PPARα is involved in high-fat diet-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Risk avoidance behaviors are essential for survival. "Uncontrollable" risk-taking behaviors in animals or humans may have severe adverse consequences. In humans, a large proportion of psychiatric disorders are accompanied by impairments in risk avoidance. Obesity is associated with psychiatric disorders. Peroxisome proliferator-activated receptor α (PPARα) takes part in regulating lipid metabolism and neuronal function. Here, we investigated the effect of high-fat diet (HFD)-induced obesity on risk avoidance and the role of PPARα in this behavior. Male PPARα-null (KO) mice and wild-type (WT) mice were assigned to four different groups: WT-CON and KO-CON (normal diet); WT-HFD and KO-HFD (high fat diet). The HFD began at week 6 and was continued until sampling. A series of behavioral tests were performed at week 11. We found that WT but not KO mice fed with a HFD exhibited weight gain and risk avoidance impairment, compared with the mice fed with a normal diet. The staining of c-Fos revealed that the hippocampus was the main brain region involved in risk avoidance behavior. Moreover, biochemical analysis suggested that the decreased levels of the brain-derived neurotrophic factor (BDNF) in the hippocampus might contribute to risk avoidance impairment induced by a HFD. These results indicated that PPARα is involved in HFD-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Index-based dietary patterns and stomach cancer in a Chinese population.

OBJECTIVES: Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population. METHODS: Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored. RESULTS: Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects. CONCLUSIONS: Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

[The cholestatic fibrosis induced by α-naphthylisothiocyanate in mice and the inflammation pathway].

Objective: To explore the development of cholestatic fibrosis induced by α-naphthylisothiocyanate (ANIT) and the inflammation pathways. Methods: Fifteen 129/Sv mice weighing (23±2) g were randomly divided into 2 groups: control group (n=5) and experiment group (n=10). The control group was fed commercial chow diet and the experiment group was fed the same diet supplemented with 0. 05% ANIT. Five mice in the experiment group were sacrificed on day 14 and 28 respectively. The gallbladder, serum and liver samples were collected. Biochemical indicators of cholestasis were detected following the procedures in the kit. Liver injury was evaluated by histopathological. Hepatic fibrosis and inflammatory response were analyzed by Q-PCR and WB. Results: Compared with the control group, total bile acid (TBA), the main cholestasis biomarker, was increased from (3. 2±0. 9) µmol/L to (31. 6±4. 3) µmol/L in A-D14 group. AST and ALT, the biomarkers of liver injury, were also increased significantly (P＜0. 05). The expression levels of fibrotic factor tissue inhibitors of metalloproteinases 1 (TIMP-1), monocyte chemoattractant protein 1 (MCP-1) and collagen protein I (Collagen I) were higher than those of control group (P＜0. 05). The expressions of fibrosis protein Collagen I and α-SMA were also up-regulated. The collagen fibers of the liver were largely deposited and the liver fibrosis occurred (P＜0. 05). The expression of inflammatory factors was higher than the control group, JNK, c-Jun and STAT3 were activated (P＜0. 05). In A-D28 group, except AST, matrix metalloproteinases 2 (MMP-2) and Collagen I indicators were slightly decreased, other indicators of cholestasis, liver injury, liver fibrosis and inflammation continued to be up-regulated or stable (P＜0. 05). Conclusion: After 14-day treatment with 0. 05% ANIT diet, significant cholestatic liver fibrosis occurred in mice. After 28 days of treatment, cholestasis liver fibrosis kept stable. The JNK inflammatory pathway played a crucial role in the development of liver fibrosis.

Dietary Intake of Fatty Acids, Total Cholesterol, and Stomach Cancer in a Chinese Population.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.

Metagenomic Characterization of Candidatus Smithella cisternae Strain M82_1, a Syntrophic Alkane-Degrading Bacteria, Enriched from the Shengli Oil Field.

The methanogenic degradation of hydrocarbons plays an important role in hydrocarbon-contaminated environments in the absence of an external electron acceptor. Members of Syntrophaceae sublineages were previously reported to be responsible for syntrophic alkane degradation. However, limited information is currently available on their physiological capabilities in nature because it is very challenging to cultivate these as-yet uncultured microbes. We herein performed metagenomic sequencing of the methanogenic hexadecane-degrading culture M82 and recovered a nearly complete genome (2.75 Mb, estimated completeness ≥97%) belonging to Syntrophaceae sublineage II. The assembly genome was tentatively named "Candidatus Smithella cisternae strain M82_1". Genes encoding alkylsuccinate synthase for alkane activation were identified, suggesting that this organism is capable of oxidizing alkanes through fumarate addition. This capability was further supported by the detection of methyl pentadecyl succinic acid and methyl tetradecyl succinic acid in cultures amended with hexadecane and pentadecane, respectively. Genes encoding enzymes for the ß-oxidation of long-chain fatty acids and butyrate were also identified. The electron transfer flavoprotein/DUF224 complex is presumed to link electron flow from acyl-CoA dehydrogenase to a membrane hydrogenase or formate dehydrogenase. Although no indications of Rnf complexes were detected, genes encoding electron-confurcating hydrogenase and formate dehydrogenase were proposed to couple the thermodynamically favorable oxidation of ferredoxin to generate H2 and formate from NADH. Strain M82_1 synthesized ATP from acetyl-CoA by substrate-level phosphorylation or F1F0-ATP synthases. These results provide an insight into the potential metabolic traits and ecophysiological roles of the syntrophic alkane degrader Syntrophaceae.

Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China.

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

Clinical Characteristics of Patients Who Underwent Surgery for Genital Tract Malformations at Peking Union Medical College Hospital across 31 Years.

BACKGROUND: Female genital malformations represent miscellaneous deviations from normal anatomy. This study aimed to explore the clinical characteristics of patients who underwent surgery for genital tract malformations at Peking Union Medical College Hospital (PUMCH) during a 31-year period. METHODS: We retrospectively reviewed surgical cases of congenital malformation of the female genital tract at PUMCH for a 31-year period, analyzed the clinical characteristics of 1634 hospitalized patients, and investigated their general condition, diagnosis, and treatment process. RESULTS: The average patient age was 27.6 ± 9.9 years. The average ages of patients who underwent surgery for uterine malformation and vaginal malformation were 31.9 ± 8.8 years and 24.7 ± 9.0 years, respectively; these ages differed significantly (P < 0.01). Among patients with genital tract malformation, the percentages of vaginal malformation, uterine malformation, vulva malformation, cervical malformation, and other malformations were 43.9%, 43.5%, 7.4%, 2.3%, and 2.8%, respectively. Among patients with uterine malformation, 34.5% underwent surgery for the genital tract malformation, whereas in patients with vaginal malformation, the proportion is 70.6%; the difference between the two groups was statistically significant (P < 0.01). The percentage of complications of the urinary system in patients with vaginal malformations was 10.2%, which was statistically significantly higher than that (5.3%) in patients with uterine malformations (P < 0.01). CONCLUSIONS: Compared to patients with uterine malformations, patients with vaginal malformations displayed more severe clinical symptoms, a younger surgical age, and a greater need for attention, early diagnosis, and treatment. Patients with genital tract malformations, particularly vaginal malformations, tend to have more complications of the urinary system and other malformations than patients with uterine malformations.

[Screening of effective ingredients of Yinzhihuang injection against cholestasis and their mechanism].

Chinese herbal medicinal formulation Yinzhihuang injection is widely used in clinic for jaundice and chronic liver diseases in eastern Asian countries. However, the pharmacologically active components and the underlying mechanism are unclear. In this study, 30 male ICR mice were randomly assigned into 6 groups： normal control, model control, chlorogenic acid group, geniposide group, baicalin group and wogonoside group. The liver function, liver pathological changes and bile acid metabolism-related gene expression in mice were assayed. The serum levels of ALT, AST, ALP, TBA in chlorogenic acid group (15.89±2.53), (18.32±2.56), (26.38±9.87) U•L⁻¹, (40.63±7.67) µmol•L⁻¹, respectively and geniposide group (20.54±2.36), (24.28±5.19), (35.09±5.03) U•L⁻¹, (42.86±7.11) µmol•L⁻¹, respectively were lower than those in the model control group (59.52±10.94), (128.37±17.97),(169.52±9.62) U•L⁻¹, (132.50±33.00) µmol•L⁻¹, respectively. Hematoxylin-eosin staining showed necrosis, infiltration of inflammation cell in chlorogenic acid group and geniposide group were milder than those in the model control group. Q-PCR analysis revealed the expression of bile acid metabolism-related genes was normalized after treatment with chlorogenic acid or geniposide. Chlorogenic acid and geniposide improved the liver injury and cholestasis effectively, and reversed the mRNA expression of bile acid metabolism-related genes induced by ANIT. So, chlorogenic acid and geniposide were protective for cholestasis, suggesting their pharmacodynamic effect in Yinzhihuang injection.

Household ventilation may reduce effects of indoor air pollutants for prevention of lung cancer: a case-control study in a Chinese population.

BACKGROUND: Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk. OBJECTIVES: To explore the association between household ventilation and lung cancer. METHODS: A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj) and their 95% confidence intervals (CI). RESULTS: Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98), bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources. CONCLUSIONS: A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.

Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor.

RATIONALE: Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). METHODS: Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI injury, the neuropathic mice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline. CONCLUSION: Curcumin can normalize the depressive-like behaviors of neuropathic mice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.

Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population.

