Ameliorating Mitochondrial Dysfunction of Neurons by Biomimetic Targeting Nanoparticles Mediated Mitochondrial Biogenesis to Boost the Therapy of Parkinson's Disease.

Mitochondrial dysfunction of neurons is the core pathogenesis of incurable Parkinson's disease (PD). It is crucial to ameliorate the mitochondrial dysfunction of neurons for boosting the therapy of PD. Herein, the remarkable promotion of mitochondrial biogenesis to ameliorate mitochondrial dysfunction of neurons and improve the treatment of PD by using mitochondria-targeted biomimetic nanoparticles, which are Cu2- x Se-based nanoparticles functionalized with curcumin and wrapped with DSPE-PEG2000 -TPP-modified macrophage membrane (denoted as CSCCT NPs), is reported. These nanoparticles can efficiently target mitochondria of damaged neurons in an inflammatory environment, and mediate the signaling pathway of NAD+ /SIRT1/PGC-1α/PPARγ/NRF1/TFAM to alleviate 1-methyl-4-phenylpyridinium (MPP+ )-induced neuronal toxicity. They can reduce the mitochondrial reactive oxygen species, restore mitochondrial membrane potential (MMP), protect the integrity of mitochondrial respiratory chain, and ameliorate mitochondrial dysfunction via promoting mitochondrial biogenesis, which synergistically improve the motor disorders and anxiety behavior of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. This study demonstrates that targeting mitochondrial biogenesis to ameliorate mitochondrial dysfunction has a great potential in the treatment of PD and mitochondria-related diseases.

Prevalence and risk factors of sub-health and circadian rhythm disorder of cortisol, melatonin, and temperature among Chinese midwives.

Objective: This study aimed to explore the influencing factors of sub-health and circadian rhythm disorder among midwives and whether circadian rhythm disorder was associated with sub-health. Methods: A multi-center cross-sectional study was conducted among 91 Chinese midwives from six hospitals through cluster sampling. Data were collected by demographic questionnaire, Sub-Health Measurement Scale version 1.0, and circadian rhythm detection. Minnesota single and population mean cosine methods were used to analyze the rhythm of cortisol, melatonin, and temperature. Binary logistic regression, nomograph model, and forest plot were performed to identify variables associated with midwives' sub-health. Results: There were 65 midwives with sub-health and 61, 78, and 48 midwives with non-validation of circadian rhythms of cortisol, melatonin, and temperature among 91 midwives, respectively. Midwives' sub-health was significantly related to age, duration of exercise, weekly working hours, job satisfaction, cortisol rhythm, and melatonin rhythm. Based on these six factors, the nomogram was presented with significant predictive performance for sub-health. Furthermore, cortisol rhythm was significantly associated with physical, mental, and social sub-health, whereas melatonin rhythm was significantly correlated with physical sub-health. Conclusion: Sub-health and circadian rhythm disorder were generally common among midwives. Nurse administrators are supposed to pay attention and take measures to prevent sub-health and circadian rhythm disorder among midwives.

Heat shock cognate 70 protein like-2 protein in camphor pollen is one of the major culprits of asthma.

AIMS: In recent decades, Cinnamomum camphora have gradually become the main street trees in Shanghai. This study aims to investigate the allergenicity of camphor pollen. MAIN METHODS: A total of 194 serum samples from patients with respiratory allergy were collected and analyzed. Through protein profile identification and bioinformatics analysis, we hypothesized that heat shock cognate protein 2-like protein (HSC70L2) is the major potential allergenic protein in camphor pollen. Recombinant HSC70L2 (rHSC70L2) was expressed and purified, and a mouse model of camphor pollen allergy was established by subcutaneous injection of total camphor pollen protein extract (CPPE) and rHSC70L2. KEY FINDINGS: Specific IgE was found in the serum of 5 patients in response to camphor pollen and three positive bands were identified by Western blotting. Enzyme-linked immunosorbent assay (ELISA), Immune dot blot and Western blot experiments confirmed that CPPE and rHSC70L2 can cause allergies in mice. Moreover, rHSC70L2 induces polarization of peripheral blood CD4+ T cells to Th2 cells in patients with respiratory allergies and mice with camphor pollen allergy. Finally, we predicted the T cell epitope of the HSC70L2 protein, and through the mouse spleen T cell stimulation experiment, we found that the 295EGIDFYSTITRARFE309 peptide induced T cells differentiation to Th2 and macrophages differentiation to the alternatively activated (M2) state. Moreover, 295EGIDFYSTITRARFE309 peptide increased the serum IgE levels in mice. SIGNIFICANCE: The identification of HSC70L2 protein can provide novel diagnostic and therapeutic targets for allergies caused by camphor pollen.

