The Natural Products as Novel Anti-obesity Agents: Mechanisms Based on Adipose Tissue.

Obesity presently stands as a formidable global public health concern, exerting a profound impact on human life and well-being. Despite the plethora of pharmacological interventions targeting obesity, their extensive use in clinical settings is hindered by the emergence of numerous adverse reactions during drug interventions. Naturally occurring compounds or extracts found in traditional Chinese medicine, fruits, and vegetables, possessing various attributes, such as metabolic modulation, thermogenic induction, appetite alteration, and inhibition of lipase activity and fat synthesis, have positioned themselves as potential anti-obesity pharmaceutical candidates. Promoting thermogenesis through the browning of adipose tissue, reducing fat tissue generation and ectopic deposition, along with the regulation of adipose factors, has emerged as a primary focus in the treatment of obesity. This shift underscores the pivotal role of adipose tissue as a critical target in obesity management. This study delves into various approaches based on adipose tissue, providing an overview of the efficacy of bioactive components derived from medicinal plants and fruits for treating obesity through adipose tissue modulation. Insights are drawn from both animal experiments and clinical applications, with a discussion of potential mechanisms underlying these effects. In conclusion, we have determined that natural compounds are significant candidates for the treatment of obesity, and adipose tissue represents a crucial target in the therapeutic process. We hope that our research will contribute novel perspectives for the development of future pharmaceuticals and dietary supplements, as well as provide innovative directions for clinical trials in the field.

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells.

BACKGROUND: Traditional Chinese medicine has used the drug Pien Tze Huang (PTH), a classic prescription, to treat autoimmune hepatitis (AIH). However, the precise mode of action is still unknown. AIM: To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T (mTreg) cells functional levels. METHODS: Following induction of the AIH mouse model induced by Concanavalin A (Con A), prophylactic administration of PTH was given for 10 d. The levels of mTreg cells were measured by flow cytometry, and intestinal microbiota was analyzed by 16S rRNA analysis, while western blotting was used to identify activation of the toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways. RESULTS: In the liver of mice with AIH, PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-2, IL-6, and IL-21 expression. Simultaneously, PTH stimulated the abundance of helpful bacteria, promoted activation of the TLR2 signal, which may enhance Treg/mTreg cells quantity to produce IL-10, and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways. CONCLUSION: PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

Effect of the Online Mindfulness-Based Stress Reduction on Anxiety and Depression Status of COVID-19 Patients Treated in Fangcang Hospitals: A Randomized Controlled Trial.

Background: As the focal point of epidemic prevention and control, the mental health of COVID-19 patients cannot be ignored. Online Mindfulness-Based Stress Reduction (MBSR) allows for the provision of conveniently accessible, effective and low-cost interventions on a large scale. We aim to evaluate the effectiveness of an online MBSR intervention in alleviating anxiety and depression among asymptomatic/mild patients limited by COVID-19-related restrictions. Methods: Fifty-eight patients treated in Sanya Fangcang hospital were randomly allocated to either to the experimental group (n = 29) following daily, for 5 days, an online-based mindfulness intervention or to the control group (n = 29). Patients from both groups underwent online questionnaires including assessment of anxiety and depression status at pre- and post-tests using Self-rating Anxiety Scale and Self-Rating Depression Scale. Results: After the online-based MBSR program, the anxiety and depression scores of the patients in the MBSR group decreased significantly in comparison to the scores of those in the control group (respectively η2 = 0.175, η2 = 0.215, p < 0.001). And the proportion of severe anxiety and depression patients in the MBSR group decreased to 0% which lower than the control group, and the proportion of light anxiety and depression patients was significantly more than that in the control group after the MBSR intervention. Conclusion: The online-based MBSR intervention appears to be an effective way of alleviating anxiety and depression symptoms among COVID-19 patients with associated quarantine in Fangcang hospital. Given the seriousness of mental health threat that could be posed by this ongoing pandemic, our study provides a new idea and method for cost-effective and time-efficient interventions in the future of epidemic prevention and control.

