ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.

ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction （补中愈淋汤） in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli （UPEC） strain UTI89 by bladder perfusion， and the successful mouse models were randomly divided into a model group， an antibiotic group， and a low- and high-dose Buzhong Yulin Decoction group， with six mice in each group. In addition， 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage， with concentrations of 1.3 g/ml and 5.2 g/ml， respectively； the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage； the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks， the number of central urine marks， and the total urine volume of the urine marks were observed by the urine marking test； HE staining was used to observe the histopathological changes in the bladder of mice； serum levels of the inflammatory factors interleukin 1β （IL-1β）， interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） were detected by ELISA； the morphology of the epithelial cells of bladder was observed by scanning electron microscopy； immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load； the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells； RT-PCR method to detect Ras-related protein Rab-11A （RAB11A） and Ras-related protein Rab-27B （RAB27B） mRNA level in bladder tissue； immunoblotting to detect microtubule-associated protein 1 light chain3 （LC3） and P62 protein levels in bladder tissue. ResultsCompared with the blank group， the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group； bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced， the total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and LC3 and P62 protein levels in bladder tissue all elevated （P＜0.05 or P＜0.01）. Compared with the model group， the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups； the average surface area of bladder epithelial cells reduced， the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated， and total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and P62 protein levels in bladder tissue all reduced （P＜0.05 or P＜0.01）， but LC3 protein levels showed no statistically significant （P＞0.05）. In the antibiotic group， the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group， the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups， the bacterial load of the bladder epithelial cells decreased， and the P62 protein level of the bladder tissue decreased （P＜0.05）. When comparing between the low- and high-dose Buzhong Yulin Decoction groups， the differences in each index were not statistically significant （P＞0.05）. ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier， increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues， thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells.

Objective:To analyze the trends in refractive error and ocular biological parameters in elementary school students over 5 years, and to investigate the patterns of change before and after myopia onset.Methods:A cohort study was adopted.A total of 1 986 first-grade students from the Anyang Childhood Eye Study were enrolled in this cohort study and their right eye data were taken for analysis, including 1 126 boys and 860 girls.Every year, cycloplegic autorefraction was performed with 1% cyclopentolate eyedrops to obtain the spherical equivalent (SE).The axial length (AL), anterior chamber depth, lens thickness, mean corneal curvature (Km) and other parameters were obtained by ocular biometry.The lens refractive power (LP) was calculated using the Bennett formula.The subjects were assigned to persistent myopia group, non-myopia group and new onset myopia group.According to the age of myopia onset, the new onset myopia group was subdivided into the 8-, 9-, 10-, 11- and 12-year-old myopia groups to compare the differences in refractive error and ocular bioparameters among groups at different time points of follow-up.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2018-030).Written informed consent form was obtained from the guardians of each subject.Results:All children had a gradual SE drift toward myopia and a gradual increase in the AL with age, and there were significant differences in SE and AL between adjacent follow-up ages within the three groups (all at P<0.05).The earlier the onset of myopia, the higher the myopia SE and the longer the AL of the eye at the same follow-up age, the differences in SE between adjacent groups were statistically significant (all at P<0.05), and the differences in AL between adjacent groups at the follow-up age of 8 to 12 years were statistically significant (all at P<0.05).In the nonmyopia group, SE drifted toward emmetropia at a slow and steady rate of (-0.23±0.27)D/year, and AL also increased slowly and steadily at (0.18±0.13)mm/year.In the new onset myopia group, the changes in SE in the third, second, and first years before myopia onset were (-0.32±0.25), (-0.45±0.33), and (-0.98±0.44)D, and the increases in AL were (0.25±0.12), (0.32±0.15), and (0.48±0.19)mm, respectively.Both SE and AL change rates began to accelerate before myopia onset and slowed down after myopia onset, with statistically significant differences in the overall comparison of SE and AL change rates at different time intervals before and after myopia onset (all at P<0.001).The AL at myopia onset in boys was (24.11±0.70)mm, which was longer than (23.60±0.66)mm in girls ( t=159.71, P<0.01).LP decreased with age in all groups, with a faster rate before the age of 9 years and a slower rate after the age of 9 years.The mean decrease rate in LP was (-0.48±0.19), (-0.44±0.20), (-0.49±0.16), (-0.51±0.18), and (-0.48±0.19)D/year in the persistent myopia group and 8~11-year-old myopia group, respectively, which were significantly faster than -0.42±0.17 D/year in 12-year-old myopia group and (0.37±0.15)D/year in nonmyopia group (all at P<0.05).There was no statistically significant difference in Km among groups at different follow-up ages (all at P>0.05). Conclusions:The AL begins to grow at an accelerated rate 3 years before myopia onset, and the increase rate of the AL slows down after the onset of myopia, but it is still significantly faster than that of non-myopic children.In this process, the decrease in LP plays a compensatory role; there is no significant change in corneal curvature.The AL of males at the onset of myopia is longer than that of females at the same age.AL is an important indicator for the prevention and control of myopia.It is important to consider gender differences and to pay more attention to the growth rate when assessing AL.