Auricular bean embedding improves urination in epidural labor analgesia: A single center randomized controlled study.

BACKGROUND: Acupoint buried beans on the auricle is a feasible method to prevent and treat postpartum urinary retention. OBJECTIVE: This study investigated the effect of auricular acupoint buried beans on postpartum urination and maternal and fetal outcomes following epidural analgesia for labor. METHODS: Two hundred forty primiparas underwent vaginal trial labor analgesia from May 2020 to January 2021 and were randomly placed into the intervention and control groups. Both groups received epidural labor analgesia. Maternal urination during labor, 2 h postpartum, and the time for first postpartum urination were recorded as primary outcomes, with maternal and infant outcomes documented as secondary results. Statistical analysis was performed using the independent sample t-test, non-parametric rank-sum, or chi-square test using the SPSS Statistics 25.0 software. RESULTS: Two hundred eight study participants were subsequently included in the results, i.e., 105 patients in the intervention group and 103 in the control group. The intervention group comprised a significantly lower number of patients with excessive residual urine volume at cervical dilatation of 5-6 cm (P< 0.05). The total postpartum score of the intervention group was lower than in the control group (P< 0.01), and the time to first urination was shorter compared with the control group (P< 0.05). In the intervention group, the time of labor analgesia, the duration of the first stage of labor, and the total labor time were shorter compared with the control group (P< 0.01). CONCLUSION: Auricular acupoint embedded beans can improve the urination status at cervical dilatation of 5-6 cm and 2 h postpartum, as well as significantly shorten the duration of labor.

Risk factors for the postoperative bladder neck contracture in patients with small-volume prostatic hyperplasia.

OBJECTIVE: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction. METHODS: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC. RESULTS: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm. CONCLUSIONS: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction.

Actual experience of the training effect of Baduanjin on patients with hemiplegic limb dysfunctions after cerebral infarction: A qualitative study.

AIM: To explore the actual experience of training effect of Baduanjin on patients with hemiplegic limb dysfunctions after cerebral infarction through semistructured interviews and promote Baduanjin training application in clinical and community settings. DESIGN: This qualitative study was conducted using the conventional content analysis approach. METHODS: Twenty-five patients with hemiplegic limb dysfunctions after cerebral infarction were recruited as participants by applying purposive sampling method between September 2017-December 2020 in the physical therapy department of a rehabilitation hospital affiliated with Fujian University of Traditional Chinese Medicine in China. Semistructured interviews were conducted after patients participated in Baduanjin training for 6 weeks. Data were analysed using qualitative content analysis method of Graneheim and Lundman. RESULTS: Three major themes were identified after analysis, namely improving functions of hemiplegic limbs, improving the condition of the entire body and the feelings of practice. The participants indicated that Baduanjin could improve the limb functions and general conditions of hemiplegic patients. Their experience in practicing Baduanjin was generally positive, and they were willing to continue practicing.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo.

OBJECTIVE: Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy. METHODS: The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression. RESULTS: rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity. CONCLUSION: Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

[Graduate training mode of acupuncture-moxibustion and tuina based on "three crosses and two integrations": a preliminary study].

In view of the core tasks and weak links in the training of medical graduate in the new era, based on the characteristics and development needs of the discipline, a new "three crosses and two integrations" graduate training mode of acupuncture-moxibustion and tuina is proposed, with "equal emphasis on inheritance and innovation, theory and practice" as the core, with "curriculum cross" as the basis, with "academic cross" as the connotation, and with "discipline cross" as the pathway. This new training mode focuses on the comprehensive cultivation of graduates' comprehensive abilities, aiming to achieve the training goal of "strong inheritance ability, excellent innovation ability, good practical ability and broad international perspective".

