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Background Phaffia rhodozyma has many desirable properties for astaxanthin production, including rapid heterotrophic metabolism and high cell densities in fermenter culture. The low optimal temperature range (17–21 °C) for cell growth and astaxanthin synthesis in this species presents an obstacle to efficient industrial-scale astaxanthin production. The inhibition mechanism of cell growth at > 21 °C in P. rhodozyma have not been investigated. Results MK19, a mutant P. rhodozyma strain grows well at moderate temperatures, its cell growth was also inhibited at 28 °C, but such inhibition was mitigated, and low biomass 6 g/L was obtained after 100 h culture. Transcriptome analysis indicated that low biomass at 28 °C resulted from strong suppression of DNA and RNA synthesis in MK19. Growth inhibition at 28 °C was due to cell membrane damage with a characteristic of low mRNA content of fatty acid (f.a.) pathway transcripts (acc, fas1, fas2), and consequent low f.a. content. Thinning of cell wall and low mannose content (leading to loss of cell wall integrity) also contributed to reduced cell growth at 28 °C in MK19. Levels of astaxanthin and ergosterol, two end-products of isoprenoid biosynthesis (a shunt pathway of f.a. biosynthesis), reached 2000 µg/g and 7500 µg/g respectively; ~2-fold higher than levels at 21 or 25 °C. Abundance of ergosterol, an important cell membrane component, compensated for lack of f.a., making possible the biomass production of 6 g/L for MK19 at 28 °C. Conclusions Inhibition of growth of P. rhodozyma at 28 °C results from blocking of DNA, RNA, f.a., and cell wall biosynthesis. In MK19, abundant ergosterol made possible biomass production 6 g/L at 28 °C. Significant accumulation of astaxanthin and ergosterol indicated an active MVA pathway in MK19 at 28 °C. Strengthening of the MVA pathway can be a feasible metabolic engineering approach for enhancement of astaxanthin synthesis in P. rhodozyma. The present findings provide useful mechanistic insights regarding adaptation of P. rhodozyma to 28 °C, and improved understanding of feasible metabolic engineering techniques for industrial scale astaxanthin production by this economically important yeast species.

Background: Phaffia rhodozyma has many desirable properties for astaxanthin production, including rapid heterotrophic metabolism and high cell densities in fermenter culture. The low optimal temperature range (17-21 °C) for cell growth and astaxanthin synthesis in this species presents an obstacle to efficient industrial-scale astaxanthin production. The inhibition mechanism of cell growth at > 21 °C in P. rhodozyma have not been investigated.Results: MK19, a mutant P. rhodozyma strain grows well at moderate temperatures, its cell growth was also inhibited at 28 °C, but such inhibition was mitigated, and low biomass 6 g/L was obtained after 100 h culture. Transcriptome analysis indicated that low biomass at 28 °C resulted from strong suppression of DNA and RNA synthesis in MK19. Growth inhibition at 28 °C was due to cell membrane damage with a characteristic of low mRNA content of fatty acid (f.a.) pathway transcripts (acc, fas1, fas2), and consequent low f.a. content. Thinning of cell wall and low mannose content (leading to loss of cell wall integrity) also contributed to reduced cell growth at 28 °C in MK19. Levels of astaxanthin and ergosterol, two end-products of isoprenoid biosynthesis (a shunt pathway of f.a. biosynthesis), reached 2000 μg/g and 7500 μg/g respectively; ~2-fold higher than levels at 21 or 25 °C. Abundance of ergosterol, an important cell membrane component, compensated for lack of f.a., making possible the biomass production of 6 g/L for MK19 at 28 °C.Conclusion: Inhibition of growth of P. rhodozyma at 28 °C results from blocking of DNA, RNA, f.a., and cell wall biosynthesis. In MK19, abundant ergosterol made possible biomass production 6 g/L at 28 °C. Significant accumulation of astaxanthin and ergosterol indicated an active MVA pathway in MK19 at 28 °C. Strengthening of the MVA pathway can be a feasible metabolic engineering approach for enhancement of astaxanthin synthesis in P. rhodozyma. The present findings provide useful mechanistic insights regarding adaptation of P. rhodozyma to 28 °C, and improved understanding of feasible metabolic engineering techniques for industrial scale astaxanthin production by this economically important yeast species.

