Radical Scavenging Capability and Mechanism of Three Isoflavonoids Extracted from Radix Astragali: A Theoretical Study.

As a valuable traditional Chinese herbal medicine, Radix Astragali has attracted much attention due to its extensive pharmacological activities. In this study, density functional theory (DFT) was used thermodynamically and kinetically in detail to predict the antioxidant activity and reaction mechanisms involved in the free radical scavenging reactions of three representative isoflavonoids (formononetin, calycosin, and calycosin-7-glucoside) extracted from Radix Astragali. Three main mechanisms, including hydrogen atom transfer (HAT), proton transfer after electron transfer (SET-PT), and sequential proton loss electron transfer (SPLET) were examined by calculating the thermodynamic parameters. It was found that HAT is the predominant mechanism in the gas phase, while SPLET is supported in the solvent environment. The isoflavonoids' order of antioxidant activity was estimated as: calycosin > calycosin-7-glucoside > formononetin. For the calycosin compound, the result revealed the feasibility of double HAT mechanisms, which involve the formation of stable benzodioxazole with significantly reduced energy in the second H+/e- reaction. In addition, the potential energy profiles and kinetic calculations show that the reaction of •OH into the 3'-OH site of calycosin has a lower energy barrier (7.2 kcal/mol) and higher rate constant (4.55 × 109 M-1 s-1) compared with other reactions in the gas phase.

Sc@B28-, Ti@B28, V@B28+, and V@B292-: Spherically Aromatic Endohedral Seashell-like Metallo-Borospherenes.

Transition-metal-doped boron nanoclusters exhibit unique structures and bonding in chemistry. Using the experimentally observed seashell-like borospherenes C2 B28-/0 and Cs B29- as ligands and based on extensive first-principles theory calculations, we predict herein a series of novel transition-metal-centered endohedral seashell-like metallo-borospherenes C2 Sc@B28- (1), C2 Ti@B28 (2), C2 V@B28+ (3), and Cs V@B292- (4) which, as the global minima of the complex systems, turn out to be the boron analogues of dibenzenechromium D6h Cr(C6H6)2 with two B12 ligands on the top and bottom interconnected by four or five corner boron atoms on the waist and one transition-metal "pearl" sandwiched at the center in between. Detailed molecular orbital, adaptive natural density partitioning (AdNDP), and iso-chemical shielding surface (ICSS) analyses indicate that, similar to Cr(C6H6)2, these endohedral seashell-like complexes follow the 18-electron rule in bonding patterns (1S21P61D10), rendering spherical aromaticity and extra stability to the systems.

Primary Care Physicians' and Patients' Perspectives on Equity and Health Security of Infectious Disease Digital Surveillance.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic facilitated the rapid development of digital detection surveillance (DDS) for outbreaks. This qualitative study examined how DDS for infectious diseases (ID) was perceived and experienced by primary care physicians and patients in order to highlight ethical considerations for promoting patients' autonomy and health care rights. METHODS: In-depth interviews were conducted with a purposefully selected group of 16 primary care physicians and 24 of their patients. The group was reflective of a range of ages, educational attainment, and clinical experiences from urban areas in northern and southern China. Interviews were audio recorded, transcribed, and translated. Two researchers coded data and organized it into themes. A third researcher reviewed 15% of the data and discussed findings with the other researchers to assure accuracy. RESULTS: Five themes were identified: ambiguity around the need for informed consent with usage of DDS; importance of autonomous decision making; potential for discrimination against vulnerable users of DDS for ID; risk of social inequity and disparate care outcomes; and authoritarian institutions' responsibility for maintaining health data security. The adoption of DDS meant some patients would be reluctant to go to the hospital for fear of either being discriminated against or forced into quarantine. Certain groups (older people and children) were thought to be vulnerable to DDS misappropriation. CONCLUSIONS: These findings indicate the paramount importance of establishing national and international ethical frameworks for DDS implementation. Frameworks should guide all aspects of ID surveillance, addressing privacy protection and health security, and underscored by principles of social equity and accountability.Annals "Online First" article.