The association between circadian rhythm of cortisol and shift work regularity among midwives-A multicenter study in Southeast China.

Objective: This article aims to explore the association between the trends of cortisol rhythm and the regularity of shift work among midwives. Methods: Midwives from six Southeast Chinese hospitals were recruited through cluster sampling in a multi-center cross-sectional study. Urine samples were collected half an hour after waking up, at 11:00, 19:00, and 23:00 on two consecutive days in a longitudinal cohort. The urinary cortisol was assayed by the chemiluminescence method. Results: A total of 86 midwives were included in this study, contributing 688 cortisol samples. The midwives displayed a circadian rhythm in cortisol secretion, with zeniths in the morning and nadirs in the evening. The trend of the first day was repeated on the second day. Although the total working hours per week of the two groups, namely the regular shift group (N = 43) and the irregular shift group (N = 43), were the same, significant main effects of groups (F = 62.569, p < 0.001), time (F = 45.304, p < 0.001), and group-by-time interaction (F = 226.695, p < 0.001) were indicated through linear mixed models. The main effect of day was not statistically significant, with F = 0.105 and p = 0.746. The fluctuation range of cortisol curve in the group with irregular schedules was slightly lower than that in the group with regular schedules. Conclusion: Our results may indicate that cortisol was more inhibited in midwives with irregular shift patterns than those with regular shift patterns. It is necessary to further study the relationship between cortisol rhythm and patterns of midwives' shifts in future so as to lay a foundation for hospital managers to develop a more reasonable scheduling system for midwives with the further purpose to minimize their occupational fatigue and ensure the safety of mothers and infants.

Quantitative comparison of the efficacies and safety profiles of three first-line non-platinum chemotherapy regimens for advanced non-small cell lung cancer.

Objectives: The purpose of this study was to quantify the efficacies and safety profiles of the three first-line non-platinum chemotherapy regimens recommended in the National Comprehensive Cancer Network guidelines. Materials and Methods: The PubMed and Cochrane Library databases were searched comprehensively, and clinical trials involving patients with advanced non-small cell lung cancer treated with one of three first-line non-platinum regimens (gemcitabine combined with vinorelbine, gemcitabine combined with docetaxel, or gemcitabine alone) were included in the analysis. A parametric proportional hazard survival model was established to analyze the time course of overall survival (OS). The objective response rate (ORR) and incidence rates of grade 3-4 adverse events (AEs) were summarized using a single-arm meta-analysis with a random-effects model. Results: Seventeen studies met the inclusion criteria. Age and performance status (PS) scores were significant predictors of OS. For each 10-years increase in age, mortality risk increased by 18.5%, and the mortality risk increased by 4% for every 10% increase in the proportion of patients with a PS score of 2. After correcting for the above factors, we found that the three first-line non-platinum chemotherapy regimens did not differ based on OS or toxicity. Conclusion: There was no significant difference in OS or toxicity among the three first-line non-platinum chemotherapy regimens. Age and PS scores were significant predictors of OS, and their heterogeneity across different studies should be considered in cross-study comparisons and sample size estimations when designing clinical trials.

Correlation between the redox activity of Polygonum multiflorum extract and its extraction technology with Chinese liquor (Baijiu): An electrochemistry-based study.

Elucidating the pharmaceutical mechanisms behind traditional Chinese medicine (TCM) is the key to promote its modernization process. In China, soaking TCM in liquor has a history of thousands of years, and many TCMs have to be processed into liquor before they can be used to treat diseases. Chinese liquor (Baijiu) contains more than 2,000 trace components, the interaction mechanism between TCM and Baijiu still remains unclear, making TCM a "mystery". The TCM industry commonly employs chromatographic and spectrographic technology to investigate the redox activity of TCM substances. However, only investigating the redox differences in specific active substances cannot provide a complete understanding of the redox activity of TCM substances. Thus, we employed the electrochemical approach to study the overall redox activity of substances in TCM in situ. The key result is that the redox substances in Baijiu function as a mediator for the redox reaction of Polygonum multiflorum extract. The redox efficiency of the extract is enhanced because of the faster electron transferability of the redox mediator in Baijiu.

