Cold Exposure-induced Alterations in the Brain Peptidome and Gut Microbiome Are Linked to Energy Homeostasis in Mice.

Energy homeostasis of mammals during cold exposure involves complicated neural regulation and is affected by gut microbiota. However, the regulatory mechanism remains unclear partially due to a lack of comprehensive knowledge of the signaling molecules involved. Herein, we performed region-resolvable quantitative profiling of the brain peptidome using cold-exposed mouse models and interrogated the interaction between gut microbes and brain peptides in response to cold. Region-specific alterations in the brain peptidome were observed during chronic cold exposure and were correlated with gut microbiome composition. Several proSAAS-derived peptides exhibited a positive correlation with Lactobacillus. The hypothalamus-pituitary axis exhibited a sensitive response to cold exposure. We obtained a candidate pool of bioactive peptides that potentially participate in the regulation of cold-induced energy homeostasis. Intervention with cold-adapted microbiota in mice decreased the abundance of hypothalamic neurokinin B and subsequently contributed to shifting the fuel source for energy consumption from lipids to glucose. Collectively, this study demonstrated that gut microbes modulate brain peptides contributing to energy metabolism, providing a data resource for understanding the regulatory mechanism of energy homeostasis upon cold exposure.

The regulatory roles of DDIT4 in TDCIPP-induced autophagy and apoptosis in PC12 cells.

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate-based flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy. However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4 (DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot (WB) and Flow cytometry (FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II (LC3II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the mTOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.

Effect of strontium-containing on the properties of Mg-doped wollastonite bioceramic scaffolds.

BACKGROUND: Bone scaffold is one of the most effective methods to treat bone defect. The ideal scaffold of bone tissue should not only provide space for bone tissue growth, but also have sufficient mechanical strength to support the bone defect area. Moreover, the scaffold should provide a customized size or shape for the patient's bone defect. METHODS: In this study, strontium-containing Mg-doped wollastonite (Sr-CSM) bioceramic scaffolds with controllable pore size and pore structure were manufactured by direct ink writing 3D printing. Biological properties of Sr-CSM scaffolds were evaluated by apatite formation ability, in vitro proliferation ability of rabbit bone-marrow stem cells (rBMSCs), and alkaline phosphatase (ALP) activity using ß-TCP and Mg-doped wollastonite (CSM) scaffolds as control. The compression strength of three scaffold specimens was probed after completely drying them while been submerged in Tris-HCl solution for 0, 2,4 and 6 weeks. RESULTS: The mechanical test results showed that strontium-containing Mg-doped wollastonite (Sr-CSM) scaffolds had acceptable initial compression strength (56 MPa) and maintained good mechanical stability during degradation in vitro. Biological experiments showed that Sr-CSM scaffolds had a better apatite formation ability. Cell experiments showed that Sr-CSM scaffold had a higher cell proliferation ability compared with ß-TCP and CSM scaffold. The higher ALP activity of Sr-CSM scaffold indicates that it can better stimulate osteoblastic differentiation and bone mineralization. CONCLUSIONS: Therefore, Sr-CSM scaffolds not only have acceptable compression strength, but also have higher osteogenesis bioactivity, which can be used in bone tissue engineering scaffolds.

A quicker degradation rate is yielded by a novel kind of transgenic silk fibroin consisting of shortened silk fibroin heavy chains fused with matrix metalloproteinase cleavage sites.

Degradation performance of silk fibroin is an important property for its medical applications. Herein we constructed a shortened silk fibroin heavy chain protein fused with a matrix metalloproteinase cleavage site (SSFH-MMP) along with a glutathione S-transferase tag ahead. The digestion assay shows it can be cut by matrix metalloproteinase-2 (MMP-2) at its MMP cleavage site. Furthermore, we introduced the SSFH-MMP into silk fibroin by genetic modification of silkworms in order to increase the degradation rate of the silk fibroin. After acquisition of a race of transgenic silkworms with the coding sequence of the MMP cleavage site in their genomic DNA, we tested some properties of their silk fibroin designated TSF-MMP. The results show that the TSF-MMP has MMP cleavage sites and yields a quicker degradation rate during dilution in MMP-2 enzyme buffer or implantation into tumor tissues compared with that of normal silk fibroin. Moreover, the TSF-MMP is in vitro non-toxic to human bone marrow mesenchymal stem cells (hBM-MSCs) indicating that the TSF-MMP may become a biomaterial with a quicker degradation rate for its medical applications.

