[Exploration of clinical pathway-oriented optimal management diagnosis and treatment model for rare diseases].

This study takes Cushing's syndrome, a rare disease, as a model, and adopts the path of "Plan, Do, Check, Action" (PDCA) to explore new methods to optimize the clinical path, can improve the quality and efficiency of diagnosis and treatment of rare diseases. After sorting out the problems existing in the previous diagnosis and treatment mode, our team optimizes the path in various ways and establishes a standard operation procedure (SOP) for the new path. In the evaluation of the optimized mode, 55 patients with Cushing's syndrome were admitted to the Department of Endocrinology, Peking Union Medical College Hospital, including 19 males and 36 females, aged (41.8±14.4) years (6-68 years). The pathway group (28 cases) and the control group (27 cases) were divided according to whether they were included in the new path management at the time of admission, and the effect of path optimization was assessed in terms of time, efficacy, safety and cost. The results showed that compared with the control group, the pathway group had a shorter time of hospitalization in the Department of Endocrinology and critical tests, such as blood cortisol rhythm, low-dose dexamethasone inhibition test, and bilateral inferior petrosal sinus sampling (all P<0.05). There was no significant differences in the decrease of total cortisol after operation, the incidence of postoperative complications, and hospitalization expenses (all P>0.05). The optimized path improves the medical efficiency while ensuring medical quality, safety and no increase in cost. This study proposes PDCA path optimization for complex diseases and establishes SOP process, which provides experience in management optimization for the patient-centered and clinical path-oriented diagnosis and treatment mode of rare diseases.

[Effects of novel bioactive glasses on promoting remineralization of artificial dentin caries].

OBJECTIVE: To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries. METHODS: (1) BGs were used in this study as follows: PSC (10.8%P2O5-54.2%SiO2-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P2O5-37.0%SiO2-53.9%CaO-3.0%CaF2, mol.%) and 45S5(6.0%P2O5-45.0%SiO2-24.5%CaO-24.5%Na2O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling. RESULTS: (1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm3 and (213.64 ± 36.01) mg/cm3 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm3, P=0.006; (36.46 ± 10.79) mg/cm3, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm3; (111.02 ± 22.06) mg/cm3], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) µm and (54.5 ± 17.8) µm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA. CONCLUSION: PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.

Antimicrobial mechanisms of traditional Chinese medicine and reversal of drug resistance: a narrative review.

OBJECTIVE: In recent years, the extensive use of antibiotics worldwide has led to an increase in the number of drug-resistant bacterial strains, thus resulting in an increasingly severe degree of bacterial resistance. For thousands of years, traditional Chinese medicine (TCM) has provided natural and unique advantages in the treatment of infectious diseases. Therefore, it is important to develop further and use TCM to treat clinical infections caused by drug-resistant bacteria. MATERIALS AND METHODS: A literature search was performed using PubMed, Web of Science, Google Scholar, and the China National Knowledge Infrastructure databases. The articles were analyzed to extract information on the antimicrobial effects of Chinese herbal medicines, compounded Chinese medicines, monomeric compounds of herbal origin, and the combined use of Chinese medicine and antimicrobial drugs and to determine the synergistic effect of the combination of Chinese medicine and antibiotics, as well as investigate the possibility of restoring the antibiotic sensitivity of drug-resistant strains. RESULTS: The mechanisms underlying the antibacterial properties of TCM involve altering membrane permeability, inhibiting protein and nucleic acid synthesis, inhibiting enzyme activity in vivo, and controlling the ability of pathogenic bacteria. In addition, the mechanism underlying TCM-induced reversal of bacterial drug resistance is discussed, particularly in terms of the elimination of resistant (R) plasmids and the inhibition of extended-spectrum ß-lactamases, bacterial biofilm formation, and bacterial efflux pump activity. CONCLUSIONS: This paper reviewed the recent relevant literature on antimicrobial action and its mechanisms, as well as the mechanisms of drug resistance reversal by TCM to provide a reference for clinical drug use, prevention and control of bacterial infection, and research and development of new drugs.

Low levels of organic compound trace elements improve the eggshell quality, antioxidant capacity, immune function, and mineral deposition of aged laying hens.