Background The yeast Phaffia rhodozyma has many desirable properties for astaxanthin production, including rapid heterotrophic metabolism and high cell densities in fermenter culture. The optimal temperature range for cell growth and astaxanthin synthesis in this species is low (17–21 °C), which presents an obstacle to efficient industrial-scale astaxanthin production. The molecular regulatory mechanisms of cell growth and astaxanthin synthesis in P. rhodozyma remain poorly understood, and the regulatory effects of temperature have not been investigated. Results MK19, a mutant P. rhodozyma strain that grows well at moderate temperatures, was generated from wild-type (WT) strain JCM9042, which is unable to grow at 28 °C. MK19 cell growth was also inhibited at 28 °C, but such inhibition was mitigated, and biomass production reached 6 g/L after 100 h culture. Transcriptome analysis indicated that low viability at 28 °C resulted from strong suppression of DNA synthesis. Growth inhibition at 28 °C was due to low mRNA content of fatty acid (f.a.) pathway genes (acc, fas1, fas2), and consequent low f.a. content. Thinning of cell wall and low mannose content (leading to loss of cell wall integrity) also contributed to reduced cell growth at 28 °C. In MK19 cultured for 48 h at 28 °C, levels of astaxanthin and ergosterol, two end-products of isoprenoid biosynthesis (a shunt pathway of f.a. biosynthesis), reached 2000 µg/g and 7500 µg/g respectively; ~2-fold higher than levels at 21 or 25 °C. Abundance of ergosterol, an important cell membrane component, compensated for lack of f.a., making possible the biomass production of 6 g/L for MK19 at 28 °C. Downregulation of crtI mRNA, whose product catalyzes four dehydrogenation steps in the phytoene-to-lycopene process, contributed to inhibition of astaxanthin synthesis in WT at 25 °C. High crtI mRNA content in MK19 (> 10-fold higher than that in WT) counteracted the inhibitory effect of high temperature on crtI transcription, making possible the efficient synthesis of lycopene which was subsequently converted to astaxanthin. Conclusion Inhibition of growth of WT P. rhodozyma at 28 °C results from blocking of DNA, f.a., and cell wall biosynthesis. Growth at this temperature could be increased by enhancement of such biosynthesis. In moderate-temperature strain MK19, precursor molecules accumulated from f.a. pathway are diverted to astaxanthin and ergosterol biosynthesis, making possible biomass production 6 g/L at 28 °C. Strengthening of the MVA pathway to make available more precursors from f.a. pathway is a feasible metabolic engineering approach for enhancement of astaxanthin synthesis in MK19 or other moderate-temperature producer strains. The present findings provide useful mechanistic insights regarding adaptation of P. rhodozyma to 28 °C, and improved understanding of transcription regulatory networks and feasible metabolic engineering techniques for industrial scale astaxanthin production by this economically important yeast species.

Background Radix Rehmanniae Preparata is a traditional Chinese herbal medicine used to treat asthma, and catalpol is one of the main active ingredients in this herb. In the present study, the effects of catalpol on asthma and the underlying mechanism were explored. Methods Mice with ovalbumin (OVA)-induced asthma were given 5 or 10 mg/kg catalpol from Day 15 to Day 28 (intraperitoneal injection). Histopathologic changes were detected by Hematoxylin and Eosin staining and Periodic Acid Schiff staining. The levels of IgE, interleukin (IL)-4, IL-5 and eotaxin were measured by ELISA. The numbers of lymphocytes, monocytes, basophils and eosinophils in the bronchoalveolar lavage fluid were determined by Wright-Giemsa staining. The expression and distribution of eotaxin and C-C chemokine receptor 3 (CCR3) were detected by immunohistochemistry and immunofluorescence. The expression of interleukin-5 receptor α (IL-5Rα) was detected by Western blot assay. Results Catalpol inhibited OVA-induced inflammation and IgE secretion in the lung. OVA-induced type 2 inflammation was suppressed by catalpol as evidenced by decreased levels of IL-4 and IL-5. Moreover, catalpol inhibited the aberrant eosinophil infiltration in the lungs, and also suppressed OVA-induced elevation of eosinophil chemokine eotaxin and its receptor CCR3. In addition, IL-5Rα expression in the bone marrow cells derived from catalpol-treated asthmatic mice was lower than that from the untreated asthmatic mice. Conclusion Our study demonstrated that catalpol attenuated OVA-induced asthma and inhibit the infiltration of inflammatory cells, especially eosinophils, into the lung. This study suggests that catalpol may become a promising drug for the treatment of asthma.