[Effects of nutritional preparation on HPO axis function and energy metabolism in uterus and ovary of rats exposed to intermittent cold].

Objective: To investigate the effects of a self-designed nutritional preparation on hypothalamic-pituitary-ovarian (HPO) axis function and energy metabolism in female SD rats exposed to intermittent cold. Methods: Female SD rats were divided into control group, cold exposure group and nutritional preparation group. The control group and cold exposure group were given distilled water by daily gavage, and the nutritional preparation group was given nutritional preparation intragastrically. After the treatment, the cold exposure group and nutritional preparation group were exposed to -10℃ in a cabin for 4 h every day. After being treated for 14 days, the serum, uterus and ovary of rats were collected. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and other hormone indicators were detected by enzyme-linked immunosorbent assay (ELISA) and colorimetry was used to detect ATPase and other energy metabolism related indicators. Results: Compared with the control group, cold exposure significantly up-regulated the protein expressions of FSHR and LHR, and notably enhanced the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in ovary and uterus (P<0.05). Nutritional preparation down-regulated the protein expressions of FSHR and LHR, and inhibited the activity of ATPase in ovary and uterus (P<0.05) compared with the cold exposure group. Conclusion: Nutritional preparations can effectively improve the expressions of HPO axis related receptors and abnormal energy metabolism in uterus and ovary caused by intermittent cold exposure.

Characteristics of menstrual cycle disorder and saliva metabolomics of young women in a high-temperature environment.

Objective: Menstrual disorders induced by high-temperature environments, can seriously damage women's reproductive health and workability. The regulation mechanism underlying it is not yet to be elucidated. Saliva is an information-rich biological fluid that can reflect systemic diseases. Here, we investigated the characteristics of menstrual cycle disorders and saliva metabolomics to provide a deeper insight of the regulation mechanism of young women in high-temperature environments. Methods: Women from high and normal temperature areas of China were selected and divided into two groups-high-temperature (H group) and control (C group). A questionnaire survey was conducted in summer (July) to investigate the incidence rate of menstrual disorders, characteristics of the disorders, and factors influencing the risk of these disorders in different regions. Metabolomics was applied to analyze the characteristics of the salivary metabolites and neurotransmitters in the two groups of women with menstrual disorders. Results: The incidence rate of menstrual disorders was significantly higher in the H group than that in the C group (p < 0.05). High-temperature environment, stress, and sleep quality were identified as critical factors associated with menstrual disorders. Non-targeted saliva metabolomics identified 64 significantly different metabolites between two groups, which mainly enriched in metabolic pathways such as carbohydrate metabolism, membrane transport, digestive system, and nucleotide metabolism (p < 0.05). N-acetylneuraminic acid, MYO, and tyramine may be candidate markers for early diagnosis of menstrual disorders in high temperature environments. Metabolites may be involving in the acute-phase response during an inflammatory process, to affecting the reproductive system by influencing the HPA axis loop. Regulations about oocyte membrane production and the luteal functions would be exerted in menstrual disorders. Targeted metabolomics of neurotransmitters revealed increased expression of histamine (HA) and glutamine and decreased expression of 5-hydroxyindole acetic acid (5-HIAA) (p < 0.05). Conclusion: Menstrual disorder characteristics induced by high temperature environments were specific. Anxiety, sleep quality and temperature feeling were the key factors to the menstrual disorder. endocrine regulation mechanism and inflammatory reactions might contribute to the development of menstrual disorders through influencing the formation of the follicular cell membrane.

A Chinese herbs complex ameliorates gut microbiota dysbiosis induced by intermittent cold exposure in female rats.

