Consistency in the prevalence and associated factors of frailty determined by two instruments among hospitalised older adults: A cross-sectional study.

AIMS AND OBJECTIVES: To investigate the consistency in the prevalence and associated factors of frailty determined by the physical-originated Fatigue, Resistance, Ambulation, Illnesses and Loss of weight (FRAIL) scale and the multidimensional Tilburg Frailty Indicators (TFI) scale. BACKGROUND: Accurate assessment of frailty and the identification of its associated factors could guide the development and implementation of holistic and individualised treatment plan. However, recommendations regarding the selection of frailty assessment tools are inconclusive. DESIGN: This is a cross-sectional study, the reporting of which followed the STROBE guidelines. METHODS: A total of 1220 older adults were recruited from a university affiliated tertiary hospital in Xi'an City, Northwest China, and administrated with a social-demographic and health-related information sheet, the FRAIL, the TFI, the Short-Form Mini-Nutritional Assessment, the Pittsburgh Sleep Quality Index and the 5-level EuroQol 5 dimensions questionnaire. Descriptive statistics and binary logistic regression analysis were used to investigate the prevalence of frailty and its associated factors. RESULTS: The prevalence of physical-originated and multidimensional frailty was 55.2% and 77.6%, respectively. The consistency between the two scales was low. Taking the combined use of the two instruments as the reference, the TFI and FRAIL could identify 89.99% and 64.02% of the participants with frailty. Polypharmacy, health-related quality of life and sleep quality were found to be associated with both physical-originated and multidimensional frailty. Nutritional status and level of physical activity were additionally identified as the independent associated factors of multidimensional frailty. CONCLUSIONS: The prevalence of frailty among hospitalised older adults is high. There is low consistency between the FRAIL and TFI in detecting frailty. The TFI exhibited higher sensitivity in detecting individuals with frailty and its associated factors. RELEVANCE TO CLINICAL PRACTICE: The findings of this study supported a single use of the TFI for the assessment of frailty in the hospital setting.

Antimicrobial Activity of Tannic Acid In Vitro and Its Protective Effect on Mice against Clostridioides difficile.

Clostridioides difficile infection (CDI), recurrently reported as an urgent threat owing to its increased prevalence and mortality, has attracted significant attention. As the use of antibiotics to treat CDI has many limitations, such as high recurrence rate, the need to actively seek and develop other drugs that can effectively treat CDI with fewer side effects has become a key issue in CDI prevention and treatment. This study aimed to evaluate the inhibitory effect of Galla chinensis (GC) and its main component, tannic acid (TA), against C. difficile in vitro and its therapeutic effect on CDI in vivo. When GC and TA concentrations were 250 and 64 mg/L, respectively, the cumulative antibacterial rate against C. difficile reached 100%. The sub-MIC of TA significantly inhibited C. difficile sporulation, toxin production, and biofilm formation in vitro. Compared with the CDI control group, TA-treated mice lost less weight and presented a significantly improved survival rate. TA significantly reduced the number of spores in feces, decreased serum TcdA level, and increased serum interleukin 10 (IL-10). Based on the inhibitory effect of TA on C. difficile in vitro and its therapeutic effect on the CDI mouse model, we consider TA as a potentially effective drug for treating CDI. IMPORTANCE Clostridioides difficile is one of the major pathogens to cause antibiotic-associated diarrhea. Although antibiotic treatment is still the most commonly used and effective treatment for CDI, the destruction of indigenous intestinal microbiota by antibiotics is the main reason for the high CDI recurrence rate of about 20%, which is increasing every year. Moreover, the growing problem of drug resistance has also become a major hidden danger in antibiotic treatment. GC has been used to treat diarrhea in traditional Chinese medicine. In the present study, we evaluated the inhibitory effect of TA, the main component of GC, on dissemination and pathogenic physiological functions of C. difficile in vitro, as well as its therapeutic efficacy in a CDI model. Overall, TA is considered to be a potentially effective drug for CDI treatment.