Background A major obstacle to industrial-scale astaxanthin production by the yeast Phaffia rhodozyma is the strong inhibitory effect of high glucose concentration on astaxanthin synthesis. We investigated, for the first time, the mechanism of the regulatory effect of high glucose (> 100 g/L) at the metabolite and transcription levels. Results Total carotenoid, β-carotene, and astaxanthin contents were greatly reduced in wild-type JCM9042 at high (110 g/L) glucose; in particular, β-carotene content at 24–72 h was only 14–17% of that at low (40 g/L) glucose. The inhibitory effect of high glucose on astaxanthin synthesis appeared to be due mainly to repression of lycopene-to-β-carotene and β-carotene-to-astaxanthin steps in the pathway. Expression of carotenogenic genes crtE, pbs, and ast was also strongly inhibited by high glucose; such inhibition was mediated by creA, a global negative regulator of carotenogenic genes which is strongly induced by glucose. In contrast, astaxanthin-overproducing, glucose metabolic derepression mutant strain MK19 displayed de-inhibition of astaxanthin synthesis at 110 g/L glucose; this de-inhibition was due mainly to deregulation of pbs and ast expression, which in turn resulted from low creA expression. Failure of glucose to induce the genes reg1 and hxk2, which maintain CreA activity, also accounts for the fact that astaxanthin synthesis in MK19 was not repressed at high glucose. Conclusion We conclude that astaxanthin synthesis in MK19 at high glucose is enhanced primarily through derepression of carotenogenic genes (particularly pbs), and that this process is mediated by CreA, Reg1, and Hxk2 in the glucose signaling pathway.

Lycopene plays an important role as an antioxidative and anticancer agent, and is an increasingly valuable commodity in the global market. Rhodobacter sphaeroides, a carotenogenic and phototrophic bacterium, is an efficient and practical host for carotenoid production. Herein, we explored the potential of metabolically engineered Rb. sphaeroides as a novel platform to produce lycopene. The basal lycopene-producing strain was generated by introducing an exogenous crtI4 from Rhodospirillum rubrum to replace the native crtI3 and deleting crtC in Rb. sphaeroides. Furthermore, knocking out zwf blocked the competitive pentose phosphate pathway and improved the lycopene content by 88%. Finally, the methylerythritol phosphate pathway was reinforced by integration of dxs combined with zwf deletion, which further increased the lycopene content. The final engineered strain produced lycopene to 10.32 mg/g dry cell weight. This study describes a new lycopene producer and provides insight into a photosynthetic bacterium as a host for lycopene biosynthesis.

The organics-degrading bacteria were isolated from sea cucumber (Apostichopus japonicus) outdoor rearing ponds sediment. The bacterial strains were selected according to the isolation growth, pathogenicity, organic degradation rate, and effects on A. japonicus growth and water quality. The screened strains were identified on physiological, biochemical, and genetic characteristics. Among 68 strains isolated, two strains (L15 and E4) were identified as potential organics-degrading probiotics. The degradation rates on sediment chemical oxygen demand (COD) were 46.95 ± 1.58 % for the L15 strain and 44.31 ± 1.44 % for the E4 strain. The L15 strain enhanced the specific growth rate (SGR) of A. japonicus by 1.97 ± 0.49 %, and the E4 strain enhanced SGR by 2.24 ± 0.44 % compared with the SGR of 0.55 ± 0.41 % in the control group without probiotics. The COD level increased by −0.9 ± 1.42 % of L15 and 47.9 ± 0.06 % of E4 inoculations after 7 days, while the COD increased by 140.6 ± 4.22 % in the control. Based on the analyses of biochemical characteristics and 16S rRNA gene sequences, the L15 and E4 strains were identified as Bacillus spp. and Pseudomonas spp., respectively.