Two new clerodane diterpenoids and a new pyran-2-one derivative with anti-neuroinflammatory activities from Croton crassifolius.

Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4‒8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1‒3 and 5 showed potential anti-neuroinflammatory activity.

Dynamics of nitrogen and phosphorus profile and its driving forces in a subtropical deep reservoir.

Nitrogen and phosphorus stratification is crucial for ecosystem dynamics in deep lakes and reservoirs. It is critical for water quality management to understand the characteristics of nitrogen and phosphorus stratification and its driving forces. In this study, high-frequency total nitrogen (TN) and total phosphorus (TP) from January 2017 to October 2019 were estimated using the datasets of high-frequency buoy parameters, including water temperature, pH, chlorophyll-a, oxidation-reduction potential, dissolved oxygen, and fluorescent dissolved organic matter. The results revealed that both nitrogen and phosphorus in water column were periodically stratified. Specifically, the stratification of nitrogen and phosphorus occurred from April to December or January of the following year. Moreover, indices of TN stratification (IC-TN) and TP stratification (IC-TP) were - 0.29 ~ 0.05 and - 0.78 ~ 0.28, respectively. Significant (P < 0.01) positive correlations were observed between RWCS (an index of thermal stability) and IC-TN (or IC-TP), indicating thermal stratification may be the main driving force of nutrient stratification at inter-month scales. Further analysis indicated that the thermal stratification may affect nitrogen and phosphorus stratification though (1) influencing algal growth and (2) affecting the release of internal sources and the material exchange between water columns. Furthermore, precipitation is also suggested as an important factor affecting the stability of nitrogen and phosphorus vertical profile in the flood season. These findings may provide important information for optimizing water quality management efforts in Qiandaohu and other subtropical deep reservoirs. In addition, the knowledge of the effect of temperature and precipitation on nutrient stratification are essential to understand future ecosystem dynamics of deep reservoirs.

Regulatory Effects of N-3 PUFAs on Pancreatic ß-cells and Insulin-sensitive Tissues.

The N-3 polyunsaturated fatty acids (PUFAs) have a wide range of health benefits, including antiinflammatory effects, improvements in lipids metabolism and promoting insulin secretion, as well as reduction of cancer risk. Numerous studies support that N-3 PUFAs have the potentials to improve many metabolic diseases, such as diabetes, nonalcoholic fatty liver disease and obesity, which are attributable to N-3 PUFAs mediated enhancement of insulin secretion by pancreatic ß-cells and improvements in insulin sensitivity and metabolic disorders in peripheral insulin-sensitive tissues such as liver, muscles, and adipose tissue. In this review, we summarized the up-to-date clinical and basic studies on the regulatory effects and molecular mechanisms of N-3 PUFAs mediated benefits on pancreatic ß-cells, adipose tissue, liver, and muscles in the context of glucose and/or lipid metabolic disorders. We also discussed the potential factors involved in the inconsistent results from different clinical researches of N-3 PUFAs.

