Xiyuan Hospital

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.

Extracellular neuritic plaques composed of amyloid‑β (Aβ) protein and intracellular neurofibrillary tangles containing phosphorylated tau protein are the two hallmark proteins of Alzheimer's disease (AD), and the separate neurotoxicity of these proteins in AD has been extensively studied. However, interventions that target Aβ or tau individually have not yielded substantial breakthroughs. The interest in the interactions between Aβ and tau in AD is increasing, but related drug investigations are in their infancy. This review discusses how Aβ accelerates tau phosphorylation and the possible mechanisms and pathways by which tau mediates Aβ toxicity. This review also describes the possible synergistic effects between Aβ and tau on microglial cells and astrocytes. Studies suggest that the coexistence of Aβ plaques and phosphorylated tau is related to the mechanism by which Aβ facilitates the propagation of tau aggregation in neuritic plaques. The interactions between Aβ and tau mediate cognitive dysfunction in patients with AD. In summary, this review summarizes recent data on the interplay between Aβ and tau to promote a better understanding of the roles of these proteins in the pathological process of AD and provide new insights into interventions against AD.

Importance: Electroacupuncture involving the lumbosacral region may be effective for women with stress urinary incontinence (SUI), but evidence is limited. Objective: To assess the effect of electroacupuncture vs sham electroacupuncture for women with SUI. Design, Setting, and Participants: Multicenter, randomized clinical trial conducted at 12 hospitals in China and enrolling 504 women with SUI between October 2013 and May 2015, with data collection completed in December 2015. Interventions: Participants were randomly assigned (1:1) to receive 18 sessions (over 6 weeks) of electroacupuncture involving the lumbosacral region (n = 252) or sham electroacupuncture (n = 252) with no skin penetration on sham acupoints. Main Outcomes and Measures: The primary outcome was change from baseline to week 6 in the amount of urine leakage, measured by the 1-hour pad test. Secondary outcomes included mean 72-hour urinary incontinence episodes measured by a 72-hour bladder diary (72-hour incontinence episodes). Results: Among the 504 randomized participants (mean [SD] age, 55.3 [8.4] years), 482 completed the study. Mean urine leakage at baseline was 18.4 g for the electroacupuncture group and 19.1 g for the sham electroacupuncture group. Mean 72-hour incontinence episodes were 7.9 for the electroacupuncture group and 7.7 for the sham electroacupuncture group. At week 6, the electroacupuncture group had greater decrease in mean urine leakage (-9.9 g) than the sham electroacupuncture group (-2.6 g) with a mean difference of 7.4 g (95% CI, 4.8 to 10.0; P < .001). During some time periods, the change in the mean 72-hour incontinence episodes from baseline was greater with electroacupuncture than sham electroacupuncture with between-group differences of 1.0 episode in weeks 1 to 6 (95% CI, 0.2-1.7; P = .01), 2.0 episodes in weeks 15 to 18 (95% CI, 1.3-2.7; P < .001), and 2.1 episodes in weeks 27 to 30 (95% CI, 1.3-2.8; P < .001). The incidence of treatment-related adverse events was 1.6% in the electroacupuncture group and 2.0% in the sham electroacupuncture group, and all events were classified as mild. Conclusions and Relevance: Among women with stress urinary incontinence, treatment with electroacupuncture involving the lumbosacral region, compared with sham electroacupuncture, resulted in less urine leakage after 6 weeks. Further research is needed to understand long-term efficacy and the mechanism of action of this intervention. Trial Registration: clinicaltrials.gov Identifier: NCT01784172.

Chemoresistance is one of the major challenges for the breast cancer treatment. Owing to its heterogeneous nature, the chemoresistance mechanisms of breast cancer are complicated, and not been fully elucidated. The existing treatments fall short of offering adequate solution to drug resistance, so more effective approaches are desperately needed to improve existing therapeutic regimens. To overcome this hurdle, a number of strategies are being investigated, such as novel agents or drug carriers and combination treatment. In addition, some new therapeutics including gene therapy and immunotherapy may be promising for dealing with the resistance. In this article, we review the mechanisms of chemoresistance in breast cancer. Furthermore, the potential therapeutic methods to overcome the resistance were discussed.

Cardiovascular disease (CVD) is the leading cause of death worldwide, especially in developed countries, and atherosclerosis (AS) is the common pathological basis of many cardiovascular diseases (CVDs) such as coronary heart disease (CHD). The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide (TMAO), an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metabolism, and atherothrombosis. We also summarize available clinical studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events (MACE), in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.

