OBJECTIVE To explore the inhibitory effect and its mechanism of asiaticoside on hypertrophic scar formation in rabbit ears based on the Wnt/ β -catenin pathway. METHODS The hypertrophic scar model in rabbit ears was established. Model rabbits were divided into the model group （normal saline）， asiaticoside low-dose group （12 mg/kg）， asiaticoside high-dose group （24 mg/kg）， and positive control group （tri amcinolone acetonide acetate 40 mg/kg）； additionally， a non-modeled control group （normal saline） was set up. There were 8 rabbits in each group. Rabbits in each group were injected with the corresponding drug solution/normal saline at the base within the scar area once daily for 28 consecutive days. After the last medication， the appearance of hypertrophic scars in rabbit ears was observed， and the hypertrophic scar index was measured； the levels of inflammatory factors [interleukin-6 （IL-6） and IL-10 ] in hypertrophic scar tissue of rabbits were determined； histopathological morphology of hypertrophic scar tissues in rabbit ears was observed， and the protein expression levels of collagen type Ⅰ （COLⅠ）， COLⅢ， Wnt4 and β -catenin in the hypertrophic scar tissues were detected. RESULTS Compared with control group， in the model group， the symptoms of hypertrophic scars were observed， the stratum corneum was thicker， and there was abnormal accumulation and disorganized arrangement of collagen. The hypertrophic scar index， IL-6 level， fibroblast density， area density of collagen fibers， mean optical density values of COLⅠ and COLⅢ， as well as the expression levels of Wnt4 and β -catenin proteins， were all significantly elevated （ P ＜0.05）， while the level of IL-10 was significantly decreased （ P ＜0.05）. Compared with the model group， the hypertrophic scars in asiaticoside low- and high-dose groups were significantly softened， with a thinned stratum corneum， and the above quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Asiaticoside can inhibit the formation of hypertrophic scars in rabbit ears and alleviate the inflammatory response in scar tissue. Its mechanism of action may be related to the inhibition of activation of the Wnt/ β -catenin pathway.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective To explore the role of long non-coding RNA smad7(Linc-smad7)in invasion and migration of pancreatic cancer(PC)cells and its mechanisms.Methods The expression level of Linc-smad7 in PC tissues and cell lines was detected by qRT-PCR assays.Transwell assays were performed to observe the effect of Linc-smad7 overexpression on the migration and invasion abilities of PaCa-2 cells.Luciferase reporter analysis was made to detect the direct binding effect of Linc-smad7 on miR-125b and miR-125b on Sirtuin1(SIRT1).qRT-PCR assays were used to detect the regulatory effect of Linc-smad7 on miR-125b expression in PaCa-2 cells.qRT-PCR and Western blotting assays were used to detect the regulatory effect of miR-125b on SIRT1 expression.Results Linc-smad7 was significantly increased in PC tissues and cell lines.Paca-2 cells with overexpressed Linc-smad7 showed higher migration and invasion abilities,while miR-125b expression was decreased.After the expression of miR-125b was increased,the expression of SIRT1 was decreased significantly.Luciferase reporter assays results suggested that Linc-smad7 directly targeted with miR-125b,and miR-125b directly bound with SIRT1.Increased Linc-Smad7 or decreased miR-125b could reverse the effect of SIRT1 inhibition on invasion and migration of PaCa-2 cells.Conclusion Linc-smad7 promotes invasion and migration of PaCa-2 cells through miR-125b/SIRT1 axis.

