Cystathionine ß-Synthase Suppresses NLRP3 Inflammasome Activation via Redox Regulation in Microglia.

Aims: Cystathionine ß-synthase (CBS) is essential for homocysteine (Hcy) transsulfuration, yielding cysteine as a common precursor of hydrogen sulfide (H2S), glutathione (GSH), and other sulfur molecules, which produce neuroprotective effects in neurological conditions. We previously reported a disruption of microglial CBS/H2S signaling in a Parkinson's disease (PD) mouse model. Yet, it remains unclear whether CBS affects nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activity and other pathologies in PD. Results: Microglial CBS expression decreased after lipopolysaccharide (LPS) stimulation. Elevated GSSG (the oxidized GSH) content and decreased H2S generation were found in the brains of microglial cbs conditional-knockout (cbscKO) mice, whereas serum and brain Hcy levels remained unaltered. Moreover, microglial cbscKO mice were susceptible to NLRP3 inflammasome activation and dopaminergic neuron losses caused by LPS injection into the substantia nigra, whereas cbs overexpression or activation produced opposite effects. In vitro studies showed that cbs overexpression or activation suppressed microglial NLRP3 inflammasome activation and interleukin (IL)-1ß secretion by reducing mitochondrial reactive oxygen species (mitoROS) level. Conversely, ablation of cbs enhanced NLRP3 expression and mitoROS generation and augmented microglial NLRP3 inflammasome activity in response to adenosine triphosphate challenge, which was blocked by the mitoROS scavenger. Innovation and Conclusion: The study demonstrated an elevated GSSG level and reduced H2S generation, which correlated with a susceptible status of microglia in the brain of cbscKO mice. Our findings reveal a critical role of CBS in restraining the microglial NLRP3 inflammasome by controlling redox homeostasis and highlight that activation or upregulation of CBS may become a potential strategy for PD treatment.

Relative vaccine effectiveness against Delta and Omicron COVID-19 after homologous inactivated vaccine boosting: a retrospective cohort study.

ObjectiveTwo COVID-19 outbreaks occurred in Henan province in early 2022-one was a Delta variant outbreak and the other was an Omicron variant outbreak. COVID-19 vaccines used at the time of the outbreak were inactivated, 91.8%; protein subunit, 7.5%; and adenovirus5-vectored, 0.7% vaccines. The outbreaks provided an opportunity to evaluate variant-specific breakthrough infection rates and relative protective effectiveness of homologous inactivated COVID-19 vaccine booster doses against symptomatic infection and pneumonia. DESIGN: Retrospective cohort study METHODS: We evaluated relative vaccine effectiveness (rVE) with a retrospective cohort study of close contacts of infected individuals using a time-dependent Cox regression model. Demographic and epidemiologic data were obtained from the local Centers for Disease Control and Prevention; clinical and laboratory data were obtained from COVID-19-designated hospitals. Vaccination histories were obtained from the national COVID-19 vaccination dataset. All data were linked by national identification number. RESULTS: Among 784 SARS-CoV-2 infections, 379 (48.3%) were caused by Delta and 405 (51.7%) were caused by Omicron, with breakthrough rates of 9.9% and 17.8%, respectively. Breakthrough rates among boosted individuals were 8.1% and 4.9%. Compared with subjects who received primary vaccination series ≥180 days before infection, Cox regression modelling showed that homologous inactivated booster vaccination was statistically significantly associated with protection from symptomatic infection caused by Omicron (rVE 59%; 95% CI 13% to 80%) and pneumonia caused by Delta (rVE 62%; 95% CI 34% to 77%) and Omicron (rVE 87%; 95% CI 3% to 98%). CONCLUSIONS: COVID-19 vaccination in China provided good protection against symptomatic COVID-19 and COVID-19 pneumonia caused by Delta and Omicron variants. Protection declined 6 months after primary series vaccination but was restored by homologous inactivated booster doses given 6 months after the primary series.

A case-case study on the effect of primary and booster immunization with China-produced COVID-19 vaccines on prevention of pneumonia and viral load among vaccinated persons infected by Delta and Omicron variants.

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.

α-synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson's disease.

