NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.

Pyroptosis is a novel process of programmed inflammatory necrosis, which is closely related to microbial infections and autoimmune diseases. In recent years it has been proved that Gasdermin D is an executive protein of pyroptosis. Cleaved Gasdermin D leads to the formation of pores in cell membrane to induce pyroptosis, and the release of inflammatory factors such as IL-1β and IL-18 aggravates the occurrence of inflammatory responses. With the deepening of Gasdermin D research, it is gradually clear its protein structure and activation sites, which has other activation pathways apart from inducing inflammasome activation. Activation of Gasdermin D does not necessarily mean cell death, even if it could induce the formation of pores in cell membrane and regulation of inflammatory cytokine secretion. These findings offer insight into Gasdermin D function and change our understanding of pyroptosis and programmed necrosis. The recent progress of Gasdermin D is highlighted in this review.

Humans ; Retrospective Studies ; Tetanus/epidemiology* ; China/epidemiology*

ObjectiveTo explore the effects of body weight and waist circumference on static and dynamic balance function in overweight and obese adults. MethodsParticipants （n=103） were selected by cluster random sampling from the Hypoglycemic Weight Loss Clinic of the Endocrinology Department of the Third Affiliated Hospital of Sun Yat-sen University. All participants were assessed for basic data collection， biochemical test， body weight， waist circumference and height measurement， static balance function assessed by balance error scoring system （BESS） and dynamic balance function assessed by functional reach test （FRT）. The BESS score and FRT distance of all participants were compared among groups according to different BMI grades and WC grades. Multivariate linear regression was used to analyze the influencing factors of participants' dynamic and static balance functions. Results① With the increase of BMI grading， the BESS score showed an upward trend， and the difference between groups was statistically significant （P = 0.004）. The BESS score of normal WC patients was lower than that of central obesity patients （P < 0.001）， which indicated that compared with normal BMI， overweight and obese people had poor dynamic and static balance ability； ② With the BMI grading， the FRT distance increased， showing a downward trend （P < 0.001）. The FRT distance in normal WC patients was significantly higher than that in central obesity patients （P < 0.001）， which indicated that the static and dynamic balance ability of central obesity patients was worse than that of normal WC patients； ③ In BMI overweight group， the FRT distance decreased significantly with the increase of WC （P = 0.02）. The results showed that under the condition of no difference in BMI， Compared with normal WC， the dynamic and static balance ability of central obese patients was worse； ④ The influence of BESS score on BMI（B=4.12，P =0.027， 95% CI=0.48-7.75）and WC（B = 3.47，P = 0.046， 95% CI = 0.07 - 6.88）was significant. The influence of FRT distance on BMI（B = -5.68，P = 0.001， 95% CI = -8.95 - 2.41）and WC（B = -4.71，P = 0.003， 95% CI = -7.83 to -1.61）was significant， which indicated that the static and dynamic balance ability of obese people was worse with the increase of BMI， and the ability of dynamic and static balance of central obesity was worse than that of normal WC. ConclusionWaist circumference is an independent factor affecting the dynamic and static balance function of overweight and obese people. Under similar BMI， the dynamic balance function of central obese people is worse than that of people with normal waist circumference， leading to higher risk of falling.

Evodiamine(EVO)is an indoloquinazoline alkaloid isolated from the fruits of Euodia rutaecarpa,which has long been used in traditional Chinese medicine to treat various diseases.Modern medical research shows that evodiamine has various pharmacological activities and extremely high medicinal value such as anti-inflammation,anti-tumor,losing weight,treating Alzheimer's,and antibacterium.Evodiamine can interact with a variety of proteins.For example,the interaction between evodiamine and TRPV1 induces its activation to exert anti-inflammatory and losing weight; the interaction with DNA topoisomerase I inhibits its function and thus inhibit bacterial proliferation; the interaction with tubulin promotes NLRP3 inflammasome activation,and exerts anti-tumor and anti-inflammatory functions.In recent years,with the in-depth study of evodiamine,pharmacological research and mechanism of evodiamine has significant improvement.Recent progress of pharmacological effect of evodiamine is highlighted in this review.

OBJECTIVE: To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on β-amyloid (Aβ) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function. METHODS: Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aβ₁-₄₂ at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi, the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aβ and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2]. RESULTS: Compared with the sham-operation group, in the model group, the escape latency was prolonged (P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced (P<0.01); the brain tissue was seriously damaged; the expression of hippocampal Aβ and RAGE was increased (P<0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased (P<0.01). Compared with the model group, the escape latency was shortened in the deqi group (P<0.05, P<0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 (P<0.05, P<0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aβ and RAGE was decreased (P<0.01, P<0.05) and the expression of LRP1 and IDE was increased in each moxibustion group (P<0.01, P<0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group (P<0.01, P<0.05); the expression of NEP was increased in deqi group (P<0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group (P<0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 (P<0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased (P<0.05, P<0.01). Compared with the non-deqi group, the expression of Aβ was reduced (P<0.05), the expression of LRP1 and ApoE was increased in the deqi group (P<0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group (P<0.05). CONCLUSION Compared with non-deqi, moxibustion with deqi could promote Aβ transport and degradation, thereby reducing Aβ level in the brain and improving cognitive function for AD rats.
Alzheimer Disease/therapy* ; Amyloid beta-Peptides/genetics* ; Angiotensin-Converting Enzyme 2 ; Animals ; Apolipoproteins E/metabolism* ; Hippocampus/metabolism* ; Male ; Moxibustion ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the mechanism of decomposed Zuoguiwan（ZGW） recipes in treating ovariectomized osteoporosis rats. Method:Forty Sprague-Dawley female rats were equally and randomly divided into Sham-operated group, ovariectomized model group, positive group, and low and high-dose ZGW groups. After 12 weeks of administration by gavage, the bone mineral density (BMD) of rats' distal femur was measured by micro-CT, the morphology of bone tissue were observed by hematoxylin-eosin staining (HE), β-cross-linked c-telopeptide of type Ι collagen (β-CTX) and bone-specific alkaline phosphatase (BALP) in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of β₂AR, OPG and RANKL were evaluated by Western blot analysis and real-time quantitative polymerase chain reaction （PCR）. Result:Compared with Sham-operated group, BMD of rats in ovariectomized model group was decreased (P<0.01), morphology of bone tissue was destroyed, serum BALP was reduced, while β-CTX was boosted (P<0.01)，mRNA and protein expressions of OPG in tibia were reduced, while RANKL were increased, and mRNA and protein expressions of β₂AR in the hypothalamus were decreased (P<0.05, P<0.01). Compared with ovariectomized model group, BMDs of rats in low and high-dose ZGW groups were increased (P<0.01), morphology of bone tissue was repaired, serum BALP and mRNA and protein expressions of OPG in tibia were up-regulated (P<0.05, P<0.01), whereas serum β-CTX and mRNA and protein expressions of β₂AR in the hypothalamus and RANKL in tibia were down-regulated (P<0.05, P<0.01). Conclusion:Yang-nourishing components in decomposed Zuoguiwan recipes can improve BMD of ovariectomized rats by regulating OPG/RANKL pathway mediated by β₂AR. "Seeking Yin in Yang" is a crucial mechanism of Zuoguiwan in treating ovariectomized osteoporosis in rats.