Effects of Qishen Dihuang Granules on Intestinal Microbiota in Experimental Autoimmune Myasthenia Gravis Model Rats.

Objective: Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532). Methods: Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG. Results: The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus-level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter. Conclusion: QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella.

Recent Advances of Fe(III)/Fe(II)-MPNs in Biomedical Applications.

Metal-phenolic networks (MPNs) are a new type of nanomaterial self-assembled by metal ions and polyphenols that have been developed rapidly in recent decades. They have been widely investigated, in the biomedical field, for their environmental friendliness, high quality, good bio-adhesiveness, and bio-compatibility, playing a crucial role in tumor treatment. As the most common subclass of the MPNs family, Fe-based MPNs are most frequently used in chemodynamic therapy (CDT) and phototherapy (PTT), where they are often used as nanocoatings to encapsulate drugs, as well as good Fenton reagents and photosensitizers to improve tumor therapeutic efficiency substantially. In this review, strategies for preparing various types of Fe-based MPNs are first summarized. We highlight the advantages of Fe-based MPNs under the different species of polyphenol ligands for their application in tumor treatments. Finally, some current problems and challenges of Fe-based MPNs, along with a future perspective on biomedical applications, are discussed.

Investigation of the Underlying Mechanism of Huangqi-Dangshen for Myasthenia Gravis Treatment via Molecular Docking and Network Pharmacology.

The herbal pairing of Huangqi and Dangshen (HD) is traditional Chinese herbal medicine and has been widely used in China, especially to treat myasthenia gravis (MG). However, the mechanism of HD on MG is unclear. Aim of the Study. This study aims to investigate HD's possible role in MG treatment. Materials and Methods. The TCMSP database was used to identify the active chemicals and their targets. The GeneCards, DisGeNET, and OMIM databases were used to search for MG-related targets. The STRING database was employed in order to identify the common PPI network targets. We next utilised Cytoscape 3.8.2 for target identification and the DAVID database for gene ontology (GO) function analysis as well as Encyclopaedia of Genomes (KEGG) pathway enrichment analysis on the selected targets. The AutoDock Vina software was used to test the affinity of essential components with the hub gene before concluding that the primary targets were corrected through molecular docking. Results. 41 active compounds were screened from HD, and the number of putative-identified target genes screened from HD was 112. There were 21 target genes that overlapped with the targets of MG, which were postulated to be potential treatment targets. Through further analysis, the results showed that the active compounds from HD (such as 7-methoxy-2-methylisoflavone, quercetin, luteolin, Kaempferol, and isorhamnetin) may achieve the purpose of treating MG by acting on some core targets and related pathways (such as EGFR, FOS, ESR2, MYC, ESR1, CASP3, and IL-6). Molecular docking findings demonstrated that these active molecules have a near-perfect ability to attach to the primary targets. Conclusion. Through network pharmacology, the findings in this study provide light on the coordinated action of several HD formula components, targets, and pathways. It provided a theoretical basis for further study of HD pharmacological action.

Quality control strategies of medicine food homology materials based on fingerprint profiling and chemometrics: Citri Reticulata Pericarpium as an example.

The study aimed to provide a reliable and feasible strategy for the comprehensive quality control of medicine food homology materials (MFHM). The high performance liquid chromatography (HPLC) fingerprints and Fourier transform mid-infrared (FT-MIR) quantized fingerprints were successfully developed to comprehensively evaluate overall quality of Citri Reticulata Pericarpium (CRP) by applying comprehensive quantified fingerprint method (CQFM). All samples were well distinguished and divided into 5 grades. In addition, through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), the identification ability of HPLC fingerprints and FT-MIR fingerprints on CRP with different storage years was discussed. The results showed that HPLC fingerprints combined with PCA had good discrimination ability, and the PLS-DA model established by the preprocessed FT-MIR fingerprint data could accurately distinguish and predict the storage period of CRP. Finally, based on 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH•) scavenging assay, combined with bivariate correlation analysis, the fingerprint-activity relationship of offline antioxidant activity of CRP samples with the fingerprints peak were studied. In general, the comprehensive strategies provide a reliable and scientific reference scheme for the quality control of MFHM in the future.

