the private sector to explore feasible models of community-based health insurance programs and expand the role of informal private providers

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Sulforaphane inhibits the proliferation of the BIU87 bladder cancer cell line via IGFBP-3 elevation.

AIM: To investigate effects of sulforaphane on the BIU87 cell line and underlying mechanisms involving IGFBP-3. METHODS: Both BIU87 and IGFBP-3-silenced BIU87 cells were treated with sulforaphane. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were determined via flow cytometry. Quantitative polymerase chain reaction and Western blotting were applied to analyze the expression of IGFBP-3 and NF-κB at both mRNA and protein levels. RESULTS: Sulforaphane (80 µM) treatment could inhibit cell proliferation, inducing apoptosis and cell cycle arrest at G2/M phase. All these effects could be antagonized by IGFBP-3 silencing. Furthermore, sulforaphane (80 µM) could down-regulate NF-κB expression while elevating that of IGFBP-3. CONCLUSIONS: Sulforaphane could suppress the proliferation of BIU87 cells via enhancing IGFBP-3 expression, which negatively regulating the NF-κB signaling pathway.

Expression and underlying roles of IGFBP-3 in paclitaxel-treated gastric cancer SGC-7901 cells.

PURPOSE: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. MATERIALS AND METHODS: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. RESULTS: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment (p<0.05). Paclitaxel treatment caused cell cycle arrest and apoptosis via downregulating Bcl-2 expression. However, the effect could be abrogated by IGFBP-3 silencing. CONCLUSIONS: IGFBP-3 exhibits anti-apoptotic effects on paclitaxel-treated SGC-7901 cells via elevating Bcl-2 expression.