Comparative Study of the Efficacy of Autologous Tooth Bone Powder and Inorganic Bovine Bone Powder on the Repair of Jaw Defects.

Context: The main pathological features of jaw cysts are bone defects. Obtaining autologous bone for transplantation repair has been associated with postoperative complications, and the amount of bone that dentist can collect is limited. Studies have found that autologous tooth bone powder is safe and has good bone-formation ability and stability. Objective: The study intended to examine the efficacy of implantation of autologous tooth bone powder and inorganic bovine bone powder, after marsupialization and second-stage curettage for large jaw cysts that dentist can't directly remove by surgery in clinical practice. Design: The research team designed a prospective randomized controlled trial. Setting: The study took place in the Head and Neck Surgery Department at Chongqing University Cancer Hospital in Chongqing, China. Participants: Participants were 60 patients at the hospital between 2016 and 2018 who had mandibular cysts that surgical operation couldn't directly remove by surgery in clinical practice. Intervention: At 4 months after curettage, the research team randomly divided participants into three groups: (1) an intervention group who received implants of autologous tooth bone powder into the bone defects, (2) a positive control group who received implants of inorganic bovine bone powder, and (3) a negative control group who received no implants of any material. Outcome Measures: The research team performed: (1) periodontal probing at a fixed anatomical point for the intervention and both control groups postintervention at one day and 4 months after surgery and recorded the changes in probing depth and (2) computed tomography (CT) scans at baseline one day before and postintervention at 4 months after the implantation to determine changes in the bone mineral density and compared them among the three groups. Results: The change in the height of the intervention group's fixed anatomical point postintervention at 4 months after surgery was significantly smaller than that of the positive control group (P < .05). In the CT scan analysis, the differences between the intervention and negative control groups and between the positive and negative control groups were statistically significant (P < .05); however, the difference between the intervention and positive control groups wasn't significant (P > .05). Conclusions: Autologous tooth bone powder and inorganic bovine bone powder can effectively repair bone defects caused by large jaw cysts and that the repaired effect may be better than that of spontaneous osteogenesis. The autologous tooth bone powder was associated with lower levels of bone loss than those seen with use of inorganic bovine bone powder.

The effects of a nurse-led integrative medicine-based structured education program on self-management behaviors among individuals with newly diagnosed type 2 diabetes: a randomized controlled trial.

BACKGROUND: International guidelines advocate providing prompt structured education to individuals with diabetes at diagnosis. However, among the few eligible structured education programs, heterogeneous intervention regimens and inconsistent findings were reported. Eligible programs for Chinese individuals with diabetes are lacking. This study aimed to investigate the effects of a nurse-led integrative medicine-based structured education program on self-management behaviors, glycemic control and self-efficacy among individuals with newly diagnosed type 2 diabetes. METHODS: Employing a randomized controlled trial, 128 individuals with type 2 diabetes diagnosed in the preceding three to nine months were recruited from four university-affiliated tertiary hospitals in Xi'an City, Northwest China, and randomly allocated to the intervention or control groups after baseline assessments. Participants in the intervention group received a 4-week nurse-led integrative medicine-based structured education program, which is theoretically based on the Health Belief Model and Self-Efficacy Theory, in line with updated diabetes management guidelines, and informed by relevant systematic reviews. Participants in the control group received routine care. Self-management behaviors and self-efficacy were measured with the Summary of Diabetes Self-Care Activities and the Diabetes Management Self-Efficacy Scale at baseline, immediate post-intervention and 12 weeks following the intervention while Glycated Hemoglobin A was measured at baseline and the 12th-week follow-up. The intervention effects were estimated using the generalized estimating equation models. RESULTS: Participants in the intervention group exhibited significantly better self-management performance in specific diet regarding intake of fruits and vegetables at both follow-ups (ß = 1.02, p = 0.011 and ß = 0.98, p = 0.016, respectively), specific diet regarding intake of high-fat foods at the immediate post-intervention follow-up (ß = 0.83, p = 0.023), blood glucose monitoring at the 12th-week follow-up (ß = 0.64, p = 0.004), foot care at both follow-ups (ß = 1.80, p <  0.001 and ß = 2.02, p <  0.001, respectively), and medication management at both follow-ups (ß = 0.83, p = 0.005 and ß = 0.95, p = 0.003, respectively). The intervention also introduced significant improvements in Glycated Hemoglobin A (ß = - 0.32%, p <  0.001), and self-efficacy at both follow-ups (ß = 8.73, p <  0.001 and ß = 9.71, p <  0.001, respectively). CONCLUSIONS: The nurse-led integrative medicine-based structured education program could produce beneficial effects on multiple diabetes self-management behaviors, glycemic control and self-efficacy. TRIAL REGISTRATION: This study was retrospectively registered in the ClinicalTrials.gov . on 25/08/2017; registration number: NCT03261895 .

