Inhibition of perilipin 2 attenuates cerebral ischemia/reperfusion injury by blocking NLRP3 inflammasome activation both in vivo and in vitro.

Cerebral ischemia/reperfusion (CI/R) usually causes neuroinflammation within the central nervous system, further prompting irreversible cerebral dysfunction. Perilipin 2 (Plin2), a lipid droplet protein, has been reported to exacerbate the pathological process in different diseases, including inflammatory responses. However, the role and mechanism of Plin2 in CI/R injury are unclear. In this study, the rat models of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R) were established to mimic I/R injury, and we found that Plin2 was highly expressed in the ischemic penumbra of tMCAO/R rats. The siRNA-mediated knockdown of Plin2 significantly decreased neurological deficit scores and reduced infarct areas in rats induced by I/R. Detailed investigation showed that Plin2 deficiency alleviated inflammation of tMCAO/R rats as evidenced by reduced secretion of proinflammatory factors and the blockade of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In vitro experiments showed that Plin2 expression was upregulated in mouse microglia subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Plin2 knockdown inhibited OGD/R-induced microglia activation and the accumulation of inflammation-related factors. Taken together, this study demonstrates that lipid droplet protein Plin2 contributes to the pathologic process of CI/R damage by impacting inflammatory response and NLRP3 inflammasome activation. Thus, Plin2 may provide a new therapeutic direction for CI/R injury.

[Effect of sequential sedation and analgesia in preventing delirium and withdrawal symptoms in children after ventilator weaning]. / åºè´¯é•‡ç—›é•‡é™å¯¹é¢„é˜²è¡Œæœºæ¢°é€šæ°”æ²»ç–—æ‚£å„¿æ’¤æœºåŽè°µå¦„åŠæ’¤è¯ååº”çš„æ•ˆæžœç ”ç©¶.

OBJECTIVES: To investigate the effect of sequential sedative and analgesic drugs in preventing delirium and withdrawal symptoms in children after ventilator weaning. METHODS: A retrospective analysis was performed on 61 children who were admitted and received mechanical ventilation support for ≥5 days in the Pediatric Intensive Care Unit of Dongguan Children's Hospital Affiliated to Guangdong Medical University from December 2019 to September 2021. The children were divided into a control group (30 children with no maintenance of analgesic and sedative drugs after ventilator weaning) and an observation group (31 children with sequential sedative and analgesic drugs maintained for 48 hours after ventilator weaning). The two groups were compared in terms of the Sophia Observation Withdrawal Symptoms Scale (SOS) score, the Pediatric Delirium Scale (PD) score, the Richmond Agitation-Sedation Scale (RASS) score, and the incidence rates of delirium or withdrawal symptoms at 24 and 72 hours after ventilator weaning. RESULTS: There was no significant difference in the incidence rate of delirium at 24 hours and 72 hours after ventilator weaning between the two groups (P>0.05). Compared with the control group, the observation group had significantly lower incidence rate of withdrawal symptoms and scores of SOS, PD, and RASS scales at 24 hours and 72 hours after ventilator weaning (P<0.01). CONCLUSIONS: Sequential sedation and analgesia after ventilator weaning can reduce the incidence of withdrawal symptoms within 72 hours after ventilator weaning, but it cannot reduce the incidence rate of delirium.

Effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury undergoing continuous renal replacement therapy. / ä¸åŒæ¶²ä½“è´Ÿè·çŠ¶æ€å¯¹æŒç»­è‚¾æ›¿ä»£æ²»ç–—è„“æ¯’ç—‡ç›¸å ³æ€¥æ€§è‚¾æŸä¼¤æ‚£å„¿é¢„åŽçš„å½±å“.

OBJECTIVES: To evaluate the effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 121 children who underwent CRRT for sepsis-associated AKI from August 2018 to March 2021 were enrolled in the retrospective study. According to the fluid load from admission or disease progression to CRRT, they were divided into three groups: low fluid load (fluid load: <5%; n=35), high fluid load (fluid load: 5% - <10%; n=35), and fluid overload (fluid load: ≥10%; n=51). Baseline data and clinical biochemical data before CRRT were collected for comparison and analysis. The Kaplan-Meier survival curve analysis was used for comparison of 28-day survival between groups. The multivariate logistic regression model was used to identify the influencing factors for the prognosis of the children. RESULTS: The survival analysis showed that the fluid overload group had a significantly higher 28-day mortality rate than the low fluid load and high fluid load groups (P<0.05). The multivariate logistic regression analysis showed that an increase in fluid overload volume was a risk factor for increased 28-day mortality in the fluid overload group, while earlier initiation of CRRT was a protective factor (P<0.05). CONCLUSIONS: Fluid overload before CRRT may increase the mortality in children with sepsis-associated AKI, and CRRT should be performed for these children as early as possible.

Optimisation of the Conversion and Extraction of Arctigenin From Fructus arctii Into Arctiin Using Fungi.

Fructus arctii is commonly used in Chinese medicine, and arctiin and arctigenin are its main active ingredients. Arctiin has low bioavailability in the human body and needs to be converted into arctigenin by intestinal microbes before it can be absorbed into the blood. Arctigenin has antiviral, anti-inflammatory, and anti-tumour effects and its development has important value. In this study, we used external microbial fermentation with Aspergillus awamori and Trichoderma reesei to process and convert arctiin from F. arctii powder into arctigenin, hence increasing its bioavailability. We developed a fermentation process by optimising the carbon and nitrogen source/ratio, fermentation time, pH, liquid volume, inoculation volume, and substrate solid-liquid ratio. This allowed for an arctiin conversion rate of 99.84%, and the dissolution rate of the final product was 95.74%, with a loss rate as low as 4.26%. After the fermentation of F. arctii powder, the average yield of arctigenin is 19.51 mg/g. Crude fermented F. arctii extract was purified by silica gel column chromatography, and we observed an arctigenin purity of 99.33%. Our technique effectively converts arctiin and extracts arctigenin from F. arctii and provides a solid basis for further development and industrialisation.

