BACKGROUND: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. OBJECTIVES: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. METHOD: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring RESULTS: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. CONCLUSION: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

SUMMARY: The objective of this study was to evaluate the maxillary molar root canal morphology in individuals from the Shandong province, China, using cone-beam computed tomography (CBCT) and classify it based on Ahmed et al. (2017) classification system to obtain a reference for clinical diagnosis and treatment. From December 2020 to June 2021, we screened CBCT data of 1,619 patients at the Jinan Stomatological Hospital who had been indicated for CBCT because of various oral abnormalities. The root and root canal morphologies of all teeth were statistically analyzed, and the root canal morphology was classified based on Ahmed et al. (2017) classification system. In the maxillary molars, three roots were the most common, accounting for 99.24 % and 74.61 % of all maxillary first and second molars, respectively. Two roots were the second most common, accounting for 0.66 % and 17.29 % of all maxillary first and second molars, respectively. Root morphology variation, e.g., fusion or furcation defect, was present in 22 (0.76 %) maxillary first molars and 765 (25.39 %) maxillary second molars, with the most common being mesiobuccal and distobuccal root fusion. Detection rates of a second mesiobuccal canal (MB2) in the maxillary first and second molars were 48.5 % and 26.5 %, respectively. Among age groups, the frequency of MB2 was the highest in the 15-24-year-old group and lowest in the 55-64-year-old group. Bilateral MB2 root canals were present in 64.8 % and 48.4 % of the maxillary first and second molars, respectively. Men and women accounted for 60.6 % and 67.8 % of the maxillary first molars, respectively, and 51.7 % and 45.6 % of the maxillary second molars, respectively. According to Ahmed et al. (2017) classification of root canal morphology, 18 and 22 root canal configurations were found in 1,453 right maxillary first molars and 1,444 left maxillary first molars, respectively. The right maxillary first molars showed three two-rooted, 14 three-rooted, and one four-rooted type. The left maxillary first molars showed two one-rooted, six two-rooted, and 14 three-rooted types. According to Ahmed et al. (2017) classification of root canal morphology, 43 and 45 root canal configurations were found in 1,507 right maxillary second molars and 1,506 left maxillary second molars, respectively. The right maxillary second molars showed 17 one-rooted, 16 two- rooted, eight three-rooted, and two four-rooted types. The left maxillary second molars showed 19 one-rooted, 13 two-rooted, 12 three- rooted, and one four-rooted type. This study showed that the maxillary molar root canal morphology is diverse in the Shandong province. Ahmed et al. (2017) classification system provides a clear description of the root canal morphology. CBCT can be used to study complex root and root canal morphologies.