Cold is a common source of stress in the alpine areas of northern China. It affects the microbial community, resulting in the invasion of pathogenic microorganisms and intestinal diseases. In recent years, studies have reported that Chinese herbal extracts and their fermentation broth have a significant beneficial effect on gut microbiota. This study aimed to investigate the probiotic effect of a self-designed Chinese herbs complex on the gut microbiota of rats exposed to cold. The rats were treated with intermittent cold exposure and Chinese herbs complex for 14 days, and the gut microbiota composition and other parameters were assayed. The 16s ribosomal DNA high-throughput sequencing and analysis confirmed that the Chinese herbs complex positively improved the gut microbiota. We found that cold exposure could lead to significant changes in the composition of gut microbiota, and affect the intestinal barrier and other physiological functions. The relative abundance of some probiotics in the genus such as Roseburia, Parasutterella, and Elusimicrobium in rats treated with Chinese herbs complex was significantly increased. Serum D-lactic acid (D-LA) and lipopolysaccharide (LPS) were increased in the cold exposure group and decreased in the Chinese herbs complex-treated group. Moreover, the Chinese herbs complex significantly increased the protein expression of occludin. In conclusion, the Chinese herbs complex is effective in restoring the gut microbiota caused by cold exposure, improving the function of the intestinal barrier, and may act as a prebiotic in combatting gut dysbiosis.

Propofol combined with remifentanil reduces the adverse reactions of patients undergoing laparoscopic cholecystectomies.

OBJECTIVE: To explore the effectiveness of using isoflurane and propofol combined with remifentanil in laparoscopic cholecystectomies (LC). METHODS: A total of 118 patients undergoing LC in our hospital from April 2018 to January 2019 were recruited as the study cohort. 56 of the patients were anesthetized with isoflurane combined with remifentanil during their operations (the IR group), and the other 62 patients were anesthetized with propofol combined with remifentanil during their operations (the PR group). The effects of the two anesthesia methods on the hemodynamics and stress responses were compared, and the postoperative recoveries, adverse reactions, analgesia, and cognitive functions were recorded. RESULTS: Compared with the IR group, the average arterial pressure, heart rate, norepinephrine, and cortisol decreased in the PR group. Compared with the IR group, the total postoperative adverse reaction rate was lower in the PR group. Compared with the IR group, the spontaneous respiration recovery times, the times to opening eyes, and the extubation times were significantly shortened in the PR group. There was no significant difference in the postoperative pain levels between the two groups. Compared with the IR group, the postoperative cognitive function assessment was better in the PR group. CONCLUSION: Compared with isoflurane combined with remifentanil, propofol combined with remifentanil has a smaller impact on the hemodynamics and cognitive functions of patients undergoing LC, and it causes a more significant reduction in the stress response. In addition, its postoperative adverse reactions are lower, so it is worthy of promoting in clinical practice.

Integrative Analysis of Vaginal Microorganisms and Serum Metabolomics in Rats With Estrous Cycle Disorder Induced by Long-Term Heat Exposure Based on 16S rDNA Gene Sequencing and LC/MS-Based Metabolomics.

Long term heat exposure (HE) leads to estrous cycle disorder (ECD) in female rats and damages reproductive function. However, the regulation mechanism of vaginal microorganisms and serum metabolomics remains unclear. This study aimed to explore the effects of microbes on the vaginal secretions of rats with ECD and describe the serum metabolomics characteristics and their relationship with vaginal microorganisms. The alterations in the serum levels of neurotransmitters were used to verify the possible regulatory pathways. The relative abundance, composition, and colony interaction network of microorganisms in the vaginal secretions of rats with ECD changed significantly. The metabolomics analysis identified 22 potential biomarkers in the serum including lipid metabolism, amino acid metabolism, and mammalian target of rapamycin and gonadotropin-releasing hormone (GnRH) signaling pathways. Further, 52 pairs of vaginal microbiota-serum metabolites correlations (21 positive and 31 negative) were determined. The abundance of Gardnerella correlated positively with the metabolite L-arginine concentration and negatively with the oleic acid concentration. Further, a negative correlation was found between the abundance of Pseudomonas and the L-arginine concentration and between the metabolite benzoic acid concentration and the abundance of Adlercreutzia. These four bacteria-metabolite pairs had a direct or indirect relationship with the estrous cycle and reproduction. The glutamine, glutamate, and dopamine levels were significantly uncontrolled. The former two were closely related to GnRH signaling pathways involved in the development and regulation of HE-induced ECD in rats. Serum neurotransmitters partly reflected the regulatory effect of vaginal microorganisms on the host of HE-induced ECD, and glutamatergic neurotransmitters might be closely related to the alteration in vaginal microorganisms. These findings might help comprehend the mechanism of HE-induced ECD and propose a new intervention based on vaginal microorganisms.