【Objective】 To reveal the integral in vivo polypharmacokinetics (PPK) similarity or difference between Jinyinhua (Lonicerae Japonicae Flos, LJF) and Shanyinhua (Lonicerae Flos, LF), and provide reference for their clinical application. 【Methods】 The PPK model and its total quantum statistical moment similarity (TQSMS) method were used to compare the integral PPK profiles of nine components with anti-inflammatory efficacy (rutin, caffeic acid, chlorogenic acid, cryptochlorogenic acid, dispsacoside B, macranthoidin B, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C) of LJF and LF. A total of 54 Specific Pathogen Free (SPF) grade Kunming (KM) mice were randomized into LJF group and LF group (n = 27), and each group was divided into nine subgroups (n = 3) according to different time points. Subsequently, mice model of p-xylene-induced ear edema was constructed by oral administration of LJF and LF. The concentrations of the nine anti-inflammatory components in plasma samples of the mice were determined by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). And the pharmacokinetics (PK) parameters of single component and the integral PPK parameters [total quantum statistical moment (TQSM) and TQSMS] of multiple components were calculated by Drug And Statistics (DAS) software and home-brew programs with Excel, respectively. 【Results】 There were significant differences in single-component PK parameters between LJF and LF (P < 0.05). Whereas, no significant differences were found in multi-component TQSM parameters, including total quantum zero moment (AUCT0-t, AUCT0-∞) and total quantum first moment (MRTT0-t, MRTT0-∞) for the total quanta (P > 0.05). Accordingly, single-component TQSMS varied from 0.220 4 to 0.968 9, and that for the total quanta was 0.828 4, suggesting no significant differences in the speed and extent of bioavailability between LJF and LF. Furthermore, in light of high TQSMS (0.828 4), the integral PPK profiles of the nine anti-inflammatory components of LJF and LF were similar under 90% confidence intervals. 【Conclusion】 The PPK model and its TQSMS method are appropriate and efficient to compare the similarity or difference of integral PPK profiles of multi-component herbal medicines. It is suggested in this research that LJF can be replaced with LF or vice versa for anti-inflammatory treatment.

Objective:To evaluate the efficacy of Qingpeng ointment in the treatment of early herpes zoster neuralgia.Methods:From January to June 2019, sixty patients with herpes zoster (34 males and 26 females, aged 12 to 48 years, onset time of 1 to 7 days) were randomly divided into experimental group and control group. Both groups were given the same antiviral and neurotrophic therapy after admission. The experimental group was treated with Qingpeng ointment for external use in addition. The numerical rating scale (NRS), sleep score (AIS) and adverse reactions of the two groups were evaluated at pre-treatment, 3, 5, 7, 15 and 30 days after treatment.Results:Compared with pre-treatment, the NRS and AIS scores of the experimental group were significantly reduced at each time from day 3, and the difference was statistically significant. The NRS and AIS scores of the control group were reduced at each time from day 7, and the difference was statistically significant. Compared with control group, the NRS scores of the experimental group on the 3rd, 5th, and 7th days and the AIS scores on the 3rd and 5th days after treatment were lower than those of the control group, and the difference was statistically significant. There were no serious adverse reactions in the two groups.Conclusions:External application of Qingpeng ointment can quickly relieve early neuralgia in patients with herpes zoster, improve the patients＇ sleep, and there is no obvious adverse reaction.

Objective:To explore the association between dopamine-β-hydroxylase (DβH), norepinephrine transporter (NET) gene polymorphisms and panic disorder(PD).Methods:The structured clinical interview for the diagnostic and statistical manual of mental disorders fourth edition (DSM-Ⅳ) axis Ⅰ disorders was administered by trained clinical psychiatrist, 139 patients with PD(PD group) and 196 healthy controls(control group) were enrolled in the study.Single nucleotide polymorphism(SNP) genotyping was performed using an improved multiplex ligation detection reaction technique.SPSS 16.0 and PLINK softwares were used to compare the allele frequency and genotype distribution.Results:(1)Compared with control group, PD group carried more G allele(76.3% vs 68.4%) and fewer A allele(23.7% vs 31.6%) in NET rs5569, and the difference was significant(χ 2=4.986, OR=0.67, 95% CI: 0.47-0.95, P<0.05). However, the correlation was no longer significant after adjusting for Bonferroni’s multiple testing( P>0.05). (2)The additive model of NET rs5569 showed a association with PD ( OR=0.68, 95% CI: 0.48-0.96, P<0.05). And the recessive model of DβH rs1611114 showed a association with PD( OR=0.42, 95% CI: 0.18-0.96, P<0.05). However, these correlations were no longer significant after adjusting for Bonferroni's multiple testing( P>0.05). (3)No matter allele or genotype, there were no significant differences in DβH (rs129882, rs1611114, rs1611115) and NET (rs2242446, rs28386840) gene polymorphisms between panic disorder group and control group(all P>0.05). Conclusion:The present study indicates that there is no significant association of DβH and NET gene polymorphisms with PD.