To observe the effects of matrix metalloproteinases(MMPs) inhibitors on microleakage with wet bonding technique.Twenty-seven premolars were randomly assigned to 3 groups. Class Ⅴ cavities were prepared in the neck of the teeth and treated with distilled water, 2% chlorhexidine (CHX) or 2% monocycline (MI) for 60 seconds. Resin was used to restore the prepared cavities following application of luting agent. Samples in each group were soaked for 1 h with 10% NaClO and then 2 layers of nail polish were applied, followed by treatment with 50wt% ammoniated silver nitrate (ASN), and developing solution in turn. Each tooth was sectioned longitudinally to 1~2 mm slices and examined with stereo microscope and scanning electron microscope (SEM). The data were analyzed with SPSS 16.0 software package for Wilcoxon rank sum test.There was varied microleakage at the margin. The difference was significant between group CHX and control group, between group MI and control group; However, there was no significant difference between group CHX and group MI.MMPs inhibitor can reduce microleakage with wet bonding technique.

An astaxanthin-overproducing (∼1000 μg g(-1)) strain of Phaffia rhodozyma, termed MK19, was established through 1-methyl-3-nitro-1-nitrosoguanidine and Co60 mutagenesis from wild-type JCM9042 (merely 35-67 μg g(-1)). The total fatty acid content of MK19 was much lower than that of the wild type. Possible causes of the astaxanthin increase were studied at the gene expression level. The expression of the carotenogenic genes crtE, crtI, pbs, and ast, which are responsible for astaxanthin biosynthesis from geranylgeranyl pyrophosphate, was highly induced at the mRNA level, leading to excessive astaxanthin accumulation. In contrast, transcription levels of the genes (hmgs, hmgr, idi, mvk, mpd, fps), responsible for the initial steps in the terpenoid pathway, were essentially the same in wild type and MK19. Although fatty acid and total ergosterol content were reduced by 40-70 mg g(-1) and 760.3 μg g(-1) , respectively, in MK19 as compared with the wild type, but the transcription levels of rate-limiting genes in fatty acid and ergosterol pathways such as acc and sqs were similar. Because fatty acids and ergosterol are two branch pathways of astaxanthin biosynthesis in P. rhodozyma, our findings indicate that enhancement of astaxanthin in MK19 results from decreased fatty acid and ergosterol biosynthesis, leading to precursor accumulation, and transfer to the astaxanthin pathway. Strengthening of the mevalonate pathway is suggested as a promising metabolic engineering approach for further astaxanthin enhancement in MK19.

Aims: The present study was designed to investigate quality of life (QOL) among caregivers of cancer inpatients, and to explore the related factors with the long-term goal to improve QOL of cancer caregivers in China. Methods: A cross-sectional study was performed during the period January–March 2008. Subjects comprised 358 caregivers of cancer inpatients. The questionnaires pertaining to QOL, sociodemographic characteristics, caregiving demands, available social resources, caregiving situation, and caregiver's health status were used. Data were collected by nurses through interviews. Results: The average QOL score of these subjects was 5.26. General linear model analysis showed that caregiver's QOL was significantly associated with, in standardized estimate sequence, spousal relationship, patient's activities of daily living, and chronic disease (no). Overall spousal relationship to patient had the strongest association with caregiver's QOL. Conclusions: Psychological well-being and social concerns of cancer caregivers were disrupted more seriously than spiritual well-being and physical well-being. In addition, spousal relationship, patient's disability, and caregiver's health status could affect the caregiver's QOL.

β-1,3-glucanosyltransferases play essential roles in cell wall biosynthesis in yeast. Kluyveromyces lactis has six putative β-1,3-glucanosyltransferase genes. KlGAS1-1 and KlGAS1-2 are homologs of Saccharomyces cerevisiae gene GAS1. RT-qPCR indicated the transcription level of KlGAS1-1 was significantly reduced while heterologous protein (thermostable xylanase B) secretion was enhanced during medium optimization. To evaluate if these two events were related, and to improve xylanase B secretion in K. lactis, we constructed KlGAS1-1 and KlGAS1-2 single deletion strains and double deletion strain, respectively. KlGAS1-1 gene deletion resulted in the highest xylanase B activity among the three mutants. Only the double deletion strain showed morphology similar to that of the GAS1 deletion mutant in S. cerevisiae. The two single deletion strains differed in terms of cell wall thickness and xylanase B secretion. Transcription levels of β-1,3-glucanosyltransferase genes and genes related to protein secretion and transport were assayed. The β-1,3-glucanosyltransferase genes displayed transcription complementation in the cell wall synthesis process. KlGAS1-1 and KlGAS1-2 affected transcription levels of secretion- and transport-related genes. Differences in protein secretion ratio among the three deletion strains were associated with changes of transcription levels of secretion- and transport-related genes. Our findings indicate that KlGAS1-1 deletion is an effective tool for enhancing industrial-scale heterologous protein secretion in K. lactis.