Lanthanide/actinide boride nanoclusters and nanomaterials based on boron frameworks consisting of conjoined Bn rings (n = 7-9).

Extensive global minimum searches augmented with first-principles theory calculations performed in this work indicate that the experimentally observed perfect inverse sandwich lanthanide boride complexes D7h La2B7- (1), D8h La2B8 (3), D9h La2B9- (7) can be extended to their actinide counterparts C2v Ac2B7- (1'), D8h Ac2B8 (3'), D9h Ac2B9- (7') with a Bn monocyclic ring (n = 7-9) sandwiched by two Ac dopants. Such M2Bn-/0 inverse sandwiches (1/1', 3/3', 7/7') can be used as building blocks to generate the ground-state C2 La4B13- (2)/Ac4B13- (2'), D2 La4B15- (4)/Ac4B15- (4'), C3v/C3 La4B18 (5)/Ac4B18 (5'), Oh Ac7B24+ (6'), Oh Ac7B24, Td Ac4B24 (8'), C1 La5B24+ (9)/Ac5B24+ (9'), and Td Ac4B29- (10') which are based on boron frameworks consisting of multiple conjoined Bn rings (n = 7-9). Detailed bonding analyses show that effective (d-p)σ, (d-p)π and (d-p)δ coordination bonds are formed between the Bn rings and metal doping centers, conferring three-dimensional aromaticity and extra stability to the systems. In particular, the perfect body-centered cubic Oh Ac7B24+ (6') and Oh Ac7B24 with six conjoined B8 rings can be extended in x, y, and z dimensions to form one-dimensional Ac10B32 (11'), two-dimensional Ac3B10 (12'), and three-dimensional AcB6 (13') nanomaterials, presenting a B8-based bottom-up approach from metal boride nanoclusters to their low-dimensional nanomaterials.

La@[La5&B30]0/-/2-: endohedral trihedral metallo-borospherenes with spherical aromaticity.

It is well-known that transition-metal-doping induces dramatic changes in the structures and bonding of small boron clusters, as demonstrated by the newly observed perfect inverse sandwich D8h [La(η8-B8)La] and D9h [La(η9-B9)La]-. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the possibility of perfect endohedral trihedral metallo-borospherene D3h La@[La5&B30] (1, 3A'1) and its monoanion Cs La@[La5&B30]- (2, 2A') and dianion D3h La@[La5&B30]2- (3, 1A'1). These La-doped boron clusters are composed of three inverse sandwich La(η8-B8)La on the waist and two inverse sandwich La(η9-B9)La on the top and bottom which share one apex La atom at the center and six periphery B2 units between neighboring η8-B8 and η9-B9 rings, with three octo-coordinate La atoms and two nona-coordinate La atoms as integrated parts of the cage surface. Detailed adaptive natural density partitioning (AdNDP) and iso-chemical shielding surface (ICSS) analyses indicate that La@[La5&B30]0/-/2- (1/2/3) are spherically aromatic in nature. The one-dimensional nanowire La4B21 (4, P31m) constructed from D3h La@[La5&B30] (1) along the C3 axis of the system appears to be metallic. The IR and Raman spectra of La@[La5&B30] (1) and photoelectron spectroscopy of the slightly distorted Cs La@[La5&B30]- (2) are theoretically simulated to facilitate their spectroscopic characterizations.

Ethics, Integrity, and Retributions of Digital Detection Surveillance Systems for Infectious Diseases: Systematic Literature Review.

