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[This corrects the article DOI: 10.3389/fmicb.2023.1212582.].
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Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.
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Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Hypoxia , Cell Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit/metabolismABSTRACT
Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has been extensively studied. While most past studies were conducted in vitro or focused on murine noroviruses, recent research has expanded to human noroviruses using in vivo or ex vivo human intestinal enteroids culture studies. The gut microbiota has been observed to have both promoting and inhibiting effects on human noroviruses. Understanding the interaction between noroviruses and the gut microbiota or probiotics is crucial for studying the pathogenesis of norovirus infection and its potential implications, including probiotics and vaccines for infection control. Recently, several clinical trials of probiotics and norovirus vaccines have also been published. Therefore, in this review, we discuss the current understanding and recent updates on the interactions between noroviruses and gut microbiota, including the impact of norovirus on the microbiota profile, pro-viral and antiviral effects of microbiota on norovirus infection, the use of probiotics for treating norovirus infections, and human norovirus vaccine development.
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Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.
Subject(s)
Caliciviridae Infections , Norovirus , Humans , Norovirus/genetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Caliciviridae Infections/geneticsABSTRACT
PURPOSE: Laparoscopic and robotic inguinal hernia mesh repair are both common surgical procedures worldwide. Postoperative hernia recurrence and seroma formation are important concerns. In ventral hernia, primary defect closure in laparoscopic surgery reduces the recurrence rate. However, there is no synthetic evidence of direct inguinal hernia defect closure versus non-closure in minimal invasive surgery. Therefore, this study investigated the efficacy of defect closure in patients undergoing minimal invasive direct inguinal hernia mesh repair. METHODS: Eligible studies were identified through a search of PubMed, Embase, Cochrane Library, and CINAHL from their inception until March 2022. Studies examining defect closure in laparoscopic direct inguinal hernia repair were included, and a meta-analysis was performed using the random-effect model. Sensitivity analyses were performed by removing one study at a time. The primary outcomes were hernia recurrence and seroma formation. Acute and chronic postoperative pain, operation time, and length of hospital stay were the secondary outcomes. RESULTS: Five nonrandomized studies and one randomized controlled trial were included. Pooled analysis revealed defect closure might reduce the hernia recurrence rate (risk difference, - 0.02; 95% confidence interval [CI] - 0.04 to - 0.00; p = 0.02). The result of seroma formation (odds ratio, 0.49; 95% CI 0.17-1.46; p = 0.20) showed no significant difference. Moreover, no significant differences were observed in acute postoperative pain, chronic pain, length of hospital stay, and operation time. CONCLUSIONS: Our study indicated defect closure seems to be an option to reduce the direct inguinal hernia recurrence rate. No significant benefits were shown in seroma formation and other secondary outcomes. Our study was mostly based on nonrandomized studies and underestimated the effect of defect closure; thus, further high-quality studies are required to draw definitive conclusions.
Subject(s)
Hernia, Inguinal , Herniorrhaphy , Laparoscopy , Humans , Hernia, Inguinal/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Pain, Postoperative/surgery , Postoperative Complications/surgery , Recurrence , Seroma , Surgical Mesh , Non-Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Various regional analgesic techniques have been used in pediatric inguinal surgery to facilitate postoperative recovery. However, each technique's relative performance was undetermined owing to the lack of quantitative analysis. METHODS: We systematically searched MEDLINE, Cochrane Library, EMBASE, and Web of Science for randomized controlled trials that compared regional analgesia in pediatric inguinal surgeries. After critical study screening and selection, a random-effects network meta-analysis was performed. The primary outcome was the time to the first rescue analgesic after surgery, and the secondary outcomes were the number of patients requiring rescue analgesics after surgery, postoperative pain scores, incidence of postoperative nausea and vomiting, and other adverse events. RESULTS: This network meta-analysis included 69 randomized controlled trials (4636 patients) that compared 10 regional analgesic techniques. Our study revealed that the quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic after pediatric inguinal surgeries, by 7.7 hours (95% confidence interval [CI], 5.0-10.3) and 6.0 hours (95% CI, 3.9-8.2) when compared with the control group, respectively. In the subgroup involving only inguinal hernia repair, the quadratus lumborum block significantly prolonged the time to the first rescue analgesic than all other regional analgesics. In contrast, in the subgroup involving orchidopexies, only the caudal block significantly prolonged the time to the first rescue analgesic when compared with the control group (4.1 hours; 95% CI, 0.7-7.5). Wound infiltration and landmark-based ilioinguinal-iliohypogastric block had relatively poor analgesic effects than other regional analgesics. No serious adverse effects related to the regional analgesic techniques were reported in any of the included studies. CONCLUSIONS: The quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic and the least rescue analgesic requirement for pediatric inguinal surgeries. Specifically, the quadratus lumborum block had the longest analgesic duration in inguinal hernia repair, and the caudal block was found to be the only regional analgesia that extended the time to the first rescue analgesic in pediatric orchidopexy. Most included randomized controlled trials had some concern or a high risk of bias, and future studies should focus on providing high-quality evidence to further clarify the analgesic effects of regional analgesia for pediatric inguinal surgeries.
