OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

Objective To explore the application value of multi-slice spiral CT(MSCT)multi-planar reconstruction(MPR)technology for CT-guided puncture biopsy of pancreatic lesions.Methods A total of 104 patients with isolated pancreatic lesions who underwent CT-guided puncture biopsy were retrospectively enrolled,including 49 cases underwent MSCT-MPR assisted guided biopsy(MPR group)and 55 underwent MSCT-guided biopsy alone(non-MPR group).The success rate of puncture biopsy,the operating time,the times of needle adjustments,radiation dose-length product(DLP)and relative complications were recorded.Based on surgical pathology or follow-up(≥12 months)results,the sensitivity of biopsy was calculated.Results The success rate of one-time puncture was 100％in both groups.No significant difference of operating time was found between MPR([15.96±4.73]min)and non-MPR group([16.22±5.76]min,t=-0.250,P=0.803).MPR group had fewer times of needle adjustments([6.53±1.24]vs.[8.15±1.90],t=-5.201,P＜0.001)and lower DLP([946.02±143.54]mGy·cm vs.[1 095.53±338.50]mGy·cm,t=-2.988,P=0.004)than non-MPR group.During biopsy,minor bleeding occurred in 1 case of MPR group and 5 of non-MPR group,then all spontaneously improved without special treatment.The diagnostic sensitivity of biopsy pathology was 95.56％(43/45)in MPR group and 92.16％(47/51)in non-MPR group.Conclusion MSCT-MPR technology could improve the accuracy of CT-guided puncture biopsy of pancreatic lesions and reduce radiation dose.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

Objective To explore the application value of multi-slice spiral CT(MSCT)multi-planar reconstruction(MPR)technology for CT-guided puncture biopsy of pancreatic lesions.Methods A total of 104 patients with isolated pancreatic lesions who underwent CT-guided puncture biopsy were retrospectively enrolled,including 49 cases underwent MSCT-MPR assisted guided biopsy(MPR group)and 55 underwent MSCT-guided biopsy alone(non-MPR group).The success rate of puncture biopsy,the operating time,the times of needle adjustments,radiation dose-length product(DLP)and relative complications were recorded.Based on surgical pathology or follow-up(≥12 months)results,the sensitivity of biopsy was calculated.Results The success rate of one-time puncture was 100％in both groups.No significant difference of operating time was found between MPR([15.96±4.73]min)and non-MPR group([16.22±5.76]min,t=-0.250,P=0.803).MPR group had fewer times of needle adjustments([6.53±1.24]vs.[8.15±1.90],t=-5.201,P＜0.001)and lower DLP([946.02±143.54]mGy·cm vs.[1 095.53±338.50]mGy·cm,t=-2.988,P=0.004)than non-MPR group.During biopsy,minor bleeding occurred in 1 case of MPR group and 5 of non-MPR group,then all spontaneously improved without special treatment.The diagnostic sensitivity of biopsy pathology was 95.56％(43/45)in MPR group and 92.16％(47/51)in non-MPR group.Conclusion MSCT-MPR technology could improve the accuracy of CT-guided puncture biopsy of pancreatic lesions and reduce radiation dose.

Objective:To identify the causative gene in patients with familial progressive hyperpigmentation (FPH) .Methods:Two families with FPH were collected in March 2005 and March 2015 respectively, and their phenotypes were observed and recorded. The causative gene was investigated by single nucleotide polymorphism (SNP) -based genome-wide linkage analysis and exome sequencing, and verified by Sanger sequencing. The candidate gene expression was determined in FPH lesions and normal skin tissues by using immunohistochemical techniques.Results:The genome-wide linkage analysis showed that the causative gene in FPH family 1 was mapped to the loci of rs1026369-rs11857925 on chromosome 15q21.1 - q22.2; a disintegrin and metalloproteinase 10 (ADAM10) gene was identified as the possible causative gene by exome sequencing; Sanger sequencing showed that a splice-site mutation c.1511+1G>A in the ADAM10 gene was co-segregated with the disease phenotype in the FPH family 1. Immunohistochemical staining demonstrated that ADAM10 was expressed in both the FPH lesions and normal skin tissues of the proband in the FPH family 1. A missense mutation c.1172C>T (p.Ser319Phe) was identified by further ADAM10 mutation analysis in another 3-generation family with FPH (family 2). Both the above mutations were not detected in 300 local healthy controls.Conclusion:ADAM10 was identified as a novel causative gene responsible for FPH.