Antimicrobial and physicochemical properties of chitosan films and chitosan films enriched with essential oils (EO) were determined in vitro and on processed meat. Antimicrobial effects of pure EO of anise, basil, coriander, and oregano, and of chitosan-essential oil films against Listeria monocytogenes and Escheri-chia coli O157:H7 were determined by an agar diffusion test. The antibacterial effects of the EO were similar when applied alone or incorporated in the films. The intensity of antimicrobial efficacy was in the following order: oregano > > coriander > basil > anise. The chitosan films and chitosan-oregano EO films were applied on inoculated bologna samples and stored 5 d at 10 °C. Pure chitosan films reduced L. monocytogenes by 2 logs, whereas the films with 1% and 2% oregano EO decreased the numbers of L. monocytogenes by 3.6 to 4 logs and E. coli by 3 logs. Pure chitosan films were 89 μm thick, whereas addition of 1% and 2% oregano EO increased thickness to 220 and 318 μm, respectively. During application on bologna discs, the films absorbed moisture, resulting in the final thickness of 143, 242, and 333 μm, respectively. Addition of oregano essential oil into the chitosan films decreased water vapor permeability, puncture and tensile strength, but increased elasticity of the films. The films have the potential to be used as active biodegradable films with strong antimicrobial effects.

Resource scheduling is crucial to data centers. However, most existing resource scheduling algorithms focus only on one-dimensional resource models, ignoring the fact that multiple resources (e.g. CPU, memory, storage, and network bandwidth) are consumed simultaneously. Competition for multiple resources has become increasingly severe as cloud computing allows uncoordinated and heterogeneous users to share a data center. In this paper, we map such a resource scheduling problem to a bounded multi-dimensional scheduling problem (B-MDKP), taking into account the requirement dependency among multi-dimensional resources. Due to the NP hardness of B-MDKP, we present Multi-dimensional Resource Integrated Scheduling (MRIS), a novel heuristic algorithm to obtain the approximate optimal solution. To demonstrate the advantage of our scheduling scheme, we have implemented MRIS in Haizea, a resource management architecture and made a detailed comparison with existing studies. Our evaluation results show that MRIS achieves high efficiency and high performance for a diverse set of workloads.

An astaxanthin-overproducing (∼1000 μg g(-1)) strain of Phaffia rhodozyma, termed MK19, was established through 1-methyl-3-nitro-1-nitrosoguanidine and Co60 mutagenesis from wild-type JCM9042 (merely 35-67 μg g(-1)). The total fatty acid content of MK19 was much lower than that of the wild type. Possible causes of the astaxanthin increase were studied at the gene expression level. The expression of the carotenogenic genes crtE, crtI, pbs, and ast, which are responsible for astaxanthin biosynthesis from geranylgeranyl pyrophosphate, was highly induced at the mRNA level, leading to excessive astaxanthin accumulation. In contrast, transcription levels of the genes (hmgs, hmgr, idi, mvk, mpd, fps), responsible for the initial steps in the terpenoid pathway, were essentially the same in wild type and MK19. Although fatty acid and total ergosterol content were reduced by 40-70 mg g(-1) and 760.3 μg g(-1) , respectively, in MK19 as compared with the wild type, but the transcription levels of rate-limiting genes in fatty acid and ergosterol pathways such as acc and sqs were similar. Because fatty acids and ergosterol are two branch pathways of astaxanthin biosynthesis in P. rhodozyma, our findings indicate that enhancement of astaxanthin in MK19 results from decreased fatty acid and ergosterol biosynthesis, leading to precursor accumulation, and transfer to the astaxanthin pathway. Strengthening of the mevalonate pathway is suggested as a promising metabolic engineering approach for further astaxanthin enhancement in MK19.

