Endocrine, genetic, and microbiome nexus of obesity and potential role of postbiotics: a narrative review.

Obesity is a public health crisis, presenting a huge burden on health care and the economic system in both developed and developing countries. According to the WHO's latest report on obesity, 39% of adults of age 18 and above are obese, with an increase of 18% compared to the last few decades. Metabolic energy imbalance due to contemporary lifestyle, changes in gut microbiota, hormonal imbalance, inherent genetics, and epigenetics is a major contributory factor to this crisis. Multiple studies have shown that probiotics and their metabolites (postbiotics) supplementation have an effect on obesity-related effects in vitro, in vivo, and in human clinical investigations. Postbiotics such as the SCFAs suppress obesity by regulating metabolic hormones such as GLP-1, and PPY thus reducing feed intake and suppressing appetite. Furthermore, muramyl di-peptides, bacteriocins, and LPS have been tested against obesity and yielded promising results in both human and mice studies. These insights provide an overview of targetable pharmacological sites and explore new opportunities for the safer use of postbiotics against obesity in the future.

Ultrasound mediated gold nanoclusters-capped gas vesicles for enhanced fluorescence imaging.

The intercellular tight junction inhibits tumor imaging efficiency of nanomaterials, and enhanced cellular drug delivery with efficient detection is an important tool for tumor diagnosis. Herein, we fabricate fluorescence gold nanoclusters (Au NCs) decorated gas vesicles (GV-Au) for ultrasound (US)-mediated enhanced cellular delivery and imaging, in which GVs are living cell derived protein bubbles. GV-Au is rod-shaped sack-like structure around 230 nm, and displays improved stability and fluorescence ability compared with free Au NCs. Flow cytometry assay confirms the intracellular localization of Au NCs and GV-Au with a respective 2.20-fold enhanced cellular uptake post US treatment. Confocal images reveal the efficient cellular uptake of GV-Au under US impact, indicating that GV-Au is suitable for cellular and in vivo fluorescence imaging. Our strategy provides a new idea for efficient fluorescence imaging by penetrating cell membranes at the presence of US treatment.

Tumor Site-Specific Cleavage Improves the Antitumor Efficacy of Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) play important roles in tumor therapy. However, traditional ADCs are limited by the extremely large molecular weight of the antibody molecules, which results in low permeability into solid tumors. The use of small ADCs may be expected to alleviate this problem, but this switch brings the new limitation of a greatly shortened blood circulation half-life. Here, we propose a new cleavable ADC design with excellent tumor tissue permeability and a long circulation half-life by fusing the small ADC ZHER2-MMAE with the Fc domain of the antibody for circulation half-life extension, and inserting a digestion sequence between them to release the small ADC inside tumors for better tumor penetration. The experimental results showed that the designed molecule Fc-U-ZHER2-MMAE has a significantly increased blood circulation half-life (7.1 h, 59-fold longer) compared to the small ADC ZHER2-MMAE, and significantly improved drug accumulation ability at tumor sites compared to the conventional full-length antibody-coupled ADC Herceptin-MMAE. These combined effects led to Fc-U-ZHER2-MMAE having significantly enhanced tumor treatment ability, as shown in mouse models of NCI-N87 gastric cancer and SK-OV-3 ovarian cancer, where Fc-U-ZHER2-MMAE treatment achieved complete regression of tumors in all or a portion of animals with no obvious side effects and an MTD exceeding 90 mg/kg. These data demonstrate the therapeutic advantages of this cleavable ADC strategy, which could provide a new approach for ADC design.

Alginate-modulated continuous assembly of iron/tannic acid composites as photothermally responsive wound dressings for hemostasis and drug resistant bacteria eradication.

Multifunctional dressing materials are highly required to combat multidrug resistant bacteria in wound infections. Here an alginate-based aerogel dressing is reported that combines photothermal bactericidal activity, hemostatic property, and free radical scavenging for skin wound disinfection and accelerated wound healing. The aerogel dressing is facilely constructed by immersing a clean nail (Fe) in a mixed solution of sodium alginate (Alg) and tannic acid (TA), followed by freezing, solvent replacement, and air drying. The Alg matrix plays an essential role in modulating the continuous assembly process between TA and Fe to allow the homogenous distribution of TA-Fe metal-phenolic networks (MPN) in the resulting composite, without forming aggregates. The photothermally responsive Nail-TA/Alg aerogel dressing is successfully applied in a murine skin wound model infected with Methicillin-resistant Staphylococcus aureus (MRSA). This work provides a facile strategy to integrate MPN with the hydrogel/aerogel matrix through in situ chemistry, which is promising for developing multifunctional biomaterials and biomedicine.