In the egg production industry, trace elements are required as additional dietary supplements to play vital roles in performance and egg quality. Compared to inorganic microelements (ITs), appropriate dose of organic trace microelements (OTs) are environmentally friendly and sufficient to satisfy the needs of hens. In order to evaluate the extent to which low-dose OTs replace whole ITs, the effects of organic copper, zinc, manganese, and iron compound on the performance, eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens were investigated. A total of 1 080 57-week-old Jing Hong laying hens were assigned to five groups with six replicates of 36 layers each for an 8-week experimental period. The birds were fed either a basal diet (control treatment (CT)) or the basal diet supplemented with commercial levels of inorganic trace elements (IT 100%) or the equivalent organic trace elements at 20%, 30%, and 50% of the inorganic elements (OT 20%, OT 30%, and OT 50%, respectively). Results showed that compared with those in the CT treatment, feeding hens with inorganic or organic microelement diet had significant effects on the eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens (P < 0.05). The eggshell strength and ratio between OT 30%, OT 50%, and IT 100% were similar at weeks 4 and 8, and the eggshell thickness of these groups was also similar at weeks 6 and 8. At week 8, the eggshell colour in OT 50% was darker than that in IT 100%. The mineral content in the eggshells of OT 50% and IT 100% significantly increased (P < 0.001), with no significant difference in effective thickness, mammillary thickness, and mammillary knob width between groups. There were no differences in the malondialdehyde content, total antioxidant capacity, and total superoxide dismutase activity in serum between OT 30%, OT 50%, and IT100%. While the catalase activities, the interleukin-1ß, interleukin-10, immunoglobulin G, and immunoglobulin M concentrations in serum were not significantly different between OT 50% and IT 100%. The mineral contents in the faeces of the organic groups were considerably reduced compared with those in IT 100% (P < 0.001). In conclusion, dietary supplementation with 30-50% organic compound microelements has the potential to replace 100% inorganic microelements in the hen industry for improving eggshell quality, mineral deposition in the eggshell, antioxidant capacity, and immune function, and reducing emissions to the environment without negative effects on laying performance.

Dietary supplementation of methionine mitigates oxidative stress in broilers under high stocking density.

We aimed to investigate whether dietary supplementation of methionine could mitigate intestinal oxidative injury in broilers under high stocking density (HSD). In the grower phase (d 22-42), 576 broilers with similar body weight were randomly chosen and divided into 8 groups in a 2 × 4 factorial experiment. Two different stocking densities (14 and 20 broilers per m2) were tested with 4 different methionine levels: 0.35%, 0.4%, 0.45%, or 0.5%. Intestinal morphological and oxidative stress markers were assessed at the end of the test period. The results showed that mortality of broilers was significantly higher in the HSD group fed 0.35% methionine diet than the other groups, which was reversed by supplementation with 0.40% to 0.50% methionine. HSD significantly decreased feed intake and daily weight gain. HSD treatment significantly decreased T-AOC, activity of GPX (P < 0.01) and increased the level of PCO (P < 0.01), MDA (P = 0.052) of plasma. The decreased glutathione peroxidase activity in the liver and jejunum caused by HSD was alleviated by additional methionine. Supplementation of methionine increased the ration of GSH/GSSG in the plasma. The jejunum villus height and ratio of villus height to crypt depth under low stocking density conditions with 0.40% methionine diet were the highest, whereas the 0.45% methionine group was the highest under HSD conditions. Thus, additional dietary supplementation of methionine mitigates oxidative stress in broilers under HSD conditions and 0.40% to 0.45% methionine can be applied in cage rearing broiler production for amelioration of oxidative stress caused by HSD.

Regeneration of pulp-dentine complex-like tissue in a rat experimental model under an inflammatory microenvironment using high phosphorous-containing bioactive glasses.