Probiotic Supplements Improve Blood Glucose and Insulin Resistance/Sensitivity among Healthy and GDM Pregnant Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Probiotic supplements may be seen as a promising way to improve glucose metabolism. This study aimed to evaluate the effects of probiotic supplements on blood glucose, insulin resistance/sensitivity, and prevention of gestational diabetes mellitus (GDM) among pregnant women. METHODS: Eleven electronic databases were searched from inception to May 2020. Two authors independently identified randomized controlled trials (RCTs), assessed the eligibility and quality of the included studies, and then extracted data. The primary outcomes were fasting plasma glucose (FPG), 1 h and 2 h plasma glucose after 75 g oral glucose tolerance test (OGTT), HbA1c, fasting plasma insulin, insulin resistance, and insulin sensitivity. Fixed and random effect models were used to pool the results. RESULTS: A total of 20 RCTs involving 2972 participants were included according to the inclusion and exclusion criteria. The pooled results of this research showed that probiotic supplements could reduce the level of FPG (mean difference (MD) = -0.11; 95% CI = -0.15 to -0.04; P=0.0007), serum insulin (MD = -1.68; 95% CI = -2.44 to -0.92; P < 0.00001), insulin resistance (MD = -0.36; 95% CI = -0.53 to -0.20; P < 0.00001), and insulin sensitivity (MD = -21.80; 95% CI = -31.92 to -11.67; P < 0.00001). Regarding the subgroup analysis of different pregnant women, the effects of probiotics on FPG, insulin, and insulin resistance were more obvious among GDM and healthy women than among overweight/obese women. Furthermore, the differences were not significant in HbA1c (MD = -0.05; 95% CI = -0.12 to 0.03; P=0.23), 1 h OGTT (MD = -0.07; 95% CI = -0.25 to 0.10; P=0.42), and 2 h OGTT (MD = -0.03; 95% CI = -0.17 to 0.12; P=0.72). CONCLUSION: This review found that probiotic supplements had certain functions to reduce the level of FPG and improve insulin, insulin resistance, and insulin sensitivity, especially for GDM and healthy pregnant women.

[Effect of moxibustion combined with Guifu Yuhe decoction on the conversion score of idiopathic constitution, serum total lgE and blood EOS in the patients with allergic acne].

OBJECTIVE: To observe the therapeutic effect of moxibustion combined with Guifu Yuhe decoction on allergic acne and the influence on immunologic function in the patients. METHODS: A total of 60 patients with allergic acne were rando-mized into an observation group (30 cases) and a control group (30 cases).Thirty healthy employees were in the healthy group. In the control group, Guifu Yuhe decoction was prescribed for oral administration, while in the observation group, on the base of the treatment as the control group, moxibustion was exerted at Dazhui (GV14) and Shenque (GV8). The treatment duration was 8 weeks. Before and after treatment, serum IgE, blood EOS, CD4+T cell, CD8+ T cell and CD4+T/CD8+T, as well as the conversion score of idiopathic constitution and the symptom score were compared in the patients of two groups. The clinical therapeutic effect was observed in the two groups. RESULTS: Before treatment, compared with the healthy group, IgE and EOS, CD4+T cell and CD8+T cell all increased (P<0.05), and CD4+T/CD8+T decreased in the two groups (P<0.05). After treatment, IgE, EOS and CD4+T cell and CD8+T cell decreased (P<0.05), and CD4+T/CD8+T increased (P<0.05) in the intra-group comparison in the patients. The changes of IgE, EOS, CD4+T cell and CD8+T cell in the observation group were more larger than those in the control group (P<0.05). After treatment, the conversion score of body constitution and symptom score all decreased in either group (P<0.05) and the scores in the observation group were lower than those of the control group (P< 0.05). The total effective rate of the observation group (29/30, 96.7%) was higher than that of the control group (22/30, 73.3%, P<0.05). CONCLUSION: Moxibustion combined with Guifu Yuhe decoction can significantly improve immune function and body constitution of the patients with allergic acne, which may be related to rectifying idiopathic constitution, improving in lymphocyte subsets dysfunction and inhibiting allergic reaction.

The use of miR122 and its target sequence in adeno-associated virus-mediated trichosanthin gene therapy.

OBJECTIVE: Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells. METHODS: A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined. RESULTS: The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells. CONCLUSION: HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

Probiotic supplements alleviate gestational diabetes mellitus by restoring the diversity of gut microbiota: a study based on 16S rRNA sequencing.

