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Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20 mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50 µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, GluA1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as GluA1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-Ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.
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Trastorno Depresivo Mayor , Ketamina , Ratas , Animales , Ketamina/farmacología , Ketamina/metabolismo , Ketamina/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/metabolismo , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/farmacología , GTP Fosfohidrolasas/uso terapéutico , Trastorno Depresivo Mayor/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Plasticidad Neuronal , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Proteína de Unión al GTP rac1/metabolismoRESUMEN
The purpose of this study was to investigate the effects of propofol anesthesia combined with remifentanil on inflammation, stress response, and immune function in children undergoing tonsil and adenoid surgery. For this aim, 126 children admitted to our hospital for elective temperature-controlled radio-frequency of tonsils and adenoids from October 2020 to September 2021 were randomly divided into an observation group (n=63) and a control group (n=63). The observation group was anesthetized with propofol in combination with remifentanil, while the control group underwent propofol combined with ketamine. The mean arterial pressure (MAP), heart rate, serum C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), epinephrine, cortisol (Cor), CD3+ T lymphocytes, CD4+ helper T lymphocytes, CD8+ suppressor T lymphocytes and CD4+/CD8+ ratio were compared between the two groups before induction of anaesthesia (T1), upon intubation (T2), at the beginning of surgery (T3), at the end of surgery (T4) and 5 min after extubation (T5). -(TNF-α). The recovery time from anaesthesia and adverse reactions after extubation were observed in the two groups. Results showed that the MAP and heart rate in both groups increased significantly at T2 compared to T1, but the observation group had lower values than the control group after the maintenance of anaesthesia (P<0.05). Serum CRP, IL-6 and TNF-α levels increased with time in both groups, and the increase was considered significant (P<0.05). In addition, serum epinephrine and Cor levels gradually rose from T1 to T4 in both groups, and then decreased at T5. The difference was statistically significant (P<0.05) between any two-time points. CRP, IL-6, TNF-α, epinephrine and Cor in the observation group were significantly lower than those in the control group from T3 to T5 (P<0.05). CD3+, CD4+ and CD4+/CD8+ ratio decreased whereas CD8+ went up in both groups at T4 and T5, and which were considered statistically significant when compared with data from T1 to T3 (P<0.05). However, CD3+, CD4+, CD8+ and CD4+/CD8+ ratios did not differ statistically significantly between the two groups at each time point (P>0.05). In the observation group, the time to recovery of spontaneous respiration, the time to resumption of limb movements and the span from discontinuation of anaesthetic to extubation were all significantly shorter than those in the control group, and the incidence of agitation during the awakening period was lower than that in the control group (P<0.05). Then propofol combined with remifentanil is more effective in inflammation, stress response and immune function in anesthetizing children undergoing tonsil and adenoid surgery. The observation group presented more stable hemodynamics, lower levels of inflammation and stress reactions, rapid awakening and fewer adverse effects, so the combination therapy was worthy of clinical promotion in pediatric surgery requiring general anesthesia.
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Tonsila Faríngea , Propofol , Tonsila Faríngea/cirugía , Anestesia General , Proteína C-Reactiva , Niño , Epinefrina , Humanos , Inmunidad , Inflamación , Interleucina-6 , Tonsila Palatina/cirugía , Propofol/farmacología , Propofol/uso terapéutico , Remifentanilo , Factor de Necrosis Tumoral alfaRESUMEN
Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).
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OBJECTIVE: Ovarian yolk sac tumor (YST) is a very rare malignant tumor in young women. This study aimed to explore the clinicopathological prognostic characteristics and reproductive outcomes of Chinese Han patients. METHODS: To describe a case series study, we reviewed the clinicopathological data of 50 YST patients treated from 2 tertiary medical academic medical centers from January 2009 to December 2019. The Akaike information criterion was used to select variables. The influence of relevant characteristics on prognosis factors was analyzed by the Cox proportional hazard model. RESULTS: The median follow-up time was 64.5 months (range from 3 to 124 months). The median age was 22.7 years (3 to 34 years). Abdominal pain (54.0%) or mass (42.0%) were the most common clinical symptoms in the early stage of diagnosis. The tumors were located bilaterally in 4 cases. 27 patients, 7 patients, 13 patients, and 3 patients were in stage I, II, III, and IV, respectively. Twenty-one stage I patients and 12 stage II to IV patients underwent fertility-preserving surgery. Of the 50 patients who received postoperative chemotherapy, 49 received the BEP regimen. At the last follow-up, 92% of the patients were still alive. The overall survival rate and disease-free survival rate were 91.6% and 90.6%, respectively. Recurrence occurred in 7 (14%) patients with a median survival time of 16.7 months (range from 3 to 50 months). Six patients had recurrence in the abdominal space. The percentage of Ki67 (P = .01) and tumor size (P = .03) were 2 important prognostic factors in multivariate analysis. In terms of survival outcomes, fertility-preserving surgery can be equivalent to radical surgery. Sixteen patients tried to conceive, and 6 patients with advanced-stage succeeded in 10 pregnancies. Of these, 6 patients successfully gave birth to 6 healthy babies. CONCLUSIONS: The diagnosis of YST of childbearing age is very rare. Because the failure of primary treatment is related to the residual disease after salvage surgery, the fertility and survival results of patients undergoing fertility-preserving surgery are promising.
