Objective To investigate the changes and clinical significance of peripheral blood mucosal-associated invariant T(MAIT)cells in children with influenza.Methods Children with influenza who received treatment in the outpatient and inpatient departments of a children's hospital from January to May 2023 were selected and divided into the common type group and the severe type group.Healthy children who underwent physical examination in this hospital during the same period were selected as the healthy control group.Within 24 hours after admission,children's venous blood was drawn for testing;ratios of MAIT cells(CD3+CD161+TCRVα7.2+cells)and MAIT cells expressing PD-1,CD69,perforin,and CD107 α were tested by flow cytometry,respectively.Differences among all the groups were compared.Results Compared with the control group,the proportion of peripheral blood MAIT cells in children with common and severe influenza gradually decreased,while the proportion of CD69-ex-pressing and perforin-positive MAIT cells increased gradually.Differences were statistically significant(all P＜0.05).There was no statistically significant difference in the proportion of MAIT cells expressing CD107(P＞0.05).The proportion of PD-1 positive MAIT cells increased(P＜0.05),but there was no statistically significant difference be-tween the common type and severe type groups(P＞0.05).Conclusion The decrease of peripheral blood MAIT cells accompanied with immune activation plays a role in the pathogenesis of influenza.

ObjectiveTo explore the influencing factors of different scores on predicting death risk of extremely low birth weight infants （ELBWI）. MethodsA total of 186 cases of ELBWI admitted by the Children's Hospital affiliated to Nanjing Medical University and the Lishui Branch of the Affiliated Zhongda Hospital of Southeast University were admitted from January 1， 2019 to January 1， 2021， and 125 ELBWIs were finally included after screening by inclusion and exclusion criteria. There were 47 cases in the death group and 78 cases in the survival group. General data and the items of score for neonatal acute physiology version Ⅱ （SNAP-Ⅱ）， simplified version of the score for neonatal acute physiology perinatal extension （SNAPPE-Ⅱ）， clinical risk index for babies （CRIB）， clinical risk index for babies Ⅱ （CRIB-Ⅱ） and the national critical illness score （NCIS） were collected. Univariate and multivariate analysis was performed and nomogram was evaluated using receiver operating characteristic curve （ROC）. ResultsIt was found that systolic blood pressure， maximum inhaled oxygen concentration， BE value and birth weight were important factors in ELBWI mortality risk assessment ［systolic blood pressure OR： 0.968， 95%CI： 0.938-0.999， P=0.043； maximum inhaled oxygen concentration OR： 1.020， 95%CI： 1.006-1.034， P=0.006； BE OR： 0.868， 95%CI： 0.786-0.959， P=0.005； birth weight OR： 0.994， 95%CI： 0.991-0.997， P=0.000］. ROC showed that the area under the curve of the above four variables is 0.71， and the 95% confidence interval is 0.610-0.799， which is better than CRIB score. ConclusionLower systolic blood pressure， higher inhaled oxygen concentration， higher BE and lower birthweight are important influencing factors to predict the death risk of ELBWI. The above four items should be included in the newly developed score assessment to obtain a more effective ELBWI prediction system.

Objective To conduct in vitro transdermal test on triamcinolone acetonide spray solution, and investigate the effects of ethanol and propylene glycol alone or in combination on the in vitro transdermal function of triamcinolone acetonide spray solution. Methods Rabbit abdominal skin was selected, and the in vitro penetration test of triamcinolone acetonide spray solution was carried out by Franz diffusion cell method, and the content of triamcinolone acetonide was determined by HPLC. The rate of transdermal absorption was compared. Results The transdermal absorption rate of the combined use of ethanol and propylene glycol was significantly higher than that of the single use (P<0.05), and the order of promoting the penetration of triamcinolone acetonide spray solution when ethanol and propylene glycol were combined by 10% ethanol + 25% propylene glycol >10% ethanol + 20% propylene glycol >15% ethanol + 25% propylene glycol >15% ethanol + 20% propylene glycol. Conclusion The combination of 10% ethanol and 25% propylene glycol could optimize the transdermal function of triamcinolone acetonide spray solution.

Humans ; Pain ; Pruritus

ObjectiveTo explore effect of Huanglian Jiedutang （HLJDT） on autophagy-related protein expression in septic mice with liver injury induced by cecal ligation and puncture （CLP）. MethodSixty eight-week-old C57BL/6 mice were randomly divided into four groups， namely， the sham operation group， model group， and low- （1.44 g∙kg^-1） and high-dose （2.88 g∙kg^-1） HLJDT groups， with 15 in each group. The septic model was established by CLP after the last administration of HLJDT for three successive days. The survival rate of mice with 24 h was observed. The mice were sacrificed 12 h after operation for collecting the serum and liver tissue. The levels of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） were detected by enzyme-linked immunosorbent assay （ELISA）， and the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum by biochemical method. The pathological changes in liver tissue were observed by hematoxylin-eosin （HE） staining， and the apoptosis index （AI） of hepatocytes by TdT-mediated dUTP-biotin nick end-labeling （TUNEL）. The expression levels of protein high-mobility group box 1 protein （HMGB1）， Beclin1， and microtubule-associated protein 1 light chain 3 （LC3）-Ⅱ/Ⅰ in the liver tissue were assayed by Western blot. ResultCompared with the sham operation group， the model group showed reduced survival rate at 12 and 24 h， elevated IL-6， TNF-α， and IL-1β levels， enhanced AST and ALT activities （P<0.05）， hepatocyte swelling， inflammatory cell infiltration， and apoptosis， and up-regulated HMGB1 （P<0.05）， Beclin1， and LC3-Ⅱ/Ⅰ （P<0.05）. Compared with the model group， each medication group exhibited increased survival rate at 12 and 24 h， lowered IL-6 and TNF-α levels， weakened AST and ALT activities （P<0.05）， alleviated liver injury and apoptosis （P<0.05）， down-regulated HMGB1 expression （ P<0.05）， and up-regulated Beclin1 and LC3-Ⅱ/Ⅰ （P<0.05）. ConclusionHLJDT alleviates the liver injury of septic mice possibly by inducing autophagy and inhibiting apoptosis.

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Humans ; Ion Channels ; Pain ; Pressure ; TRPM Cation Channels ; TRPV Cation Channels ; Temperature

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer’s disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.