Use of traditional Chinese medicine for the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients: An evidence mapping study.

Background: The potential effectiveness of traditional Chinese medicine (TCM) against "epidemic diseases" has highlighted the knowledge gaps associated with TCM in COVID-19 management. This study aimed to map the matrix for rigorously assessing, organizing, and presenting evidence relevant to TCM in COVID-19 management. Methods: In this study, we used the methodology of evidence mapping (EM). Nine electronic databases, the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal, ClinicalTrials.gov, gray literature, reference lists of articles, and relevant Chinese conference proceedings, were searched for articles published until 23 March 2022. The EndNote X9, Rayyan, EPPI, and R software were used for data entry and management. Results: In all, 126 studies, including 76 randomized controlled trials (RCTs) and 50 systematic reviews (SRs), met our inclusion criteria. Of these, only nine studies (7.14%) were designated as high quality: four RCTs were assessed as "low risk of bias" and five SRs as "high quality." Based on the research objectives of these studies, the included studies were classified into treatment (53 RCTs and 50 SRs, 81.75%), rehabilitation (20 RCTs, 15.87%), and prevention (3 RCTs, 2.38%) groups. A total of 76 RCTs included 59 intervention categories and 57 efficacy outcomes. All relevant trials consistently demonstrated that TCM significantly improved 22 outcomes (i.e., consistent positive outcomes) without significantly affecting four (i.e., consistent negative outcomes). Further, 50 SRs included nine intervention categories and 27 efficacy outcomes, two of which reported consistent positive outcomes and two reported consistent negative outcomes. Moreover, 45 RCTs and 38 SRs investigated adverse events; 39 RCTs and 30 SRs showed no serious adverse events or significant differences between groups. Conclusion: This study provides evidence matrix mapping of TCM against COVID-19, demonstrating the potential efficacy and safety of TCM in the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients, and also addresses evidence gaps. Given the limited number and poor quality of available studies and potential concerns regarding the applicability of the current clinical evaluation standards to TCM, the effect of specific interventions on individual outcomes needs further evaluation.

Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet ß Cells.

Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet ß cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet ß cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet ß cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet ß cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet ß cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet ß cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet ß cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet ß cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet ß cells.

Research hotspots and trends of Kinesio Taping from 2011 to 2020: a bibliometric analysis.

The purpose of this study was to explore the research hotspots and trends of Kinesio Taping in the last decade and provide new sights in future studies. Publications in the area of Kinesio Taping were searched from the Web of Science Core Collection database between 2011 and 2020. Citespace software was used to analyze data on countries/regions, institutions, authors, co-cited references, and keywords. A total of 677 publications were obtained in the last decade. We identified the most prolific countries, institutions, and authors in the field of Kinesio Taping from 2011 to 2020. The annual number of publications showed an upward trend. The most prolific country and institution were Turkey and Hacettepe University, respectively. The author with the biggest number of publications was Gul Baltaci from Turkey. The top 5 most frequent keywords were "pain", "tape", "strength", "exercise", and "reliability". The keywords with the highest centrality were "proprioception", followed by "reliability", "clinical trial", "ankle", and "pain". Ten clusters were found and the biggest one was "quadricep". The top 9 keywords with the strongest bursts were detected and "trial" had the highest burst strength. The results from the bibliometric analysis provide hotspots and trends in the field of Kinesio Taping. It is still in the development stage of the past decade. Pain relief, sports injury prevention and treatment, and proprioception enhancement to improve postural control were the hotspots from 2011 to 2020. High-quality trials and standardized criteria for applications are needed in the future.

Trends in research related to menopausal hormone therapy from 2000 to 2021: A bibliometric analysis.

We conducted the present bibliometric analysis to explore menopausal hormone therapy (MHT)-related research trends between 2000 and 2021. The Web of Science database was systematically searched from 2000 to 2021 to retrieve MHT-related publications. Visualization mapping and keyword cluster graphs were utilized to illustrate the research topics and hotpots. We included 11,616 MHT-related publications for this bibliometric analysis. The results showed that (1) MHT-related research had a very slow increase in the past 22 years, and the trend fluctuated. Sum of times cited and average citations per item had the same trend: a sharp decline from 2002 to 2003, and a rapid increase from 2003 to 2006, reaching the peak in 2006, then following a downward trend. The average H-index was 57, peaking in 2001; (2) the USA, the League of European Research Universities, and Dr. JoAann Manson from Harvard University contributed the most; (3) Menopause: The Journal of The North American Menopause Society had the most significant number of MHT-related publications; (4) the research hotpots primarily focused on MHT for treating menopausal symptoms and the impact of MHT on women's health. According to previous studies, MHT was the most effective treatment for managing vasomotor symptoms of menopause, but results from the clinical trials and observational studies regarding MHT adverse events remain inconsistent. Mechanisms are fundamental when clinical studies give conflicting results. Therefore, future studies should focus on adverse events and their mechanisms.