The damage effect of heat stress and psychological stress combined exposure on uterus in female rats.

AIMS: Explore the effects of heat stress and psychological stress combined exposure on the uterus and its underlying mechanisms. MAIN METHODS: Sixty female Sprague-Dawley rats were randomly assigned to four groups: control group, psychological stress group, high ambient temperature group, and high ambient temperature combined with psychological stress group. All treatments were administered for two weeks. During this period, the estrous cycle, body weights and rectal temperature were measured regularly. Then, ovarian weight coefficient, serum estradiol (E2) and progesterone (P) concentration, uterine histomorphological alterations, levels of tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD), and the expressions of ovarian hormone receptors, leukemia inhibitory factor (LIF) and its receptor, homeobox gene A10 (HoxA10), Wnt5a, Wnt7a, ß-catenin, and P-ß-cateninY142 in the uterus and endometrium were detected. KEY FINDINGS: High temperature combined with psychological stress lead to body weight, body temperature, ovarian hormones and estrus cycle disorder, uterine gland ducts expansion and endometrial thickness reduction, and the decreased expression of endometrial receptivity markers (LIF and HoxA10). Further, disturbed expression of E2 and P receptors in endometrium, elevated MDA and TNF-α levels, and decreased Wnt5a, Wnt7a and P-ß-cateninY142 content were found. Our data suggested that co-exposure to high temperature and psychological stress could aggravate uterine damage probably by inducing ovarian hormonal disorder and the subsequent oxidative stress and inflammation, and reduce the endometrial function through suppressing Wnt signaling. SIGNIFICANCE: This will provide the scientific basis for improving female reproductive health, and preventing and treating reproductive disorders.

[Effects of Nano-SiO2 combining with cold on cytotoxicity and secretion of inflammatory factors in A549 cells].

Objective: To investigate the effects of nano-SiO2 and cold on the cytotoxicity and secretion of inflammatory factors in human lung adenocarcinoma epithelial cell line A549. Methods: A549 was used as experimental subject, a single factor multilevel experiment was designed, A549 cells were exposed to 10, 50, 100, 200 µg/ml nano-SiO2 particles and/or cultured at 31℃, 33℃, 35℃ for 48 h. After that, cell morphology was observed and relative cell survival rate was detected. According to the results of single factor analysis and based on the selection of nano-SiO2 dose and temperature that significantly reduced the relative survival rate of A549 cells, the experiment was designed according to 2×2 factor analysis , they were divided into 4 groups: control group(37℃), Nano-SiO2 exposure group, low temperature exposure group, Nano-SiO2 and low temperature composite group. After exposure for 48 h, the supernatant of cell culture medium was collected for detecting the LDH activity by colorimetric method and the levels of cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) were determined by ELISA. The mRNA levels of cellular IL-6 and IL-8 were detected by qRT-PCR. Results: The activities of A549 cells in 100 µg/ml Nano-SiO2 group and 31℃ low temperature group were decreased significantly. Under the combined conditions, the activity of A549 cells was most inhibited (P＜0.01), and the levels of inflammatory factors IL-6 and IL-8 and mRNA were significantly increased (P＜0.01). Conclusion: 100 µg/ml Nano-SiO2 combined with 31℃ cold exposure can synergistically reduce the activity of A549 cells and increase the expression level of inflammatory factors IL-6 and IL-8 .

Pathophysiological Changes in Female Rats with Estrous Cycle Disorder Induced by Long-Term Heat Stress.