AIM: To investigate the effects of a bioactive glass with a high proportion of phosphorus (BG-hP) on the repair and regeneration of dental pulps in rats under an inflammatory microenvironment. METHODOLOGY: Human dental pulp cells (hDPCs) stimulated with 1 µg mL-1 lipopolysaccharide (LPS) were co-cultured with 0.1 mg mL-1 BG-hP. Cell proliferation was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assays. The expression of inflammation-related genes and odontogenic differentiation-related genes was determined by real-time PCR. Alizarin red staining was used to detect the formation of mineralized nodules. Coronal pulp tissues of rat molars were stimulated with 10 mg mL-1 LPS and then treated with BG-hP. The expression of inflammation-related genes in pulp tissue was determined by real-time PCR. Haematoxylin-eosin staining and Masson staining were performed to observe the inflammatory response and mineralized matrix formation, after subcutaneous implantation in nude mice, at 3 days and 4 weeks, respectively. Analysis of variance was performed to measure statistical significance (P < 0.05). RESULTS: BG-hP significantly reduced expression of interleukin-6 (IL-6) and IL-8 and significantly upregulated the expression of IL-10, IL-4 and transforming growth factor-ß1 of the LPS-stimulated hDPCs (P < 0.05). BG-hP significantly inhibited the initial cell number (P < 0.05), but the hDPCs stimulated by LPS and co-cultured with BG-hP maintained the same proliferation rate as the untreated hDPCs. BG-hP significantly promoted the expression of dentine matrix protein-1 and dentine sialophosphoprotein and the mineralization capacity of the LPS-stimulated hDPCs (P < 0.05). Furthermore, BG-hP significantly downregulated the expression of Il-6 and reduced the inflammatory response of the LPS-stimulated pulp tissue 3 days after subcutaneous implantation (P < 0.05). Four weeks after subcutaneous implantation, BG-hP induced the formation of a continuous layer of dentine-like structure with dentinal tubules and polarizing odontoblast-like cells aligned along it in the LPS-stimulated pulp tissue. CONCLUSION: The present preliminarily results demonstrated that the bioactive glass with a high proportion of phosphorus inhibited the inflammatory response and promoted the formation of a pulp-dentine complex in a rat experimental model. This study provides a foundation for the construction of materials with the dual functions of exerting anti-inflammatory effects and promoting tissue regeneration to meet the needs of dental pulp repair and regeneration.

Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine.

BACKGROUND: γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid, or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible, non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally friendly biological material. METHODS: The review concentrates on the reports revealing the functions and potential use of γ-PGA and its derivatives in medicine. RESULTS & DISCUSSION: γ-PGA is described to possess several properties that may be exploited in medicine. The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/ deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and contrast agent. CONCLUSION: γ-PGA could be potentially considered as a potential biomedical material in the field of medicine.

Preventive effects of Polygonum orientale L. on ovariectomy-induced osteoporosis in rats.

Objective: The aim of the present study was to evaluate the effects of ethyl acetate extract of Polygonum orientale L. (POE) on ameliorating postmenopausal osteoporosis in ovariectomized (OVX) rats.Methods: Six-month-old female rats were randomly divided into seven groups: sham-operated; OVX; OVX with estradiol valerate; OVX with alendronate; and OVX with POE in graded doses (3.75, 5.0, or 7.5 g/kg/day). Administration began at week 6 after ovariectomy for 12 weeks. A comprehensive assessment of bone quality was performed, including serum biochemical markers, serum inflammatory factors, bone oxidative stress markers, bone mechanics, and bone histomorphometry.Results: POE treatment significantly decelerated OVX-induced body weight gain without affecting the uterus index and produced a significant decrease in the levels of serum bone turnover markers (p < 0.05 or p < 0.01). Biomechanical testing demonstrated that POE (5.0 and 7.5 g/kg/day) treatments significantly prevented the reduction in maximum stress and Young's modulus in OVX rats (p < 0.05). Compared with the OVX group, POE (3.75, 5.0, or 7.5 g/kg/day) treatments significantly increased trabecular bone mineral density by 35.03, 38.42, and 42.02%, respectively.Conclusion: Our findings suggest that POE has potential effects in regulation of bone metabolism and prevention of bone loss in postmenopausal osteoporosis.

Inhibition of autophagy by 3-MA promotes hypoxia-induced apoptosis in human colorectal cancer cells.

