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Pregnant women themselves are at higher risk for psychological symptoms. The impact of ongoing COVID-19 may increase the risk. However, it is uncertain whether COVID-19 affects pregnant women's psychological symptoms directly or indirectly being mediated.This survey was conducted in four obstetrics and gynecology hospitals in Beijing from February 28, 2020, to April 26, 2020. Pregnant women who visited the antenatal-care clinic were mobilized to finish the online questionnaires, including the Generalized Anxiety Disorder 7-Item Scale, Patient Health Questionnaire-9, Connor-Davidson resilience scale, and Insomnia Severity Index.A total of 828 pregnant women were included in the analysis. The estimated self-reported rates of anxiety, depression, insomnia, and any of the three were 12.2 %, 24.3 %, 13.3 %, and 33.1 %, respectively. Mediating effect analysis showed that pregnant women's response to COVID-19 was not directly associated with psychological symptoms but indirectly through the mediating effect of maternal concerns, which accounted for 32.35 % of the total effect. Stratified analysis by psychological resilience showed that women's attitude toward COVID-19 (OR, 2.68, 95 % CI: 1.16-6.18) was associated with a higher risk of psychological symptoms in those with poor psychological resilience.The study was a non-probability sampling survey, and the causal relationship between maternal concerns and psychological symptoms could not be determined due to the study's design.Under public health emergencies such as COVID-19, routine antenatal care should still be prioritized, and concerns related to childbirth-related caused by such emergencies should also be addressed, especially for those with weak psychological resilience.

Summary Background In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012–15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age–sex–residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20–1·72] and 12-month prevalence OR 1·41 [1·12–1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68–3·38] and 12-month OR 2·80 [95% CI 1·88–4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39–2·51] and 12-month OR 1·85 [95% CI 1·40–2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Background Pulmonary microvascular endothelial cells (PMVECs) are initial targets of sepsis-induced acute lung injury (ALI). During the apoptosis of PMVECs, tight junctions (TJ) and adherens junctions (AJ) are firstly damaged. Previous studies have suggested hydrogen treatment can protect lung microvasculature of mice from sepsis-induced endothelial dysfunction and maintain the coherence of pulmonary endothelium, but the underlying mechanism remains unclear. Methods We investigated the role of hydrogen-rich medium on regulating intercellular junction proteins under lipopolysaccharide (LPS) treatment which mimicked sepsis in vitro. Changes of cytoskeleton regulatory protein ROCK and RhoA as well as PMVEC apoptotic rate were examined. Results LPS treatment reduced the expression levels of occludin and VE-cadherin in PMVECs, while hydrogen-rich medium can recover these changes. Furthermore, H2 can significantly ameliorate the excessive expression of ROCK and RhoA under sepsis-mimicking condition. The application of RhoA activator U-46619 resulted in a more significant elevation in cell apoptotic rate as well as reduction in the expression of junctional proteins. Using H2 can almost completely inhibit the effects of RhoA activator. Conclusions Our findings suggest that RhoA is a crucial protein in the signaling pathway of LPS-induced endothelial cell dysfunction. Hydrogen treatment can prevent LPS-induced junctional injury and cell death by inhibiting the activity of RhoA.

Neuropathic pain is a complication after a spinal nerve injury. The inflammasomes are now identified to be responsible for triggering inflammation in neuropathic pain. Autophagy participates in the process of neuropathic pain and can regulate the inflammasome activation in different diseases. Our previous research reported that hydrogen exerted a protective effect against neuropathic pain. Therefore, we focused on the mechanism and role of autophagy and inflammasome, by which hydrogen alleviated the hyperpathia induced by neuropathic pain. The results showed that neuropathic pain stimulated activation of inflammasome NLRP3 and autophagy pathway in the microglial cells of the spinal cord. The inhibition of NLRP3 inhibited the hyperpathia induced by spinal nerve litigation surgery. The absence of autophagy aggravated the inflammasome activity and hyperpathia. Hydrogen promoted autophagy related protein expression, inhibited the inflammasome NLRP3 pathway activation, and relieved the hyperpathia induced by neuropathic pain. Hydrogen treatment could alleviate hyperpathia by autophagy-mediated NLRP3 inactivation.