High-temperature exposure is detrimental to women's reproductive health; however, the impact caused by long-term high temperature is not comprehensive, and a stable model of estrous cycle disorder induced by a high temperature is yet lacking. Herein, we aimed to establish a stable and effective model of estrous cycle disorder in female rats induced by long-term heat stress to study its physiological and pathological characteristics and explore the underlying mechanism. In the present study, female Sprague-Dawley rats with normal estrous cycles were exposed to the temperature of 38 ± 0.5°C, relative humidity (RH) of 55 ± 5% (2 h/d, 1 time/d) hot cabin at more than 90 days. Consequently, after long-term heat stress, no difference was detected in body weight and rectal temperature, but the estrus cycle was prolonged, the uterine organ index was increased, pathological changes occurred, the increase latitude of stress hormones heat shock protein 70 (Hsp70) and corticosterone (CORT) decreased, estradiol (E2) and luteinizing hormone (LH) levels decreased, follicle stimulating hormone (FSH) and prolactin (Prl) levels increased, gonadotropin-releasing hormone (GnRH) and thyroid hormone (T4) showed no difference, and insulin (INS) decreased significantly. Moreover, the mRNA expression of the sex hormone receptor in the uterus and ovary was altered. Therefore, the estrous cycle disorder in female rats can be induced by regular heat stress for 90 days, which can be considered the pioneer method. Subsequently, prominent physiological and pathological characteristics and disruption in the hypothalamic-pituitary-gonadal (HPG) axis were noted.

Effects of Caffeine on Event-Related Potentials and Neuropsychological Indices After Sleep Deprivation.

Objective: Caffeine is a central nervous system stimulant that can effectively alleviate brain fatigue and low cognitive efficiency induced by total sleep deprivation (TSD). Recent studies have demonstrated that caffeine can improve subjective attention and objective behavioral metrics, such as arousal level, reaction time, and memory efficiency. However, only a few studies have examined the electrophysiological changes caused by the caffeine in humans following sleep disturbance. In this study, an event-related potential (ERP) technique was employed to measure the behavioral, cognitive, and electrophysiological changes produced by caffeine administration after TSD. Methods: Sixteen healthy subjects within-subject design performed a visual Go/No-Go task with simultaneous electroencephalogram recording. Behavioral and ERP data were evaluated after 36 h of TSD, and the effects of ingestion of either 400 mg of caffeine or placebo were compared in a double-blind randomized design. Results: Compared with placebo administration, the Go hit rates were significantly enhanced in the caffeine condition. A simple effect analysis revealed that, compared with baseline, the Go-P2 amplitude was significantly enhanced after TSD in the caffeine consumption condition. A significant main effect of the drug was found on No-Go-P2, No-Go-N2 amplitude, and Go-P2 latency before and after TSD. Conclusion: Our findings indicate that caffeine administration has acute effects on improving the efficiency of individual automatic reactions and early cognitive processes. Caffeine was related to the preservation of an individual's arousal level and accelerated response-related decisions, while subjects' higher-level recognition had limited improvement with prolonged awareness.

Oxidative damage to lung tissue and peripheral blood in endotracheal PM2.5-treated rats.

OBJECTIVE: To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. METHODS: PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length (microm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. RESULTS: The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length (microm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. CONCLUSION: PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length (microm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

[Effects of cold exposure on estrous cycle of female C57BL/6 mice].

OBJECTIVE: To study the effects of cold exposure on estrous cycle of female C57BL/6 mice. METHODS: Twelve healthy female C57BL/6 mice were randomly divided into two groups: control group and cold exposure group, 6 in each group. Cold exposure group was exposed to 4℃, 4 h per day, while control group stayed in normal conditions. Vaginal smears were used to observe the estrous cycle. After 2 weeks, blood and uteri were collected from each mouse after anesthetized and weighted. Serum levels of estradiol(E2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(Prl) and progesterone(P) were determined by using mouse ELISA kits. The uterus and ovary pathological slices were prepared to observe the structural changes. RESULTS: Compared with the control group, body weight gain showed no significant differences (P＞0.05). The cold group had significant lower coefficients of uterus and the diestrus phase was significantly increased after cold exposure (P＜0.01). Serum level of FSH in cold group was higher and Prl was lower significantly (P＜0.01). Pathological examination of uterus and ovary showed that uterine glands of cold group were expanded and the amount of follicles was decreased significantly. CONCLUSION: Cold exposure might increase mouse estrous cycle and affect their reproductive function.

Neuraxial adjuvants for prevention of perioperative shivering during cesarean section: A network meta-analysis following the PRISMA guidelines.