RESUMEN: El objetivo de este estudio fue evaluar la morfología del conducto radicular del molar superior en individuos de la provincia de Shandong, China, utilizando tomografía computarizada de haz cónico (CBCT) y clasificarla con base en el sistema de clasificación de Ahmed et al. (2017) para obtener una referencia para diagnóstico clínico y tratamiento. Desde diciembre de 2020 hasta junio de 2021, analizamos los datos de CBCT de 1619 pacientes en el Hospital Estomatológico de Jinan a quienes se les indicó CBCT debido a diversas anomalías orales. Las morfologías de la raíz y del conducto radicular de todos los dientes se analizaron estadísticamente, y la morfología del conducto radicular se clasificó según el sistema de clasificación de Ahmed et al. (2017). En los molares superiores, tres raíces fueron las más comunes, representando el 99,24 % y el 74,61 % de todos los primeros y segundos molares superiores, respectivamente. Dos raíces fueron las segundas más comunes, representando el 0,66 % y el 17,29 % de todos los primeros y segundos molares superiores, respectivamente. La variación de la morfología de la raíz, por ejemplo, fusión o defecto de furcación, estuvo presente en 22 (0,76 %) primeros molares superiores y 765 (25,39 %) segundos molares superiores, siendo la fusión radicular mesiovestibular y distovestibular la más común. Las tasas de detección de un segundo canal mesiovestibular (MB2) en los primeros y segundos molares superiores fueron del 48,5 % y 26,5 %, respectivamente. Entre los grupos de edad, la frecuencia de MB2 fue más alta en el grupo de 15 a 24 años y más baja en el grupo de 55 a 64 años. Los conductos radiculares MB2 bilaterales estaban presentes en el 64,8 % y el 48,4 % de los primeros y segundos molares superiores, respectivamente. En los hombres y en las mujeres representaron el 60,6 % y el 67,8 % de los primeros molares superiores, respectivamente, y el 51,7 % y el 45,6 % de los segundos molares superiores, respec- tivamente. Según la clasificación de la morfología del conducto radicular de Ahmed et al. (2017) se encontraron configuraciones de conducto radicular 18 y 22 en 1453 primeros molares superiores derechos y 1444 primeros molares superiores izquierdos, respectivamente. Los primeros molares superiores derechos mostraron tres tipos de dos raíces, 14 de tres raíces y uno de cuatro raíces. Los primeros molares superiores izquierdos mostraron dos tipos de una raíz, seis de dos raíces y 14 de tres raíces. Según la clasificación de la morfología del conducto radicular de Ahmed et al. (2017) se encontraron configuraciones de conducto radicular 43 y 45 en 1507 segundos molares superiores derechos y 1506 segundos molares superiores izquierdos, respectivamente. Los segundos molares superiores derechos mostraron 17 tipos de una raíz, 16 de dos raíces, ocho de tres raíces y dos de cuatro raíces. Los segundos molares superiores izquierdos mostraron 19 de una raíz, 13 de dos raíces, 12 de tres raíces y uno de cuatro raíces. Este estudio mostró que la morfología del conducto radicular del molar superior es diversa en la provincia de Shandong. El sistema de clasificación de Ahmed y colaboradores proporciona una descripción clara de la morfología del conducto radicular. CBCT se puede utilizar para estudiar morfologías complejas de raíces y conductos radiculares.

Abstract Background The prognostic significance of nutrition indicators in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. Objectives This systematic review and meta-analysis aimed to assess the prognostic value of serum albumin (SA), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) in patients with HFpEF. Methods Databases of PubMed, Embase, The Cochrane Library, and Web of Science were systematically searched for all studies published up to January 2022. The prognostic significance of SA, GNRI, and PNI for HFpEF was explored. Pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the STATA 15.0 software. The Quality of Prognosis Studies tool was used to assess the quality of studies. Results Nine studies met the inclusion criteria, and 5603 adults with HFpEF were included in the meta-analysis. The analyses showed that a decreased SA or GNRI was significantly related to high all-cause mortality (HR: 1.98; 95% CI: 1.282–3.057; p = 0.002; and HR: 1.812;95% CI: 1.064–3.086; p = 0.029, respectively). Furthermore, a lower SA indicates a bad composite outcome of all-cause mortality and HF rehospitalization (HR: 1.768; 95% CI: 1.483–2.108; p = 0.000), and a lower GNRI was significantly associated with high cardiovascular mortality (HR: 1.922; 95% CI: 1.504–2.457;p = 0.000). However, a lower PNI did not correlate with all-cause mortality (HR: 1.176; 95% CI: 0.858–1.612, p=0.314). Conclusions Our meta-analysis indicates that SA and GNRI may be useful indicators to predict the prognosis of patients with HFpEF.