Preparation and evaluation of chiral open-tubular columns supported with zeolite silica nanoparticles and single/dual chiral selectors using capillary electrochromatography with amperometric detection.

In this work, novel stationary phase coatings by zeolite SiO2NPs coupled with ß-cyclodextrin (ß-CD) or ß-CD/L-phenylalanine were developed for chiral open-tubular capillary electrochromatography (OT-CEC). The OT columns were prepared taking advantage of the strong adhesion of polydopamine in one-step method. Scanning electron micrography and electroosmotic flow were used to characterize the prepared single/dual-selector OT columns. Chiral separation of four chiral analytes (catechin/epicatechin, ephedrine/pseudoephedrine, ritodrine and salbutamol) was carried out in order to evaluate the performance of the prepared columns in OT-CEC with amperometric detection system. In terms of migration time, peak area, resolution, and selectivity factor of catechin/epicatechin and salbutamol, the run-to-run, day-to-day, and column-to-column repeatability were within 8.9%. Under the optimum conditions, the developed methods were applied for the analyses of Chinese herbal medicine Catechu herbs and salbutamol aerosol samples.

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study.

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.

Yishen Huazhuo Decoction Induces Autophagy to Promote the Clearance of Aß1-42 in SAMP8 Mice: Mechanism Research of a Traditional Chinese Formula Against Alzheimer's Disease.

BACKGROUND: Studies have found that autophagy could promote the clearance of Aß. To promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. OBJECTIVE: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. METHODS: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl's staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aß, LAMP1, and autophagy related proteins. RESULTS: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD group increased significantly (P=0.02<0.05). Nissl's staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group that the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aß1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. CONCLUSION: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aß1-42 to improve memory impairment in SAMP8 mice.

[Simultaneous determination of four anthraquinones in Polygonum multiflorum by QAMS].

A simple, specific and selective quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of anthraquinones and anthraquinone glycosides in Polygonum multiflorum was developed. Four main anthraquinones and its glycosides, emodin, emodin-8-O-ß-D-glucoside, physcion and physcion-8-O-ß-D-glucoside were selected as analytes to evaluate the quality of P. multiflorum. Emodin was used as the internal standard, and the relative correction factors(RCFs) between emodin and the other three anthraquinones were calculated. Comparison of the contents of the four components in 30 batches of P. multiflorum from different regions and 12 batches decoction pieces from different manufacturers by QAMS and external standard method(ESM) showed that there was no significant difference between QAMS and ESM for quantification of the four main components by using relative error results, and the QAMS method was accurate and reliable, and had a good repeatability. In addition, compared with the results calculated by the difference method between total anthraquinone and free anthraquinone in the content determination of P. multiflorum in Chinese Pharmacopoeia, the results of direct determination combined anthraquinone by QAMS were very close to that by measured the external standard method. Therefore, simultaneous quantification of four main anthraquinones by using QAMS is suitable to evaluate the quality of P. multiflorum. Then the optimized assay method of the combined anthraquinone contents showed simple and feasible, which could be replaced and improved the quantification method of the combined anthraquinone in the current Chinese Pharmacopeia.