BACKGROUND: The COVID-19 pandemic has increased the importance of the deployment of digital detection surveillance systems to support early warning and monitoring of infectious diseases. These opportunities create a "double-edge sword," as the ethical governance of such approaches often lags behind technological achievements. OBJECTIVE: The aim was to investigate ethical issues identified from utilizing artificial intelligence-augmented surveillance or early warning systems to monitor and detect common or novel infectious disease outbreaks. METHODS: In a number of databases, we searched relevant articles that addressed ethical issues of using artificial intelligence, digital surveillance systems, early warning systems, and/or big data analytics technology for detecting, monitoring, or tracing infectious diseases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and further identified and analyzed them with a theoretical framework. RESULTS: This systematic review identified 29 articles presented in 6 major themes clustered under individual, organizational, and societal levels, including awareness of implementing digital surveillance, digital integrity, trust, privacy and confidentiality, civil rights, and governance. While these measures were understandable during a pandemic, the public had concerns about receiving inadequate information; unclear governance frameworks; and lack of privacy protection, data integrity, and autonomy when utilizing infectious disease digital surveillance. The barriers to engagement could widen existing health care disparities or digital divides by underrepresenting vulnerable and at-risk populations, and patients' highly sensitive data, such as their movements and contacts, could be exposed to outside sources, impinging significantly upon basic human and civil rights. CONCLUSIONS: Our findings inform ethical considerations for service delivery models for medical practitioners and policymakers involved in the use of digital surveillance for infectious disease spread, and provide a basis for a global governance structure. TRIAL REGISTRATION: PROSPERO CRD42021259180; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259180.

The unified quantum mechanical structure of tubular molecular rotors with multiple equivalent global minimum structures: the 18*C2h → D9d case of La-[B2@B18]-La.

La-[B2@B18]-La demonstrates decisive changes of the properties of molecular rotors, from multiple (here 18) equivalent individual global minimum structures to a quantum mechanical unified structure. This affects their geometries, their symmetries (18*C2h → D9d), the generation of energy bands, and high-resolution spectroscopy.

Perfect Spherical Tetrahedral Metallo-Borospherene Ta4B18 as a Superatom Following the 18-Electron Rule.

Cage-like metallo-borospherenes exhibit unique structures and bonding. Inspired by the newly reported smallest spherical trihedral metallo-borospherene D 3h Ta3B12 - (1), which contains two equivalent B3 triangles interconnected by three B2 units on the cage surface, we present herein a first-principles theory prediction of the perfect spherical tetrahedral metallo-borospherene T d Ta4B18 (2), which possesses four equivalent B3 triangles interconnected by six B atoms, with four equivalent nonacoordinate Ta centers in four η9-B9 rings as integrated parts of the cage surface. As the well-defined global minimum of the neutral, Ta4B18 (2) possesses four 10c-2e B9(π)-Ta(dσ) and eight 10c-2e B9(π)-Ta(dδ) coordination bonds evenly distributed over four Ta-centered Ta@B9 nonagons, with the remaining 18 valence electrons in nine 22c-2e totally delocalized bonds following the 18-electron principle (1S21P61D10) of a superatom. Such a bonding pattern renders spherical aromaticity to the tetrahedral complex, which can be used as building blocks to form the face-centered cubic crystal Ta4B15 (3). The IR, Raman, and UV-vis spectra of Ta4B18 (2) are theoretically simulated to facilitate its future experimental characterizations.

Cage-like La4B24 and Core-Shell La4B290/+/- : perfect spherically aromatic tetrahedral metallo-borospherenes.

Cage-like and core-shell metallo-borospherenes exhibit interesting structures and bonding. Based on extensive global searches and first-principles theory calculations, we predict herein the perfect tetrahedral cage-like Td La4B24 (1) and core-shell Td La4B29 (2), Td La4B29+ (3), and Td La4B29- (4) which all possess the same geometrical symmetry as their carbon fullerene counterpart Td C28, with four equivalent interconnected B6 triangles on the cage surface and four nona-coordinate La centers in four conjoined η9-B9 rings. In these tetra-La-doped boron complexes, La4[B@B4@B24]0/+/- (2/3/4) in the structural motif of 1 + 4 + 28 contain a B-centered tetrahedral Td B@B4 core in a La-decorated tetrahedral La4B24 shell, with the negatively charged tetra-coordinate B- at the center being the boron analog of tetrahedral C in Td CH4 (B- ~ C). Detailed orbital and bonding analyses indicate that these Td lanthanide boride complexes are spherically aromatic in nature with a universal La--B9 (d-p) σ and (d-p) δ coordination bonding pattern. The IR, Raman, and UV-Vis or photoelectron spectra of these novel metallo-borospherenes are computationally simulated to facilitate their spectral characterizations. Graphical abstract.