Primary biliary cholangitis (PBC) is an autoimmune disease. Although PBC has the features of autoimmune disease, it has poor response to immunosuppressants and good response to the drugs participating in bile acid metabolism, such as ursodeoxycholic acid. Studies have shown that the bicarbonate secretion of biliary epithelial cells is impaired in PBC patients, and bile acid not blocked by HCO3- umbrella enters biliary epithelial cells and mediates their damage and apoptosis, leading to the expression of autoantibodies in apoptotic cells and immunologic injury. In order to explore the role of HCO3- umbrella secreted by biliary epithelial cells in the pathogenesis of PBC, this article briefly introduces the physiological function and production mechanism of HCO3- umbrella and the influencing factors for HCO3- secretion, and it is pointed out that reduced HCO3- secretion may be a key link in the pathogenesis of PBC and a potential therapeutic target.

Objective:To investigate the efficacy and safety of dexmedetomidine in noninvasive continuous positive airway pressure(NCPAP)for acute respiratory failure in children.Methods:Clinical data of children with acute respiratory failure who underwent NCPAP from January 2018 to March 2020 in PICU of Hunan Children′s Hospital were prospectively collected.They were randomly divided into dexmedetomidine group(group D)and midazolam group(group M), with a total of 100 children.We compared the sedation depth of the two groups at 7 time points after sedation at 0.5 h(t1), 1 h(t2), 2 h(t3), 6 h(t4), 12 h(t5), 24 h(t6), and 48 h(t7), time to reach proper sedation, NCPAP time, NCPAP failure rate, oxygenation index(P/F value)before sedation(T0)and 1h(T1), 24h(T2), and 48h(T3)after sedation, and the main vital signs and adverse reactions before sedation(T0)and 1h(T1), 24h(T2), 48h(T3)after sedation.Results:(1)The proportion of proper sedation at T4, T5, T6 and T7 after sedation in group D was higher than that in group M[98%(49/50)vs.84%(42/50), 94%(47/50)vs.90%(45/50), 96%(48/50)vs.88%(44/50), 90%(45/50)vs.88%(44/50), χ2=6.538, 8.043, 8.174, 7.678, all P<0.05]. Time to reach proper sedation in group D was shorter[(58.6±7.9)s vs.(66.7±9.3)s, t=4.682, P<0.01]. (2)The treatment time and failure rate of NCPAP in group D were lower than those in group M[(134.9±25.5)h vs.(147.8±24.3)h, 10%(5/50)vs.28%(14/50), all P<0.05]. P/F after NCPAP treatment in the two groups was improved as compared with that before treatment(all P<0.01), and the improvement was more significant in group D than in group M at T2 and T3 after sedation[(199.3±26.1)vs.(188.5±24.2)mmHg, (212.2±25.4)mmHg vs.(200.8±24.8)mmHg, t=2.132, 2.278, all P<0.05]. (3)There were no significant differences in heart rate(HR), mean arterial pressure(MAP), and respiratory rate(RR)before sedation between the two groups(all P>0.05). HR and RR after sedation in both groups decreased as compared with those before sedation( P<0.01). HR at T1, T2, and T3 after sedation in group D decreased more significantly than that in group M[(116.3±17.6)bpm vs.(124.8±14.1)bpm, (110.2±18.4)bpm vs.(121.9±15.2)bpm, (108.5±18.7)bpm vs.(117.6±12.8)bpm, t=0.479, -3.474, -2.840, all P<0.05]. There was no significant difference in RR after sedation between the two groups( t=1.872, 1.632, 1.675, all P>0.05). MAP at T1 in group D decreased as compared with T0( P<0.01). MAP at T1 in group D was lower than that in group M[(65.5±5.1)mmHg vs.(68.0±5.7)mmHg, t=-2.297, P=0.024]. (4)There was no significant difference in the incidence of total adverse reactions between the two groups[20%(10/50)vs.14%(7/50), P=0.595]. The incidence of bradycardia was higher in group D than in group M[16%(8/50)vs.2%(1/50), P=0.031]. Conclusion:The incidence of adverse reactions of dexmedetomidine and midazolam in the sedation of NCPAP in children with acute respiratory failure is similar, but the sedative effect of dexmedetomidine is better than that of midazolam in the improvement of pulmonary oxygenation.

