Deficiency Syndrome Research Articles

EF yolov8s: A Human–Computer Collaborative Sugarcane Disease Detection Model in Complex Environment

The precise identification of disease traits in the complex sugarcane planting environment not only effectively prevents the spread and outbreak of common diseases but also allows for the real-time monitoring of nutrient deficiency syndrome at the top of sugarcane, facilitating the supplementation of relevant nutrients to ensure sugarcane quality and yield. This paper proposes a human–machine collaborative sugarcane disease detection method in complex environments. Initially, data on five common sugarcane diseases—brown stripe, rust, ring spot, brown spot, and red rot—as well as two nutrient deficiency conditions—sulfur deficiency and phosphorus deficiency—were collected, totaling 11,364 images and 10 high-definition videos captured by a 4K drone. The data sets were augmented threefold using techniques such as flipping and gamma adjustment to construct a disease data set. Building upon the YOLOv8 framework, the EMA attention mechanism and Focal loss function were added to optimize the model, addressing the complex backgrounds and imbalanced positive and negative samples present in the sugarcane data set. Disease detection models EF-yolov8s, EF-yolov8m, EF-yolov8n, EF-yolov7, and EF-yolov5n were constructed and compared. Subsequently, five basic instance segmentation models of YOLOv8 were used for comparative analysis, validated using nutrient deficiency condition videos, and a human–machine integrated detection model for nutrient deficiency symptoms at the top of sugarcane was constructed. The experimental results demonstrate that our improved EF-yolov8s model outperforms other models, achieving mAP_0.5, precision, recall, and F1 scores of 89.70%, 88.70%, 86.00%, and 88.00%, respectively, highlighting the effectiveness of EF-yolov8s for sugarcane disease detection. Additionally, yolov8s-seg achieves an average precision of 80.30% with a smaller number of parameters, outperforming other models by 5.2%, 1.9%, 2.02%, and 0.92% in terms of mAP_0.5, respectively, effectively detecting nutrient deficiency symptoms and addressing the challenges of sugarcane growth monitoring and disease detection in complex environments using computer vision technology.

Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features

BackgroundOculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders.ObjectivesTo determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders.Patients and methodsDue to the new emerging symptoms that weren’t reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses.ResultsExtensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM_000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM_015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested.ConclusionsThis study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide.

Efficacy and safety of refined nursing combined with Zhao's Thunder-Fire Moxibustion in treating patients with gastric cancer of Spleen-Qi Deficiency Syndrome: A clinical study.

To investigate the efficacy and safety of refined nursing combined with Zhao's thunder-fire moxibustion in treating patients with gastric cancer (GC) of spleen-Qi deficiency syndrome. This was a retrospective study. Ninety patients with GC of spleen-Qi deficiency syndrome admitted to Baoding Hospital of Traditional Chinese Medicine from February 2022 to March 2023 were randomly divided into the observation group and the control group. Patients in the control group were intervened with XELOX chemotherapeutic regimen + routine nursing. On this basis, patients in the observation group were additionally treated with refined nursing combined with Zhao's thunder-fire moxibustion. Changes in Traditional Chinese Medicine (TCM) syndrome scores, KPS scores for physical status, and quality of life (QOL) scores were observed and compared between the two groups before and after treatment. After treatment, the scores of anorexia, fatigue and weakness, postprandial abdominal bloating, loose stools, mental fatigue and laziness to speak decreased significantly in the two groups (P< 0.05), and each TCM syndrome score in the observation group was significantly lower than that in the control group (P< 0.05). After treatment, KPS and QOL scores in the observation group were significantly higher than those in the control group (P< 0.05). The overall nursing satisfaction was 93.3% (42/45) in the observation group, which was significantly higher than 71.1% (32/45) in the control group (P< 0.05). Refined nursing combined with Zhao's thunder-fire moxibustion can alleviate the clinical symptoms of patients with GC of spleen-Qi deficiency syndrome, reduce chemotherapeutic-induced adverse reactions, with high clinical application value.

Exploring the lived experiences of women living with HIV in rural Zimbabwe: A qualitative study.