wu h., chi t.-s., chen l., wang l. & jin y.-p. (2010) Occupational stress among hospital nurses: cross-sectional survey. Journal of Advanced Nursing66(3), 627–634. Abstract Aim. This paper is a report of a study conducted to explore factors associated with occupational stress among female hospital nurses in China. Background. Nursing is a highly stressful occupation, and high levels of occupational stress are believed to affect the physical and mental health of nurses. Occupational stress among nurses is the result of exposure to a combination of working environment and personal factors. Method. A cross-sectional study was conducted in 2008. The study population consisted of 2613 female nurses from 20 hospitals in the Liaoning province of China. Occupational stress was measured by questionnaires that included the Chinese version of Personal Strain Questionnaire, and data were collected on respondents’ demographics, working situations, occupational roles, and personal resources. Of the nurses solicited for enrolment in the study, 79·2% returned the completed questionnaire. A general linear regression model was applied to analyse the factors associated with occupational stress. Results. Mean Personal Strain Questionnaire score was 86·9, and this score was correlated, in descending order of standardized estimate, with role boundary, role insufficiency, responsibility, social support, self-care, nurse–patient relationship, chronic disease, role overload, rational coping and night shift. Conclusion. Role boundary and role insufficiency were the factors that had the highest association with occupational stress. Occupational health education and occupational training programmes may be necessary to improve the knowledge and ability of nurses to cope with job demands and reduce occupational stress.

A moderate-temperature mutant strain of the yeast Phaffia rhodozyma, termed MK19, was selected by 1-methyl-3-nitro-1-nitrosoguanidine (NTG) and Co60 mutagenesis. MK19 displayed fast cell growth and elevated astaxanthin content at 25 degrees C, whereas optimal temperature for growth and astaxanthin synthesis of wild-type P. rhodozyma was 17-21 degrees C. Optimized astaxanthin yield for MK19 after 4 days culture in shaking flask at 25 degrees C, determined by response surface methodology, was 25.8 mg/l, which was 17-fold higher than that of the wild-type. MK19 was tolerant of high initial concentration of glucose (100 g/l) in optimized medium. Total fatty acid content of MK19 was much lower than that of the wild-type. Acetyl-CoA is a common precursor of fatty acid and terpenoid biosynthesis, and it is possible that decreased fatty acid synthesis results in transfer of acetyl-CoA to the carotenoid biosynthetic pathway. Our results indicate that astaxanthin content is negatively correlated with fatty acid content in P. rhodozyma. Nutrient analysis showed that MK19 cells are enriched in lysine, vitamin E, and other rare nutrients, and have potential application as fish food without nutritional supplementation. This moderate-temperature mutant strain is a promising candidate for economical industrial-scale production.

Doctors, the major workforce in hospitals, are doing heavy emotional and physical work which may lead to depressive symptoms. However, in China, few studies are available pertaining to the prevalence and associated factors of depressive symptoms among doctors. The aim of this study was to evaluate the prevalence of depressive symptoms and to explore its associated factors among Chinese doctors in public hospitals. This cross-sectional study was performed during the period of September/October 2008. The study population comprised of 1,890 doctors registered and working in the 20 national hospitals in Liaoning province, northeast of China. A questionnaire that comprised depressive symptoms assessed by the Chinese Version of the Center for Epidemiologic Studies Depression Scale (CES-D), demographic factors, work conditions, occupational stress, and coping strategies was distributed to these doctors. A total of 1,488 effective respondents became our subjects (effective response rate 78.7%). Multivariate logistic regression was used to explore the factors related to depressive symptoms. The prevalence of depressive symptoms among doctors was 65.3%. Multivariate logistic analyses showed that high role insufficiency (OR 2.15, 95% CI 1.66–2.78), worse doctor–patient relationship (OR 2.07, 95% CI 1.62–2.64), having a chronic disease (OR 1.73, 95% CI 1.31–2.27), serious role boundary (OR 1.54, 95% CI 1.21–2.00), and role overload (OR 1.42, 95% CI 1.11–1.81) were positively associated with depressive symptoms; whereas adequate rational coping (OR 0.58, 95% CI 0.45–0.76) and social support (OR 0.75, 95% CI 0.57–0.98) were negatively associated with depressive symptoms. Most Chinese doctors probably have depressive symptoms. Role insufficiency, doctor–patient relationship, and rational coping seemed to be crucial in relation to depressive symptoms. Efficient interventions such as taking further education course, improving communications with patients, and improving the ability of rational coping should be considered by health administrators aiming at improving the quality of Chinese doctors’ mental health from the view point of depressive symptoms.