The reporting quality of N-of-1 trials and protocols still needs improvement.

OBJECTIVE: To evaluate the reporting quality of single-patient (N-of-1) trials and protocols based on the CONSORT Extension for N-of-1 trials (CENT) statement and the standard protocol items: recommendations for interventional trials (SPIRIT) extension and elaboration for N-of-1 trials (SPENT) checklist to examine the factors that influenced reporting quality. METHODS: Four electronic databases were searched to identify N-of-1 trials and protocols from 2015 to 2020. Quality was assessed by two reviewers. We calculated the overall scores based on binary responses in which "Yes" was scored as 1 (if the item was fully reported), and "No" was scored as 0 (if the item was not clearly reported or not definitely stated). RESULTS: A total of 78 publications (55 N-of-1 trials and 23 protocols) were identified. The mean reporting score (SD) of the N-of-1 trials and protocols were 29.24 (0.89) and 29.61 (1.83), respectively. For the items related to outcomes, sample size, allocation concealment protocol, and informed consent materials, the reporting quality was low. Our results showed that the year of publication (t = -0.793, p = 0.872 for the trials and t = 1.352, p = 0.623 for the protocols) and the impact factor of the journal (t = 1.416, p = 0.619 for the trials and t = 0.359, p = 0.667 for the protocols) were not factors associated with better reporting quality. CONCLUSION: With the publication of the CENT 2015 statement and the SPENT 2019 checklist, authors should adhere to the relevant reporting guidelines and improve the reporting quality of N-of-1 trials and protocols.

More work is needed on cost-utility analyses of robotic-assisted surgery.

OBJECTIVE: To comprehensively analyze the cost-utility of robotic surgery in clinical practice and to investigate the reporting and methodological quality of the related evidence. METHODS: Data on cost-utility analyses (CUAs) of robotic surgery were collected in seven electronic databases from the inception to July 2021. The quality of the included studies was assessed using the CHEERs and QHES checklists. A systematic review was performed with the incremental cost-effectiveness ratio as the outcome of interest. RESULTS: Thirty-one CUAs of robotic surgery were eligible. Overall, the identified CUAs were fair to high quality, and 63% of the CUAs ranked the cost-utility of robotic surgery as "favored," 32% categorized as "reject," and the remaining 5% ranked as "unclear." Although a high heterogeneity was present in terms of the study design among the included CUAs, most studies (81.25%) consistently found that robotic surgery was more cost-utility than open surgery for prostatectomy (ICER: $6905.31/QALY to $26240.75/QALY; time horizon: 10 years or lifetime), colectomy (dominated by robotic surgery; time horizon: 1 year), knee arthroplasty (ICER: $1134.22/QALY to $1232.27/QALY; time horizon: lifetime), gastrectomy (dominated by robotic surgery; time horizon: 1 year), spine surgery (ICER: $17707.27/QALY; time horizon: 1 year), and cystectomy (ICER: $3154.46/QALY; time horizon: 3 months). However, inconsistent evidence was found for the cost-utility of robotic surgery versus laparoscopic surgery and (chemo)radiotherapy. CONCLUSIONS: Fair or high-quality evidence indicated that robotic surgery is more cost-utility than open surgery, while it remains inconclusive whether robotic surgery is more cost-utility than laparoscopic surgery and (chemo)radiotherapy. Thus, an additional evaluation is required.

Efficacy and safety of phytoestrogens in the treatment of perimenopausal and postmenopausal depressive disorders: A systematic review and meta-analysis.