Invigorating spleen, replenishing qi and tonifying kidney method treatment of traditional Chinese medicine for myasthenia gravis: A protocol for systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease related to the production of autoantibodies. It is mediated by antibodies against acetylcholine receptor (AChR), muscle specific kinase (MuSK) or other AChR related proteins in the postsynaptic muscle membrane, which interfere with the transmission of signals at the neuromuscular junction, resulting in clinical symptoms of skeletal muscle weakness and fatigue, leading to the occurrence and development of MG. At present, the incidence rate of Mg is increasing year by year. At present, the method of invigorating spleen, replenishing qi and tonifying kidney in traditional Chinese medicine has been widely used in the clinical treatment of MG, and the effect is good. The purpose of this study was to systematically evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in the treatment of MG. METHODS: We will search from the following eight databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Sinomed, Wanfang, and Vip. All randomized controlled trial (RCT) literature has been searched and classified since the establishment of the database to date. In this study, two researchers independently screened and evaluated the quality of the retrieved literature. Cochrane risk bias assessment tool was used to evaluate the risk of bias. The meta-analysis uses RevMan 5.3 software provided by Cochrane Collaboration Network for meta analysis. RESULTS: This study compared the main outcome indicators: clinical response rate, recurrence rate, incidence of adverse reactions, quantitative myasthenia gravis score (QMG). Secondary outcomes were clinical absolute score, quality of life score (QOL), levels of inflammatory factors such as IL-6, IL-10, and serum acetylcholine receptor antibody (AChR-Ab) levels. CONCLUSION: The purpose of this study was to evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in treating MG, and to provide evidence based medicine.

Clinical prognosis of intraoperative blood salvage autotransfusion in liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

Background: Intraoperative blood salvage autotransfusion(IBSA) has been widely used in a variety of surgeries, but the use of IBSA in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is controversial. Numerous studies have reported that IBSA used during LT for HCC is not associated with adverse oncologic outcomes. This systematic review and meta-analysis aims to estimate the clinical prognosis of IBSA for patients with H+CC undergoing LT. Methods: MEDLINE, Embase, Web of Science, and Cochrane Library were searched for articles describing IBSA in HCC patients undergoing LT from the date of inception until May 1, 2022, and a meta-analysis was performed. Study heterogeneity was assessed by I2 test. Publication bias was evaluated by funnel plots, Egger's and Begg's test. Results: 12 studies enrolling a total of 2253 cases (1374 IBSA and 879 non-IBSA cases) are included in this meta-analysis. The recurrence rate(RR) at 5-year(OR=0.75; 95%CI, 0.59-0.95; P=0.02) and 7-year(OR=0.65; 95%CI, 0.55-0.97; P=0.03) in the IBSA group is slightly lower than non-IBSA group. There are no significant differences in the 1-year RR(OR=0.77; 95% CI, 0.56-1.06; P=0.10), 3-years RR (OR=0.79; 95% CI, 0.62-1.01; P=0.06),1-year overall survival outcome(OS) (OR=0.90; 95% CI, 0.63-1.28; P=0.57), 3-year OS(OR=1.16; 95% CI, 0.83-1.62; P=0.38), 5-year OS(OR=1.04; 95% CI, 0.76-1.40; P=0.82),1-year disease-free survival rate(DFS) (OR=0.80; 95%CI, 0.49-1.30; P=0.36), 3-year DFS(OR=0.99; 95%CI, 0.64-1.55; P=0.98), and 5-year DFS(OR=0.88; 95%CI, 0.60-1.28; P=0.50). Subgroup analysis shows a difference in the use of leukocyte depletion filters group of 5-year RR(OR=0.73; 95%CI, 0.55-0.96; P=0.03). No significant differences are found in other subgroups. Conclusions: IBSA provides comparable survival outcomes relative to allogeneic blood transfusion and does not increase the tumor recurrence for HCC patients after LT. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022295479.