The macrophage is an innate immune response cell that plays an important role in the development of sepsis. Dexmedetomidine (DEX) is a sedation drug, which have anti-oxidative, anti-inflammatory and anti-apoptosis effects and can be used on sepsis patients in the ICU. However, its mechanisms of action remain poorly understood. PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine protein kinase that recognizes damaged mitochondria and leads to mitophagy. This study investigated the effects of DEX on Lipopolysaccharides(LPS)-induced macrophage injury and explained the underlying mechanisms. The results showed that LPS treatment caused mitochondrial damage, mitochondria-dependent apoptosis and PINK1-mediated mitophagy; at the same time, PINK1 has a protective effect on LPS-induced macrophage apoptosis and inflammation by mitophagy that eliminates dysfunctional mitochondria. DEX could promote the clearance of damaged mitochondria characterized by low Mitochondrial membrane potential (MMP) and high reactive oxygen species(ROS), thus exerting a protective effect in LPS treated macrophages, and PINK1 mediated mitophagy is required for this protective effect.

Sepsis-induced hepatic dysfunction is considered as an independent risk factor of multiple organ dysfunction syndrome (MODS) and death. Mitophagy, a selective form of autophagy, plays a major role in sepsis-induced organ damage. We have demonstrated that hydrogen gas (H2), a selective antioxidant, exerts protective effects in septic mice. Here, we hypothesize that the therapeutic effects of H2 on septic animals with liver damages may be exerted through regulation of the Fun14 domain-containing protein 1 (FUDNC1)-induced mitophagy pathway. Male C57BL/6J mice were subjected to sham or cecal ligation and puncture (CLP) operation and treated with 2% H2 gas inhalation for 3 h starting at 1 h after sham or CLP surgery. To verify the role of FUNDC1, the cell-penetrating peptide P (NH2-GRKKRRQRRRPQDYESDDESYEVLDLTEY-COOH) (1 mg/kg) that functions as a FUNDC1 inhibitor was intraperitoneally injected into mice 24 h before the sham or CLP operation. To evaluate the severity of septic liver injury, the 7-day survival rate, liver histopathologic score, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respiration control ratio (RCR), and FUDNC1, P-18-FUDNC1, P62, LC3B-II, Tim23, and caspase-1 levels were evaluated after the sham or CLP operation. The results demonstrated that 2% H2 gas inhalation resulted in an increase in the 7-day survival rate, ALT and AST levels, RCR, and P62 and LC3B-II expression but decreased the histological score and FUDNC1, P-18-FUDNC1, Tim23, and caspase-1 levels after sepsis. However, no significant differences were reported between the CLP + peptide P and CLP + H2 + peptide P groups. These observations indicate that 2% H2 gas inhalation for 3 h may serve as an effective therapeutic strategy for sepsis-induced liver injury through the regulation of FUNDC1-dependent mitophagy.

This study estimated the prevalence, correlates, severity and functional impairment of disabilities attributed to neurotic disorders in the Chinese population. Data from a representative national sample of 2,526,145 non-institutionalized residents were obtained from the Second China National Sample Survey on Disabilities (CNSSD) in 2006. The data were analyzed to estimate prevalence, correlates, severity and functional impairment of disability attributable to neurotic disorders by gender, age, region, and other key socio-demographic and economic factors. The disability prevalence attributed to neurotic disorders was 0.032% (805/2,526,145) in China. Women, rural residents, unemployed job status, low education level and those who were divorced or widowed showed higher prevalence rates than their counterparts. Proportions of mild, moderate, severe and extremely severe of neurotic attributed disability only accounted for 78.48%, 9.14%, 6.5% and 5.9%, respectively. Finally, these findings provide evidence that, prevalence rates of disability attributable to neurotic disorders vary greatly among different population groups and regions. Multiple disabilities including disability attributable to neurotic disorders can bring much more impairment to individuals than disability attributable to neurotic disorder only.