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Tumor del Seno Endodérmico , Neoplasias Ováricas , Centros Médicos Académicos , Adulto , China/epidemiología , Tumor del Seno Endodérmico/patología , Femenino , Fertilidad , Humanos , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas/patología , Embarazo , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Postoperative delirium (POD) commonly occurs in patients following major surgeries and is associated with adverse prognosis. The modes of anesthesia may be associated with POD occurrence. General anesthesia (GA) causes loss of consciousness in the patient by altering the levels of some neurotransmitters as well as signaling pathways. We conducted this meta-analysis to investigate the effect of GA vs. regional anesthesia (RA) on POD incidence in surgical patients. Methods: The databases of Pubmed, Embase, and Cochrane Library were searched till October 22, 2021. The eligible criteria were participants aged 18 years or older, patients undergoing surgery under GA and RA, and articles reporting the effect of GA vs. RA on POD incidence. RevMan 5.3 was used to perform statistical analyses. Results: A total of 21 relevant trials with a total of 1,702,151 patients were included. The pooled result using random-effects model with OR demonstrated significant difference in POD incidence between patients with GA and RA (OR = 1.15, 95% CI: [1.02, 1.31], I 2 = 83%, p for effect = 0.02). We did not obtain the consistent pooled result after sensitivity analysis (OR = 0.95, 95% CI: [0.83, 1.08], I 2 =13%, p for effect = 0.44) and excluded the articles without the information on preoperative cognitive or neuropsychological assessment (OR = 1.12, 95% CI: [1.00, 1.25], I 2 =80%, p for effect = 0.05), respectively. Conclusion: This meta-analysis could not identify that GA was significantly associated with POD occurrence in surgical patients compared with RA.
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Background: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation. Methods: The authors searched the databases of PubMed, Embase, and Cochrane Library for studies published until January 2, 2021, that reported remimazolam sedation for endoscopic procedures. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Cochrane Review Manager Software 5.3 was used to perform the statistical analyses. Results: Seven relevant studies involving a total of 1,996 patients were identified. We conducted a meta-analysis of the different controls used in the studies, that is, the placebo, midazolam, and propofol. The results demonstrated that remimazolam had a strong sedative effect, and its sedative efficiency was significantly higher than that of placebo [OR = 0.01, 95% CI: (0.00, 0.10), I 2 = 30%, p <0.00001]. The sedative efficiency of remimazolam was significantly higher than that of midazolam [OR = 0.12, 95% CI: (0.08, 0.21), I 2 = 0%, p < 0.00001] but lesser than that of propofol [OR = 12.22, 95% CI: (1.58, 94.47), I 2 = 0%, p = 0.02]. Regarding the adverse events, remimazolam is associated with a lower incidence of hypotension than placebo and midazolam. Similarly, remimazolam was associated with a lower incidence of hypotension and hypoxemia than propofol. Conclusions: Remimazolam is a safe and effective sedative for patients undergoing endoscopic procedures. The sedative efficiency of remimazolam was significantly higher than that of midazolam but slightly lower than that of propofol. However, the respiration and circulation inhibitory effects of remimazolam were weaker than those of midazolam and propofol.
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ABSTRACT: Malignant transformation arising in mature cystic teratoma (MT-MCT) is a rare neoplasm of the ovary. Herein, we aimed to evaluate the clinicopathological features and treatment outcome of the Han Chinese women with MT-MCT.In this retrospective study, the clinical data of patients who had been surgically treated from January 2000 to November 2019 and in whom the diagnosis of MCT was confirmed based on the pathology were included. Fourteen patients with MT-MCT from a total of 569 cases (2.46% incidence) of MCT were reviewed.The mean age of patients with MT-MCT was 51.3 (range, 31-71) years, while the mean age of patients with MCT was 45.3 (range, 17-62) years. Upon gross examination, the mean size of MT-MCT was 14.0 (range, 11-25) cm, whereas the mean size of MCT was 7.5 (range, 4-10) cm. Primary surgical staging was performed in all cases. Complete cytoreduction and suboptimal surgical resection were performed in 12 (85.7%) and 2 (14.3%) cases, respectively. Thirteen patients with malignant transformation of squamous cell carcinoma (SCC) whose Federation International of Gynecology and Obstetrics stage was >1 received chemotherapy, comprising carboplatin and paclitaxel. Response to the chemotherapy regimen was complete in 12 patients; 1/12 patients died within the median follow-up period of 16.5âmonths. The 5-year overall survival rate and disease-free survival rates were 31.2% and 31.6%, respectively.From the data generated, we conclude that the rate of MT-MCT increases with age. The MT-MCT was much higher in women of postmenopausal age than in younger women. We described our experience of successfully treating patients with malignant transformation of SCC with primary surgical staging and adjuvant chemotherapy (cisplatin, paclitaxel, bleomycin, and etoposide) that might improve survival in patients with advanced-stage disease.