Didang Tang inhibits intracerebral hemorrhage-induced neuronal injury via ASK1/MKK7/JNK signaling pathway, network pharmacology-based analyses combined with experimental validation.

Background: Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease, which is also a principal consideration for disability. Didang tang (DDT) is a classic traditional Chinese medicine formula for treating ICH. However, its pharmacological mechanism of action has not been elucidated. Materials and methods: The TCMSP and BATMAN-TCM databases were used to collect chemical compounds and predict targets of DDT. Protein targets in ICH were identified by GeneCards, OMIM, and DrugBank databases. DDT compounds-ICH targets and protein-protein interaction (PPI) networks were constructed for topological analysis and hub-targets screening. Further, Key biological processes and signaling pathways were identified by GO and KEGG enrichment analyses. Then, an ICH rat model and a Cobaltous Chloride (CoCl2)-induced PC12 cells model were established. Cell viability and lactate dehydrogenase (LDH) release were detected using cck8 and LDH kits. Apoptosis levels were detected by TUNEL assessment and flow cytometry. IL-1ß levels were detected by ELISA, while key protein expressions were determined by Western blot. Results: A total of 126 active compounds related to DDT and 3,263 therapeutic targets for ICH were predicted. The functional enrichment of the GO and KEGG pathways combined with literature studies suggested that DDT is most likely to influence MAPK and apoptotic signaling pathways for ICH treatment. In vitro and in vivo experiments have shown that DDT remarkably inhibited apoptosis and increased the expression of Bcl-2, while inhibiting Bax and cleaved-Caspase 3. For other enriched core proteins, DDT suppressed the phosphorylation of Src and the expression of c-Myc and IL-1ß, and up-regulated the level of MMP-9. The further results showed that, DDT decreased the phosphorylation of ASK1, MKK7, JNK and c-JUN. Conclusion: Based on network pharmacology and experimental validation results, our in vivo and in vitro study indicated that ASK1/MKK7/JNK pathway might be the critical target for DDT against ICH.

Manual Acupuncture or Combination of Rehabilitation Therapy to Treat Poststroke Dysphagia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Backgroundand Objective. Poststroke dysphagia is one of the most common stroke complications with high morbidity and long course, while acupuncture treatment is easily accepted by patients due to its reliability, feasibility, simple operation, low price, and quick effect. Our objective was to evaluate the efficacy of manual acupuncture in poststroke dysphagia patients. Methods. Databases including Medline, Web of Science, PubMed, Cochrane Library databases, EMBASE, CNKI (China National Knowledge Infrastructure), WanFang (WanFang Database), and VIP (Chongqing VIP) were searched from inception until Aug 19, 2022. Data were analyzed using Revman 5.3, Stata 14.0, and TSA 0.9.5.10 Beta software. Evidence quality evaluation was performed by using GRADE profiler 3.6. Results. A total of 33 randomized control trials (RCTs) enrolled 2680 patients. Meta-analysis results revealed that compared to rehabilitation, acupuncture decreased water swallow test (WST) and standard swallowing assessment (SSA) scores. Meanwhile, in contrast to rehabilitation alone, integration of acupuncture with rehabilitation effectively decreased WST and SSA scores; improved swallowing scores of videofluoroscopic swallowing study (VFSS), swallowing scores of Fujishima Ichiro, Barthel index (BI), and swallowing quality of life questionnaire (SWAL-QOL); reduced the aspiration rates as well as aspiration pneumonia; and shortened the duration of empty swallowing and the duration of 5 mL water swallowing. Pooled analysis did not reveal any significant differences in dysphagia outcome severity scores (DOSS) (p=0.15 > 0.05p) between the acupuncture group combined with rehabilitation group and the rehabilitation group alone. After the risk-of-bias assessment, these studies were not of low quality, except in terms of allocation concealment and blindness. Evidence quality evaluation showed that allocation concealment and blindness led to a downgrade and primary outcomes' evaluation of acupuncture combined with rehabilitation were ranked as moderate-quality evidence while acupuncture alone was ranked as low-quality. Conclusion. This meta-analysis provided positive pieces of evidences that acupuncture and acupuncture combined with rehabilitation were better than using rehabilitation alone in the treatment of poststroke dysphagia.