Protective effect of garlic on the development of cancer has been reported in the in vitro and in vivo experimental studies; however, few human epidemiologic studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was used to estimate adjusted ORs and their 95% confidence intervals (CI), and to evaluate ratio of ORs (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44-0.72) with a monotonic dose-response relationship (Ptrend < 0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking [synergy index (SI) = 0.70; 95% CI, 0.57-0.85; and ROR = 0.78; 95% CI, 0.67-0.90], as well as high-temperature cooking oil fume (ROR = 0.77; 95% CI, 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation.

Rapidly increasing rates of hip fracture in Beijing, China.

The age-specific rates of hip fractures have been declining in most countries in the West but a few studies suggest that the rates might be increasing in areas of Asia that are undergoing urbanization. We previously conducted a population-based study of hip fracture rates in Beijing, China, in 1990 to 1992 that included validation of hip fracture cases. Using a similar approach to validate cases, we estimated the age-specific hip fracture rates in Beijing, China, for 2002 to 2006. Specifically, we obtained hospital discharge data for hip fractures that were reported to the Beijing Bureau of Public Health. To confirm the diagnoses, Beijing residence, and find cases missed by the public records we checked individual cases in the public health records against medical records in a random sample of Beijing hospitals. The rates from public health data were adjusted for these under- and overestimations. We found that between 1990 and 1992 and 2002 and 2006, the adjusted age-specific rates of hip fracture over age 50 years increased 2.76-fold (95% confidence interval [CI], 2.68-2.84) in women and 1.61-fold (95% CI, 1.56-1.66) in men. Over age 70 years, the age-specific rates increased 3.37-fold (95% CI, 3.28-3.47) in women and 2.01-fold (95% CI, 1.95-2.07) in men. From 2002 to 2006, the rates over age 50 years increased 58% in women and 49% in men. We conclude that the rate of hip fracture has been rising very rapidly in Beijing, China. Therefore, the burden of hip fractures may be shifting rapidly from the West to urbanizing areas of the East.

Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved.

Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45 mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6-hydroxydopamine (6-OHDA), or depletion of descending serotonin by p-chlorophenylalanine (PCPA), abolished curcumin's antinociceptive effect on mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic action of curcumin on mechanical stimuli was totally blocked by chronic co-treatment with the ß(2)-adrenoceptor antagonist ICI 118,551, or by acute co-treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co-treatment with the 5-HT(1A) receptor antagonist WAY-100635 chronically, or with the irreversible mu-opioid receptor antangonist ß-funaltrexamine acutely, completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli. Collectively, these findings indicate that the descending monoamine system (coupled with spinal ß(2)-adrenoceptor and 5-HT(1A) receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

[A pharmacodynamics study of an intravitreal amphotericin B drug delivery system for the treatment of experimental Aspergillus fumigatus endophthalmitis].

OBJECTIVE: To observe a new amphotericin B drug delivery system (AmB-DDS), and investigate the therapeutic effects of AmB-DDS on an experimental Aspergillus fumigatus endophthalmitis. METHODS: (1) In order to observe the effects of AmB-DDS, thirty-four New Zealand albino rabbits were intravitreal injected Aspergillus fumigatus suspension (10(3) colony forming unit, CFU) in applanation of vitreous body before therapy 48 hours. All models were randomly divided into five groups. Group A was the empty control group, treated nothing after Aspergillus fumigatus injection, group B was the empty DDS implantation combined with vitrectomy, no treatment after DDS implanted, group C: AmB 5 microg-injection combined with vitrectomy, the injection was repeated two week later, group D: 250 microg AmB-DDS intravitreal implantation combined with vitrectomy, Group E: 500 microg AmB-DDS intravitreal implantation combined with vitrectomy. Aqueous flare, cells, anterior vitreous cells and vitreous opacity were graded, and vitreous humor smear and culture were performed at different time points after operation in 8 weeks. Two months after operation, light microscopy was used histology evaluation. (2) To observe the release of AmB-DDS in Group H (6 eyes), 500 microg AmB-DDS were implanted in the eye of the rabbits after vitrectomy, vitreous humor was aspirated and the concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC). RESULTS: The inflammation response was lower in groups C, D, E than groups A, B. There was no significant statistical difference between group A and group B (P > 0.05), but differences among C, D, E and groups A, B were significant (P < or = 0.005). The inflammation grade was lower in group E than group C (P < or = 0.005). There was significant statistical difference between the cure effect of group E and group D (chi(2) = 10.494, P = 0.003). All of vitreous humor smears was positive in 1.5 months after surgery, but the culture was only positive in group A, and B. Pathological examination indicated that normal structure was disappeared in the eyes with Aspergillus endophthalmitis. At the first day after surgery, AmB were observed by analysis of HPLC, there was sustained AmB release in the group of AmB-DDS application during the observation periods. CONCLUSIONS: The degradable AmB-DDS can effectively suppress the inflammation of the rabbit model of Aspergillus fumigatus endophthalmitis. As an alternative to the current routine therapy, it can be used for the treatment of Aspergillus fumigatus endophthalmitis.