The cell-to-cell transfer of α-synuclein (α-Syn) greatly contributes to Parkinson's disease (PD) pathogenesis and underlies the spread of α-Syn pathology. During this process, extracellular α-Syn can activate microglia and neuroinflammation, which plays an important role in PD. However, the effect of extracellular α-Syn on microglia autophagy is poorly understood. In the present study, we reported that extracellular α-Syn inhibited the autophagy initiation, as indicated by LC3-II reduction and p62 protein elevation in BV2 and cultured primary microglia. The in vitro findings were verified in microglia-enriched population isolated from α-Syn-overexpressing mice induced by adeno-associated virus (AAV2/9)-encoded wildtype human α-Syn injection into the substantia nigra (SN). Mechanistically, α-Syn led to microglial autophagic impairment through activating toll-like receptor 4 (Tlr4) and its downstream p38 and Akt-mTOR signaling because Tlr4 knockout and inhibition of p38, Akt as well as mTOR prevented α-Syn-induced autophagy inhibition. Moreover, inhibition of Akt reversed the mTOR activation but failed to affect p38 phosphorylation triggered by α-Syn. Functionally, the in vivo evidence showed that lysozyme 2 Cre (Lyz2cre )-mediated depletion of autophagy-related gene 5 (Atg5) in microglia aggravated the neuroinflammation and dopaminergic neuron losses in the SN and exacerbated the locomotor deficit in α-Syn-overexpressing mice. Taken together, the results suggest that extracellular α-Syn, via Tlr4-dependent p38 and Akt-mTOR signaling cascades, disrupts microglial autophagy activity which synergistically contributes to neuroinflammation and PD development.

[Descriptive epidemiological study on disabilities attributed to non-dementia organic mental disorder in China].

OBJECTIVE: To describe the prevalence rates of disabilities attributed to non-dementia organic mental disorder and their demographic and regional distributions in China for supporting policy maker to prevent mental disabilities. METHODS: Using the data from the second China National Survey on Disability, the prevalence rates were statistically analysed. RESULTS: There were 1 200 people with non-dementia organic mental disabilities in 2 526 145 respondents, the point prevalence rate of disabilities attributed to non-dementia organic mental disorder was 0.475‰, ranking the third in all mental disabilities. Among the disabled, more male and more people with lower education level, being unemployed, divorced, widowed and unmarried were found. The decline of disability prevalence rates in different ethnic groups was found in the sequence of Uighur, Tibetan, Hui-Chinese (Muslims), Han-Chinese and Mongolian. The disability prevalence rates in Uighur and Tibetan were double higher than those in Han-Chinese and Hui-Chinese with statistical significances. The disability prevalence rates increased with age. Regarding the region distribution of non-dementia organic mental disabilities, the prevalence rate in western region was higher than that in eastern region. Among the eight economic regions, the prevalence rates in the underdeveloped southwest, south, northwest regions were significantly higher than those in the others. The proportions of extremely severe, severe, moderate, and mild disability were 36.8%, 17.0%, 14.3%, and 31.9%. The severest impairment on function of daily activities was found in the disabled. CONCLUSION: The proportion of non-dementia organic mental disabilities is relative high in all mental disabilities, therefore it should be focused for prevention and treatment. The disabled in males, with lower economic and education level, worse marital status, and being unemployed should receive more attention.

[Surveillance of adverse events following immunization in Henan Province, China between 2010-2011].