Resumo Fundamento O significado prognóstico dos indicadores nutricionais em pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP) não é claro. Objetivo Esta revisão sistemática e metanálise teve como objetivo avaliar o valor prognóstico da albumina sérica (AS), o índice de risco nutricional geriátrico (IRNG) e o índice nutricional prognóstico (INP) em pacientes com ICFEP. Método Os bancos de dados PubMed, Embase, The Cochrane Library e Web of Science foram sistematicamente pesquisados para todos os estudos publicados até janeiro de 2022. O significado prognóstico de IRNG, GNRI e INP para ICFEP foi explorado. A taxa de risco agrupada (HR) e o intervalo de confiança (IC) de 95% foram estimados usando o software STATA 15.0. A Ferramenta de Estudos de Qualidade de Prognóstico foi usada para avaliar a qualidade dos estudos. Resultados Nove estudos preencheram os critérios de inclusão e 5.603 adultos com ICFEP foram incluídos na metanálise. As análises mostraram que uma diminuição de AS ou IRNG estava significativamente relacionada à alta mortalidade por todas as causas (HR: 1,98; 95% IC: 1,282–3,057; p = 0,002; e HR: 1,812;95% IC: 1,064–3,086; p = 0,029, respectivamente). Além disso, uma AS mais baixa indica um resultado composto ruim de mortalidade por todas as causas e reinternação por IC (HR: 1,768; IC 95%: 1,483–2,108; p = 0,000), e um IRNG mais baixo foi significativamente associado a alta mortalidade cardiovascular (HR: 1,922; 95% IC: 1,504–2,457; p = 0,000). No entanto, um INP mais baixo não se correlacionou com mortalidade por todas as causas (HR: 1,176; IC 95%: 0,858–1,612, p=0,314). Conclusões Nossa metanálise indica que AS e IRNG podem ser indicadores úteis para prever o prognóstico de pacientes com ICFEP.

Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge–beliefs–behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Abstract To select the optimal condition of 1064 nm Q-switched Nd:YAG laser irradiation and study the molecular mechanism of laser irradiation for skin rejuvenation. Sixty male, 6-week-old SKH-1 hairless mice were equally divided into 6 groups: 3d, 7d, 21d, 28d, 42d and 56d of 1064 nm laser irradiation at both 0 J/cm2 (left region) and 1.5 J/cm2 (right region) fluence. The basic skin performances were analysed via quantifying hydroxyproline content and skin hydration in the dermis and epidermis. The Collagen I, MMP2 and TIMP1, as well as ERK 1/2, p38MAPK, JNK and ERK5 signaling pathways levels were detected by qRT-PCR. Laser irradiation led to a marked increase in hydroxyproline content and skin hydration in the dermis and epidermis compared to the non-irradiated area. After laser irradiation, collagen I was markedly up-regulated, MMP2 was significantly decreased and TIMP1 was unchanged. Moreover, qRT-PCR results revealed ERK 1/2 and p38MAPK signaling pathways were activated after laser irradiation. we are firstly proves that 1064 nm laser irradiation can inhibit collagen degradation by stimulating the activation of ERK1/2 and p38MAPK signaling pathways. Additionally, the condition of laser irradiation lasting 21d at fluence of 1.5 J/cm2 displays the best effect of skin rejuvenation in our study.

Abstract Green bactericides are excellent strategies for reducing food spoilage. Phloretin was regarded as efficient, broad-spectrum and safe preservative, which showed enormous potential in food industry. Inhibitory mechanism of phloretin on Listeria monocytogenes was systematically elucidated through integrity of cell membrane, intracellular protein content, energy level, and nucleic acid morphological character. SEM and TEM results showed minimal injury of cell membrane, which was further proved by a leakage of potassium ions, ATP and little protein and nucleic acid. There were drastic reduction of intracellular or total protein and ATP compared to cell without phloretin treatment. However, the specific activity of hexokinase and isocitrate dehydrogenase were unaffected after phloretin treatment. From these results, we concluded that phloretin’s bacteriostatic mechanism is decreasing the intracellular protein content and energy level resulting from DNA aggregation. This finding was prospective to fully illustrate the phloretin’s mechanism and develop it into a natural preservative in food industry.

