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The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.
Experiments are conducted in a wave tank to investigate wave scattering by a three-dimensional submerged horizontal rectangular plate in a channel. The free-surface elevation around the plate is presented for various water depths and depths of submergence of the plate. The wave forces and moments are obtained using an underwater load measuring system. The numerical simulations are performed with a parallelized three-dimensional boundary element method. The numerical set-up follows closely the set-up of the laboratory experiments. The numerical results are compared with the experimental results for non-breaking waves. In most cases a good agreement is found for the free-surface elevation, the vertical force and the moment. A physical interpretation of the flow around the plate is provided. The pressure distribution on the lower surface of the plate differs from the linear distribution from the leading edge to the trailing edge that is obtained in the equivalent two-dimensional problem. The reflection by the lateral walls is investigated.
Frequent freezing injury greatly influences winter wheat production; thus, effective prevention and a command of agricultural production are vital. The freezing injury monitoring method integrated with ‘3S’ (geographic information systems (GIS), global positioning system (GPS) and remote sensing (RS)) technology has an unparalleled advantage. Using HuanJing (HJ)-1A/1B satellite images of a winter wheat field in Shanxi Province, China plus a field survey, crop types and winter wheat planting area were identified through repeated visual interpretations of image information and spatial analyses conducted in GIS. Six vegetation indices were extracted from processed HJ-1A/1B satellite images to determine whether the winter wheat suffered from freezing injury and its degree of severity and recovery, using change vector analysis (CVA), the freeze injury representative vegetation index and the combination of the two methods, respectively. Accuracy of the freezing damage classification results was verified by determining the impact of freezing damage on yield and quantitative analysis. The CVA and the change of normalized difference vegetation index (ΔNDVI) monitoring results were different so a comprehensive analysis of the combination of CVA and ΔNDVI was performed. The area with serious freezing injury covered 0.9% of the total study area, followed by the area of no freezing injury (3.5%), moderate freezing injury (10.2%) and light freezing injury (85.4%). Of the moderate and serious freezing injury areas, 0.2% did not recover; 1.2% of the no freezing injury and light freezing injury areas showed optimal recovery, 15.6% of the light freezing injury and moderate freezing injury areas showed poor recovery, and the remaining areas exhibited general recovery.
To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors.
Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present).
COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99).
The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA−) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA− diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA− diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.
Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case-fatality rate that is caused by infection with the SFTS virus (SFTSV). Five electronic databases were systematically searched to identify relevant articles published from 1 January 2011 to 1 December 2019. The pooled rates with 95% confidence interval (CI) were calculated by a fixed-effect or random-effect model analysis. The results showed that 92 articles were included in this meta-analysis. For the confirmed SFTS cases, the case-fatality rate was 0.15 (95% CI 0.11, 0.18). Two hundred and ninety-six of 1384 SFTS patients indicated that they had been bitten by ticks and the biting rate was 0.21 (95% CI 0.16, 0.26). The overall pooled seroprevalence of SFTSV antibodies among the healthy population was 0.04 (95% CI 0.03, 0.05). For the overall seroprevalence of SFTSV in animals, the seroprevalence of SFTSV was 0.25 (95% CI 0.20, 0.29). The infection rate of SFTSV in ticks was 0.08 (95% CI 0.05, 0.11). In conclusion, ticks can serve as transmitting vectors of SFTSVs and reservoir hosts. Animals can be infected by tick bites, and as a reservoir host, SFTSV circulates continuously between animals and ticks in nature. Humans are infected by tick bites and direct contact with patient secretions.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
Coated copper sulphate (CCS) could be used as a Cu supplement in cows. To investigate the influences of copper sulphate (CS) and CCS on milk performance, nutrient digestion and rumen fermentation, fifty Holstein dairy cows were arranged in a randomised block design to five groups: control, CS addition (7·5 mg Cu/kg DM from CS) or CCS addition (5, 7·5 and 10 mg Cu/kg DM from CCS, respectively). When comparing Cu source at equal inclusion rates (7·5 mg/kg DM), cows receiving CCS addition had higher yields of fat-corrected milk, milk fat and protein; digestibility of DM, organic matter (OM) and neutral-detergent fibre (NDF); ruminal total volatile fatty acid (VFA) concentration; activities of carboxymethyl cellulase, cellobiase, pectinase and α-amylase; populations of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes; and liver Cu content than cows receiving CS addition. Increasing CCS addition, DM intake was unchanged, yields of milk, milk fat and protein; feed efficiency; digestibility of DM, OM, NDF and acid-detergent fibre; ruminal total VFA concentration; acetate:propionate ratio; activity of cellulolytic enzyme; populations of total bacteria, protozoa and dominant cellulolytic bacteria; and concentrations of Cu in serum and liver increased linearly, but ruminal propionate percentage, ammonia-N concentration, α-amylase activity and populations of Prevotella ruminicola and Ruminobacter amylophilus decreased linearly. The results indicated that supplement of CS could be substituted with CCS and addition of CCS improved milk performance and nutrient digestion in dairy cows.