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Antineoplásicos/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción/métodos , Quistes Ováricos/patología , Neoplasias Ováricas/patología , Ovario/cirugía , Teratoma/patología , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , China , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Quistes Ováricos/terapia , Neoplasias Ováricas/terapia , Estudios Retrospectivos , Teratoma/terapia , Resultado del Tratamiento , Carga Tumoral , Adulto JovenAsunto(s)
Anestésicos por Inhalación , Delirio del Despertar , Éteres Metílicos , Niño , Humanos , Sulfato de Magnesio/efectos adversos , Anestesia General/efectos adversos , Anestésicos por Inhalación/efectos adversos , Agitación Psicomotora/tratamiento farmacológico , Agitación Psicomotora/etiología , Periodo de Recuperación de la AnestesiaRESUMEN
Several studies have investigated the relationship between serum Se concentration and cervical cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum selenium levels and cervical cancer. Twelve studies investigating the association by univariate analysis and five studies by multivariate analysis were identified after a systematic search of PubMed, Wanfang, CNKI, and SinoMed databases. Standard mean differences (SMD) or odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. In univariate analysis, serum selenium levels in cervical cancer cases were significantly lower than in controls (SMD = -4.86, 95% CI -6.03-3.69). Subgroup analysis showed consistent results. In multivariate analysis, serum selenium levels in cervical cancer cases were also significantly lower than in controls (OR = 0.55, 95% CI 0.42-0.73). After treatment, the serum selenium levels increased significantly (SMD = 2.59, 95% CI 0.50-4.69). In conclusion, high serum selenium levels were associated with cervical cancer, and selenium exposure might be a protective factor for cervical cancer.
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Selenio/sangre , Neoplasias del Cuello Uterino/sangre , Estudios de Casos y Controles , Femenino , Humanos , Análisis Multivariante , Neoplasias del Cuello Uterino/terapiaRESUMEN
Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment. The sucrose preference test and open-field test were used to assess behavioral changes. The expression levels of excitatory amino acid transporters (EAATs) were measured by western blot. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect hippocampal glutamate concentrations. We found that the expression of EAAT2 and EAAT3 were obviously downregulated, and extracellular concentrations of glutamate were significantly increased in the hippocampi of depressive-like rats. Ketamine (10, 25, and 50mg/kg) upregulated the expression of EAAT2 and EAAT3, decreased the hippocampal concentration of extracellular glutamate, and alleviated the rats' depressive-like behavior. The antidepressant effect of ketamine may be linked to the regulation of EAAT expression and the enhancement of glutamate uptake in the hippocampus of depressive-like rats.
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Sistema de Transporte de Aminoácidos X-AG/metabolismo , Anestésicos/farmacología , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Ketamina/farmacología , Animales , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Hipocampo/metabolismo , Masculino , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Dietary fat intake is potentially associated with the onset of esophageal carcinoma (EC), but evidence from observational studies has remained unclear. This study aimed to evaluate the role of fat intake in the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). A systematic search was conducted in PubMed and Web of Science to identify all relevant studies. Study-specific relative risks (RR) for the highest versus the lowest intake categories and 95% confidence intervals (CI) were pooled using a random-effects model. Seventeen case-control studies (2058 EAC cases, 1581 ESCC cases and 11696 controls) and two prospective cohort studies (494, 978 participants and 630 EAC cases and 215 ESCC cases) were identified. In EAC, the RRs (95% CI) were 1.69 (1.14-2.50) for total fat intake, 1.88 (1.28-2.77) for saturated fat (SFA) intake, 1.04 (0.86-1.27) for polyunsaturated fat (PUFA) intake and 1.70 (1.01-2.84) for monounsaturated fat (MUFA) intake. In ESCC, the RRs (95% CI) were 1.12 (0.84-1.51) for total fat, 1.38 (0.91-2.08) for SFA, 0.95 (0.55-1.62) for PUFA and 1.04 (0.65-1.66) for MUFA. In conclusion, total fat, SFA and MUFA intake were associated with EAC risk, but fat intake showed no significant association with ESCC risk. Large-scale prospective cohort studies are needed to confirm our findings.