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BACKGROUND: Single-injection regional analgesia techniques can provide effective analgesia for abdominal hysterectomy. However, few randomized controlled trials (RCTs) have directly compared these techniques for total abdominal hysterectomy (TAH), and the best strategy remains unknown. OBJECTIVES: In this network meta-analysis, we compared the analgesic efficacy of single-injection regional analgesia techniques in patients who underwent TAH. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane, and CINAHL databases for relevant trials from inception until April 2022. RCTs that examined single-injection regional analgesia techniques for TAH were included. Random-effects network meta-analyses were performed using the frequentist approach. The primary outcome was 24-hour cumulative morphine equivalent consumption. The secondary outcomes were pain scores, time to first request for rescue analgesia, and rates of postoperative nausea and vomiting (PONV). RESULTS: In total, 36 RCTs were included. Network meta-analyses indicated that the erector spinae plane block provided superior analgesia in terms of reduced morphine consumption, low PONV incidence, and longer time to first analgesia request. Moreover, compared with control (i.e., sham or placebo), the quadratus lumborum block provided superior analgesia in terms of time to first analgesia request and resting pain scores. LIMITATIONS: (1) Few studies have examined single-injection regional analgesia techniques other than the transversus abdominis plane block (TAPB) and wound infiltration, leading to a few indirect effect estimates. (2) Heterogeneity existed due to analgesic type/dose, plane block timing, and injection site. (3) Objective outcomes, such as length of hospital stay, were lacking; most studies only included the patient-reported subjective pain score. CONCLUSION: Single-injection blocks are effective analgesic techniques for TAH. Among them, the erector spinae plane block and quadratus lumborum block seem to have superior effects. Further studies should evaluate techniques other than TAPB and wound infiltration to draw definitive conclusions.
Subject(s)
Analgesia , Pain, Postoperative , Humans , Female , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Network Meta-Analysis , Postoperative Nausea and Vomiting , Analgesics, Opioid/therapeutic use , Morphine/therapeutic use , Analgesia/methods , Hysterectomy/adverse effects , Abdominal MusclesABSTRACT
Coronavirus disease 2019 (COVID-19) patients have distinct clinical features in the pediatric groups. However, there is a paucity of research focused on clinical manifestation within pediatric group in Taiwan. This study is to conduct a retrospective study of the clinical features of COVID-19 in Taiwan pediatric patients. A retrospective study was conducted on pediatric patients (Aged ≤ 18 years) in a Northern Taiwan hospital from May 1st, 2021 to June 30th, 2021. Thirty-eight patients were included from emergency room. They were laboratory confirmed COVID-19 through specimens from nasopharyngeal swab by real-time reverse-transcription polymerase chain reaction (RT-PCR). Data including RT-PCR cycle threshold (Ct) values, clinical and epidemiological features were collected and analyzed. Thirty-eight patients aged from 7-month to 18-year-old were included. The median age of patients was 15-year-old. The patients had sex ratio of 23 males to 15 females. More than half patients were infected from family members. Asymptomatic patients were 47.37%. In the symptomatic patients, fever (34.21%) was the most predominant symptom. Cough, nasal obstruction and sore throat were also common. Asymptomatic children had significantly higher Ct-values than symptomatic children, and diagnosed patients with Ct-values more than 19 were associated with asymptomatic infection (P = .0084). Ct-values higher than 19 were associated with asymptomatic infection, which may be a predictor of pediatric disease severity. Our results highlight the distinct clinical manifestations and outcomes in pediatric COVID-19 patients. Compared to the adults, pediatric patients aged ≤ 18 years with COVID-19 in Taiwan mainly had mild disease.
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COVID-19 , Adolescent , Adult , Asymptomatic Infections , COVID-19/diagnosis , COVID-19/epidemiology , Child , Female , Humans , Male , Retrospective Studies , Taiwan/epidemiology , Tertiary Care CentersABSTRACT
The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
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Gastrointestinal Microbiome/genetics , Metagenome , Metagenomics/methods , Virome/genetics , Virus Diseases/drug therapy , Animals , COVID-19/therapy , Humans , Mice , Obesity/complications , SARS-CoV-2/genetics , Virus Diseases/therapy , Viruses/classification , Viruses/geneticsABSTRACT
PURPOSE: According to criteria recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), we analyzed the effects of branched-chain amino acid (BCAA)-rich supplements on muscle strength, muscle mass, and physical performance in older people. METHODS: We searched PubMed, Embase, Cochrane Library, and CINAHL from inception until March 2021. Randomized controlled trials that examined the effect of BCAA-rich supplements on older people were included. Random-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were stratified by participant and supplementation characteristics. Meta-regression analyses were performed to examine the effect of continuous variables. RESULTS: Thirty-five studies were included in this meta-analysis. Quality assessment revealed that 14 of 35 RCTs had some potential bias. The overall standardized mean difference (SMD) in muscle strength, muscle mass, and physical performance between the supplement and control groups was 0.35 (95% CI = [0.15, 0.55], P = 0.0007), 0.25 (95% CI = [0.10, 0.40], P = 0.0008), and 0.29 (95% CI = [0.00, 0.57], P = 0.05), respectively. Subgroup analysis revealed that essential amino acid supplementation improved handgrip strength more significantly than whey protein supplementation in older people. Meta-regression analysis revealed a significant linear relationship between improvements in handgrip strength and body mass index. CONCLUSIONS: BCAA-rich supplementation by older people may have beneficial effects on muscle mass and strength. However, the included studies had high heterogeneity, and the results must be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42020206674.