Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Treatment of tibial bone defects caused by infection: a retrospective comparative study of bone transport using a combined technique of unilateral external fixation over an intramedullary nail versus circular external fixation over an intramedullary nail.

BACKGROUND: The purpose of the study was to assess and compare the clinical efficacy of bone transport with either circular or unilateral external fixators over an intramedullary nail in the treatment of tibial bone defects caused by infection. METHODS: Between May 2010 and January 2019, clinical and radiographic data were collected and analyzed for patients with bone defects caused by infection. Thirteen patients underwent bone transport using a unilateral external fixator over an intramedullary nail (Group A), while 12 patients were treated with a circular external fixator over an intramedullary nail (Group B). The bone and functional outcomes of both groups were assessed and compared using the Association for the Study and Application of the Method of the Ilizarov criteria, and postoperative complications were evaluated according to the Paley classification. RESULTS: A total of 25 patients were successfully treated with bone transport using external fixators over an intramedullary nail, with a mean follow-up time of 31.63 ± 5.88 months. There were no significant statistical differences in age, gender, previous surgery per patient, duration of infection, defect size, and follow-up time between Group A and Group B (P > 0.05). However, statistically significant differences were observed in operation time (187.13 ± 21.88 min vs. 255.76 ± 36.42 min, P = 0.002), intraoperative blood loss (39.26 ± 7.33 mL vs. 53.74 ± 10.69 mL, P < 0.001), external fixation time (2.02 ± 0.31 month vs. 2.57 ± 0.38 month, P = 0.045), external fixation index (0.27 ± 0.08 month/cm vs. 0.44 ± 0.09 month/cm, P = 0.042), and bone union time (8.37 ± 2.30 month vs. 9.07 ± 3.12, P = 0.032) between Group A and Group B. The excellent and good rate of bone and functional results were higher in Group A compared to Group B (76.9% vs. 75% and 84.6% vs. 58.3%). Statistically significant differences were observed in functional results (excellent/good/fair/poor, 5/6/2/0 vs. 2/5/4/1, P = 0.013) and complication per patient (0.38 vs. 1.16, P = 0.012) between Group A and Group B. CONCLUSIONS: Bone transport using a combined technique of external fixators over an intramedullary nail proved to be an effective method in treating tibial bone defects caused by infection. In comparison to circular external fixators, bone transport utilizing a unilateral external fixator over an intramedullary nail resulted in less external fixation time, fewer complications, and better functional outcomes.

Robotic Actuation-Mediated Quantitative Mechanogenetics for Noninvasive and On-Demand Cancer Therapy.

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high-power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation-mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death-associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase-dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early- and middle-stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late-stage tumor (500 mm3) are realized in tumor-bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage-derived therapy represents a quantitative strategy for cancer treatment.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation.

BACKGROUND: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex's UA-lowering and nephroprotective effects in vivo. METHODS: A mouse with HUA was used to investigate the complex's hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. RESULTS: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. CONCLUSIONS: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.

Innovative explorations: unveiling the potential of organoids for investigating environmental pollutant exposure.

As the economy rapidly develops, chemicals are widely produced and used. This has exacerbated the problems associated with environmental pollution, raising the need for efficient toxicological evaluation techniques to investigate the toxic effects and mechanisms of toxicity of environmental pollutants. The progress in the techniques of cell culture in three dimensions has resulted in the creation of models that are more relevant in terms of biology and physiology. This enables researchers to study organ development, toxicology, and drug screening. Adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) can be obtained from various mammalian tissues, including cancerous and healthy tissues. Such stem cells exhibit a significant level of tissue memory and ability to self-assemble. When cultivated in 3D in vitro environments, the resulting organoids demonstrate a remarkable capacity to recapitulate the cellular composition and function of organs in vivo. Recently, many tumors' tissue-derived organoids have been widely used in research on tumor pathogenesis, drug development, precision medicine, and other fields, including those derived from colon cancer, cholangiocarcinoma, liver cancer, and gastric cancer. However, the application of organoid models for evaluating the toxicity of environmental pollutants is still in its infancy. This review introduces the characteristics of the toxicity responses of organoid models upon exposure to pollutants from the perspectives of organoid characteristics, tissue types, and their applications in toxicology; discusses the feasibility of using organoid models in evaluating the toxicity of pollutants; and provides a reference for future toxicological studies on environmental pollutants based on organoid models.

GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITR+CD8+ T lymphocytes in CDE Mice.