Metal-centered monocyclic carbon wheel clusters with record coordination numbers in planar species.

The highest coordination number identified to date in planar species is CN = 10 in metal-centered monocyclic boron wheel clusters D 10h M©B10 - (M = Ta and Nb) (Galeev et. al., Angew. Chem. Int. Ed., 2012, 51, 2101). Extensive global minimum searches and first-principles theory calculations performed herein indicate that the experimentally observed LaC13 + and LaC14 + possess the well-defined global minima of perfect metal-centered monocyclic carbon wheel D 13h La©C13 + (1) and slightly off-centered C 2v La©C14 + (4) (1A1) with record coordination numbers of CN = 13 and 11 in planar structures, respectively, further pushing the boundary of our understanding of chemical structures and bonding. Detailed molecular orbital, nucleus-independent chemical shift, and ring current analyses indicate that D 13h La©C13 + (1) is σ + π dually aromatic in nature, with 14 totally delocalized in-plane σ electrons and 14 totally delocalized out-of-plane π electrons each matching the 4N + 2 aromatic rule (N σ = N π = 3). Similar σ + π dually aromatic metal-centered monocyclic wheel clusters D 13h Ca©C13 (2), C 13v Ac©C13 + (3), C 2v Y©B6C6 + (5), and C 2v Sc©B5C6 (6) have also been obtained with CN = 13, 13, 12, and 11, respectively. The results obtained in this work effectively enrich the chemical structures and bonding patterns of planar hypercoordinated complexes.

International incidence trends in early- and late-onset colorectal cancer: a population-based study.

PURPOSE: Knowing the global incidence of colorectal cancer (CRC), by sex and age of onset, is of great importance for understanding the disease burden of CRC. METHODS: The CRC incidence data, by cancer site, age of onset, sex, country, and year, were retrieved from the Cancer Incidence in Five Continents Vol. Plus database. Estimated annual percentage changes (EAPC) were calculated to quantify the temporal trends in the CRC age-standardized incidence rate. RESULTS: Globally, the incidence of late-onset CRC was heterogeneous and remained increasing in most countries. The highest incidence of late-onset colon and rectal cancer was both found in males in Slovakia (156.5/100,000 and 121.5/100,000, respectively). The most pronounced increases were mostly observed in developing countries, such as Brazil (colon cancer: EAPC = 5.87, 95% CI 3.18, 8.63; rectal cancer: EAPC = 4.68; 95% CI 2.78, 6.62). The highest incidence of early-onset colon and rectal cancer was found in females in Switzerland (4.2/100,000) and in males in South Korea (4.6/100,000), respectively. The incidences of early-onset CRC were increased in parts of countries, including countries experiencing a decline in late-onset CRC incidence, such as the USA, Germany, and Australia. The temporal trends of colon cancer were mostly aligned with those of rectal in most countries, independent of sex and age of onset. CONCLUSION: The increase of early-onset CRC incidence suggests more prevention initiatives are urgently warranted for young adults in the near future. Targeted and effective prevention measures are still needed among elderly populations.

Perfect cubic La-doped boron clusters La6&[La@B24]+/0 as the embryos of low-dimensional lanthanide boride nanomaterials.