Soil meso- and micro-fauna community in response to bamboo-fungus agroforestry management.

Bamboo-fungus agroforestry management is an ecological model of sustainable production of moso bamboo forest, and Stropharia rugosoannulata has been widely planted in moso bamboo forest. However, little attention has been paid to soil fauna community in bamboo-fungus agroforestry system. Thus, the aim of this study was to investigate the response of soil fauna communities to agroforestry management, and to explore the relationships between soil fauna communities and soil properties. An experiment with 0, 1, 2 and 3 years of planting was carried out in an existing moso bamboo forest. The community composition of soil meso- and micro-fauna was investigated, and the soil properties were determined. Results showed that a total of 2968 individuals of soil meso- and micro-fauna, belonging to 8 classes and 13 groups were detected. The group number and density of soil fauna was highest right and then decreased. Planting Stropharia rugosoannulata in moso bamboo forest increased the density of dominant groups, but did not change its composition. Shannon-Weiner diversity index (H), Margalef richness index (D) and Density-Group diversity index (DG) were the highest one year after planting the fungus, while Simpson dominance index (C) was the lowest in the meantime. Contents of soil moisture (SMC), organic matter (SOM), total nitrogen (TN), total phosphorus (TP) and total potassium (TK) increased first and then decreased with the increase of planting years, peaking at 1 year after planting, while the pH value continued to increase. Responses of soil fauna community were associated with soil physicochemical properties. Redundancy analysis (RDA) showed that SOM was the main environmental factor driving the variation of soil fauna community, followed by TP and TN. In conclusion, planting Stropharia rugosoannulata in moso bamboo increased the diversity and abundance of soil fauna communities due to its contribution to abundance of organic matter and supply of nutrients.

Targeting autophagy in atherosclerosis: Advances and therapeutic potential of natural bioactive compounds from herbal medicines and natural products.

Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.

Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

Melatonin supplementation for the treatment of infantile spasms: protocol for a randomised placebo-controlled triple-blind trial.

INTRODUCTION: Infantile spasms (IS) is a type of severe epileptic encephalopathy that occurs in infancy and early childhood. IS is characterised clinically by epileptic spasms, often accompanied by sleep disorder and abnormal circadian rhythm. The endogenous circadian rhythm disorder, in turn, can make spasms worse. Melatonin has also been found to have anticonvulsant and neuroprotective properties by adjusting the circadian rhythm. However, there are lack of relevant studies on controlling IS by using melatonin. This study aims to analyse the therapeutic effect of melatonin supplementation for the treatment of IS. METHODS AND ANALYSIS: This is a triple-blinded (trial participant, outcome assessor and the data analyst), prospective, randomised controlled trial to be conducted in the Department of Paediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China from November 2020. Patients (n=70) aged 3 months to 2 years with IS will be recruited in this study after receiving written consent from their parents or guardians. Patients will be randomly divided into two equal groups and treated with a combination of adrenocorticotropic hormone, magnesium sulfate and either melatonin or placebo. Clinical data from the patients in the two groups before and after the treatment will be collected and compared. The primary outcome will be assessed 2 weeks later by seizure diaries and reported as the average reduced rate of spasms frequency. Secondary outcomes include the response rate (the rate of spasms-free), electroencephalogram hypsarrhythmia assessment and the psychomotor development assessment (Denver Developmental Screening Test). Sleep quality and safety will also be assessed. ETHICS AND DISSEMINATION: The protocol for this study was approved by the Ethics Committee of Chinese PLA General Hospital (reference number S2020-337-01) and was reported according to the Standard Protocol Items: Recommendations for Interventional Trials statement. Findings of this research will be disseminated through national and international meetings, conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000036208.