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial.

BACKGROUND AND PURPOSE: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT). METHODS: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus). RESULTS: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found. CONCLUSIONS: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

[Establishment of extraction method for Gardeniae Fructus extract and its application in evaluating different Gardeniae Fructus decoction pieces].

In this experiment,the gradation analysis method was used to evaluate the quality of different pieces of Gardeniae Fructus through the extraction rate difference and the difference analysis of the main components in the extract. In this experiment cold-dip and hot-dip methods were used to compare the yield of Gardeniae Fructus extract and the content of chemical constituents with water,25%,50%,75% and 95% ethanol fractions. By weighted calculation,the optimal extraction method of Gardeniae Fructus was determined,and this was verified by practical application. RESULTS:: showed that for the water-soluble extract,cold dip method was better than the hot dip method; and for alcohol-soluble extract,75% ethanol under cold dip method was best. The verification results showed that water-soluble extracts under cold dip methods could be used to significantly distinguish the raw Gardeniae Fructus( GF) and processed( stir-baked) GF( GFP) collected from the market. Meanwhile,this method could be also used to distinguish the same batch of GF,GFP and carbonized GF( GFC) with significant differences,respectively( P<0. 05). Ethanol-soluble extract can be used to clearly distinguish GFP and GFC pieces in the same batch( P<0. 05). The results of content determination showed that the variation coefficient of components in GF processed products was higher than that in extracts,and the content of hydroxygeniposide was the most significant component between GF and its processed products. It is suggested that the method of water-soluble extract of GF and the determination of the content of gardoside should be combined together to evaluate the quality of GF and its heat processed products.

[Effect of electroacupuncture on neurological deficit and activity of TLR2/NF-κB signaling in ce-rebral ischemia /reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neurological behavior and activity of Toll-like receptor 2 / nuclear factor kappa B (TLR2/NF-κB) signaling of the ischemic cerebral area in cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its mechanisms underlying improvement of CIRI. METHODS: A total of 120 male SD rats were randomly divided into blank control, sham operation, model, EA and EA＋NF-κB inhibitor (Pyrrolidine Dithiocarbamate Hydrochloride, PDTC, EA＋PDTC) groups which were further divided into 3, 7, 14 and 28 d subgroups (n＝6 in each subgroup). The CIRI model was established by occlusion of the middle cerebral artery for 90 min, followed by reperfusion. EA (1－20 Hz, 6 V) was applied to "Shuigou" (GV26), "Neiguan" (PC6), "Sanyinjiao" (SP6) and "Weizhong" (BL40) for 30 min, once a day for 28 days. For rats of the EA＋PDTC group, PDTC solution (120 mg/kg) was intraperitoneally injected on the 3rd day after successful modeling and before EA intervention. The neurological deficit severity (Zea Longa score) was assessed 3, 7, 14 and 28 days after modeling. The expression levels of TLR2, Interleukin-1 receptor-associated kinase (IRAK) and NF-κB mRNAs in the ischemic penumbra region of brain tissue were detected by real-time fluorescence quantitative PCR. RESULTS: Following modeling, the neurological deficit scores were significantly increased from the 3rd day on after CIRI (P<0.05), the expression levels of TLR2 mRNA on day 3, 7, 14 and 28, and IRAK mRNA on day 3 and 7, as well as NF-κB mRNA on day 3, 7 and 14 were significantly up-regulated in the model group relevant to the blank control group (P<0.05). After EA intervention, the neurological deficit scores were significantly decreased in the EA group on day 3, 7 and 28 and in the EA＋PDTC group on day 3, 7, 14 and 28 in comparison with those of the model group (P<0.05). In addition, the expression levels of TLR2 mRNA and NF-κB mRNA on day 3, 7 and 14 in the EA group, and on day 3, 7, 14 and 28 in the EA＋PDTC group, IRAK mRNA on day 3 in the EA and EA＋PDTC group were significantly down-regulated (P<0.05), but those of IRAK mRNA on day 14 and 28 in the EA group were significantly up-regulated in comparison with those of the model group (P<0.05). The effect of the EA＋PDTC was obviously superior to that of simple EA in down-regulating the expression of TLR2 (on day 28), and IRAK (on day 3, 14, 28), and NF-κB (on day 3, 7 and 14) (all P<0.05). CONCLUSION: EA stimulation can improve the symptoms of neurological deficits in CIRI rats, which may be related to its effect in suppressing the expression of TLR2, NF-κB and IRAK mRNAs of the ischemic cerebral tissue, i．e., down-regulating the activity of TLR2/NF-κB signaling.