【Objective】 To establish an enzyme-linked immunosorbent assay (ELISA) method for the determination of residual human coagulation factor Ⅺ in human prothrombin complex and validate the method. 【Methods】 Human factor Ⅺ was reacted with the capture antibody coated on the microtiter plate. After appropriate washing steps, biotinylated primary antibody was bound to the captured protein. Excess primary antibody was washed away and bound antibody was reacted with horseradish peroxidase conjugated streptavidin. TMB substrate was used for color development at 450 nm. The dilution reliability, accuracy, specificity, repeatability, intermediate precision, linearity, range and durability were verified. 【Results】 The verification results showed that the accuracy and specificity of this method met the experimental requirements, with an average recovery rate of 109.2% and RSD of 6.93%. The repeatability RSD was 6.78%, and the intermediate precision RSD was 6.75%, indicating good precision. The linear regression correlation coefficient of standard curve was 0.999 9, showing good accuracy and precision within the linear range. The durability was verified by the incubation time and the validity period of reagent kit opening. The results showed that the RSD of the incubation time change was 6.62%, indicating that the incubation time of this detection method was controlled between 28 to 32 minutes, and there was no significant impact on the results. The RSD of the detection results before and after the reagent kit was opened and stored under conditions for 7 days was 3.84%, indicating that the preservation of the reagent kit according to the conditions for 7 days after opening has no effect on the FⅪ detection results. Both indicated that the method had good durability. The dilution reliability results showed that there was a "hook" effect in the detection of FⅪ residue in human prothrombin complex, which could be solved by diluting 100 to 200 times. 【Conclusion】 This method can be used for the determination of FⅪ residues of human prothrombin complex in laboratory.