OBJECTIVE: To analyze the epidemiological features of adverse events following immunization (AEFI) in Henan Province, China and to evaluate the safety of vaccines currently used in Henan. METHODS: The AEFI cases reported in Henan from January 1, 2010 to December 31, 2011 were collected through the China Surveillance System of Information on National Immunization Program. The descriptive method was used for epidemiological analysis. RESULTS: A total of 2415 cases of AEFI were reported in Henan from January 1, 2010 to December 31, 2011, and 1238 (51.26%) of them were found in Zhengzhou, Luoyang, and Jiaozuo cities. The male-to-female ratio was 1.32:1. Seven hundred and ninety-nine (33.08%) of these cases were less than one year old. Measles vaccine and DPT vaccine (against diphtheria, pertussis, and tetanus) were the main causes of AEFI, contributing to 61.24% of cases; the incidence rates of AEFI among people receiving measles and DPT vaccines were 30.3/105 and 5.0/105, respectively. 1528 cases (63.27%) developed AEFI after the first dose of vaccination. Inflammation and allergic symptoms were the predominant adverse effects caused by the top 5 vaccines AEFI-causing vaccines, and the clinical manifestations were significantly different among AEFI cases caused by different vaccines (χ2=304.5, P<0.001). Among the 2415 AEFI cases, 1946 (80.58%) had common adverse reaction, 348 (14.41%) had rare adverse reaction, 98 (4.06%) had coupling disease, 13 (0.51%) had psychogenic reaction, and 10 (0.41%) had reaction for unknown reasons. The prognosis of most AEFI cases was good, with a cure rate as high as 90.64%. CONCLUSIONS: AEFI occurs mostly in young children and after the first dose of vaccination. This should be brought to the attention of vaccination service personnel and the children's parents.

[Parenting skills situation and need assessment among parents of primary school pupils].

OBJECTIVE: To investigate parenting skills and need among parents of primary school pupils and to explore influencing factors. METHODS: A total of 1 394 parents of rural and urban primary school pupils were recruited by multistage stratified random clustered sampling method. They were asked to complete a self-report questionnaire regarding demographic and socioeconomic backgrounds, parenting scale, parenting need assessment, parent-to-child interaction attitudes, social support, physical/mental maltreatment experiences in childhood and so forth. RESULTS: Apart from TV/film/broadcasting, rural parents' utilization of other parenting deliveries was less than that of urban parents. Urban and rural parents both had high needs for parenting skills. Parents' physical/mental maltreatment experiences in childhood were risk factors for dysfunctional parenting. Positive parent-to-child interaction attitudes and high social support were protective factors against dysfunctional parenting. Mothers, parents of boys, middle/low family incomes, and parents with positive parent-to-child interaction attitudes had higher demands for parenting skills. CONCLUSION: We should make full use of mass media, interpersonal communication to meet the needs of parenting for parents, especially rural parents. More attention should be paid to parents with childhood maltreatment experiences, low social support and less positive parent-to-child interaction attitudes.

Peer physical aggression and its association with aggressive beliefs, empathy, self-control, and cooperation skills among students in a rural town of China.

This study explored the prevalence of peer physical aggression (PPA) and its association with aggressive beliefs, empathy, self-control, and cooperation skills among 1,719 7th-to-9th-grade students in a rural town in the central China province of Henan. The data were collected by the self-administered questionnaire anonymously. Results showed that 17.9% of the students reported that they had one or more times of physical aggressive behaviors toward their peers in the past 12 months. The reported rate of PPA was significantly higher in boys (24.7%) than in girls (10.7%). After adjusting the factors of gender and grade, result of logistic regression analysis showed that having a higher level of aggressive beliefs was PPA risk factor; a higher level of self-control was protective factor, but there were no significant association between PPA and the factors of empathy and cooperation skills. These results indicated that helping students to decrease their aggressive beliefs and to improve their self-control skill would aid in the prevention of youth violence.

[A descriptive analysis of mortality of brain tumor in China during 2004 - 2005].