Objective To establish a method for measurement of ²³⁹Pu in fecal samples based on inductively coupled plasma-mass spectrometry (ICP-MS), and to provide a novel method for assessing the internal exposure of workers. Methods Fecal samples were collected from workers and labeled. The samples were pretreated with carbonization ashing and microwave digestion devices, purified on TEVA resin, and measured using ICP-MS. Results The detection limit of ²³⁹Pu in fecal samples based on ICP-MS was 1.91 × 10⁻⁴ Bq. Conclusion In the routine monitoring of class S substances characterized by a 5 μm aerodynamic diameter during 12 months, the committed effective dose corresponding to the detection limit is 0.17 mSv. This value meets the requirements of relevant national standards and ICP-MS can be used as a novel means for accurate evaluation of internal exposure for workers.

Objective:To construct a quality evaluation index system for postoperative rehabilitation in children with developmental dislocation of the hip (DDH) .Methods:From August to November 2021, a quality evaluation index system for postoperative rehabilitation in children with DDH was established through literature review, group discussion, and Delphi expert consultation. The analytic hierarchy process was used to determine the weights of various indicators. The positive coefficient of experts was expressed by the effective response rate of the questionnaire. The authority level of experts was represented by the authority coefficient ( Cr) , which was determined by the expert judgment coefficient ( Ca) and the expert familiarity level ( Cs) . The degree of coordination of expert opinions was represented by the Kendall harmony coefficient (Kendall's W) . The degree of concentration of expert opinions was represented by the average score of importance assignment, coefficient of variation, and full score rate. Results:The effective response rates of the two rounds of expert consultation questionnaires were 90.00% and 100.00%, respectively. The Cr of experts in two rounds were 0.785 and 0.815, and the Kendall harmony coefficients were 0.098-0.193 and 0.147-0.212 ( P<0.05) . In the second round of expert consultation, the average scores of importance assignment for all levels of indicators were≥4.0, with coefficients of variation of 0-0.24 and a full score rate of ≥50%. The final quality evaluation index system for postoperative rehabilitation in children with DDH included 3 first-level indicators, 9 second-level indicators, and 37 third-level indicators. In the consistency test results of each indicator at all levels, all of the CI were <0.001, and all of the CR were<0.001. Conclusions:The construction process of the quality evaluation index system for postoperative rehabilitation in children with DDH is scientific, and the weight distribution of the indicators is reasonable, which can be used as an effective tool for evaluating the postoperative rehabilitation quality of DDH children.

Objective To preliminarily study and establish a method for measurement of the transuranic nuclide ²⁴¹Am in fecal samples, and to provide technical support for internal radiation monitoring of staff. Methods Fecal samples were collected with a self-made stool sampler and treated with a self-made carbonization and ashing furnace. DGA resin was used to separate and purify ²⁴¹Am from fecal samples. With ²⁴³Am as the tracer, the orthogonal method was used for condition optimization. Results The optimum conditions for separation and purification were: the acidity of HNO₃ added into the column, 6 mol/L; column flow rate, 0.6 mL/min; and the volume of analytical solution,12 mL. The method based on inductively coupled plasma mass spectrometry showed a detection limit of 9.79×10⁻⁴ Bq for ²⁴¹Am in fecal samples, which was satisfactory and feasible. Conclusion This method fills the vacancy of ²⁴¹Am measurement in fecal samples to some extent, which is of practical significance for internal radiation monitoring and protection for analysts.

Chemical constituents from the air dried parts of Cichorium glandulosum were studied. The chemical constituents of C. glandulosum were separated and purified by means of silica gel, Sephadex-LH 20, ODS column chromatography and semi-preparative high performance liquid chromatography. The structure was elucidated by physicochemical characteristics and spectral data. One new flavonoid glycoside was isolated from C. glandulosum, and identified as quercetin-3-O-［6″-O-(3-ethoxy-1, 3-dioxopropyl)］-β-D-glucopyranoside(1).