[Analysis on acupoint selection rules of acupuncture for Alzheimer's disease based on complex network].

OBJECTIVE: To explore the acupoint selection rules of acupuncture for Alzheimer's disease (AD) in modern clinical practice by complex network technology. METHODS: The relevant articles of clinical trials were retrieved from CNKI published before December 2017. Using Microsoft Excel 2010, the database was established. Using Gephi 0.8.2 software, the complex network mode was built and its topological structure was analyzed. RESULTS: Finally, 81 articles were eligible and 114 acupoint prescriptions were extracted. The constructed complex network of acupoint prescriptions for AD was characteristics as small world effect and scale-free property, the crucial acupoints included Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Yintang (GV 29), Shenmen (HT 7), Shenting (GV 24), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3). In acupoint combination, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Sanyinjiao (SP 6) were the most common, and the combination of the distal and nearby points was predominant. Using k-core for acupoint optimization, 29 core acupoints were screened and they were mostly located on the governor vessel and the head and neck, with the highest use frequency. 82.76% of acupoints were specific acupoints and the influential points were dominant. Using community structure partition, these acupoints were classified into two groups, i.e. deficiency syndrome and excess syndrome. CONCLUSION: The selection of local acupoints is the first choice in acupuncture treatment for AD. The combination of distal and nearby points is the most common and the special points are the core. In clinical practice, the great consideration is provided on mind regulation, integration of disease and symptoms, the mutual treatment of the primary and the secondary as well as the deficiency and the excess.

Correction: Cognitive Improvement during Treatment for Mild Alzheimer's Disease with a Chinese Herbal Formula: A Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0130353.].

Health-related quality of life and its influencing factors for patients with hypertension: evidence from the urban and rural areas of Shaanxi Province, China.

BACKGROUND: Hypertension is an important public health issue in China, but there are few studies on health-related quality of life (HRQoL) for patients with hypertension in China. This study aims to examine the HRQoL as measured by EQ-5D and investigate the factors that influence HRQoL for patients with hypertension in Shaanxi Province, China. METHODS: Data were collected from the Shaanxi's fifth National Health Service Survey conducted in 2013. EQ-5D was employed to measure the HRQoL for patients with hypertension. The Chinese population-based preference trade-off time (TTO) model was used to convert the EQ-5D values. All descriptive analyses, including demographic characteristics, socio-economic status and clinical characteristics, were stratified by urban and rural residence. Tobit regression model was used to investigate the influencing factors of HRQoL. RESULTS: A statistically significant difference was observed between the EQ-5D utility scores of urban (0.891) and rural hypertension patients (0.870). The urban hypertension patients showed significantly higher utility scores than the rural patients in three of the five dimensions, namely usual activities, pain / discomfort and anxiety / depression. The influencing factors of HRQoL for hypertension patients in China included age, marital status, education level, employment status, physical activity and medical examination. For patients aged 55 years and above, EQ-5D utility score decreased significantly with increasing age. The EQ-5D score increased with higher education level. Married patients showed a higher EQ-5D score than divorced and widowed patients, and employed patients showed a higher score than unemployed and retired patients. Regular physical activity and medical examination had a positive effect on the HRQoL of hypertension patients. CONCLUSIONS: Our study indicated that urban hypertension patients might have higher HRQoL than rural patients in Shaanxi, China. To enhance HRQoL, it is necessary to strengthen the health education for hypertension patients to improve hypertension prevention and to adopt healthy habits such as regular physical activity. It is also important to strengthen the management and monitoring of hypertension in the elderly, and further implement the free medical examination program for the elderly under the public health programs.

Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway.

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

Cognitive Improvement during Treatment for Mild Alzheimer's Disease with a Chinese Herbal Formula: A Randomized Controlled Trial.

OBJECTIVES: To explore the efficacy of Chinese herbal formula compared with donepezil 5 mg/day in patients with mild Alzheimer's disease (AD). METHODS: Patients with mild AD meeting the criteria were randomized into Chinese herbal formula Yishen Huazhuo decoction (YHD) group and donepezil hydrochloride (DH) group during the 24-week trial. The outcomes were measured by ADAS-cog, MMSE, ADL, and NPI with linear mixed-effect models. RESULTS: 144 patients were randomized. The mean scores of ADAS-cog and MMSE in both YHD group and DH group both improved at the end of the 24-week treatment period. The results also revealed that YHD was better at improving the mean scores of ADAS-cog and MMSE than DH. Linear mixed-effect models with repeated measures showed statistical significance in time × group interaction effect of ADAS-cog and also in time × group interaction effect of MMSE. The data showed YHD was superior to DH in improving the scores and long term efficacy. CONCLUSIONS: Our study suggests that Chinese herbal formula YHD is beneficial and effective for cognitive improvement in patients with mild AD and the mechanism might be through reducing amyloid-ß (Aß) plaque deposition in the hippocampus. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12002846.

Qingnaoyizhi decoction suppresses the formation of glial fibrillary acidic protein-positive cells in cultured neural stem cells by inhibiting the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.

OBJECTIVE: Inactivation of the Janus kinase 2 in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis. (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis plays a crucial role in determining the fate of neural stem cells (NSCs). Qingnaoyizhi decoction (QNYZD) has been used for the treatment of vascular dementia and has shown to improve synaptic remodeling. The aim of this study was to evaluate the effect of cerebrospinal fluid (CSF) containing QNYZD (CSF-QNYZD) on the differentiation of cultured NSCs and the involvement of the JAK2/STAT3 pathway. METHODS: The protein expression levels of glial fibrillary acidic protein (GFAP), tubulin, drosophila mothers against decapentaplegic protein (SMAD-1), STAT3, and phosphorylated-STAT3 were detected by western immunoblot analysis in the groups: control, CSF, JAK/STAT inhibitor (AG490), CSF-QNYZD, and CSF-XDZ (CSF-Xidezhen). The differentiation of NSCs was determined by immunofluorescence staining. The proliferation of NSCs was measured using the Cell Counting Kit-8 proliferation assay. RESULTS: Compared with the control group, CSF-QNYZD and AG490 significantly increased the number and expression of tubulin-positive cells, reduced the number and expression of GFAP-positive cells, and down-regulated the expression of p-STAT3. However, CSF-QNYZD also decreased the expression of SMAD-1 and STAT3. CONCLUSION: Enhanced neuronal differentiation may be associated with the down-regulation of glial differentiation instead of promoting proliferation in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis.

[Effective Components of three kinds of shen-supplementing Chinese medicine on self-renewal and neuron-like differentiation of NSCs in AD mouse embryos: an experimental research].