For clinical studies with continuous outcomes, when the data are potentially skewed, researchers may choose to report the whole or part of the five-number summary (the sample median, the first and third quartiles, and the minimum and maximum values) rather than the sample mean and standard deviation. In the recent literature, it is often suggested to transform the five-number summary back to the sample mean and standard deviation, which can be subsequently used in a meta-analysis. However, if a study contains skewed data, this transformation and hence the conclusions from the meta-analysis are unreliable. Therefore, we introduce a novel method for detecting the skewness of data using only the five-number summary and the sample size, and meanwhile, propose a new flow chart to handle the skewed studies in a different manner. We further show by simulations that our skewness tests are able to control the type I error rates and provide good statistical power, followed by a simulated meta-analysis and a real data example that illustrate the usefulness of our new method in meta-analysis and evidence-based medicine.

α-linolenic acid (ALA, 18:3n-3) is a carboxylic acid composed of 18 carbon atoms and three cis double bonds, and is an essential fatty acid indispensable to the human body. This study aims to systematically review related studies on the dietary sources, metabolism, and pharmacological effects of ALA. Information on ALA was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library, and Europe PMC using a combination of keywords including "pharmacology," "metabolism," "sources." The following findings are mainly contained. (a) ALA can only be ingested from food and then converted into eicosapentaenoic acid and docosahexaenoic acid in the body. (b) This conversion process is relatively limited and affected by many factors such as dose, gender, and disease. (c) Pharmacological research shows that ALA has the anti-metabolic syndrome, anticancer, antiinflammatory, anti-oxidant, anti-obesity, neuroprotection, and regulation of the intestinal flora properties. (d) There are the most studies that prove ALA has anti-metabolic syndrome effects, including experimental studies and clinical trials. (e) The therapeutic effect of ALA will be affected by the dosage. In short, ALA is expected to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of ALA.

Background Pyroptosis is a new programmed cell death discovered in recent years. Pyroptosis plays an important role in various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using a bibliometric analysis to help understand the future development of basic and clinical research. Methods The articles and reviews regarding pyroptosis were culled from Web of Science Core Collection. Countries, institutions, authors, references and keywords in this field were visually analyzed by using CtieSpace and VOSviewer software. Results A total of 2845 articles and reviews were included. The number of articles regarding pyroptosis significantly increased yearly. These publications mainly come from 70 countries led by China and the USA and 418 institutions. We identified 605 authors, among which Thirumaladevi Kanneganti had the most significant number of articles, and Shi JJ was co-cited most often. Frontiers in immunology was the journal with the most studies, and Nature was the most commonly cited journal. After analysis, the most common keywords are nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, cell death, gasdermin D, mechanism, caspase-1, and others are current and developing areas of study. Conclusion Research on the pyroptosis is flourishing. Cooperation and exchanges between countries and institutions must be strengthened in the future. The related pathway mechanism of pyroptosis, the relationship between pyroptosis and other types of programmed cell deaths as well as the role of pyroptosis in various diseases have been the focus of current research and developmental trends in the future research.

mice. The effects are more pronounced for the high dose. This anti-atherosclerotic effect of BBR may be partly attributed to changes in composition and functions of gut microbiota which may be associated with anti-inflammatory and metabolism of glucose and lipid. Notably, gut microbiota alterations showed different sensitivity to BBR dose.

BACKGROUND: Observational studies suggest that the risk and clinical prognosis of coronavirus disease 2019 (COVID-19) are related to low vitamin D status; however, the data are inconsistent. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the association between low vitamin D status and COVID-19. METHODS: A systematic search was conducted with PubMed, Embase, and the Cochrane Library from database inception to September 25, 2020. The standardized mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) was applied to estimate pooled results. Random - or fixed-effect models based on heterogeneity were used for the meta-analysis. Funnel plots and Egger regression tests were used to assess publication bias. RESULTS: A total of ten articles with 361,934 participants were selected for meta-analysis. Overall, the pooled OR in the fixed-effect model showed that vitamin D deficiency or insufficiency was associated with an increased risk of COVID-19 (OR = 1.43, 95% CI 1.00-2.05). In addition, COVID-19-positive individuals had lower vitamin D levels than COVID-19-negative individuals (SMD = -0.37, 95% CI = -0.52 to -0.21). Significant heterogeneity existed in both endpoints. Funnel plots and Egger regression tests revealed significant publication bias. CONCLUSIONS: This systematic review and meta-analysis indicated that low vitamin D status might be associated with an increased risk of COVID-19 infection. Further studies are needed to evaluate the impact of vitamin D supplementation on the clinical severity and prognosis in patients with COVID-19. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no: CRD42020216740.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