As an alternative pathway for liver regeneration, liver progenitor cells and their derived ductular reaction cells increase during the progression of many chronic liver diseases. However, the mechanism underlying their hepatocyte repopulation after liver injury remains unknown. Here, we conducted progenitor cell lineage tracing in mice and found that fewer than 2% of hepatocytes were derived from liver progenitor cells after 9 weeks of injury with a choline-deficient diet supplemented with ethionine (CDE), and this percentage increased approximately three-fold after 3 weeks of recovery. We also found that the proportion of liver progenitor cells double positive for the ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL, also called Tnfsf18) and SRY-related HMG box transcription 9 (Sox9) among nonparenchymal cells increased time-dependently upon CDE injury and reduced after recovery. When GITRL was conditionally knocked out from hepatic progenitor cells, its expression in nonparenchymal cells was downregulated by approximately fifty percent, and hepatocyte repopulation increased by approximately three folds. Simultaneously, conditional knockout of GITRL reduced the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumour necrosis factor receptor (GITR)-positive CD8+ T lymphocytes. Mechanistically, GITRL stimulated cell proliferation but suppressed the differentiation of liver progenitor organoids into hepatocytes, and CD8+ T cells further reduced their hepatocyte differentiation by downregulating the Wnt/ß-catenin pathway. Therefore, GITRL expressed by liver progenitor cells impairs hepatocyte differentiation, thus hindering progenitor cell-mediated liver regeneration.

[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Traditional Chinese medicine inspired dual-drugs loaded inhalable nano-therapeutics alleviated idiopathic pulmonary fibrosis by targeting early inflammation and late fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a highly debilitating and fatal chronic lung disease that is difficult to cure clinically. IPF is characterized by a gradual decline in lung function, which leads to respiratory failure and severely affects patient quality of life and survival. Oxidative stress and chronic inflammation are believed to be important pathological mechanisms underlying the onset and progression of IPF, and the vicious cycle of NOX4-derived ROS, NLRP3 inflammasome activation, and p38 MAPK in pulmonary fibrogenesis explains the ineffectiveness of single-target or single-drug interventions. In this study, we combined astragaloside IV (AS-IV) and ligustrazine (LIG) based on the fundamental theory of traditional Chinese medicine (TCM) of "tonifying qi and activating blood" and loaded these drugs onto nanoparticles (AS_LIG@PPGC NPs) that were inhalable and could penetrate the mucosal barrier. Our results suggested that inhalation of AS_LIG@PPGC NPs significantly improved bleomycin-induced lung injury and fibrosis by regulating the NOX4-ROS-p38 MAPK and NOX4-NLRP3 pathways to treat and prevent IPF. This study not only demonstrated the superiority, feasibility, and safety of inhalation therapy for IPF intervention but also confirmed that breaking the vicious cycle of ROS and the NLRP3 inflammasome is a promising strategy for the successful treatment of IPF. Moreover, this successful nanoplatform is a good example of the integration of TCM and modern medicine.

miR-638 suppresses cervical cancer progression by inhibiting NCAPG2 under the treatment of Tetrandrine.

BACKGROUND: The interaction of microRNA with Chinese herbal medicines is a promising therapeutic approach for prevention of cervical cancer. METHODS: Western blotting or qRT-PCR were carried out to identify the expression of NCAPG2 and miR-638. A tetrandrine (TET) cell model was used to explore the effects of miR-638 and its target gene NCAPG2 using CCK-8, transwell, wound healing, and western blot assays. Furthermore, luciferase activity assay was conducted to measure the interaction among TET, NCAPG2 and miR-638. RESULTS: Under TET treatment, Hela and SiHa cells exhibited repressed cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and these effects were further enhanced by high expression of miR-638. In contrast, NCAPG2 expression was low in TET-treated cells and had an opposite effect to that of miR-638. CONCLUSION: We highlighted that miR-638 suppresses cervical cancer progression by inhibiting NCAPG2 under tetrandrine treatment.

Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.

Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.

Transcriptome analysis reveals the effect of acidic environment on adventitious root differentiation in Camellia sinensis.

The generation of adventitious roots (ARs) is the key to the success of cuttings. The appropriate environment for AR differentiation in tea plants is acidic. However, the mechanism is unclear. In this study, pH 4.5 was suitable condition for the differentiation of AR in tea plants. At the base of cuttings, the root primordia differentiated ARs more rapidly at pH 4.5 than pH 7.0, and nine AR differentiation-related genes were found to be differentially expressed in 30 days, the result was also validated by qRT-PCR. The promoter regions of these genes contained auxin and brassinosteroid response elements. The expression levels of several genes which were involved in auxin and brassinosteroid synthesis as well as signaling at pH 4.5 compared to pH 7.0 occurred differential expression. Brassinolide (BL) and indole-3-acetic acid (IAA) could affect the differentiation of ARs under pH 4.5 and pH 7.0. By qRT-PCR analysis of genes during ARs generation, BL and IAA inhibited and promoted the expression of CsIAA14 gene, respectively, to regulate auxin signal transduction. Meanwhile, the expression levels of CsKNAT4, CsNAC2, CsNAC100, CsWRKY30 and CsLBD18 genes were up-regulated upon auxin treatment and were positively correlated with ARs differentiation.This study showed that pH 4.5 was the most suitable environment for the root primordia differentiation of AR in tea plant. Proper acidic pH conditions promoted auxin synthesis and signal transduction. The auxin initiated the expression of AR differentiation-related genes, and promoted its differentiated. BL was involved in ARs formation and elongation by regulating auxin signal transduction.

The Epidemiological Characteristics of Pulmonary Tuberculosis in Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021.