The study of human immunodeficiency virus (HIV)-related stigma and discrimination has been burgeoning with important implications for public health and society, as it negatively impacts people living with HIV. However, data on the experiences of rural women living with HIV/Acquired Immune Deficiency Syndrome (AIDS) in Zimbabwe are lacking. Women represent 50% of the global pandemic, while deaths from AIDS-related illnesses have exceeded 35 million. This study aimed to explore the experiences of rural women living with HIV/AIDS in Zimbabwe. Forty rural women living with HIV were selected from 6 villages (one village per district) of Matabeleland South Province in Zimbabwe. A qualitative descriptive research design using in-depth individual interviews from 22 purposefully selected rural women living with HIV and 3 focus groups, was used to collect the study data. The transcripts of the interviews were analyzed using interpretative phenomenological analysis. Three interconnected themes were identified: social prejudice, social discrimination, and psychosocial dysfunction. A key finding in the themes was that women living with HIV in rural Zimbabwe were psychosocially dysfunctional because of social prejudice and discrimination perpetrated against them by significant others in their communities. The findings provide a valuable understanding of women's experiences of living with HIV and AIDS in Africa's low-income countries. These results can be used by researchers, clinicians, mental health providers, and policymakers to address the unique needs of rural women living with HIV/AIDS.

Disease burden of AIDS in last 30-year period and its predicted level in next 25-years based on the global burden disease 2019

BackgroundThis study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years.MethodsComprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model.ResultsFrom 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender.ConclusionsThe global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

Characterization of the gut butyrate-producing bacteria and lipid metabolism in African green monkey as a natural host of simian immunodeficiency virus infection.

Natural hosts of simian immunodeficiency virus (SIV), such as the African green monkey (AGM), possess the ability to avoid acquired immune deficiency syndrome (AIDS) despite lifelong infection. The underlying mechanisms are not completely understood. This study aimed to characterize the gut microbiome and metabolite profiles of different nonhuman primates (NHPs) to provide potential insight into AIDS resistance. Fresh feces from Cynomolgus macaques (CMs), and Rhesus macaques (RMs), SIV- AGMs (AGM_N), and SIV+ AGMs (AGM_P) were collected and used for metagenomic sequencing and metabonomic analysis. Compared with CMs and RMs, significant decreases in the abundances of Streptococcus , Alistipes , Treponema , Bacteroides , and Methanobrevibacter ( P < 0.01), and significant increases in the abundances of Clostridium , Eubacterium , Blautia , Roseburia , Faecalibacterium , and Dialister ( P < 0.01) were detected in AGM_N. Compared with AGM_N, a trend toward increased abundances of Streptococcus and Roseburia were found in AGM_P. The levels of metabolites involved in lipid metabolism and butanoate metabolism significantly differed among AGM_P, AGM_N and CM ( P < 0.05). Our data, for the first time, demonstrated distinguishing features in the abundances of butyrate-producing bacteria and lipid metabolism capacities between different NHP hosts of SIV infection. These findings may correlate with the different characteristics observed among these hosts in the maintenance of intestinal epithelial barrier integrity, regulation of inflammation, and provide insights into AIDS resistance in AGMs.

Top stories on calcium release deficiency syndrome

Top stories on calcium release deficiency syndrome

Increasing Knowledge through Counseling Activities of HIV/AIDS at Yakbado SMTK Dogiyai District

Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is a health problem in the world, including Indonesia. The number of HIV/AIDS cases continues to increase from year to year. HIV/AIDS is a deadly disease for which no cure has been found needed innovation to cure HIV/AIDS sufferers. Therefore, it is necessary to carry out counseling to prevent an increase in HIV/AIDS sufferers in public. Counseling activities about HIV/AIDS were carried out on August 25 2023 at SMTK Yakbado, Dogiyai Regency, using counseling and questionnaires in the form of Pre-Test and Post Test tested statistically. The results of statistical tests show that there was an increase in knowledge before and after counseling about HIV/AIDS from the results (pretest 6.30% and posttest 7,88%) from 28 Students with 10 questions.