OBJECTIVE: To analyze the level of mortality of brain tumor and its changes at different periods in China. METHODS: Death records for tumor of brain and central nervous system, which the code of international classification of diseases-10 (ICD-10) were C70-C72, were extracted from the database of the Third National Retrospective Sampling Survey of Death Causes in China during 2004 to 2005. The corresponding population data was linked to the data of death records, that the total population was 142 660 482 person years (72 970 241 person years in male, 69 690 241 person years in female). Then crude death rate, age-specific death rate, the constitute proportion to all death caused by tumor and the age-standardized death rate were calculated by taking reference of Chinese standard population or the world standard population. The indexes of mortality were compared with that of previous retrospective surveys of death causes at 1973 - 1975 and 1990 - 1992. RESULTS: The result showed that during 2004 to 2005, the number died from brain tumor was 4463 and the crude death rate in China was 3.13/100 000, which accounted for 2.30% of the all number died from tumor (193 841 cases). The age-standardized death rate by Chinese standard population was 2.37/100 000 and the age-standardized death rate by the world standard population was 2.90/100 000. Of which, there were 2556 death cases for males with crude death rate of 3.50/100 000. While for females, the crude death rate was 2.74/100 000 (1907 death cases). Age-standardized death rates by Chinese standard population in male and female were 2.71/100 000 and 2.03/100 000 respectively. The age-standardized death rate by world standard population was 3.31/100 000 for male and for female that was 2.48/100 000. The age-specific death rate of brain tumor in China was increasing as age growing. The crude death rates were 3.78/100 000 (1809/47 899 806), 2.80/100 000 (2654/94 760 676), and the age-standardized death rates by Chinese standard population were 2.71/100 000 and 2.20/100 000 for urban and rural area respectively, and the crude death rates of brain tumor in east, middle and west region were 3.60/100 000 (1894/52 556 694), 3.14/100 000 (1565/49 781 225), 2.49/100 000 (1004/40 322 563). The age-standardized death rates by Chinese population were 2.57/100 000, 2.43/100 000 and 2.02/100 000. Compared to the data in the first survey during 1973 to 1975, in which the crude death rate was 1.13/100 000 and age-standardized death rate by Chinese standard population was 1.10/100 000, the crude death rate and age-standardized death rate by Chinese standard population were increased by 176.99% and 115.45% respectively. While compared with the second survey during 1990 to 1992, that crude death rate was 1.89/100 000 and age-standardized death rate by Chinese standard population was 1.74/100 000, the rising percent of the rates were 65.61% and 36.21% respectively. CONCLUSION: The level of mortality of brain tumor has been changing with an increasing trend from the period of 1973 - 1975 to the period of 2004 - 2005. The rate in male was higher than that of female with great diversity in different areas in China.

[Period survival analysis of esophageal cancer in Linzhou city of Henan province].

OBJECTIVE: To analyze the survival level and variation of esophageal cancer in Linzhou city of Henan province from 1988 to 2004, and evaluate the effects of diagnosis and treatments on esophageal cancer in this area. METHODS: All incidence and death records for esophageal cancer during 1988 to 2004 were collected from Linzhou Tumor Registry. Cases with duplicate information or death certificate only were excluded. A total of 12,160 cases of esophageal cancer were collected, of which, 6914 cases were male, and 5246 cases were female. The sex-specific and age-specific probabilities of survival in 1992, 1997 and 2002 were calculated and linked to the data of incidence and death on esophageal cancer in this area. Five-year observed survival rate and five-year relative survival rate during 1990 to 1994, 1995 to 1999, 2000 to 2004 were calculated respectively using period survival analysis and cohort survival analysis and Z test. RESULTS: The 5-year relative survival rates among the three-episode were 28.24%, 35.24% and 40.76% respectively during 1988 to 2004. This showed an increasing trend by periods (Z values were 3.94 and 3.07, P < 0.05). The 5-year observed survival rates in men among the three-episode were 13.67%, 18.08% and 22.46% respectively, the 5-year relative survival rates were 29.94%, 36.96% and 38.40%. The 5-year observed survival rates in women among the three-episode were 15.56%, 19.29% and 28.01% respectively, the 5-year relative survival rates were 26.78%, 33.12% and 43.70%. During the two former periods, there was no significant difference in the 5-year observed survival rate and relative survival rate between men and women (Z values of observed survival rate were 1.48 and 0.88, P > 0.05. Z values of relative survival rate were 1.27 and 1.50, P > 0.05). In the third period, the 5-year observed survival rate and relative survival rate in women was higher than that in men (observed survival rate Z = 3.56, P < 0.05; relative survival rate Z = 2.09, P < 0.05). The relative survival rate that calculated using period method (respectively 35.24% and 40.76%) was higher than that using cohort method (respectively 28.77% and 33.35%) from 1995 to 1999, and from 2000 to 2004. CONCLUSION: The survival rate on esophageal cancer in Linzhou city was increasing in the three different periods. This indicated a rising status in the secondary prevention and clinical diagnosis and treatments on esophageal cancer.