Background Previous studies about comorbidity have primarily focused on disorders based on diagnostic criteria instead of symptoms. This study aimed to describe the prevalence and risk factors of anxiety comorbid depression based on a population-based sample in Chifeng City Inner Mongolia and explored the gender differences of depressive subtypes in anxiety patients. Methods This study was a cross-sectional study conducted among 6376 community residents. Logistics analysis and multiple-group latent class analysis was used in exploring the risk factors and subtypes of anxiety comorbid depressive symptoms. Results A total of 4528 respondents were interviewed in this study. The lifetime prevalence estimates for anxiety in the total sample was 5.70%. Among residents who had ever had anxiety, most of them reported having depressive symptoms while 15.79% of them met the criteria of MDD. Logistics analysis showed childhood adversities were associated with anxiety comorbid depressive symptoms. The results of multiple-group latent class analysis showed that the latent class probabilities were different between males and females. Conclusion The prevalence rates of comorbidity were similar to the reports of previous regional surveys in China with statistically significant differences of comorbidity occurring between males and females. Precision prevention should therefore be targeted towards different kinds of populations.

Background Lungs are one of the most common target organs of sepsis [ 1 ]. Hydrogen gas (H 2 ), which has selective anti-oxidative effects, can be effectively used to treat septic mice. Mitochondrial dysfunction and dynamics play important roles in sepsis-induced organ damage. Methods By using cecal ligation and puncture (CLP), a classic septic model, we explored the role of 2% H 2 treatment in sepsis-induced acute lung injury (ALI) linked to mitochondrial function and dynamics. We randomized male Institute for Cancer Research (ICR) mice into 4 groups: sham, sham + H 2 , CLP and CLP + H 2 . At 24 h after CLP or sham operations, we used histological examination and transmission electron microscopy (TEM) to observe lung slices. We analyzed oxygenation index (PaO 2 /FiO 2 ), mitochondrial-membrane potential (MMP), adenosine triphosphate (ATP) levels, respiration control ratio (RCR) and mitochondrial-respiration complex activities (I and II) using commercial kits, and dynamin-related protein 1 (Drp1) and mitofusin-2 (MFN2) using Western blot. Results Therapy with 2% H 2 increased PaO 2 /FiO 2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H 2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability (YLDs). However, nationally representative epidemiological data for depressive disorders, in particular depressed adults’ mental health services use, are still unavailable in China. The present study is a part of the Chinese National Mental Health Survey (CMHS), 2012–15, which reported the prevalence, treatment, and associated disability of depressive disorders in the Chinese general population. Methods: The CMHS recruited a representative sample of 28140 Chinese residents (≥ 18 years) by using multistage proportional-to-population-size sampling method. Trained investigators interviewed participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder (MDD), dysthymic disorder (DD), and depressive disorder not otherwise specified (DD-NOS). Participants with 12-month depressive disorders were asked whether they ever received any 12-month treatment for their emotional problems and the specific types of treatment providers. The Quick Inventory of Depressive Symptomatology and Sheehan Disability Scale (SDS) were used to evaluate the severity of and role impairments associated with 12-month depressive symptoms. Findings: The weighted lifetime and 12-month prevalence rates of any depressive disorder were 6.8% (95%CI: 5.8-7.8%) and 3.6% (95%CI: 3.0-4.2%), respectively; the corresponding figures were 3.4% (95%CI: 2.0-3.9%) and 2.1% (95%CI: 1.8-2.4%) for MDD, 1.4% (95%CI: 1.1-1.7%) and 1.0% (95%CI: 0.8-1.3%) for DD, and 3.2% (95%CI: 2.6-3.9%) and 1.4% (95%CI: 1.1-1.7%) for DD-NOS. Overall, 77.2% of persons with 12-month depressive disorders had role impairment of any SDS domain: 82.2% for MDD, 81.5% for DD, and 64.6% for DD-NOS. Depressed participants reported an average of 41.0 days out of role in the past year due to depression; the corresponding figures were 49.7 days for MDD, 54.9 days for DD, and 12.2 days for DD-NOS. In total, 88.9% of individuals with 12-month depressive disorders had clinically significant depressive symptoms: 93.7% for MDD, 91.7% for DD, and 77.5% for DD-NOS. MDD and DD had similar proportions of “severe” or “very severe” depressive symptoms (43.0% and 42.1%), which were higher than DD-NOS (13.9%). 9.5% of participants with 12-month depressive disorders were treated in any treatment sector: 3.6% in the specialty mental health (SMH), 1.5% in the general medical (GM), 0.3% in the human services (HS), and 3.3% in the complementary-alternative medical (CAM) sector. Respondents with MDD and DYS had the highest proportion of seeking treatment in SMH sector (4.7% and 3.0%) while those with DD-NOS had the highest proportion of seeking treatment in CAM sector (most treatments were Traditional Chinese Medicine) (3.3%). Only 0.5% of participants with depressive disorders were treated adequately. Rates of treatment adequacy of MDD and DYS in SMH sector were 9.2% and 2.4%, respectively. Both rates in GM sector were 0%. Interpretation: Compared to western countries, our data show a relatively low prevalence of depressive disorders in China. Nevertheless, their associated role impairments, symptom severities, and disabilities are severe. Importantly, the treatment rates are rather low, let alone adequate treatment. Nationwide programs aiming at removing barriers in availability, accessibility, and acceptability to mental healthcare are needed in China. Funding: The study was funded by the Special Research Project for Non-profit Public Service of the Chinese Ministry of Health (grant number 201202022), the National Twelfth Five-Year Plan for Science and Technology Support of the Chinese Ministry of Science and Technology (grant numbers 2012BAI01B01 & 2015BAI13B00) and the National Key R&D Program of China (grant numbers 2017YFC0907800, 2017YFC0907801). Declaration of Interests: The authors have no conflicts of interest to declare Ethical Approval: The study protocol of CMHS was approved by the Ethics Committee of the Sixth Hospital of Peking University (No.: IMH-IRB-2013-13-1).