La-doped boron nanoclusters have received considerable attention due to their unique structures and bonding. Inspired by recent experimental observations of the inverse sandwich D 8h La2B8 (1) and triple-decker C 2v La3B14 - (2) and based on extensive global searches and first-principles theory investigations, we present herein the possibility of the perfect cubic La-doped boron clusters O h La6&[La@B24]+ (3, 1A1g) and O h La6&[La@B24] (4, 2A2g) which appear to be the embryos of the metallic one-dimensional La10B32 (5) nanowire, two-dimensional La3B10 (6) nanosheet, and three-dimensional LaB6 (7) nanocrystal, facilitating a bottom-up approach to build cubic lanthanide boride nanostructures from gas-phase clusters. Detailed molecular orbital and bonding analyses indicate that effective (d-p)σ, (d-p)π and (d-p)δ covalent coordination interactions exist in La6&[La@B24]+/0 (3/4) clusters, while the 1D La10B32 (5), 2D La3B10 (6), and 3D LaB6 (7) crystals exhibit mainly electrostatic interactions between the trivalent La centers and cubic B24 frameworks, with weak but discernible coordination contributions from La (5d) ← B (2p) back-donations. The IR and Raman spectra of La6&[La@B24]+/0 (3/4) and band structures of La10B32 (5) and La3B10 (6) are computationally simulated to facilitate their future characterizations.

Predicting lanthanide boride inverse sandwich tubular molecular rotors with the smallest core-shell structure.

Lanthanide-boron binary clusters possess interesting structures and bonding which may provide insights into designing new boride nanomaterials. Inspired by the recently discovered mono-decker inverse sandwich D9h La2B9- (1A'1) (1) and based on the extensive first-principles theory calculations, we predict herein the possible existence of a series of bi-decker inverse sandwich di-lanthanide boron complexes including D9d La2[B18] (3A1g) (2), D9d La2[B18]2- (1A1g) (3), and C2h La2[B2@B18] (1Ag) (4) which all contain a tubular Bn ligand (n = 18, 20) sandwiched by two La atoms at the two ends. In these novel clusters, La2[B2@B18] (4) as a tubular molecular rotor with the smallest core-shell structure reported to date in boron-based nanoclusters possesses a B2-bar rotating constantly and almost freely inside the B18 tube around it at room temperature. Detailed bonding analyses indicate that these complexes are stablized by effective (d-p)σ, (d-p)π, and (d-p)δ coordination interactions between the La centers and Bn bi-decker ligand. Six multi-center fluxional σ-bonds between the B2-core and B18 tube in La2[B2@B18] (4) are found to be responsible for its unique fluxional behaviors. The IR and Raman spectra of the concerned species are simulated to facilitate their experimental characterization.

Fluxional Bonds in Planar B19 - , Tubular Ta@B20 - , and Cage-Like B39.

Based on detailed bonding analyses on the fluxional behaviors of planar B19 - , tubular Ta@B20 - , and cage-like B39 - , we propose the concept of fluxional bonds in boron nanoclusters as an extension of the classical localized bonds and delocalized bonds in chemistry. © 2018 Wiley Periodicals, Inc.

Hydrogen-rich saline protects rat from oxygen glucose deprivation and reperusion-induced apoptosis through VDAC1 via Bcl-2.

BACKGROUND: Hydrogen is received as an inert gas that thought to be non-functional in vivo previously. Recently, emerging evidences showed that in ischemia/reperfusion (IR) condition, hydrogen reduced cellular reactive oxygen species (ROS) production and ameliorated cell apoptosis. However, the underlying mechanism of hydrogen on IR-induced apoptosis remains elusive. Here we tried to unravel the mode of action of hydrogen with rat adrenal medulla cell line PC-12 in vitro. METHODS: The mitochondrial functions before and after oxygen glucose deprivation and reperfusion (OGD/RP) were determined with corresponding dyes. The expression of Bcl-2, Bax, VDAC1, cytochrome c and caspase 9 was detected using qRT-PCR and Western Blotting method. Then Bcl-2 inhibitor, AB-199, was applied to investigate the role of Bcl-2 in OGD/RP-induced cell apoptosis. Finally, we manipulated the expression of VDAC1 with plasmids transfection to understand the effects of VDAC1 on Bcl-2-mediated anti-apoptosis in OGD/RP. RESULTS: In this study, we demonstrated that hydrogen-rich saline (HRS) reduced OGD/RP-mediated neuronal loss by stimulating the expression of Bcl-2, which suppressed the activity of VDAC1. Consequently, HRS maintained the mitochondrial functions, restrained the release of cytochrome c and caspase 9 activation, resulting in ameliorated cell viability. CONCLUSIONS: HRS ameliorated OGD/RP-induced PC-12 cell apoptosis and provided a novel treatment option for ischemia.