BACKGROUND: Perioperative shivering is clinically common during cesarean sections under neuraxial anesthesia, and several neuraxial adjuvants are reported to have preventive effects on it. However, the results of current studies are controversial and the effects of these neuraxial adjuvants remain unclear. AIM: To evaluate the effects of neuraxial adjuvants on perioperative shivering during cesarean sections, thus providing an optimal choice for clinical application. METHODS: A systematic review and network meta-analysis were conducted following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. Analyses were performed using Review Manager 5.3 and Stata 14.0. We searched PubMed, EMBASE, Web of Science, and Cochrane Central databases for eligible clinical trials assessing the effects of neuraxial adjuvants on perioperative shivering and other adverse events during cesarean sections. Perioperative shivering was defined as the primary endpoint, and nausea, vomiting, pruritus, hypotension, and bradycardia were the secondary outcomes. RESULTS: Twenty-six studies using 9 neuraxial adjuvants for obstetric anesthesia during caesarean sections were included. The results showed that, compared with placebo, pethidine, fentanyl, dexmedetomidine, and sufentanil significantly reduced the incidence of perioperative shivering. Among the four neuraxial adjuvants, pethidine was the most effective one for shivering prevention (OR = 0.15, 95%CI: 0.07-0.35, surface under the cumulative ranking curve 83.9), but with a high incidence of nausea (OR = 3.15, 95%CI: 1.04-9.57) and vomiting (OR = 3.71, 95%CI: 1.81-7.58). The efficacy of fentanyl for shivering prevention was slightly inferior to pethidine (OR = 0.20, 95%CI: 0.09-0.43), however, it significantly decreased the incidence of nausea (OR = 0.34, 95%CI: 0.15-0.79) and vomiting (OR = 0.25, 95%CI: 0.11-0.56). In addition, compared with sufentanil, fentanyl showed no impact on haemodynamic stability and the incidence of pruritus. CONCLUSION: Pethidine, fentanyl, dexmedetomidine, and sufentanil appear to be effective for preventing perioperative shivering in puerperae undergoing cesarean sections. Considering the risk-benefit profiles of the included neuraxial adjuvants, fentanyl is probably the optimal choice.

[Effect on conception and offspring development in female parenatal rats following intratracheal instillation of nano-C/ZnO and C-ZnO composite nanoparticles].

OBJECTIVE: To explore the effects of nanoparticles with different chemical components on pregnancy outcome of pregnancy rats and their offspring. METHODS: Pregnant rats were divided into four groups (Nano-CB group, Nano-ZnO group, nanoparticles of C-ZnO composite group and Control group) and administered with nanoparticles by intratracheal instillation at the dose of 7.5 mg/kg bw once a day for 5 days. After spontaneous delivery, the pregnancy rates, birth numbers, four-day survival rates and neurology development were recorded and analyzed. RESULTS: 57.2% and 66.7% of pregnancy rates in Nano-ZnO group and Composite nanoparticles group were more lower than those of Control group (100%). Difference of birth numbers between groups was not significant. Body weights of young rats in Nano-ZnO group at the day of 4, 7 and 21 were more higher than those of other groups. Results of water maze experiment showed that the 2nd and 3rd latent time of Composite nanoparticles group were more longer than those of other groups, while the differences in latent times among Nano-CB group, Nano-ZnO group and Control group were not significant. There was no statically significant difference between particle groups and Control group in experiments of plane righting reflex and air righting reflex. CONCLUSION: Under our experiment condition, ZnO nanoparticles could exert reproduction toxic effect on rats, whereas could promote the growth and neurology development of offspring. In addition, nanoparticles of C-ZnO Composite could exhibit adverse effect on recent memory of the offspring.

[Study of C-ZnO composite nanoparticles on viability inhibition and DNA damage of mouse embryo fibroblasts].