Probiotics effectively prevent and improve metabolic diseases such as diabetes by regulating the intestinal microenvironment and gut microbiota. However, the effects of probiotics in gestational diabetes mellitus are not clear. Here, we showed that probiotic supplements significantly improved fasting blood glucose in a gestational diabetes mellitus rat model. To further understand the mechanisms of probiotics in gestational diabetes mellitus, the gut microbiota were analyzed via 16S rRNA sequencing. We found that compared with the normal pregnant group, the gestational diabetes mellitus rats had decreased diversity of gut microbiota. Moreover, probiotic supplementation restored the diversity of the gut microbiota in gestational diabetes mellitus rats, and the gut microbiota structure tended to be similar to that of normal pregnant rats. In particular, compared with gestational diabetes mellitus rats, the abundance of Firmicutes and Actinobacteria was higher after probiotic supplementation. Furthermore, activating carbohydrate metabolism and membrane transport pathways may be involved in the potential mechanisms by which probiotic supplements alleviate gestational diabetes mellitus. Overall, our results suggested that probiotic supplementation might be a novel approach to restore the gut microbiota of gestational diabetes mellitus rats and provided an experimental evidence for the use of probiotic supplements to treat gestational diabetes mellitus.

Korean red ginseng alleviate depressive disorder by improving astrocyte gap junction function.

ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG), a processed product of Panax ginseng C. A. Mey, show significant anti-depressive effect in clinic. However, its mechanism is still unclear. AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potential pathogenesis of depression. Therefore, this study's objective is to investigate whether the antidepressant effect of KRG is related to GJIC. MATERIALS AND METHODS: Rat were restraint 8 h every day for 28 consecutive days to prepare depression models, and meanwhile, rats were intragastrically administrated with normal saline, KRG solutions (25, 50 or 100 mg/kg) or fluoxetine (10 mg/kg) 1 h before stress. The behavioral performance was determined by forced swimming test, sucrose preference test and open field test. GJIC was determined by the Lucifer yellow (LY) diffusion distance in prelimb cortex (PLC). In addition, the level of Cx43, one of executors of GJIC, was tested by Western blot. To find out the protective effect of KRG against GJIC dysfunction directly, rats were intracranially injected with carbenoxolone (CBX, blocker of GJIC), and meanwhile normal saline, KRG (100 mg/kg) or fluoxetine (10 mg/kg) was administered daily. The behavioral performance of these rats was detected, and the LY localization injection PLC area was used to detect the gap junction function. RESULTS: Chronic resistant stress (CRS) induced depressive symptoms, as manifested by prolonged immobility time in forced swimming test and decreased sucrose consumption ratio. Administration of KRG alleviated these depressive symptoms significantly. GJIC determination showed that KRG improved the LY diffusion and increased Cx43 level in prefrontal cortex (PFC) significantly, indicated that GJIC dysfunction was alleviated by the treatment of KRG. However, the astrocytes number was also increased by the treatment of KRG, which maybe alleviate depression-like symptoms by increasing the number of astrocytes rather than improving GJIC. Injection of CBX produced depressive symptoms and GJIC dysfunction, as manifested by decreased sucrose consumption ratio and prolonged immobility time in forced swimming test, but no astrocytes number changes, KRG also reversed depressive symptoms and GJIC dysfunction, suggested that the improvement of depressive-like symptoms was improved by GJIC. CONCLUSIONS: KRG alleviate depressive disorder by improving astrocytic gap junction function.

Treatment of HBV Cirrhosis with Fuzheng Huayu Tablet () and Entecavir: Design of a Randomized, Double-Blind, Parallel and Multicenter Clinical Trial.

BACKGROUND: Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B (CHB), but it has a limited effect on cirrhosis. Chinese medicines (CMs), particularly Fuzheng Huayu Tablet (, FZHY), have an antifibrotic effect in patients with CHB. OBJECTIVE: To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus (HBV) cirrhosis, this study was designed as a randomized, placebo-controlled, double-blind, parallel assignment, multicenter trial at 20 centers in China. The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV, and randomly assigned into 2 groups, receiving entecavir (0.5 mg, daily) and FZHY placebo (1.6 g, 3 times a day), or entecavir (0.5 mg, daily) and FZHY (1.6 g, 3 times a day), respectively. The primary endpoint was histological improvement at week 48. The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study. Adverse events such as stomach upset, headache, fatigue, dizziness, nausea will be strictly recorded. DISCUSSION: Through this study, we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY. Protocol version: Version 1.3, Date: 2014.12.4. TRIAL REGISTRATION NUMBER: NCT02241590.