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Objective:To describe the epidemiological and clinical characteristics of patients with novel coronavirus (2019-nCoV) -infected pneumonia in Enshi, Hubei, and to improve the awareness of the disease, which is key for surveillance and control measures of 2019-nCoV pneumonia in the region.Methods:The first 66 laboratory-confirmed 2019-nCoV patients in Enshi between January 23, 2020 and February 1, 2020 were included. Their epidemiological data, demographic data, clinical data and therapeutic effect were retrospectively analyzed.Results:Among the first 66 patients with confirmed 2019-nCoV, patients had an average age of 46±9 years, 35 (53.0%) patients were male and 31 (47.0%) female; 38 (57.6%) patients were Han, 18 (27.3%) were Tujia, and 10 (15.1%) were Miao. Thirty-seven (56%) patients had chronic diseases such as coronary heart disease, chronic bronchus, inflammation, diabetes, hypertension, hypothyroidism, and rheumatoid arthritis. All the patients had a history of exposure or indirect exposure in Wuhan epidemic area, mainly history of Wuhan sojourner. The mean incubation period varied from 2.5-16 days, with the 95th percentile of the distribution at 7 days. The main clinical manifestation were fever [66 (100%) patients], dry cough [56 (84.8%)], chest tightness [21 (31.8%)], shortness of breath [8 (12.1%)], massive fatigue [23 (34.8%)], muscle ache [6 (9.1%)], headache [4 (6.1%)], sore throat [13 (19.7%) ], rhinorrhoea [11 (16.7%) ], and diarrhea [ 5 (7.6%)]. Six (9.1%) critically ill patients and 4 (6.1%) critically ill patients had dyspnea. White blood cell counts were normal or decreased in 51 (77.3%) patients, and increased in 15 (22.7%). Lymphocyte counts were reduced or normal in 58 (87.9%) patients, and increased in 8 (12.1%) patients. Most patients had elevated CRP and erythrocyte sedimentation, and some patients had normal ranges of liver function, renal function, and electrolytes. Ten severely ill patients had elevated liver enzymes and cardiac enzymes (especially K and CKMB). There were significant differences in inflammatory markers among patients of different nationalities. Arterial blood gas analysis in 56 (84.8%) mild patients showed no significant abnormalities. Chest CT scans of 66 patients showed single or multiple small patchy shadows and interstitial changes, which were evident in the extrapulmonary band. All patients were hospitalized and isolated for treatment. Of the 66 patients received oxygen therapy, most of them received antiviral therapy (abidol/Kaletra, 0.2 g po tid/2 pills po bid) and interferon (aerosol inhalation), few patient received antibacterial therapy (Tanreqing, 20 mL ivgtt qd) and glucocorticoid therapy (methylprednisolone, 40 mg ivgtt bid), and supplemented by traditional Chinese medicine treatment. Six (9.1%) severely ill patients and 4 (6.1%) critically ill patients treated with non-invasive or invasive ventilator.Conclusions:The patients in this study are all imported cases. Most patients have mild clinical symptoms. The lungs show single or multiple small patchy shadows and interstitial changes, which are obvious with extrapulmonary bands. Seek medical treatment as soon as possible, and the above-mentioned symptomatic treatment scheme is effective. The overall morbidity and mortality in this region are lower than those in other parts of the province, and the mortality and critical illness rate of ethnic minority patients are lower than those of Han patients. There are significant differences in inflammatory markers such as leukocytes and lymphocytes among patients of different nationalities.
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Resolvin D1 (RvD1), an endogenous lipid mediator derived from docosahexaenoic acid, has been reported to promote a biphasic activity in anti-inflammatory response and regulate inflammatory resolution. The present study aimed to determine the endogenous expression pattern of RvD1 in a rat model of self-resolution of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) and inflammation. The ARDS model was induced by administrating LPS (2mg/kg) via tracheotomy in 138 male Sprague-Dawley rats. At specified time points, lung injury and inflammation were respectively assessed by lung histology and analysis of bronchoalveolar lavage fluid and cytokine levels. The expression of endogenous RvD1 was detected by high performance liquid chromatography and tandem mass spectrometry. The results showed that histological lung injury peaked between 6h (LPS6h) and day 3, followed by recovery over 4-10 days after LPS administration. Lung tissue polymorph nuclear cell (PMN) was significantly increased at LPS6h, and peaked between 6h to day 2. The levels of interleukin (IL)-6 and IL-10 were significantly increased at LPS6h and remained higher over day 10 as compared to baseline. Intriguingly, the endogenous RvD1 expression was decreased gradually during the first 3 days, followed by almost completely recovery over days 9-10. The finding indicated that endogenous RvD1 underwent a decrease in expression followed by gradual increase that was basically coincident with the lung injury recovery in a rat model of self-resolution LPS-induced ARDS and inflammation. Our results may help define the optimal therapeutic window for endogenous RvD1 to prevent or treat LPS-induced ARDS and inflammation.