OBJECTIVE: Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer. Therefore, the aim of our study was to use human colorectal cancer HCT116 cells to explore whether inhibition of autophagy by 3-Methyladenine (3-MA, an autophagy inhibitor) is able to enhance hypoxia-induced apoptosis in vitro. MATERIALS AND METHODS: HCT116 cells were treated with 3-MA, hypoxia, or 3-MA plus hypoxia, and the autophagy, apoptosis and proliferation of the HCT116 cells were investigated. Western blot analysis was used to detect autophagy specificity protein microtubule-associated protein light chain 3 (LC3) expression. Effects on apoptosis were evaluated by using flow cytometry (JC-1 staining to measure mitochondrial membrane potential) and annexin V-propidium iodide (PI) staining. RESULTS: The results showed that the treatment of HCT116 cells in vitro with hypoxia alone increased autophagy as well as apoptosis, whereas combination treatment with 3-MA and hypoxia markedly inhibited hypoxia-induced autophagy, but increased hypoxia-induced cell apoptosis. CONCLUSIONS: Autophagy might play a role as a self-defense mechanism in hypoxia-treated colon cancer cells, and its inhibition could be a promising strategy for the adjuvant chemotherapy of colon cancer.

[Research on ancient literature of Lingguizhugan Decoction, a classical prescription].

Derived from Zhang Zhongjing's Shang han za bing lun (Treatise on Cold Pathogenic and Miscellaneous Diseases)of the Han Dynasty, Lingguizhugan Decoction was composed of 4 Chinese herbs: Poria, Ramulus Cinnamomi, Rhizoma Atractylodis Macrocephalae, and Radix et Rhizoma Glycyrrhizae, for treating fullness and discomfort in chest and hypochondrium, phlegm and fluid retention, dizziness etc. The relevant descriptions and records in ancient Chinese medical works were collected, and as a result, altogether 162 items from 106 kinds of ancient book were available. Through statistical analysis, it was found that most of them followed the original records of composition, dosage and indications in Zhang's original work, only with some extensions in the scope of its clinical application.

Identification of a 62-kDa major allergen from Artemisia pollen as a putative galactose oxidase.

BACKGROUND: Around 20 years ago, a 60- to 70-kDa protein was reported as a major allergen of mugwort (Artemisia vulgaris) pollen. This study was to identify and characterize its molecular properties. METHODS: Sera from 113 Chinese and 20 Dutch Artemisia-allergic/sensitized subjects (and pools thereof) were used to identify the 60- to 70-kDa allergen. Pollen extracts of seven Artemisia species were compared by immunoblotting. Transcriptomics and proteomics (mass spectrometry) of A. annua pollen were used to identify the putative 60- to 70-kDa Artemisia allergen. Both the natural purified and recombinant allergens were evaluated for IgE reactivity by ImmunoCAP. Fourteen Chinese Artemisia-allergic patients were tested intradermally with purified natural allergen. RESULTS: Immunoblots revealed two major bands at 12 and 25 kDa, and a weak band at 70 kDa for all seven Artemisia species. Using a combined transcriptomic and proteomic approach, the high molecular mass allergen in A. annua pollen was shown to be a 62-kDa putative galactose oxidase, with a putative N-glycosylation site. More than 94% of Artemisia pollen-allergic patients had IgE response to this allergen. Although recognition of a nonglycosylated recombinant version was only confirmed in a minority (16%) and at much lower IgE levels, this discrepancy cannot be explained simply by reactivity to the carbohydrate moiety on the natural allergen. Intradermal testing with the natural allergen was positive in five of nine sensitized patients. CONCLUSIONS: The previously reported 60- to 70-kDa allergen of Artemisia pollen is most likely a 62-kDa putative galactose oxidase here designated Art an 7.

Being Adaptive to Pain Enhances Sham Acupuncture Analgesia: A Crossover Healthy Human Study.