Elucidating phytoplankton limiting factors in lakes and reservoirs of the Chinese Eastern Plains ecoregion.

Knowledge of phytoplankton limiting factors is essential for cost-efficient lake eutrophication management. Herein, we propose a statistical framework to explore site-specific phytoplankton limiting factors and their dependence on water depth (WD) in 54 lakes in the Chinese Eastern Plains ecoregion. First, the maximal chlorophyll a (Chla) response to total N (TN) or P (TP), representing a region-specific "standard" model where phytoplankton were primarily N- or P-limited, was quantified using a 95% quantile regression. Second, site-specific limiting factors were identified using analogical residual analysis. N- or P-limitation was inferred if FractionTN (i.e. fraction of Chla observed and predicted by the "standard" model for a given TN) > 0.95 or FractionTP >0.95; if both FractionTN and FractionTP <0.95 in a specific environmental condition (e.g. high non-algal turbidity), light limitation was suggested. As a result, 5%, 7%, 4%, 36%, 16%, 2%, and 30% of the sampling sites were limited by N, P, N+P, light availability, rapid flushing, abundant macrophytes, and unmeasured factors, respectively. Bloom control suggestions in the short run are proposed considering these actual limiting factors. Furthermore, the maximal FractionTN or FractionTP response to WD was explored, reflecting the effect of WD on FractionTN (or FractionTP) without significant confounders. The results indicated that phytoplankton in the studied freshwaters would be potentially light-limited, N-limited, N+P-co-limited, or P-limited depending on WD (<1.8, 1.8-2.1, 2.1-5.2, or >5.2 m, respectively), because N will gradually become surplus with increasing WD, while at very shallow depths, strong sediment re-suspension induces light limitation. This finding implies that long-term nutrient management strategies in the studied freshwaters that have WDs of 0-2.1, 2.1-5.2, and >5.2 m can entail control of N, N+P, and P, respectively. This study provides essential information for formulating context-dependent bloom control for lakes in our study area and serves as a valuable reference for developing a cost-efficient eutrophication management framework for other regions.

Keratinase improves the growth performance, meat quality and redox status of broiler chickens fed a diet containing feather meal.

The objective of this study was to assess the effects of dietary supplementation of keratinase on the production of broilers fed a diet containing feather meal. A total of 162 1-d-old Cobb 500 male broiler (n = 9 cages/diet with 6 chicks/cage) were randomly allocated to 3 dietary treatments. The broilers were fed a corn-soybean-feather meal based diet (BD), or BD supplemented with keratinase at 100,000 or 200,000 U/kg for 6 weeks. Compared to the control, dietary supplementation with 200,000 U/kg keratinase increased (P < 0.05) body weight gain (3.6-4.3%) and reduced feed conversion ratio (2.4-5.6%) during the various experimental periods, and also improved (P < 0.05) apparent total tract digestibility of ash and calcium by 45.0% and 8.8%, respectively. Meanwhile, dietary supplementation of keratinase at 100,000 U/kg reduced (P < 0.05) the drip loss (29.2%), while 200,000 U/kg keratinase supplementation increased (P < 0.05) the pH value (1.6%) at 45 min and decreased (P < 0.05) the lightness (L* value; 13.6%) and drip loss (22.1%) of pectoral muscle. Moreover, dietary supplementation of keratinase at both levels of 100,000 and 200,000 U/kg increased (P < 0.05) Glutathione peroxidase activity (82.5-87.5%) and decreased the Malondialdehyde concentration (14.5-18.3%) in the pectoral muscle. In conclusion, dietary supplementation of keratinase at 200,000 U/kg can improve the performance, meat quality, apparent total tract digestibility of nutrients, and redox status of broiler chickens fed a diet containing feather meal.