Background: The sudden epidemic of COVID-19 in China caused attention globally Health staff are in heavy workload and at high-risk infection The aims of this

The pond-ditch circulation system (PDCS) is an efficient and economical solution for the restoration of degraded rural water environments. However, little is known about nitrous oxide (N2O) and nitric oxide (NO) emissions in the microbial removal process of nitrogen in PDCSs, and their contribution to nitrogen removal. The aim of this study was to quantify N2O and NO emissions from the PDCS, evaluate their capacities, and elucidate the key environmental factors controlling them. The results showed that N2O and NO fluxes were in the ranges 1.1-2055.1μgNm-2h-1 and 0.1-6.8μgNm-2h-1 for the PDCS, respectively. Meanwhile, the N2O and NO fluxes from the two ponds in the PDCS were significantly higher than those in the static system. Moreover, the amount of N2O and NO emissions in the PDCS accounted for 0.17-4.32% of the total nitrogen (TN) removal. According to the partial least squares (PLS) approach and Pearson's correlation coefficients, nitrate nitrogen in water (W-NO3--N), dissolved oxygen in water (W-DO), dissolved oxygen in sediment (DO), pH in water (W-pH), pH in sediment (pH), total kjeldahl nitrogen (TKN), and soil organic carbon (SOC) significantly affected the N2O flux (p