Cage-like Ta@B complexes (n = 23-28, q = -1-+ 3) in 18-electron configurations with the highest coordination number of twenty-eight.

Inspired by recent observations of the highest coordination numbers of CN = 10 in planar wheel-type complexes in D10h Ta@B10- and CN = 20 in double-ring tubular species in D10d Ta@B20- and theoretical prediction of the smallest endohedral metalloborospherene D2 Ta@B22- (1) with CN = 22, we present herein the possibility of larger endohedral metalloborospherenes C2 Ta@B23 (2), C2 Ta@B24+ (3), C2v Ta@B24- (4), C1 Ta@B25 (5), D2d Ta@B26+ (6), C2 Ta@B272+ (7), and C2 Ta@B283+ (8) based on extensive first-principles theory investigations. These cage-like Ta@Bqn complexes with B6 pentagonal or B7 hexagonal pyramids on their surface turn out to be the global minima of the systems with CN = 23, 24, 24, 25, 26, 27, and 28, respectively, unveiling the highest coordination number of CN = 28 in spherical environments known in chemistry. Detailed bonding analyses show that 1-8 as superatoms conform to the 18-electron configuration with a universal σ + π double delocalization bonding pattern. They are effectively stabilized via spd-π coordination interactions between the Ta center and ηn-Bn ligand which match both geometrically and electronically. Such complexes may serve as embryos of novel metal-boride nanomaterials.

[Changes in the expression of EphA5/ephrinA5 in the CA3 region of the hippocampus in rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy].

OBJECTIVE: To investigate the changes in the expression of EphA5 and its ligand ephrinA5 in the hippocampus of rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy (TLE). METHODS: A total of 240 Sprague-Dawley rats were randomly divided into control group and TLE group, with 120 rats in each group. A rat model of lithium-pilocarpine TLE was established, and then the rats were divided into subgroups at 12 and 24 hours and 7, 15, 30, and 60 days after epilepsy was induced. In-situ hybridization was used to measure the mRNA expression of ephrinA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; immunohistochemistry was used to measure the protein expression of EphA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; Neo-Timm silver staining was used to observe mossy fiber sprouting in the CA3 region of the hippocampus in 2 rats. RESULTS: In-situ hybridization showed mRNA expression of ephrinA5 in the CA3 region of the hippocampus, but this was not found in the dentate gyrus. Compared with the control group at the same time point, the TLE group had a significant reduction in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced (P<0.05); at 30 and 60 days after epilepsy was induced, the TLE group had a gradual increase in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus, and there was no significant difference between the TLE and control groups (P>0.05). Immunohistochemistry showed that EphA5 protein was expressed in the CA3 region and the dentate gyrus of the hippocampus and had a similar trend of change as ephrinA5 mRNA. Neo-Timm silver staining showed that the TLE group developed marked mossy fiber sprouting in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced. CONCLUSIONS: Downregulation of ephrinA5 and EphA5 in the CA3 region of the hippocampus may participate in the mechanism of mossy fiber sprouting and is closely associated with the development and progression of epilepsy.

Factors associated with health-related quality of life among family caregivers of disabled older adults: a cross-sectional study from Beijing.