Objective To investigate the effect of U50488H on the ultrastructure and organ function in septic shock rats. Methods Forty SD male rats were randomly(random number) divided into 5 groups: sham group, septic shock group, U50488H+septic shock group, nor-BNI+U50488H+septic shock group, and nor-BNI+septic shock group, with 8 rats in each group. Cecal ligation and puncture (CLP) was performed to induce septic shock in the septic shock group. Rats in the U50488H+septic shock group were treated with U50488H injection by intravenous at the shock point, and other procedures were the same as the septic shock group. Rats in the nor-BNI+U50488H+septic shock group were treated with nor-BNI injection by intravenous 3.5 h after abdomen closed, and other procedures were the same as the U50488H+septic shock group. Except for U50488H injection, rats in the nor-BNI+septic shock group received procedures the same as the nor-BNI+U50488H+septic shock group. Albumin, cardiac troponin I (cTnI) and N terminal pro B type natriuretic peptide (NT-proBNP) in serum were measured at abdomen-closed, 3, 6, and 12 h after CLP. The changes of histology and ultramicro structure under electron microscope of lung, heart, liver and kidney of rats were observed at 12 h after CLP. Statistical analysis was performed using SPSS 19.0. Comparison among groups was carried out using ANOVA, and Student's t-test was used for multiple comparisons as post-hoc. Results At 6 and 12 h of CLP, serum albumin of the septic shock group were significantly lower than those of the sham group (P<0.01), while those in the cTnI and NT-pro BNP groups were higher at 3, 6, and 12 h of CLP (P<0.01). Compared with the septic shock group, serum albumin of the U50488H+septic shock group increased significantly (P<0.01), whereas the serum levels of cTnI and NT-pro BNP decreased remarkably at 3, 6 and 12 h of CLP (P < 0.05, P < 0.01, respectively). Compared with the sham group, the alveolar wall was severely damaged, the alveolar septum and blood vessel wall were thickened obviously; the myocardial fiber was swollen, necrotic, and the infiltration of central granulocyte was increased significantly; hepatocyte showed edema, vacuolar-like steatosis, fatty degeneration, spotty and focal necrosis; and slight edema and vacuolar degeneration were found in the glomerulus endothelial in the septic shock group. Compared with the septic shock group, the ultrastructural damage of the lung, heart, liver and kidney of the U50488H+ septic shock group was significantly improved. All the above effects of U50488H could be blocked by nor-BNI (a selective κ-opioid receptor antagonist) (P<0.01). Conclusions U50488H can promote the recovery of serum albumin, and protect organ function in septic shock rats.

Objective To study the effects of concentration of glucose on the proliferation of bone marrow mesenchymal stem cells (BMMSCs).Methods BMMSCs passaged to the 4th to 6th were inoculated and cultured.The control group was treated with DMEM/F12 (1∶1) standard medium,and the basal glucose concentration was 5.5 mmol/L.The experimental group was treated with DMEM/F12 (1∶1) high-glucose medium with the concentration of 20.5,25.5,30.5 and 35.5 mmol/L respectively,and continuously cultured for 15 d.The absorbance (A) values of each group once per day were measured by thiazolyl blue (MTT) colorimetry.Results Compared with the control group,the absorbance was increased at the 2nd,3rd,and 5th days in the 20.5 and 30.5 mmol/L groups,and the differences were statistically significant (all P＜0.05).For the 25.5 mmol/L group,the absorbance was increased at the 2nd,3rd,5th and 8th days,and the differences were statistically significant (all P＜0.05).For the 35.5 mmol/L group,the absorbance was increased at the 2nd,3rd,5th and 8th days and decreased at the 8th day,and the differences were statistically significant (all P＜0.05).The results of 20.5,25.5,30.5 and 35.5 mmol/L groups were further compared one another.The results showed that the absorbance at the 4th and 12th days in the 35.5 mmol/L group were lower than that of the 20.5 mmol/L group,and the differences were statistically significant (all P＜0.05).The absorbance at the 11th and 14th days in the 30.5 and 35.5 mmol/L groups were lower than that of the 20.5 mmol/L group,and the differences were statistically significant (all P＜0.05).Conclusions High-glucose environment can promote the proliferation of BMMSCs in a short time.However,with the prolongation of culture time,this effect is gradually weakened because of the inhibiting effect of high-glucose environment to the cell proliferation.