Humans ; Hypopigmentation ; RNA, Long Noncoding/genetics* ; Vitiligo/genetics*

Objective:To investigate the role of miRNA-181 targeting phosphatase and tensin homologue deleted on chromosome ten (PTEN) in regulating phosphatidylinositol-3-kinase/Akt signaling pathway (PI3K/Akt) signaling pathway in renal injury of hyperuricemia rats.Methods:Forty male Wistar rats were randomly divided into control group, model group, negative control group and miRNA-181 inhibition group. Their serum uric acid, creatinine and urea nitrogen were tested. HE staining was used to observe the renal histopathological changes in each group. The expression of miRNA-181, PTEN, PI3K and Akt mRNA in renal tissue of rats in each group was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Western blotting analysis of PTEN, PI3K, Akt and p-Akt protein expression in renal tissue of rats in each group. The targeting relationship between miRNA-181 and PTEN was confirmed by double luciferase reporter gene experiment. One-way analysis of variance (ANOVA) was used for the comparison between multiple groups, with the same variance. LSD- t test was used for further comparison between the two groups. If the variance was not the same, Tamhane's T2 test was used for further comparison between the two groups. Independent sample t-test was used to compare between the two groups. Results:Compared with the control group (135±21) mmol/L; (27.8±2.1) μmol/L; (6.8±0.5) μmol/L, the contents of uric acid [(213±28) mmol/L, (214±23) mmol/L, creatinine (49.2±2.3) μmol/L, (48.6±2.2) μmol/L and urea nitrogen (11.5±2.7) μmol/L; (11.7±2.5) μmol/L] in the model group and the negative control group were significantly increased ( Furic acid=26.739, Fcreatinine=259.055, Furea nitrogen=12.921, all P<0.05); compared with the nega-tive control group, the contents of uric acid (169±21) mmol/L, creatinine (33.7±1.8) μmol/L and urea nitrogen (9.1±1.7) μmol/L in the miRNA-181 inhibition group were decreased (LSD- turic acid=4.356, LSD- tcreatinine=15.773, LSD- turea nitrogen=2.858, all P<0.05). The expression level of miRNA-181 in renal tissue of the model group and the negative control group (1.88±0.16, 1.84±0.18) was significantly higher than that of the control group (0.53±0.08) ( F=193.554, P<0.05), while the expression level of PTEN protein (0.18±0.02, 0.16±0.02) and mRNA (0.48±0.08, 0.44±0.07) were lower than that of the control group (1.27±0.06, 1.27±0.16) ( Fprotein=515.116, FmRNA=141.470, all P<0.05) ); after inhibiting miRNA-181, the expression level of miRNA-181 (1.35±0.58) in renal tissue increased significantly (LSD- t=10.341, P<0.05), and the expression level of PTEN protein (0.84±0.05) and mRNA (0.90±0.08) increased on average (LSD- tprotein=20.471, Tamhane's T2 mRNA=13.881, all P<0.05). The results of double luciferase reporter gene analysis showed that PTEN was the target gene of miRNA-181. Compared with the control group (0.18±0.02, 0.09±0.01, 0.05±0.02, 1.06±0.07, 0.96±0.06), the expression level of PI3K (1.01±0.06, 1.00±0.06), Akt (0.90±0.05, 0.95±0.04), p-Akt protein (0.99±0.07, 0.97±0.05) and the expression level of PI3K (3.63±0.18, 3.68±0.22), Akt mRNA (2.38±0.05, 2.34±0.12) in the renal tissue of the model group and the negative control group were significantly increased ( FPI3K protein=169.979, FAkt protein=393.411, Fp-Akt protein=164.201, FPI3K mRNA=563.944, FAkt mRNA=141.470, all P<0.05); after inhibiting the expression of miRNA-181, the expression level of PI3K (0.69±0.06), Akt (0.42±0.03), p-Akt protein (0.50±0.05) and the expression level of PI3K (2.40±0.09), Akt mRNA (1.40±0.12) in the renal tissue of the rats were decreased (LSD- tPI3K protein=7.432, LSD- tAkt protein=18.291, LSD- tp-Akt protein=9.595, Tamhane's T2 PI3K mRNA=17.070, Tamhane's T2 Akt mRNA=17.357, all P<0.05). Conclusion:Inhibition of miRNA-181 expression can target PTEN to inhibit PI3K / Akt signaling pathway to protect renal injury in hyperuricemia rats.

Objective To investigate the clinical significance of restrictive foramen ovale ( RFO ) monitored by fetal echocardiography during the middle to late stage of pregnancy . Methods The detection rate ,echocardiographic features and outcome in fetuses with RFO without cardiac malformations from 7319 pregnant women received prenatal echocardiography were retrospectively reviewed and analyzed . Results RFO was found in 40 of 7319 (0 .55％ ) fetuses . The inclusion criteria including a narrow right to left shunt of less than 2 .5 mm in diameter across atrial septum , enlarged right atrium , increased right-to-left ventricular size ratio ,and increased size ratio of main pulmonary artery to aorta were present in 40 fetuses . The direct ultrasound characters of RFO included limited opening of oval valve ( 70％ ) and foramen ovale diameter less than 2 .5 mm (30％ ) . And atrial septal aneurysm ( 62 .5％ ) ,redundant primum atrial septum (57 .5％ ) ,abnormal ductus arteriosus ( 57 .5％ ) might also be present commonly in RFO . As the gestational weeks increased , the size ratio of right-to-left atrium , right-to-left ventricle and the main pulmonary artery to aorta also increased significantly( P =0 .004 , P <0 .001 , P <0 .001) . Among the 40 fetuses with RFO ,21 cases ( 52 .5％ ) gave birth in full term ,8 cases ( 20％ ) which were detected severe tricuspid regurgitation gave birth in early cesarean section ,5 cases ( 12 .5％ ) had induced labor and 6 cases (15％ ) were lost in the follow-up . Of the 29 newborns ,only 1 case died of heart failure ,and the other 28 subjects recovered both from heart structure or cardiac function within four months . Conclusions RFOwithout cardiac malformations presents echocardiographic features characterized by a narrow right to left shunt of less than 2 .5 mm in diameter across atrial septum . Fetal echocardiography can monitor the dynamic change of fetal heart structure and function based on the increase of right heart load and decrease of left heart volume ,which has important clinical significance for assessing fetal intrauterine condition and prognosis .