Moxibustion versus non-moxibustion for immune reconstitution inflammatory syndrome in patients with HIV: A 48-week prospective cohort study: 艾灸V.S.非艾灸治疗HIV感染者免疫重建炎性综合征:一项48周的前瞻性队列研究

ObjectiveTo assess the effects of moxibustion on immune reconstitution inflammatory syndrome (IRIS) in patients with acquired immune deficiency syndrome (AIDS) by tracking T-cell subsets over a 48-week prospective cohort study. MethodsPatients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group. The non-moxibustion group received standard western treatment, including 48 weeks of antiretroviral therapy (ART). The moxibustion group received ART combined with moxibusion therapy, administered three times weekly. Each treatment lasted 10 weeks, with four courses completed over 48 weeks, separated by 2-week breaks. At different time points, plasma levels of CD4+, CD8+, CD45RA+, CD45RO+, CD4+CD28+, CD8+CD38+, and CD4+CD38+ were compared between the two groups. ResultsA total of 200 eligible patients were included and divided into two groups, with 100 in the non-moxibustion group and 100 in the moxibustion group. At Week 24, the CD4+T cell count was (180.71 ± 79.62) cells/μL in the non-moxibustion group and (218.22 ± 82.02) cells/μL in the moxibustion group. By Week 36, the counts were (204.83 ± 96.78) cells/μL and (239.35±81.90) cells/μL, respectively. At Weeks 24 and 48, the CD8+ T cell and CD45RO+ counts were higher in the moxibustion group than in the non-moxibustion group (P < 0.05). By Week 48, the CD45RA+ count was also higher in the moxibustion group (P < 0.05). At Week 24, the CD4+CD25+ count was lower in the moxibustion group than in the non-moxibustion group (P < 0.05). ConclusionMoxibustion enhances immune function in patients with AIDS and IRIS by regulating T-HIVcell subsets and increasing CD4+ and CD8+ T lymphocyte counts.

Support provided by outreach team leaders to caregivers of HIV/AIDS orphans in the North-West province of South Africa

BackgroundThe human immunodeficiency virus (HIV) and acquired immunodeficiency deficiency syndrome (AIDS) epidemic have left an overwhelming impact on communities worldwide, particularly in Sub-Saharan Africa, where its effects on family structures are particularly pronounced. Caregivers of HIV/AIDS orphans encounter challenges in fulfilling their caring duties. Consequently, they rely on the outreach team leaders (OTLs) for support to care for HIV/AIDS orphans.AimThis study aimed to explore and describe support provided by OTLs to caregivers of HIV/AIDS orphans in the North West Province of South Africa.MethodsThe exploratory, descriptive, and contextual design meaning the study was conducted was in the contexts where caregivers of HIV/AIDS orphans reside. The study was conducted in five local municipalities in the Ngaka Modiri Molema district of the North West Province of South Africa. Ward-based outreach nurses were participants in the study. Semi-structured focus group interviews were used for data collection. Thematic analysis was used to analyze data. Throughout the study, ethical principles were adhered to. The study also adhered to four trustworthiness principles: credibility, confirmability, transferability, and dependability.ResultsThree main themes emerged from this study: the conduction of home visits to caregivers of HIV/AIDS orphans, the coordination of a multidisciplinary team for support, and the facilitation of support groups.ConclusionsThis study revealed that that caregivers of children orphaned by HIV/AIDS benefitted from the support provided by OTLs in the North West province of South Africa. The support provided by OTLs harnessed positive relationship between caregivers and children orphaned by HIV/AIDS.

Motivation, responsibilities, and experiences of HIV/AIDS counselors in the Volta Region of Ghana: a descriptive phenomenological study