We have reported a model that distinguishes pain adaptive individuals (PA) from those who are pain non-adaptive (PNA). The present randomised, cross-over, participant-assessor blinded study aimed to determine the impact of pain adaptability on individuals' response to real and sham acupuncture. Healthy volunteers (nine PA and 13 PNA) were randomly allocated to receive real and sham acupuncture on the left hand and forearm in two separate acupuncture sessions. Pressure pain thresholds (PPTs) were measured at bilateral forearms and right leg before, immediately after and 20 minutes after the end of acupuncture. Ratings to pinprick and suprathreshold PPT were also recorded. The two groups were comparable in their demographic and baseline data. Analgesia induced by real or sham acupuncture did not differ on any outcome measures. PA responded to acupuncture needling better than PNA, and to sham needling (20% increase in PPT) better than to real acupuncture (7.9%). Those differences were at 20 min after end of acupuncture in the areas distant to the needling sites. PNA reported little changes in PPT. Being adaptive to pain was associated with enhanced distant analgesia in response to sham acupuncture. Our finding might partly explain varied acupuncture analgesia in clinical practice and trials.

Establishment of a hepatocyte line for studying biosynthesis of long-chain polyunsaturated fatty acids from a marine teleost, the white-spotted spinefoot Siganus canaliculatus.

A hepatocyte line was established from the liver of white-spotted spinefoot Siganus canaliculatus to study the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA). The cells from the line, designated S. canaliculatus hepatocyte line (SCHL), grew and multiplied well in Dulbecco's modified Eagle's medium (DMEM)-F12 medium supplemented with 20 mM 4-(2-hydroxyethyl) piperazine-1-ethanesulphonic acid (HEPES), 10% foetal bovine serum (FBS) and 0·5% rainbow trout Oncorhychus mykiss serum at 28° C, showing an epithelial-like morphology and the normal chromosome number of 48 (2n) and have been subcultured for over 60 passages. The identity of the hepatocytes was confirmed by periodic acid Schiff (PAS) staining. The mRNA expression of all genes encoding the key enzymes for LC-PUFA biosynthesis including two desaturases (Δ4 Fad and Δ6-Δ5 Fad) and two elongases (Elovl4 and Elovl5), were detected in all cells from passages 5 to 60 and their expression levels became stable after passage 35 and showed responses to various PUFA incubation. This is similar to the situation determined in the liver of S. canaliculatus that were fed diets containing different fatty acids. These results indicated that SCHL was successfully established and can provide an in vitro tool to investigate lipid metabolism and regulatory mechanisms of LC-PUFA biosynthesis in teleosts, especially marine species.

Cross-resistance between voriconazole and fluconazole for non-albicans Candida infection: a case-case-control study.

Cross-resistance (CR) between voriconazole and fluconazole for non-albicans Candida (NAC) species is not uncommon, but little is known about the risk factors and clinical consequences associated with this resistance phenotype. A case-case-control study was performed at a university-affiliated hospital in China between November 2012 and April 2016. The two case groups respectively comprised patients with a mono-resistance (MR) NAC infection (fluconazole or voriconazole resistance) and patients with a CR NAC infection (fluconazole and voriconazole resistance). Patients with a no-resistance (NR) NAC infection were included as the control group. Models were adjusted for demographic and clinical risk factors, and the risk of resistance associated with exposure to specific antibiotics or non-antibiotics were assessed. Of 259 episodes, 33 (12.7%) and 27 (10.4%) were identified as MR and CR NAC infections, respectively. The broad use of azoles was strongly associated with the emergence of MR and CR NAC infections (adjusted odds ratio [95% confidence interval] = 2.69 [1.10-6.58] and 2.53 [1.02-6.28], respectively). The time at risk (1.02 [1.00-1.03]) with 12 days as a breakpoint was also an independent risk factor for CR NAC infection. The number of species associated with a high minimum inhibitory concentration (≥128 µg/mL) of fluconazole was higher for CR NAC infections than for MR NAC infections. Different resistance phenotypes (CR vs. MR vs. NR) were associated with all-cause mortality rates. These findings indicate a worrisome propensity of CR NAC infections and emphasize the need for strict antifungal stewardship.

Green light inhibits GnRH-I expression by stimulating the melatonin-GnIH pathway in the chick brain.