Because of the aging population and the shortage of standardized institutional solutions for long-term care (LTC) in China, family caregivers in Beijing are increasingly called upon to provide home care for disabled older adults. Caregivers face a heavy care burden, and decreased physical and mental health (MH). This study aims to describe health-related quality of life (HRQoL) and to identify its predictors for Chinese family caregivers of disabled older adults.A total of 766 caregivers were recruited from 5 communities in the Dongcheng District of Beijing. Measures included the 36-item Short-Form Health Survey (SF-36), the Zarit Caregiver Burden Interview (ZBI) scales, and the Chinese Social Support Rating Scale (SSRS). Hierarchical multiple regression (HMR) analysis was used to identify the predictors.HMR analysis showed that each block of independent variables (demographic characteristics of disabled older adults, demographic characteristics of caregivers, caregiving context, and subjective caregiver burden) had contributed significantly to caregivers' physical and mental quality of life. Subjective caregiver burden explained the greatest amount of total variance in all MH subscales and the 2nd greatest amount of variance in most physical subscales. Therefore, subjective caregiver burden was the strongest predictor of HRQoL.Our findings suggest that a decrease in caregiver burden can improve caregivers' HRQoL, and additional social support is important in decreasing the impact of caregiving on HRQoL. Importantly, an LTC system should be established in China as soon as possible.

Non-pharmacological interventions for caregivers of patients with schizophrenia: A meta-analysis.

It has been estimated that about 50-80% of patients with schizophrenia live with or closely contact with their caregivers, and rely on them for housing, and emotional and financial supports. Caregiving experience is usually described as stressful for their caregivers. Non-pharmacological interventions seem to be beneficial to improving life quality. However, there is still no meta-analysis focused on this topic to give an overview.We searched the electronic databases includingPubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure, respectively from the beginning of database to July 2015 for all the randomized controlled trialsevaluating the caregiver interventions. Continuous data were expressed mean differences (MD) with 95% confidential intervals (CIs). Standardized mean difference was planned to express, if different scales were used to measure the same outcome. We pooled the results using a random-effect model.As a result, nine studies met the inclusion criteria, comprising 608 randomized participants. In which, 321 participants were in interventional group, while 287 participants were in control group. Concerning the care burden, there was significant difference found between non-pharmacological interventions and control groups (n=290, MD -2.10, 95% CI -3.46 to -0.74, P=0.002; level of heterogeneity τ(2)=1.81, χ(2)=62.13, df=3, P<0.00001, I(2)=95%). However, no differences were found in family support, family functioning and satisfaction. Of note, our meta-analysis demonstrated the efficacy of non-pharmacological interventions for caregivers of schizophrenia, and supported the application in the clinical practice. However, all the conclusions should be explained cautiously and further confirmation is required by well-designed trials with large sample.

[The influence of intracellular keratin 8 on hepatitis C virus replication].

The level of intracellular keratin 8(KRT-8) is associated with liver diseases, whose expression is increased in hepatitis C virus(HCV)-infected patients with hepatocarcinoma and in cultural cells infected with HCV. However, it is not clear whether KRT-8 will impact HCV replication. In this paper, the HCV replication was analyzed in response to high expression and silence of KRT-8. The inhibitory activities against wild-type and mutant HCV were also analyzed by silence of KRT-8 or combined with known anti-HCV drug telaprevir. Results showed that the protein level of KRT-8 was increased in proportion with the HCV replication. The high expression was found to facilitate HCV replication, while the silence of KRT-8 was able to inhibit HCV replication and enhanced the anti-HCV activity of telaprevir. It also inhibited A156 T and D168 V mutant HCV, which are resistant to protease inhibitors. These results suggest that KRT-8 is a co-factor for HCV replication. Down-regulation of KRT-8 can inhibit wild type and mutant HCV replication to enhance the anti-HCV activity of known anti-HCV drugs. Therefore, KRT-8 may be a new target in the development of anti-HCV agents.