Objective: This study aims to understand the characteristics and current situation of pulmonary tuberculosis (PTB) data of Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021, and to provide data support and a scientific basis for the prevention and control of PTB in the county. Methods: The data were collected from the National Notifiable Disease Reporting System (NNDRS), which included information reported such as the gender, ethnicity, age, occupation, and diagnostic classification of reported PTB cases. Descriptive statistics were used to describe the characteristics of PTB patients. The SPSS 21.0 data analysis tool was used to analyze patient data, investigating the epidemiological characteristics of PTB in the region. Results: There were 4962 PTB cases reported from 2011 to 2021 in Ganxian District, with a decreasing trend. In terms of months, March and September had the highest cumulative number of reported cases, with 511 cases (10.3%) and 515 cases (10.4%), respectively. In terms of reported cases by area, Meilin Town and Jiangkou Town had the highest number, with 603 and 519 cases, respectively. In terms of gender, there were more male patients (3743 cases) than female patients (1,219 cases) , which had statistically significant differences (χ2 = 27.0, P < .001). The majority of cases were secondary PTB, with farmers being the most affected (a total of 4287 cases) compared to other occupations. In addition, most patients were aged between 40 and 70 years (a total of 2790 cases). Regarding treatment outcomes, out of 4,962 PTB patients, 2088 were cured, with a cure rate of 42.1%. Conclusion: Based on the characteristics of PTB in the area, future prevention and control work should focus on males, farmers, young students, and the elderly, while also focusing on the prevention and control of secondary PTB.

The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.

Nutrients transport behavior in inlet river in the Yellow River Delta in winter.

The nutrients such as dissolved inorganic nitrogen (DIN, NH4+-N, NO2--N, and NO3--N), dissolved inorganic phosphorus (DIP, PO43-) and dissolved SiO2 (DSi) funneled by the inlet river are the dominant factors to coastal eutrophication. This study investigated nutrient transport process in typical inlet rivers in the Yellow River Delta. The indicator of coastal eutrophication potential and concentration ratio between upstream and downstream stations were used to evaluate the influence of different sources to the nutrient risks. It showed that urban areas are the most important source of the nutrients in studied rivers. The harbor and mariculture would have greater risk because of their proximity close to the coastal area. Wetland was a vital conversion to eliminate the river nutrients, and the retention could reach 80 %. It is imperative to protect and construct wetlands to reduce the nutrient pollution in the inlet river.

Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis.

BACKGROUND: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. METHODS: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. RESULTS: From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. CONCLUSIONS: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

An individual's characteristics, such as medical, biochemical, social, and behavioural may affect their response to interventions aimed at preventing gestational diabetes, which occurs during pregnancy. Here, we evaluated the published literature on interventions such as diet, lifestyle, drug treatment and nutritional supplement and looked at which individual participant characteristics were associated with response to these interventions. Certain participant characteristics were associated with greater prevention of gestational diabetes through particular treatments. Some interventions were more effective when started prior to conception. Future studies should consider individual characteristics when assessing the effects of preventative measures.

Lignans as multi-targeted natural products in neurodegenerative diseases and depression: Recent perspectives.

As the global population ages, the treatment of neurodegenerative diseases is becoming more and more important. There is an urgent need to discover novel drugs that are effective in treating neurological diseases. In recent years, natural products and their biological activities have gained widespread attention. Lignans are a class of metabolites extensively present in Chinese herbal medicine and possess good pharmacological effects. Latest studies have demonstrated their neuroprotective pharmacological activity in preventing acute/chronic neurodegenerative diseases and depression. In this review, the pharmacological effects of these disorders, the pharmacokinetics, safety, and clinical trials of lignans were summarized according to the scientific literature. These results proved that lignans mainly exert antioxidant and anti-inflammatory activities. Anti-apoptosis, regulation of nervous system functions, and modulation of synaptic signals are also potential effects. Despite the substantial evidence of the neuroprotective potential of lignans, it is not sufficient to support their use in the clinical management. Our study suggests that lignans can be used as prospective agents for the treatment of neurodegenerative diseases and depression, with a view to informing their further development and utilization.

Pharmacological action of Hedysarum polysaccharides: a review.

Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.

Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety.

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it.

Hydrated alginate polysaccharide fabrics grafted with sliver nanocrystals for wearable thermal and health management.

The creation of functional components with precise chemistries on carbohydrate polymers is of great significance for future wearable biomedicine and health management. Among various carbohydrate polymers, marine polysaccharide featured with antimicrobial, biodegradable and biocompatible properties is an ideal platform while the water-swelling nature makes it difficult to form stable interface. Here, well-dispersed silver nanoparticles have been in-situ assembled on hydrated alginate fabric (AF), involving chemical absorption of Ag ions and in-situ reduction of conductive Ag layer. Owing to the stable complex formed between Ag ions and carboxyl groups, the Ag-grafted AF exhibits superior Joule heating capability, including low operating voltage (1-3 V), high saturation temperature (63 °C), rapid response time (25 s) and outstanding durability against harsh conditions. Furthermore, the Ag-grafted AF demonstrates noticeable inhibition against E. coli and S. aureus as compared with the pristine AF. This work provides a rational strategy for the functionalization of hydrated polysaccharide and enables wearable thermotherapy devices for human health management.