Background Traumatic brain injury (TBI) can lead to cognitive dysfunction and motor dysfunction. TBI is a potential risk factor for subsequent dementia. Hyperphosphorylation of Tau and ApoE4 has been found in patients with TBI. A significant increase in miR-203 was also found in the peripheral blood of TBI mice. Thus, we hypothesize that miR-203 inhibitor protects against neuronal damage and behavioral deficits by inhibition of Tau phosphorylation, ApoE4 expression and apoptosis. Methods TBI mice were induced and treated with miR-203 inhibitor. Tau phosphorylation and ApoE4, hippocampal long-term potentiation (LTP), learning and memory, and motor function were separately detected by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. Caspase-3 activity and bcl-2 expression were detected by ELISA. Results TBI induction led to increased phosphorylation of Tau and ApoE4 expression. Administration of miR-203 inhibitor suppressed TBI induced ApoE4 expression and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction. miR-203 inhibitor treatment also improved motor function. In addition, miR-203 inhibitor treatment inhibited neuronal apoptosis by inhibiting caspase-3 activity and increasing bcl-2 expression. Conclusion miR-203 inhibitor treatment can rescue TBI-induced neural damage by inhibiting neuronal apoptosis and dementia markers like ApoE4 expression and Tau phosphorylation.

Endothelial injury is a primary cause of sepsis and sepsis-induced organ damage. Heme oxygenase-1 (HO-1) plays an essential role in endothelial cellular defenses against inflammation by activating nuclear factor E2-related factor-2 (Nrf2). We found that molecular hydrogen (H2) exerts an anti-inflammatory effect. Here, we hypothesized that H2 attenuates endothelial injury and inflammation via an Nrf2-mediated HO-1 pathway during sepsis. First, we detected the effects of H2 on cell viability and cell apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated by LPS. Then, we measured cell adhesion molecules and inflammatory factors in HUVECs stimulated by LPS and in a cecal ligation and puncture (CLP)-induced sepsis mouse model. Next, the role of Nrf2/HO-1 was investigated in activated HUVECs, as well as in wild-type and Nrf(-/-) mice with sepsis. We found that both 0.3 mmol/L and 0.6 mmol/L (i.e., saturated) H2-rich media improved cell viability and cell apoptosis in LPS-activated HUVECs and that 0.6mmol/L (i.e., saturated) H2-rich medium exerted an optimal effect. H2 could suppress the release of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and high-mobility group box 1 protein (HMGB1). Furthermore, H2 could elevate anti-inflammatory cytokine IL-10 levels in LPS-stimulated HUVECs and in lung tissue from CLP mice. H2 enhanced HO-1 expression and activity in vitro and in vivo. HO-1 inhibition reversed the regulatory effects of H2 on cell adhesion molecules and inflammatory factors. H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway.

Background Sepsis is a potentially fatal whole-body inflammation caused by severe infection. Hydrogen gas (H2) is effective for treating sepsis. In this study, we hypothesized that the protective function of H2 in mice with septic lung injury occurred through the activation of heme oxygenase 1 (HO-1) and its upstream regulator nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Materials and methods Male institute of cancer research mice were subjected to sepsis by cecal ligation and puncture (CLP) with the presence or absence of H2. Beginning at 1 and 6 h after CLP or sham operation, respectively, 2% H2 was inhaled for 1 h. We intraperitoneally injected the HO-1 inhibitor zinc protoporphyrin IX (40 mg/kg) 1 h before CLP. To assess the severity of septic lung injury, we observed the 7-d survival rate, wet/dry weight ratio of lung, lung histopathologic score, oxygenation index, and so forth. Serum and homogenates from the lung, liver, and kidney were acquired for measuring the levels of high-mobility group box 1 (HMGB1) at 6, 12, and 24 h after CLP or sham operation. Furthermore, the protein and messenger RNA expression of Nrf2, HO-1, and HMGB1 was measured at 6, 12, and 24 h. Results Septic mice had a lower survival rate and more severe lung injury compared with the sham group. However, therapy with H2 increased the survival rate and alleviated the severity of lung injury, reduced the HMGB1 level, and increased the HO-1 and Nrf2 levels in septic mice. Moreover, the HO-1 inhibitor zinc protoporphyrin IX significantly eliminated the protective effect of H2 on septic lung injury. Conclusions H2 plays a significant role in regulating the release of the inflammatory cytokine HMGB1 in septic mice, which is partially mediated through the activation of HO-1 as a downstream molecule of Nrf2.