ABSTRACT Target of rapamycin (TOR) is a very critical protein in plants, which connects with biological process, glycometabolism, life span, and photosynthesis. Here, the evolutionary relationship, conserved motif, gene structure and cis-acting elements of TOR were analyzed. Promoter cis-acting elements analysis indicated various cis-acting elements respond to light, auxin, ABA and multiple signal pathway. Transcriptome sequencing and the co-expression network of VvTOR, sugar and abscisic acid (ABA) related genes from Vitis vinifera L. Cabernet Sauvignon berries indicated that VvTOR might participate in sugar and ABA signaling. The expression of VvTOR in grape suspension cells analyzed by quantitative real-time PCR showed that VvTOR responded to ABA and glucose treatment. These results predicted the potential functions of VvTOR in glucose metabolism and ABA signal pathway.

Abstract Enteromorpha prolifera polysaccharide (EP) is a water-soluble sulfated polysaccharide with many types of biological activities. In this study, the crude polysaccharide was extracted from Enteromorpha prolifera and degraded by different physical, chemical, and biological methods. The results showed that the enzymatic degradation products displayed the best tyrosinase inhibitory activity. The optimal enzymatic degradation conditions were as follows: 30 °C, pH 5.5, 750 U/mL enzyme dosage for 2 h. The enzymatic hydrolysates were then divided into six EP fractions (EPFs) by an ultrafiltration membrane. The in vitro tyrosinase inhibitory activity of these fractions showed that the smaller the molecular weight of EPF, the better the inhibitory effect on tyrosinase. The antioxidant and tyrosinase inhibitory effect of the most effective EPF, a molecular weight below 5 kDa, (EPF5), was further confirmed on B16 cells. A kinetic study of tyrosinase inhibitory activity revealed that EPF5 is a competitive-uncompetitive mixed-type inhibitor of tyrosinase. These findings suggested that EPF5 has significant potential as a skin-whitening agent in cosmetics as well as an antibrowning agent in the food and agriculture industries.

Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4’-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4+ T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4+ T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.

Abstract MYB is a large family of plant transcription factors. Its function has been identified in several plants, while there are few reports in Medicago truncatula. In this study, we used RNA-seq data to analyze and identify R2R3-MYB genes in the genome of Medicago truncatula. Phylogenetic analysis classified 150 MtMYB genes into 21 subfamilies with homologs. Out of the 150 MtMYB genes, 139 were distributed among 8 chromosomes, with tandem duplications (TD) and segment duplications (SD). Microarray data were used for functional analysis of the MtMYB genes during growth and developmental processes providing evidence for a role in tissues differentiation, seed development processes, and especially the nodulation process. Furthermore, we investigated the expression of MtMYB genes in response to abiotic stresses using RNA-seq data, which confirmed the critical roles in signal transduction and regulation processes under abiotic stress. We used quantitative real-time PCR (qRT-PCR) to validate expression profiles. The expression pattern of M. truncatula MYB genes under different abiotic stress conditions suggest that some may play a major role in cross-talk among different signal transduction pathways in response to abiotic stresses. Our study will serve as a foundation for future research into the molecular function of M. truncatula R2R3-MYB genes.

In order to achieve hot processing products with expected microstructures, the construction of corresponding relationships between micro-evolution mechanisms and hot processing parameters is essential. In this study, such corresponding relationships of as-cast AlCu4SiMg alloy were constructed by double evaluating processing maps and Zener-Holloman (Z) parameter maps. Based on the stress-strain data obtained from a series of isothermal compression experiments, the processing maps of AlCu4SiMg alloy were constructed at the strain of 0.3, 0.5, 0.7 and 0.9 s-1. The processing maps revealed that the optimal hot deformation parameter windows corresponding to dynamic recrystallization (DRX) micro-evolution mechanism mainly appear at high temperature and moderate strain rate. On the other hand, the response maps of Z parameter at discrete strains were constructed, and the ideal processing windows were calibrated at the domains with relatively low lnZ-value. A phenomenon was found that the optimal deformation parameter windows identified by Z parameter are more conservative than those identified by processing map. By integrating processing maps and Z parameter maps, the optimal processing parameter windows corresponding to DRX micro-evolution mechanism for AlCu4SiMg alloy were finally obtained.