OBJECTIVE: To observe the regulatory effects of psoralen, oleanolic acid, and stilbene glucoside, three active components of psoralea fruit, glossy privet fruit and tuber fleeceflower root respectively, on Aß25-35induced self-renewal and neuron-like differentiation of neural stem cells (NSCs). METHODS: Embryonic NSCs werein vitro isolated and cultured from Kunming mice of 14-day pregnancy, and randomly divided into the control group, the Aß25-35 group, the Aß25-35 +psoralen group, the Aß25-35 +oleanolic acid group, and the Aß25-35 + stilbene glucoside group. The intervention concentration of Aß25-35 was 25 µmol/L, and the intervention concentration of three active components of Chinese medicine was 10(-7)mol/L. The effect of three active components of Chinese medicine on the proliferation of NSCs was observed by counting method. The protein expression of Tubulin was observed by Western blot and immunofluorescence. The ratio of Tubulin+/DAPI was caculated. Results Compared with the control group, the sperical morphology of NSCs was destroyed in the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin /DAPI all decreased (P <0.01, P <0.05). Compared with the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin + /DAPI all increased in the three Chinese medicine treated groups (P <0. 01, P <0. 05). CONCLUSIONS: 25 µmol/L Aß25-35 could inhibit self-renewal and neuron-like differentiating of NSCs. But psoralen, oleanolic acid, and stilbene glucoside could promote self-renewal of NSCs and neuron-like differentiation.

Cerebrospinal fluid pharmacology: an improved pharmacology approach for chinese herbal medicine research.

Despite many successful applications of Chinese herbal medicine (CHM) in the treatment and prevention of neurological diseases (ND), the fully scientific understanding of CHM's action mechanisms had been hampered for lack of appropriate methods to explore the combinatorial rules, the synergistic mechanisms, and the molecular basis of CHM. As an improved pharmacology approach, cerebrospinal fluid pharmacology (CSFP), based on the fact that cerebrospinal fluid plays an important role in the health maintenance of specific survival environment for neurons and glial cells, has been constructed and applied to CHM research for treating ND. In the present review, the concept and advantages of CSFP are briefly introduced. The approaches and key technologies of CSFP in CHM research are also collated and analyzed. Furthermore, the developing tendency of CSFP is summarized, and its framework in CHM research is also proposed. In summary, CSFP provides a new strategy not only to eliminate some barriers of CHM research for treating ND, but also to broaden the pharmacology research for bridging the gap between CHM and modern medicine. Moreover, the advancements in CSFP will bring about a conceptual move in active ingredients discovery of CHM and make a significant contribution to CHM modernization and globalization.

[Effect of electroacupuncture on cerebral PKC isozyme expression levels in cerebral ischemia-reperfusion rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dingzhongxian" (MS 5) and "Dingpangxian" (MS 8) on the expression of cerebral protein kinase C (PKC) isozymes in local cerebral ischemia reperfusion injury (CI/RI) rats so as to explore its underlying mechanism in protecting ischemic brain tissue. METHODS: Seventy-two Wistar rats were randomized into normal control (n = 8), CI/RI model (model, n = 32), and EA (n = 32) groups. The later two groups were further divided into 4, 12, 24 and 72 h subgroups, respectively, with 8 rats in each. CI/RI model was established by occlusion of the middle cerebral artery under anesthesia and reperfusion for 4, 12, 24 and 72 h, respectively. EA (1 mA, 2 Hz/15 Hz) was applied to "Dingzhongxian" (MS5) and "Dingpangxian" (MS8) for 10 min every time, and once again every 12 h after modeling. The expression of PKCgamma and PKCdelta in the ischemic cortex tissue was detected using immunohistochemistry. TdT-mediated dUTP Nick-End Labeling was used to detect neuronal apoptosis of the local ischemic cerebral cortex. RESULTS: In comparison with the normal group, the expression levels of cerebral PKCgamma and PKCdelta proteins as well as the number of the apoptotic neurons at time-points of 4, 12, 24 and 72 h after modeling were increased apparently in the model group (P < 0.01); while compared with the model group, cerebral PKCgamma and PKCdelta protein expressions and the apoptotic neuronal number were decreased considerably in the EA group (P < 0.01, P < 0.05). No significant differences were found among the 4 time-points in the expression levels of PKCgamma and PKCdelta and apoptotic neuronal number in the model group and EA group (P > 0.05). CONCLUSION: EA intervention can effectively down-regulate expressions of cerebral PKCgamma, PKCdelta proteins and apoptotic neuronal number in cerebral ischemia rats, which may contribute to its effect in protecting the ischemic cerebral tissue.