BACKGROUND: Depression is one of the most common and specific symptoms among menopausal women, leading to significant personal, family, and economic burdens. Some studies have shown that phytoestrogens can help relieve symptoms of depression. OBJECTIVES: This systematic review and meta-analysis aim to assess the efficacy and safety of phytoestrogens in treating depression among menopausal women. METHODS: A comprehensive search for relevant studies published until November 25, 2020, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMBASE. Statistical analyses were performed with R 4.0.3.and Review Manager 5.4. RESULTS: 2183 studies were identified and 10 studies with 15 independent reports were included, involving 1248 participants. The quality of the four studies was assessed as high risk, six studies were assessed as unclear. The analyses conducted according random effects model indicated the significant positive effect on depressive symptoms for postmenopausal women compared with the placebo (SMD = -0.62; 95% CI = -1.13 to -0.12; Q = 45.62, df = 14, P < .01; I2  = 79%). The low dose phytoestrogens (25 mg/d ≤ dose ≤ 100 mg/d) have better effectiveness (SMD = -0.52; 95% CI = -0.85 to -0.20; I2  = 79%, P< .01) than high dose (dose > 100 mg/d) and ultralow dose (0 < dose < 25 mg/d), but showed no statistical significance (Q = 0.81 df = 2, P = .67). Isoflavones had better effectiveness (SMD = -0.48; 95% CI = -0.75 to 0.21; I2  = 75%, P < .01) than lignans of phytoestrogens (SMD = -0.22; 95% CI = -0.37 to 0.08; I2  = 0%, P = .96). The duration of intervention affects the efficacy of phytoestrogens (ß = -0.03; 95% CI: [-0.05, 0.00]; P = .045). The effectiveness varies in regions. The adverse reactions frequently reported were gastrointestinal symptoms and cold or upper respiratory tract infection. CONCLUSIONS: Phytoestrogen can relieve depression symptoms among menopausal, especially for postmenopausal women who take low doses(25 mg/d ≤ dose ≤ 100 mg/d) of phytoestrogens for a long-term duration. Although mild adverse reactions have been reported, phytoestrogen could be considered as a complementary treatment for postmenopausal depression.

Study on the anti-tumor mechanism related to immune microenvironment of Bombyx Batryticatus on viral and non-viral infections of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value<0.001) and the correlation between AKR1C3 and macrophages M1 was poor in NVIR group (cor = 0.064, P-value = 0.36). Additionally, survival curve of AKR1C3 showed that poor prognosis in VIR group can be related to high level of AKR1C3 (HR = 2.32, 95 % CI: 1.18-4.56, P-value = 0.012), and no signified gene can be found in NVIR group (P-value>0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

Diagnostic accuracy of machine-learning-assisted detection for anterior cruciate ligament injury based on magnetic resonance imaging: Protocol for a systematic review and meta-analysis.

BACKGROUND: Although many machine learning algorithms have been developed to detect anterior cruciate ligament (ACL) injury based on magnetic resonance imaging (MRI), the performance of different algorithms required further investigation. The objectives of this current systematic review are to evaluate the diagnostic accuracy of machine-learning-assisted detection for ACL injury based on MRI and find the current best algorithm. METHOD: We will conduct a comprehensive database search for clinical diagnostic tests in PubMed, EMBASE, Cochrane Library, and Web of science without restrictions on publication status and language. The reference lists of the included articles will also be checked to identify additional studies for potential inclusion. Two reviewers will independently review all literature for inclusion and assess their methodological quality using Quality Assessment of Diagnostic Accuracy Studies version 2. Clinical diagnostic tests exploring the efficacy of machine-learning-assisted system for detecting ACL injury based on MRI will be considered for inclusion. Another 2 reviewers will independently extract data from eligible studies based on a pre-designed standardized form. Any disagreements will be resolved by consensus. RevMan 5.3 and Stata SE 12.0 software will be used for data synthesis. If appropriate, we will calculate the summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of machine-learning-assisted diagnosis system for ACL injury detection. A hierarchical summary receiver operating characteristic (HSROC) curve will also be plotted, and the area under the ROC curve (AUC) is going to calculated using the bivariate model. If the pooling of results is considered inappropriate, we will present and describe our findings in diagrams and tables and describe them narratively. RESULT: This is the first systematic assessment of machine learning system for the detection of ACL injury based on MRI. We predict it will provide highquality synthesis of existing evidence for the diagnostic accuracy of machine-learning-assisted detection for ACL injury and a relatively comprehensive reference for clinical practice and development of interdisciplinary field of artificial intelligence and medicine. CONCLUSION: This protocol outlined the significance and methodologically details of a systematic review of machine-learning-assisted detection for ACL injury based on MRI. The ongoing systematic review will provide high-quality synthesis of current evidence of machine learning system for detecting ACL injury. REGISTRATION: The meta-analysis has been prospectively registered in PROSPERO (CRD42019136581).