OBJECTIVE: To study the cytotoxicity and DNA damage induced by C-ZnO composite nanoparticles in Mouse embryo fibroblasts(MEF) cells. METHODS: MEF cells were treated with the suspension of carbon nanoparticles, zinc oxide nanoparticles and composite nanoparticles at the concentrations of 5, 10, 20, 50, 100 microg/ml. Cellular morphology and MTT assay were carried out to evaluate the viability of cells treated with particles for 24 h, 48 h and 72h respectively. Single cell gel electrophoresis (SCGE, comet assay) was performed to assess DNA damage induced by nanoparticles at the doses of 5 microg x ml(-1) and 10 microg x ml(-1). RESULTS: Three types of nanoparticles could induce morphologic change and viability inhibition with significant logarithmic time-effect and dose-effect relationship. Median lethal concentrations (IC50) of carbon nanoparticles, zinc oxide nanoparticles and composite nanoparticles were 21.85, 21.94 and 461.10 mcirog/ml respectively. The inhibitory effect on cellular viability of Zinc oxide nanoparticles increased significantly with the dose enhances. The most DNA damage was induced by composite nanoparticles at lower concentrations. CONCLUSION: Nanoparticles with different chemical composition induced distinct cytotoxicity and DNA damage in MEF cells. The metal content of composite nanoparticles played an important role in the toxic effect.

Impact of Cold Exposure on the Reproductive Function in Female Rats.

Female reproductive system diseases caused by exposure to a cold environment are widely considered as important human health challenges. Although the projection of female reproduction in cold temperature has been studied, a holistic view on the probable effects of cold exposure on the functions of the female reproductive system has not been achieved. Our aim was to evaluate the effects of cold exposure to the functions of the ovary and uterus in female rats. For this purpose, female rats were randomly grouped as follows: (1) the cold group was exposed to -10°C, 4 h per day for 2 weeks, and (2) the normal temperature (23 ± 1°C) group was used as control. Alterations were observed in different parameters, including body weight gain, organ coefficients, estrus cycle, and pathology of the cold-exposed female rats. Similarly, the serum reproductive hormones and mRNA expression were evaluated. Cold exposure induced estrus cycle irregularity and some alterations in the morphology of the ovary. Cold exposure impairs the function of the ovary probably by changing the level of serum LH and increasing LHR expression. Cold exposure induced a significant reduction of uterine epithelium height. Cold exposure causes alterations in the morphology of the uterus probably because of the effect of progesterone, the increase in the PR level, and the decrease in the ER level.

Therapeutic Efficacy of Methazolamide Against Intermittent Hypoxia-Induced Excessive Erythrocytosis in Rats.

Zhang, Zhiqing, Zhonghai Xiao, Bingnan Deng, Xiaohua Liu, Wei Liu, Hongjing Nie, Xi Li, Zhaoli Chen, Danfeng Yang, and Ruifeng Duan. Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats. High Alt Med Biol 19:69-80, 2018.-This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia + acetazolamide (30 mg·kg-1·d-1), and five hypoxia + methazolamide groups (5, 10, 30, 90, and 120 mg·kg-1·d-1). Excessive erythrocytosis was induced through 4 weeks of hypobaric hypoxia (8 hours O2 10%/16 hours O2 21%). Rats were then treated for 4 weeks, and their body weight was measured. Hematological, hemorheological, and biochemical parameters were analyzed. Renal hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry. Proteomic analysis of plasma was conducted to determine the most differentially expressed proteins. Methazolamide with doses lower than 30 mg·kg-1·d-1 had no significant effects on body weight compared with the hypoxia control group (p > 0.05). Methazolamide dose-dependently reduced the hemoglobin concentration, hematocrit (Hct), and blood viscosity. Hct/blood viscosity, an oxygen delivery index, dose-dependently increased after methazolamide treatment. A methazolamide dose of 10 mg·kg-1·d-1 showed similar efficacy to an acetazolamide dose of 30 mg·kg-1·d-1 for all the above parameters. Plasma levels of low-density lipoprotein cholesterol, total cholesterol, creatinine, and hemoglobin increased substantially after long-term hypoxia, but decreased after methazolamide treatment. HIF-1α and VEGF both increased substantially after long-term hypoxia and decreased in the kidney after methazolamide treatment. The most differentially expressed protein was haptoglobin, an endogenous protective factor, which was depleted in rats with excessive erythrocytosis and increased substantially after methazolamide treatment. In summary, methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia. It also has beneficial effects on oxygen transport and lipid metabolism, which are encouraging with regard to the development of methazolamide-based chronic mountain sickness therapies.