To study the mechanism by which monochromatic light affects gonadotrophin-releasing hormone (GnRH) expression in chicken hypothalamus, a total of 192 newly-hatched chicks were divided into intact, sham-operated and pinealectomy groups and exposed to white (WL), red (RL), green (GL) and blue (BL) lights using a light-emitting diode system for 2 weeks. In the GL intact group, the mRNA and protein levels of GnRH-I in the hypothalamus, the mean cell area and mean cell optical density (OD) of GnRH-I-immunoreactive (-ir) cells of the nucleus commissurae pallii were decreased by 13.2%-34.5%, 5.7%-39.1% and 9.9%-17.3% compared to those in the chicks exposed to the WL, RL and BL, respectively. GL decreased these factors related to GnRH-I expression and the effect of GL was not observed in pinealectomised birds. However, the mRNA and protein levels of hypothalamic gonadotrophin-inhibitory hormone (GnIH) and GnIH receptor (GnIHR), the mean cell area and mean cell OD of the GnIH-ir cells of the paraventricularis magnocellularis, and the plasma melatonin concentration in the chicks exposed to GL were increased by 18.6%-49.2%, 21.1%-60.0% and 8.6%-30.6% compared to the WL, RL and BL intact groups, respectively. The plasma melatonin concentration showed a negative correlation with GnRH-I protein and a positive correlation with GnIH and GnIHR proteins. Protein expression of both GnRH-I and GnIHR showed a negative correlation in the hypothalamus. After pinealectomy, GnRH-I expression increased, whereas plasma melatonin concentration, GnIH and GnIHR expression decreased, and there were no significant differences among the WL, RL, GL and BL groups. Double-labelled immunofluorescence showed that GnIH axon terminals were near GnRH-I neurones, some GnRH-I neurones coexpressed with GnIHR and GnIH neurones coexpressed with melatonin receptor subtype quinone reductase 2. These results demonstrate that green light inhibits GnRH-I expression by increasing melatonin secretion and stimulating melatonin receptor-GnIH-GnIH receptor pathway in the chick brain.

The injury of serotonin on intestinal epithelium cell renewal of weaned diarrhoea mice.

Diarrhoea is a common cause of death in children and weaned animals. Recent research has found that serotonin (5-HT) in the gastrointestinal tract plays an important role in regulating growth and the maintenance of mucosa, which protect against diarrhoea. To determine the influence of 5-HT on intestinal epithelium cell renewal under weaned stress diarrhoea, a weaned-stress diarrhoea mouse model was established with senna infusion (15 mL/Kg) via intragastric administration and stress restraint (SR). Mice with an increase in 5-HT were induced by intraperitoneal injection with citalopram hydrobromide (CH, 10 mg/Kg). The results demonstrated that compared with the control animals, diarrhoea appeared in weaned stress mice and the 5-HT content in the small intestine was significantly increased (P<0.05). Further, the caspase-3 cells and cells undergoing apoptosis in the small intestine were significantly increased, but the VH (villus height), V/C (villus height /crypt depth), and PCNA-positive rate significantly decreased. Compared with the control animals, CH increased the intestinal 5-HT content, caspase-3 cells and cells undergoing apoptosis but decreased the VH and V/C. Compared with both control and weaned stress animals, weaned stress animals that were pre-treated with CH showed higher 5-HT concentrations, positive caspase-3 cells and cells undergoing apoptosis but lower VH, V/C and PCNA-positive rate. In vitro, a low concentration of 5-HT inhibit, IEC-6 cell line apoptosis but a higher concentration of 5-HT promoted it. Therefore, weaned stress diarrhoea mice were accompanied by a 5-HT increase in the small intestine and vice versa, and the increase in 5-HT induced by CH caused diarrhoea. In brief, 5-HT and diarrhoea slowed the intestinal epithelium cell renewal and injured the abortion function and mucosal barrier by decreasing VH, V/C and proliferation and increasing epithelium cell apoptosis.

Azadircta indica as a modulator of membrane stability parameters and surface changes during 1,2 dimethylhydrazine-induced colorectal carcinogenesis.