The 2019 coronavirus disease (COVID-19) has become a global pandemic. Several studies report that ABO blood group polymorphism may be related to COVID-19 susceptibility and clinical outcomes; however, the results are controversial. We conducted a systematic review and meta-analysis to investigate whether ABO blood groups are associated with increased COVID-19 morbidity and mortality. A total of 715 articles were retrieved from seven databases. Ten articles were selected for meta-analysis after removal of duplicates and two levels of screenings. Overall, individuals with blood group A [odds ratio (OR) = 1.33, 95% confidence interval (CI) 1.14 to 1.56] and B (OR = 1.06, 95% CI 1.00 to 1.13) had a substantially higher risk of COVID-19, whereas this was not the case for blood group AB (OR = 1.07, 95% CI 0.88 to 1.30). Individuals with blood group O was not prone to develop the disease (OR = 0.71, 95% CI 0.60 to 0.84). Moreover, the risk of COVID-19 was significantly associated with the Rh-positive blood group (OR = 1.22, 95% CI 0.99 to 1.50). A meta-analysis of 5 studies suggested that blood group A was associated with a significantly increased risk of COVID-19 mortality (OR = 1.25, 95% CI 1.02 to 1.52). Mild publication bias was found in the included studies. This systematic review and meta-analysis indicated that blood groups A and B may be risk factors for COVID-19, whereas the blood group O appears to be protective. Blood group A may be related to unfavourable outcomes. Further rigorous and high-quality research evidence is needed to confirm this association.

Background Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

Datura metel is a plant that contains several different neurologically active phytochemicals which affect human health. On-going research has examined the potential role of the human neuroindoles, melatonin and serotonin, in medicinal plants with neurological efficacy. In this report, we describe the quantification of melatonin and serotonin in flowers and developing fruits of Datura metel and the effects of cold stress on the levels of these neuroindoles in the reproductive tissues of this plant. Melatonin and serotonin were found at the highest levels in the least developed flower buds with decreasing concentrations as the flower buds matured. Cold stress significantly increased the concentration of melatonin in young flower buds. In the developing fruit, melatonin was present at relatively stable, high concentrations for the first 10 days after anthesis. After 10-15 days, the ovule had grown to a sufficient size for excision and analysis and melatonin was found to be at the highest concentrations in the developing ovule with minimal concentrations of the neuroindoles in the fleshy fruit. Together, these data indicate that melatonin may play a role in protecting the reproductive tissues during flower and seed formation in a Datura species.

BACKGROUND: Inflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular mechanisms by which berberine confers an anti-inflammatory effect in macrophages by upregulation of autophagy. METHODS: J774A.1 macrophages were incubated with various doses of ox-LDL for various times. We evaluated the inflammatory factors and autophagy proteins (LC3II/LC3I, and SQSTM1/p62) to ascertain the optimal dose and time. Ox-LDL-induced inflammatory factors and autophagy in J774A.1 cells were tested by the AimPlex multiplex assay, Western blotting, confocal microscopy, and transmission electron microscopy in the presence of berberine or chloroquine (CQ). Adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor compound C was used to evaluate the AMPK/mTOR signaling pathway. RESULTS: Berberine dose- and time-dependently reduced ox-LDL-induced inflammation and increased the ratio of LC3II/LC3I, and SQSTM1/p62 in J774A.1 cells. CQ significantly attenuated the berberine-induced autophagy and anti-inflammation. In addition, berberine increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR. AMPK inhibitor compound C abolished berberine-induced autophagy and promoted p-mTOR/mTOR expression in J774A.1 cells. CONCLUSION: Berberine treatment inhibits inflammation in J774A.1 cells by inducing autophagy, which is mediated through activation of the AMPK/mTOR signaling pathway. Importantly, this study provides new insight into berberine's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.