During the development of sepsis, the complication in central nervous system (CNS), appearing early and frequently relative to other systems, can obviously increase the mortality of sepsis. Moreover, sepsis survivors also accompany long-term cognitive dysfunction, while the ultimate causes and effective therapeutic strategies of brain injury in sepsis are still not fully clear. We designed this study to investigate the effects of 2% hydrogen gas (H2) on brain injury in a mouse model of sepsis. Male ICR mice were underwent cecal ligation and puncture (CLP) or sham operation. 2% H2 was inhaled for 60min beginning at both 1 and 6h after sham or CLP operation, respectively. H2 concentration in arterial blood, venous blood and brain tissue was detected after H2 inhalation separately. The survival rate was observed and recorded within 7 days after sham or CLP operation. The histopathologic changes and neuronal apoptosis were observed in hippocampus by Nissl staining and TUNEL assay. The permeability of brain-blood barrier (BBB), brain water content, inflammatory cytokines, activities of antioxidant enzymes (SOD and CAT) and oxidative products (MDA and 8-iso-PGF2α) in serum and hippocampus were detected at 24h after sham or CLP operation. The expressions of nucleus and total nuclear factor erythroid 2-related factor 2 (Nrf2) and cytoplasmic heme oxygenase-1(HO-1) in hippocampus were measured at 24h after sham or CLP operation. We assessed their cognitive function via Y-maze and Fear Conditioning test on day 3, 5, 7 and 14 after operation. H2 treatment markedly improved the survival rate and cognitive dysfunction of septic mice. CLP mice showed obvious brain injury characterized by aggravated pathological damage, BBB disruption and brain edema at 24h after CLP operation, which was markedly alleviated by 2% H2 treatment. Furthermore, we found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.

Neuropathic pain is evoked by aberrant sensory processing in the peripheral or central nervous system, which is characterized by persistent pain, tactile allodynia, or hyperalgesia. Neuroinflammation is associated with the initiation and maintenance of persistent pain in both the peripheral and central nervous systems. Hydrogen sulfide plays important regulatory roles in different physiological and pathological conditions. Therefore, we investigated the effect of hydrogen sulfide on allodynia, hyperalgesia and cytokine release in rats with neuropathic pain and the related regulatory mechanism. Neuropathic pain was established by chronic constriction injury (CCI) of the sciatic nerve in rats. Nuclear factor erythroid-2 (NF-E2)-related factor 2 (Nrf2) siRNA, hemin, Sn-protoporphyrin (SnPP)-IX and/or NaHS were administered to rats with neuropathic pain, and the spinal cord was collected to detect the expression of Nrf2, hemeoxygenase-1 (HO-1), nuclear factor-kappa B (NF-κb) and the cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and high mobility group box (HMGB)-1 by Western blot (WB) analysis, reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence or enzyme-linked immunosorbent assay (ELISA). Mechanical allodynia, thermal hyperalgesia and the number of paw lifts were measured at different time points after operation. In the present research, neuropathic pain induced Nrf2 and HO-1 expression in the microglial cells of the spinal cord; Nrf2 and HO-1 were necessary to alleviate the hyperalgesia of CCI-induced rats; NaHS mitigated the hyperalgesia and allodynia induced by the CCI operation; and NaHS mitigated the excessive release of the cytokines TNF-α, IL-1β, IL-6 and HMGB1 via the Nrf2/HO-1 pathway in the microglial cells of the spinal cord. These results indicated that NaHS exhibited antinociceptive and anti-inflammatory effects that were associated with the activation of the Nrf2/HO-1 pathway in the spinal cord of rats with neuropathic pain.