[Diagnosis value of MRI in acute rotator interval injury].

OBJECTIVE: To compare clinical application of 1.5 T MRI in acute rotator interval injury. METHODS: Totally 160 patients with acute rotator cuff tear by clinical diagnosis were retrospectively analyzed by MRI examination and arthroscopy from March 2016 to February 2019, including 122 males and 38 females, aged from 22 to 71 years old with an average of (42.35±3.48) years old. Based on the results of arthroscopy as the gold standard, the shape and signal changes of rotator cuff, rotator interval, peripheral bursa, bone and soft tissue were observed by MRI on axial, oblique coronal and oblique sagittal imagese. RESULTS: The direct MRI signs of acute rotator interval injury displayed thickening, diminution, distortion, interruption of the coracohumeral ligament and superior glenohumeral ligament complex with highsignal intensity on fat-suppression by proton weighted sequence. The indirect MRI signs displayed rotator cuff, peripheral bone and soft tissue injury. The consistency of the results between the two methods was quite satisfactory (Kappa=0.85), and the concordance rate of the two methods has statistically significant (Z=10.75, P<0.00). There was no statistical difference in the inconsistent parts between two methods (χ2= 0.400, P>0.05). The true positive rate, true negative rate, false positive rate and false negative rate of MRI diagnosis of rotator interval injury were 93.75%, 91.30%, 94.74%, 5.26%, 8.70% respectively. CONCLUSION: MRI could clearly display acute rotator interval, and could accurately diagnose acute rotator interval injury, which provide more accurate imaging basis for clinical diagnosis and treatment.

Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets.

Fructus arctii, also known as great power seed, is the dried fruit of Arctium lappa of the family Compositae. It is a commonly used veterinary herbal medicine, and arctigenin is the main active ingredient. The aim of this study was to characterize the absorption, distribution, metabolism, and excretion of arctigenin and Fructus arctii powder in piglets. These data were used to provide a theoretical reference for the development and clinical use of new veterinary drugs. Sixteen healthy piglets (mean weight 30.0 ± 5.0 kg) were divided into two groups. One group was administered 2.0 mg/kg body weight (bw) arctigenin intravenously, and the other was administered 1.0 g/kg.bw Fructus arctii powder by gavage. Blood samples were collected from the anterior vena cava at different time points, and the concentration of arctigenin in the plasma of the piglets was determined using high-performance liquid chromatography (HPLC). Arctigenin conformed to a two-compartment model with no absorption, and the main pharmacokinetic parameters were as follows: distribution half-life (t 1/2α)-0.166 ± 0.022 h; elimination half-life (t 1/2ß)-3.161 ± 0.296 h; apparent volume of distribution (V d)-0.231 ± 0.033 L/kg; clearance rate (CLb)-0.057 ± 0.003 L/(h.kg); and area under the curve (AUC)-1.189 ± 0.057 g.h/mL. The pharmacokinetic parameters of arctigenin following oral administration of the Fructus arctii powder were as follows: absorption half-life (t 1/2ka)-0.274 ± 0.102 h, t 1/2α-1.435 ± 0.725 h, t 1/2ß-63.467 ± 29.115 h, V d-1.680 ± 0.402 L/kg, CLb-0.076 ± 0.028 L/(h kg), peak time (t max)-0.853 ± 0.211 h, peak concentration (C max)-0.430 ± 0.035 g/mL, and AUC-14.672 ± 4.813 g/mL. These results indicated that intravenous arctigenin was sparingly distributed in tissues. In contrast, orally administered Fructus arctii powder was rapidly absorbed, more widely distributed, and more slowly eliminated than the intravenous arctigenin, which may indicate its sustained pharmacological effects.

[Epidemiological analysis of new cases of pneumoconiosis in Ningxia Hui Autonomous Region, China from 2006 to 2010].

OBJECTIVE: To investigate the epidemiological characteristics of pneumoconiosis in Ningxia Hui Autonomous Region, China from 2006 to 2009. METHODS: Statistical analysis was performed on the types, populations, ages, and geographic distribution of the pneumoconiosis cases in Ningxia from 2006 to 2010, as reported in China Information System for Diseases Control and Prevention. RESULTS: A total of 625 new cases of pneumoconiosis (4 death cases) occurred throughout Ningxia from 2006 to 2010. Of the new cases, 538 (86.1%) suffered stage I pneumoconiosis, 70 (11.2%) stage II pneumoconiosis, and 17 (2.72%) stage III pneumoconiosis. Silicosis and coal-workers' pneumoconiosis were the dominant types of pneumoconiosis, accounting for 97.44% (609/625) of all cases. Of the 625 cases, 557 (89.12%) were distributed in Shizuishan City, and 563 (90.08%) were engaged in coal and metallurgical industries. Most cases were in the 35-year-old group and 45-year-old group, and the lengths of dust-exposed service mostly ranged from 10 to 29 years. CONCLUSION: In Ningxia, pneumoconiosis control should focus in the state-owned, middle-sized coal enterprises in Shizuishan City. Health surveillance should be enhanced in the workers with more than 10 years of dust-exposed service or aged more than 35 years, so as to reduce the incidence of occupational diseases.