BackgroundThe provision of professional counseling services for persons living with human immunodeficiency virus (PLHIV) is crucial in the prevention and treatment continuum of the disease. However, for counselors of people infected with the human immunodeficiency virus (HIV) leading to acquired immune deficiency syndrome (AIDS) to give their best, their motivations to become counselors and the challenges they face in their line of duty need to be contextually understood and addressed. We ascertained the roles, motivations, and experiences of HIV/AIDS counselors in the Volta Region of Ghana to inform HIV/AIDS counseling decision-making in the region and the country.MethodsA phenomenological study conducted among sixteen (16) HIV/AIDS counselors from five HIV/AIDS sentinel sites in the Volta region of Ghana, recruited through a purposive sampling approach and interviewed to ascertain their HIV/AIDS counseling-related experiences. The data were thematically analyzed using the Atlas. ti software, and sub-themes supported with verbatim quotes.ResultsFive motives for becoming an HIV/AIDS counselor were found. These include being randomly assigned to the unit, developing interest in the job, because of the status of a relative, witnessing bad attitudes of healthcare providers, and seeing HIV- clients lacking knowledge of the condition. The study found that these counselors performed six core roles: providing nutritional counseling, educating clients on HIV, treatment, and medication provision, conducting testing and comprehensive counseling of clients, providing social support to clients, and offering financial support to clients. The experiences these counselors had were boosting clients’ health status, counseling clients back to a normal mental state, cooperation from clients, participants gaining knowledge on HIV through counseling, counseling clients to accept their status, and when a client delivered an HIV-negative baby. Their negative experiences included clients denying their HIV status, clients defaulting on their treatment, uncooperative clients, death of clients due to fear of breach of confidentiality, self-stigmatization among clients, and the myths some people hold towards HIV/AIDS.ConclusionBy organizing capacity-building training programs for HIV/AIDS counselors in the Volta region and addressing the negative experiences they encounter, they could be empowered to provide effective counseling, curative, and social services to people living with HIV in the region, leading to improved health outcomes.

Development of a sports nutrition knowledge questionnaire for elite track and field athletes

Background: Satisfactory nutrition knowledge among athletes is important to encourage proper dietary habits to overcome deficiencies and enhance sports performance. Identifying knowledge gaps in sports nutrition is essential for improving athletes' understanding through a tool that evaluates both general nutrition knowledge (GNK) and sports nutrition knowledge (SNK). This study aims to develop the Athletic Sports Nutrition Knowledge Questionnaire (A-SNKQ) specifically for Sri Lankan track and field athletes. Methods: The development of the A-SNKQ followed an extensive step-wise approach. Firstly, a systematic literature review was conducted on existing SNK questionnaires for athletes. Secondly, sports nutrition guidelines were incorporated into the questionnaire. Thirdly, information from local literature was gathered to ensure contextual relevance. Lastly, a qualitative study involving key athletic stakeholders was conducted to gain cultural insights. Results: The final version of the questionnaire consists of 32 questions in 12 sub-sections under two main sections: GNK section covers macronutrients, micronutrients, energy balance, hydration, and weight management, SNK section addresses carbohydrate loading, pre-training, training and post-training meals, sports supplements, supplement label reading, isotonic drinks, doping, and relative energy deficiency syndrome in sports. Conclusions: The GNK section addresses the fundamental nutritional concepts, while SNK focuses on the knowledge associated with the sporting performance of athletes.

In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy

Ethnopharmacological relevanceIn accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. Aim of the studyTo investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. Materials and methodsNetwork pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. ResultsUPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. ConclusionsOur study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

AYA With GATA2 Deficiency Syndrome With Evolving Myeloid Neoplasia: Case Presentation

AYA With GATA2 Deficiency Syndrome With Evolving Myeloid Neoplasia: Case Presentation

Comprehensive biomarker analysis of metabolomics in different syndromes in traditional Chinese medical for prediabetes mellitus

BackgroundPrediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated.PurposeTo obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians’ decision making and benefit individuals at risk.MethodsAccording to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group). Plasma samples from patients were collected for clinical index assessment and untargeted metabolomics using liquid chromatography-mass spectrometry.ResultsAmong patients with the syndrome of spleen deficiency with dampness encumbrance (PXSK), those with PreDM (PDMPXSK group) had elevated levels of 2-hour post-load blood glucose (2-h PG), glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (SBP) than those in the normal blood glucose group (NDMPXSK group, P < 0.01). Among patients with the syndrome of dampness-heat in the spleen (SRYP), the levels of body mass index (BMI), fasting blood glucose (FBG), 2-h PG, HbA1c, and fasting insulin (FINS) were higher in the PreDM group (PDMSRYP group) than those in the normal blood glucose group (NDMSRYP group, P < 0.05). In both TCM syndromes, the plasma metabolomic profiles of PreDM patients were mainly discriminatory from the normal blood glucose controls of the same syndrome in the levels of lipid species, with the PXSK syndrome showing a more pronounced and broader spectrum of alterations than the SRYP syndrome. Changes associated with PreDM common to both syndromes included elevations in the levels of 27 metabolites which were mainly lipid species encompassing glycerophospholipids (GPs), diglycerides (DGs) and triglycerides (TGs), cholesterol and derivatives, and decreases in 5 metabolites consisting 1 DG, 1 TG, 2 N,N-dimethyl phosphatidylethanolamine (PE-NMe2) and iminoacetic acid. Correlation analysis identified significant positive correlations of 3α,7α,12α,25-Tetrahydroxy-5β-cholestane-24-one with more than one glycaemia-related indicators, whereas DG (20:4/20:5) and PC (20:3/14:0) were positively and PC (18:1/14:0) was inversely correlated with more than one lipid profile-related indicators. Based on the value of correlation coefficient, the top three correlative pairs were TG with PC (18:1/14:0) (r = − 0.528), TG with TG (14:0/22:4/22:5) (r = 0.521) and FINS with PE-NMe (15:0/22:4) (r = 0.52).ConclusionOur results revealed PreDM patients with different TCM syndromes were characterized by different clinical profiles. Common metabolite markers associated with PreDM shared by the two TCM syndromes were mainly lipid species encompassing GP, GL, cholesterol and derivatives. Our findings were in line with the current view that altered lipid metabolism is a conserved and early event of dysglycaemia. Our study also implied the possible involvement of perturbed bile acid homeostasis and dysregulated PE methylation during development of dysglycaemia.

Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5-8% of all kidney cancer cases and is associated with syndromes such as von Hippel-Lindau syndrome, Birt-Hogg-Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.

Design, synthesis, molecular dynamics studies and biological evaluations of 4-hydroxy-5-pyrrolinone-3-carbohydrazides as HIV-1 integrase inhibitors

Acquired immune deficiency syndrome (AIDS) diseases despite the efficacy of anti-HIV therapy, remain one of the human's most serious problems. Hence, the introduction of novel anti-HIV agents as first-line therapy is still required. HIV integrase lacking human enzyme homologous is an interesting target for developing new anti-HIV drugs. Following our attempts to describe active integrase inhibitor structures, here a series of novel 4-Hydroxy-5-pyrrolinone-3-carbohydrazides as HIV integrase inhibitor agents were identified. Biological results showed that all compounds could inhibit integrase strand transfer reaction and also exhibited anti-HIV activity in a cell-based assay. The interaction between integrase and designed compounds was investigated using molecular docking and molecular dynamics simulations.

Implementation of “Test and Treat” Strategy: Analysis of Deaths of People Living with HIV from 2017 to 2022 in Baise City, China

Background: Acquired immune deficiency syndrome (AIDS) remains a significant public health concern in China. Treatment coverage has been expanded by revising the antiretroviral therapy (ART) for people living with HIV (PLWH). Several years after implementing the new “Test and Treat” strategy, it is essential to evaluate its impact on people living with HIV since its implementation. Objectives: This study was conducted to comprehensively analyze the deaths of PLWH from 2017 to 2022 in Baise City, China. Methods: A retrospective cohort study was conducted to comprehensively analyze the deaths of PLWH in Baise from 2017 to the first half of 2022. The data was acquired from the AIDS Information System (AIDSIS). The all-cause and AIDS-related mortality rates were calculated for PLWH, along with the proportion of specific death causes. Interrupted time series analysis was utilized to examine changes in all-cause mortality pre- and post-implementation of the new strategy. Kaplan-Meier curves were drawn to compare the mortality risk within 1 year of diagnosis between treated and untreated patients, as well as between late discoverers and non-late discoverers. Related factors of death were also analyzed using the Cox proportional hazards regression model. Results: During the observation period, among a total of 8,922 PLWH cases, 1,265 people died, resulting in an all-cause mortality rate of 4.19 per 100 person-years. Acquired immune deficiency syndrome -related deaths numbered 438, accounting for 34.62% of the total deaths, with a mortality rate of 1.45 per 100 person-years. There were 730 non-AIDS-related deaths, representing 57.71%, with a mortality rate of 2.42 per 100 person-years. The overall mortality rate from all causes within 1 year after diagnosis was 5.58 per 100 person-years. No significant difference was identified in the all-cause mortality rate between the periods before and after the implementation of the new strategy. Untreated PLWH and late discoverers exhibited a high risk of death within 1 year of diagnosis. Most deaths were caused by common chronic diseases, while AIDS-related mortality was mainly due to opportunistic infections. Factors such as gender, age at diagnosis, occupation, educational background, ethnic group, infection route, history of ART, and baseline CD4 level were associated with the risk of all-cause mortality and AIDS-related mortality. Conclusions: After the implementation of the “Test and Treat” strategy, no significant difference in mortality among PLWH was recorded in Baise City, China. We recommend that the health department strengthen the testing of PLWH and improve treatment options. Additionally, we suggest encouraging the maintenance of long-term ART treatment and taking measures to prevent and control tuberculosis and common chronic diseases in individuals who are HIV positive.

Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway

BackgroundBuyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine to treat the syndrome of qi deficiency and blood stasis. Platelets play an important role in regulating thrombus and inflammation after ischemic injury, studies have shown that BYHWD regulate myocardial fibrosis and exert anti-inflammatory effects through IL-17 and TLR4 pathways, but the mechanism of platelet activation by BYHWD in stable coronary heart disease is still unknown. In the present study, model of left anterior descending coronary artery ligation was applied to investigate the mechanisms of BYHWD on modulating platelets hyperreactivity and heart function after fibrosis of ischemic myocardial infarction (MI).MethodsMyocardial infarction model was constructed by ligation of the left anterior descending coronary artery. The rats were randomly divided into five groups: sham, model, MI with aspirin (positive), MI with a low dosage of BYHWD (BYHWD-ld) and MI with a high dosage of BYHWD (BYHWD-hd) for 28 days.ResultsCoronary artery ligation prominently induced left ventricle dysfunction, increased cardiomyocyte fibrosis, which was accompanied by platelets with hyperreactivity, and high levels of inflammatory factors. BYHWD obviously reversed cardiac dysfunction and fibrosis, increased the thickness of the left ventricular wall, and inhibited aggregation ratio and CD62p expression. BYHWD restored the mitochondrial respiration of platelets after MI, concomitant with an increased telomere expression and decreased inflammation. According to the result of transcriptome sequencing, we found that 106 differentially expressed genes compared model with BYHWD treatment. Enrichment analysis screened out the Ras-related protein Rap-1 (Rap1) signaling pathway and platelet activation biological function. Quantitative real-time PCR and Western blotting were applied to found that BYHWD reduced the expression of Rap1/PI3K-Akt/Src-CDC42 genes and attenuated the overactivity of PI3 kinase/Rap1/integrin α(IIb)β(3) pathway.ConclusionBYHWD reduced inflammation and platelet activation via the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway and improved heart function after MI.Graphical

In-silico Study of Secondary Metabolites as Potential Inhibitors of NEF and P24 Protein of HIV-1

Introduction: Acquired immune deficiency syndrome (HIV/AIDS) has been a major global health concern for over 38 years. No safe and effective preventive or therapeutic vaccine has been developed although many products have been investigated. Methods: This computational study was conducted on plant-based active compounds against HIV-1 NEF and p24 protein to obtain and complexes with high binding scores were used for two-dimensional interaction studies via Ligplot to explore hydrogen bond and hydrophobic bond formation. ADMET analysis for best phytocompounds was performed using DruLito, ALOGPS, and PROTOX II. Results: According to the study conducted, phytocompounds like, Protostrychnine, Isostrychnine, Pseudo-Alpha-Colubrine, Alpha-Colubrine, Camptothecin, Benzo[f]quinoline, and (+) -Camptothecin are safe to be considered as a potential drug candidate after experimental validation against NEF and p24 proteins of HIV-1. While, Picrasidine M, Chaetochromin, 3’,3’-Binaringenin, and Sequoiaflavone displayed high binding scores of -10.8, -8.2, -9.5, -9.2 and -9.0, -8.8, -10.6, -9.0 respectively for NEF and p24 protein. All drugs belong to the toxicity class of either 4 or 5. They are inactive for hepatotoxicity and carcinogenicity but active for immunogenicity. Conclusion: For further validation of the results the phytocompounds can be extracted through solvent extraction method and tested on cell lines or animal models for their effectiveness.