Background: Cancer centers have increasingly offered integrative medicine therapies in response to their patients' unmet needs. We evaluated the growth of integrative medicine in leading academic cancer centers in the United States as reflected by their public-facing websites. Methods: We performed a systematic review of 45 National Cancer Institute (NCI)-designated comprehensive cancer center websites. Two researchers independently evaluated whether the websites provided information regarding integrative medicine modalities and, if so, whether the services were provided in the same health system. They compared the proportion of cancer centers providing the information on each modality in 2016 with the data from the prior study in 2009. Results: The most common integrative medicine therapies mentioned on the 45 NCI-designated comprehensive cancer center websites were exercise (97.8%) and acupuncture and meditation (88.9% each), followed by yoga (86.7%), massage (84.4%), and music therapy (82.2%). The majority of the websites also provided information on nutrition (95.6%), dietary supplements (93.3%), and herbs (88.9%). The most common therapies offered in the health systems were acupuncture/massage (73.3% each), meditation/yoga (68.9% each), and consultations about nutrition (91.1%), dietary supplements (84.4%), and herbs (66.7%). Compared with 2009, there was a statistically significant increase in the number of websites mentioning acupuncture, dance therapy, healing touch, hypnosis, massage, meditation, Qigong, and yoga (all P < .05). Conclusions: Leading US cancer centers increasingly present integrative medicine content on their websites, and the majority of them provide these services to patients in the same health systems.

Alzheimer’s disease (AD) is the most common form of dementia characterized by progressive loss of cognitive functions due to neuronal death mainly in the hippocampal and cortical brain. Sulforaphene (SF) is one of the main isothiocyanates isolated from a Chinese herb Raphani Semen. In this study, we aimed to investigate the neuroprotective effects of SF using in vitro and in vivo models of AD. Streptozotocin (STZ) was intracranially injected into the rats; then, SF (25 and 50 mg/kg) was given orally once a day for 6 consecutive weeks. After drug treatment, the cognitive functions were assessed using the Morris Water Maze Test (MWMT). After the MWMT, the rats were euthanized and brain tissues were collected. In the in vitro test, BV-2 microglia were pretreated with SF (1 and 2 μ M) for 1 h and then stimulated with lipopolysaccharide (LPS) for another 23 h. Both molecular and histological methods were used to unravel the action mechanisms and elucidate the signaling pathway. The MWMT results showed that SF treatment significantly improved the STZ-induced cognitive deficits in rats. SF treatment markedly suppressed the production of tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6) but increased the release of IL-10 in the STZ-treated rats. In addition, SF significantly inhibited the phosphorylation of tau protein at Thr205, Ser396, and Ser404 sites, while enhancing the ratios of p-Akt (Ser473)/Akt and p-GSK-3 β (Ser9)/GSK-3 β in the hippocampus of the STZ-treated rats. On the other hand, SF (1 and 2 μ M) treatment also markedly attenuated the cytotoxicity induced by LPS in BV-2 cells. In addition, SF treatment obviously suppressed the releases of nitric oxide (NO), TNF- α , and IL-6 in the LPS-stimulated BV-2 cells. Moreover, SF treatment significantly mitigated the nuclear translocation of p-NF- κ B p65 and the ratio of p-GSK-3 β (Ser9)/GSK-3 β in LPS-stimulated BV-2 cells. Taken together, SF possessed neuroprotective effects against the STZ-induced cognitive deficits in rats and LPS-induced neuroinflammation in BV-2 cells via modulation of the PI3K/Akt/GSK-3 β pathway and inhibition of the NF- κ B activation, suggesting that SF is a promising neuroprotective agent worthy of further development into AD treatment.

Cognitive impairment (CI) refers to the dysfunction of memory, language, visual space, execution, calculation, understanding, and judgment in one or more aspects. With global aging, CI will become prevalent worldwide. At present, there is no effective cure for CI. However, Nobel laureate Tu Youyou’s research on artemisinin has inspired Chinese researchers to focus on traditional Chinese herbs (TCHs) for the treatment of CI. Traditional Chinese Medicine (TCM) has led to a theory for an independent CI system. The pathogenesis of such impairment involves deficiency, phlegm, and stagnation and involves a range of organs, including the brain, kidneys, heart, liver, and spleen. Our current understanding of the etiology and pathogenesis of this condition has led to the realization that TCHs can improve cognitive dysfunction. Clinical research has shown that TCHs can improve the neuropsychological scale score of patients, the TCM symptom score, and the patient’s quality of life. Research has also suggested that TCHs can retard A[Formula: see text] deposits and tauopathy, regulate the metabolism of cholinergic neurotransmitters, and so on. However, due to their complexity, little is known of the safety and efficacy of TCHs in patients with CI. It is likely that we will be able to identify the precise mechanisms associated with the action of TCHs in such patients due to the integration of multiple technologies. This paper summarizes the pharmacokinetics, curative effect, and mechanisms of action of traditional Chinese herbs in order to provide a scientific basis for the improvement of cognitive dysfunction by TCHs.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.