Objective:To investigate the effect of the timing of continuous renal replacement therapy (CRRT) administration on the prognosis of acute kidney injury (AKI) in children.Methods:The medical records of children with AKI who were admitted to the Intensive Care Unit of Hunan Children′s Hospital from March 2015 to February 2020 and underwent CRRT were prospectively analyzed.The children who met the criteria were divided into early group (defined as AKI 1 and 2) and delayed group (defined as AKI 3) according to AKI stage.The general conditions, indicators when CRRT was initiated, and prognosis of the children in two groups were recorded.Results:(1) A total of 39 children were included in the study, including 23 in the early group and 16 in the delayed group.There were no significant differences in age, gender, body weight and proportion of mechanical ventilation between two groups ( P>0.05). The score of critical cases in the early group was higher than that in the delayed group ( P=0.008). (2) There were no significant differences in serum potassium and bicarbonate when CRRT was initiated between two groups ( P>0.05). The urine output in the early group was higher than that in the delayed group ( P>0.001). The serum creatinine and urea nitrogen in the early group were lower than those in the delayed group ( P>0.05). (3) The 28-day survival rate and proportion of renal function recovery at 28 days in the early group were significantly higher than those in the delayed group ( P>0.05). The duration of CRRT, ICU stay and duration of mechanical ventilation in the early group were shorter than those in the delayed group ( P>0.05). Conclusion:Early initiation of CRRT at AKI stage 1 and 2 can improve the 28-day survival rate and renal function recovery of survivors when critically ill children are complicated with AKI.

Objective:To compare the four nucleic acid detection method of hepatitis A virus.Methods:Using method A, B, and C real-time fluorescent quantitative RT-PCR(RT-qPCR)and method D droplet chip digital PCR(RT-dPCR)to detect the sensitivity of HAV plasmid and gradient dilution HAV vaccine respectively. Specific detection of related viral nucleic acid was performed. Methods A, B, and C were used to detect 40 artificially contaminated HAV oysters, commercially available oysters and serum samples, and HAV vaccine samples, and compare the detection rates. The recovery rates of method A and D on artificially contaminated oysters were compared with low concentration of HAV.Results:Both method A and B could detect HAV plasmids up to 10 copies/μL. In the detection of HAV vaccine with gradient dilution, the slope, R 2 value and amplification efficiency of method A, B, and C were all within the acceptable range (-3.446~-3.297, 0.991-0.998, -95.07%-101.051%). For 40 specimens from different sources, the positive detection rates of method A, B, and C were 50% (20/40), 47.5% (19/40), 55% (22/40), and the difference was not statistically significant ( χ2=0.467, P=0.792). Methods A and D have no significant difference in the detection sensitivity of gradient dilution vaccines. For the detection of artificially contaminated oysters with low concentration of HAV, the recovery rate of method D was higher than that of method A, but the difference was not statistically significant (F=0.294, P=0.642). Conclusions:There is no significant difference between method A, B, and C, which is more convenient and fast. When detecting low concentrations of HAV in food, Methods D had a slight advantage, but the detection cost is slightly higher. The detection method can be selected according to the actual situation.