OBJECTIVE: The aim of the present study was to study the modulatory potential of Azadirta indica on colonic surface abnormalities and membrane fluidity changes following 1,2 dimethylhydrazine-induced [DMH] colon carcinogenesis. MATERIALS AND METHODS: Brush border membranes [BBM] were isolated from the colon of rats and the viscosity as well as fluidity parameters were assessed by using the membrane extrinsic fluorophore pyrene. RESULTS: DMH treatment resulted in a significant increase in lipid peroxidation [LPO]. Reduced glutathione levels [GSH] and the activities of glutathione reductase [GR], glutathione transferase [GST], superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx] were found to be significantly decreased following DMH treatment. On the other hand, supplementation with AI, DMH-treated rats resulted in a significant decrease in the levels of lipid peroxidation but caused a significant increase in the levels of GSH as well in the activities of GR, GST, SOD, CAT and GPx. The results further demonstrated a marked decrease in membrane microviscosity following DMH treatment. On the other hand, a significant increase was observed in the excimer/monomer ratio and fluidity parameter of DMH-treated rats when compared to normal control rats. However, the alterations in membrane microviscosity and the fluidity parameters were significantly restored following A. indica treatment. Further, histological as well as colon surface alterations were also observed following DMH treatment, which however were greatly prevented upon AI co-administration. CONCLUSIONS: The study, therefore, concludes that A. indica proves to be useful in modulating the colonic surface abnormalities and membrane stability following DMH-induced colon carcinogenesis.

Trends and correlation of antibacterial usage and bacterial resistance: time series analysis for antibacterial stewardship in a Chinese teaching hospital (2009-2013).

The purpose of this investigation was to describe the effect of antibacterial stewardship and evaluate the trends and correlation of antibacterial resistance and usage from 2009 to 2013 in a tertiary-care teaching hospital in northwest China. Antibacterial usage was expressed as defined daily doses per 100 patients per day (DDDs/100 PDs). Hospital-wide population-level data and time series analysis were used to evaluate the trends and determine associations between antibacterial exposure and acquisition of resistance. Yearly consumption of overall antibacterials significantly decreased from 66.54 to 28.08 DDDs/100 PDs (ß = -10.504, p < 0.01). The resistant rates of the five most frequently isolated species (including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae) significantly decreased or remained stable, and none of them showed a statistically significant upward trend. The medical quality indicators got better or remained stable. Autoregressive integrated moving average (ARIMA) models demonstrated that the monthly resistance rate of P. aeruginosa to imipenem was strongly correlated with antipseudomonal carbapenems usage (ß = 34.94, p < 0.001), as did the correlation of P. aeruginosa to meropenem with antipseudomonal third-generation cephalosporins usage (ß = 32.76, p < 0.01) and K. pneumoniae to amikacin with aminoglycosides usage (ß = 22.01, p < 0.001). The decreased antibacterial use paralleled the improved bacterial resistance without deteriorating medical quality indicators during antimicrobial stewardship. It also suggests that optimum antibiotic use is necessary to alleviate the threat posed by resistant microorganisms at the hospital level.

QTL verification of grain protein content and its correlation with oil content by using connected RIL populations of high-oil maize.

Maize with high grain protein and oil contents offers great advantages for human food and animal feed. In this study, grain protein contents of 282 and 263 F7:8 recombinant inbred lines (RILs) of 2 crosses were evaluated in 4 environments within and between populations. The RILs were developed from crosses between an inbred high-oil maize line and 2 normal dent inbred maize lines. A total of 16 single-population QTLs and 19 joint-population QTLs were identified for protein content, and 21 QTLs were detected for protein-oil in each of the 4 environments tested and in combination. Most of the QTLs for protein content were greatly influenced by variation among populations and environments. Seven QTLs showed generational consistency compared with QTLs detected in the 2 F2:3 populations. However, 7 and 6 QTLs were detected in only the RIL and F2:3 populations, respectively. Protein and protein-oil QTLs with the same parental effects were detected at bins 3.03-3.05, 5.04-5.06, 6.03-6.05, 8.03-8.04, and 8.04-8.06, demonstrating that tightly linked and/or pleiotropic QTLs are controlling both traits at these bins. Four single-population QTLs and 11 joint-population QTLs identified at bins 3.02-3.03, 3.05, 7.01, 8.02, 8.03, 8.04-8.05, 8.05, 9.03, and 9.05 with intervals <5 cM could be used in marker-assisted selection. Along with the previously detected QTLs qPRO1-8-1 and qPRO1-5-1 at bins 8.03-8.04 and 5.02-5.04, the QTLs detected herein could be used to develop near isogenic lines and chromosome segment substitution lines in future studies.