A saponin from astragalus promotes pancreatic ductal organoids differentiation into insulin-producing cells.

BACKGROUND: Islet transplantation is an effective treatment for the type 1 and severe type 2 diabetes, but it is restricted by the severe lack of pancreas donors. In vitro differentiation of pancreatic progenitors into insulin-secreting cells is one of the hopeful strategies in the cell transplantation therapy of diabetes. Isoastragaloside I is one of the saponin molecules found in Astragalus membranaceus, which has been demonstrated to alleviate insulin resistance and glucose intolerance in obese mice. STUDY DESIGN: We established mouse pancreatic ductal organoids (mPDOs) with progenitor characteristics and an insulin promoter-driven EGFP reporter system to screen astragalus saponin components for monomers that can promote insulin-producing cell differentiation. METHODS: mPDOs treated with or without astragalus saponin monomers were investigated by the insulin promoter-driven EGFP reporter, quantitative PCR, immunofluorescence and flow cytometry to evaluate the expression of endocrine progenitor and ß-cell markers. RESULTS: Isoastragaloside I significantly promoted the expression of ß-cell differentiation genes, which was demonstrated by the activation of the insulin promoter-driven EGFP reporter, as well as the significant increase of mRNA levels of the endocrine progenitor marker Ngn3 and the ß-cell markers insulin1 and insulin2. Immunostaining studies indicated that the ß-cell-specific C-peptide was upregulated in isoastragaloside I-treated mPDOs. FACS analysis revealed that the ratio of C-peptide-secreting cells in isoastragaloside I-treated mPDOs was over 40%. Glucose tolerance tests demonstrated that the differentiated mPDOs could secrete C-peptide in response to glucose stimulation. CONCLUSIONS: We discover a novel strategy of inducing pancreatic ductal progenitors to differentiate into insulin-producing cells using isoastragaloside I. This approach can be potentially applied to ß-cell transplantation in diabetes therapies.

Human developmental toxicity mechanism of polybrominated biphenyl exposure and health risk regulation strategy for special populations.

Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with abnormal conditions. Hence, in this study, we used molecular docking, molecular dynamics, Taguchi experimental design, and fractional factorial experimental design to identify the developmental toxicity characteristics of 10 typical developmental toxic pollutants such as PBBs to which humans are frequently exposed. Furthermore, the correlation and sensitivity analyses of molecular developmental toxicity and structural parameters were performed. The molecular key structural parameters of the pollutants affecting human development were screened. Moreover, the supplementary food factors that could alleviate the developmental toxicity of pollutants were screened to develop supplementary food schemes to prevent or alleviate human developmental toxicity in the special population (e.g., pregnant women, infants) exposed to the pollutants. The results showed that the developmental toxicity was controlled by the main effects of the 10 pollutants. Among the 10 pollutants with developmental toxicity, the most significant pollutant with the main effects was PBB-153 (37.06%). In addition, the correlation and sensitivity analyses of the molecular developmental toxicity of the pollutants and structural parameters showed that the total energy value and infrared C-H vibration frequency of the pollutants were significantly correlated with human developmental toxicity. Accordingly, 15 supplementary food cofactors were selected for the Taguchi experiment design, among which the top seven cofactors were designed by fractional factorial analysis. The most significant cofactor that alleviated the developmental toxicity of PBB-153 exposure was the combination of carotene and docosahexaenoic acid (DHA), with an improvement of 17.28%. The combination of carotene and DHA significantly alleviated the effects of toxicity caused by most of the other pollutants, indicating that the selected supplementary food has certain universality. In this study, we developed a method to identify the characteristics of the developmental toxicity of pollutant exposure and developmental toxicity alleviation. Our study provided theoretical support for the regulation strategy of developmental toxicity caused by pollutants such as PBBs.