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Se can enhance lactation performance by improving nutrient utilization and antioxidant status. However, sodium selenite (SS) can be reduced to non-absorbable elemental Se in the rumen, thereby reducing the intestinal availability of Se. The study investigated the impacts of SS and coated SS (CSS) supplementation on lactation performance, nutrient digestibility, ruminal fermentation and microbiota in dairy cows. Sixty multiparous Holstein dairy cows were blocked by parity, daily milk yield and days in milk and randomly assigned to five treatments: control, SS addition (0.3 mg Se/kg DM as SS addition) or CSS addition (0.1, 0.2 and 0.3 mg Se/kg DM as CSS addition for low CSS (LCSS), medium CSS (MCSS) and high CSS (HCSS), respectively). Experiment period was 110 days with 20 days of adaptation and 90 days of sample collection. Dry matter intake was higher for MCSS and HCSS compared with control. Yields of milk, milk fat and milk protein and feed efficiency were higher for MCSS and HCSS than for control, SS and LCSS. Digestibility of DM and organic matter was highest for CSS addition, followed by SS addition and then control. Digestibility of CP was higher for MCSS and HCSS than for control, SS and LCSS. Higher digestibility of ether extract, NDF and ADF was observed for SS or CSS addition. Ruminal pH decreased with dietary Se addition. Acetate to propionate ratio and ammonia N were lower, and total volatile fatty acids (VFAs) concentration was greater for SS, MCSS and HCSS than control. Ruminal H ion concentration was highest for MCSS and HCSS and lowest for control. Activities of cellobiase, carboxymethyl-cellulase, xylanase and protease and copies of total bacteria, fungi, Ruminococcus flavefaciens, Fibrobacter succinogenes and Ruminococcus amylophilus increased with SS or CSS addition. Activity of α-amylase, copies of protozoa, Ruminococcus albus and Butyrivibrio fibrisolvens and serum glucose, total protein, albumin and glutathione peroxidase were higher for SS, MCSS and HCSS than for control and LCSS. Dietary SS or CSS supplementation elevated blood Se concentration and total antioxidant capacity activity. The data implied that milk yield was elevated due to the increase in total tract nutrient digestibility, total VFA concentration and microorganism population with 0.2 or 0.3 mg Se/kg DM from CSS supplementation in dairy cows. Compared with SS, HCSS addition was more efficient in promoting lactation performance of dairy cows.
Many studies showed the differences in subjective response to sexual stimuli between heterosexual and homosexual men. However, the underlying neurobiological factors of sexual orientation are largely unknown. We addressed the question what is the major attribution of the expected differences in brain activation, i.e. neural circuits or different cognitive process. Twenty-eight healthy male volunteers, 14 heterosexuals and 14 homosexuals, were scanned by functional Magnetic Resonance Imaging while subjects were viewing different types of stimuli, i.e. heterosexual couple stimuli (HCS), gay couple stimuli (GCS), lesbian couple stimuli (LCS) and neutral stimuli (NS). SPM02 was used for data analysis. Rating of sexual attractiveness was assessed. Subjective sexual arousal was induced by HCS and GCS in heterosexual and homosexual men, respectively. And sexual disgust was induced by GCS and LCS in heterosexual and homosexual men, respectively. As compared to viewing NS, viewing sexual stimuli induced significant different brain activations most of which had characteristic for cognitive process. These observations suggested that different cognitive pattern was major attribution of different subjective response to sexual stimuli between heterosexual and homosexual men.
Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS. In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.
Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.
Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.
Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.
Finding the prediction factors for the risks of post-stroke depression (PSD) is important to stroke survivors. However, most existing studies focused only on general clinical data, which limited the predictive ability. To improve the predictive ability, this study proposed a comprehensive PSD risk prediction model with social psychological factors, neurological, cognitive functional factors and general clinical factors.
The study recruited 188 stroke patients. Patients were diagnosed by DSM-IV criteria. Predictors were collected within a week after stroke. Boosted regression trees (BRT) was used to classify these predictors, and then a predictive model was constructed based on the selected predictors. The receiver operating characteristic (ROC) curve was used to determine the performance of the predictive model .
The risk prediction model was constructed with 6 factors: Body Mass Index (BMI), cerebral infraction history (CI), Social Support Rating Scale (SSRS), Eysenck Personality Questionnaire-Neuroticism (EPQ-N), factor 1 of the 20 items Toronto Alexithymia Scale (TAS-F1) and Snaith-Hamilton-Pleasure Scale (SHARPS). In the contribution of risk prediction factors, social psychological factors was more than 0.60. ROC curve of prediction model was 0.826 (p<0.001; 95% CI) and the accuracy of prediction was 0.81 (p<0.001). Transforming the prediction model to a tree diagram, it was convenient to clinic operation.
A PSD risk prediction model with good prediction performance was constructed to achieve diagnose concisely and clearly. The social psychological factors play an important role for diagnosing PSD in the early period.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.