Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Objective To explore the role of β-1,3-galactosyltransferase 2(B3galt2)in mice with cerebral ischemic injury.Methods Adult male C57BL/6J mice were randomly divided into the sham,suture-occluded middle cerebral artery occlusion(MCAO)model,MCAO model+lentiviral vector control(LV-GFP),and MCAO model+lentiviral vector overexpression B3galt2(LV-B3galt2)groups,with six mice in each group.Neurological deficit scoring and rotating rod experiments were performed 24 h after ischemia in each group,and 2,3,5-triphenyltetrazolium chloride(TTC)staining was used to determine the infarction volume.The number of neurons in the ischemic cerebral cortex was determined in each group using Nissl staining.The levels of oxidative stress-related factors in the brain tissues were detected using the relevant kits.Results Compared with the sham group,the MCAO model group showed increased infarct volume and neurological deficits(P<0.05),significantly decreased number of neurons in the ischemic cerebral cortex and levels of super-oxide dismutase(SOD)and glutathione peroxidase(GSH)(all P<0.05),and significantly increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA)(all P<0.05).Compared with the MCAO model group,the LV-B3galt2 group had reduced volume of cerebral infarction,significantly improved neurological deficits(all P<0.05),significantly increased number of neurons in the ischemic cerebral cortex of mice,significantly decreased levels of ROS and MDA(P<0.05),and significantly elevated levels of SOD and GSH(all P<0.05).Conclusion B3galt2 overexpression can reduce brain injury in an ischemic damage mouse model,and its mechanism may be through the inhibition of oxidative stress reactions.

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (r_s=0.333, P=0.024). CONCLUSIONS JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.
Humans ; Child ; Hypoxia-Inducible Factor 1, alpha Subunit ; Prognosis ; Hypoxia ; Lymphoma, Non-Hodgkin

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

Objective: To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating. Materials and Methods: Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland–Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate. Results: LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480). Conclusion Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.
Carcinoma, Squamous Cell/therapy* ; Chemoradiotherapy ; Humans ; Quality of Life ; Retrospective Studies ; Tonsillar Neoplasms/therapy*

ObjectiveTo investigate the effect of Loki Zupa on airway remodeling in asthma based on ultra-performance liquid chromatography-tandem mass spectrometry（UPLC-MS）combined with network pharmacology and experimental verification. MethodThe chemical constituents in Loki Zupa were identified by UPLC-MS. The potential active constituents of Loki Zupa were screened out based on literature retrieval， oral availability （OB） and drug-likeness （DL） in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and Lipinski's rule of five in SwissADEM. The constituent targets of Loki Zupa were obtained through the SwissTargetPrediction. The relevant targets of airway remodeling in asthma were screened out from Online Mendelian Inheritance in Man（OMIM）， GeneCards， DrugBank， and DisGeNET. The STRING was used to conduct protein-protein interaction （PPI） among the main targets. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses were carried out through DAVID. Finally， an asthmatic airway remodeling model was induced by ovalbumin （OVA） in mice， followed by hematoxylin and eosin（HE）， periodic acid Schiff（PAS）， and Masson staining for the observation of the pathological conditions of lung tissues. The inflammatory cells in the bronchoalveolar lavage fluid（BALF） of mice were detected. The protein expression levels in mouse lung tissues were detected by Western blot and key signaling pathways were further determined. ResultEighty-two constituents were detected in the negative ion mode and 74 in the positive ion mode by UPLC-MS. Thirty-six candidate constituents and 578 predicted targets of Loki Zupa were screened out through network pharmacology， and 173 common targets with airway remodeling in asthma were obtained， including key compounds such as sebacic acid， pectolinarigenin， naringenin， apigenin， and potential targets such as protein kinase B1（Akt）1 and hypoxia-inducible factor 1α（HIF-1α）. As predicted by KEGG enrichment analysis， Loki Zupa mainly exerted the effect against airway remodeling in asthma through phosphatidylinositol 3-kinase （PI3K）/Akt， HIF-1α， mitogen-activated protein kinase （MAPK）， and other signaling pathways. Animal experiments showed that the compound formula of Loki Zupa could reduce the proliferation of airway goblet cells in asthmatic mice， improve the deposition of collagen under the airway epithelium， and decrease the up-regulated relative expression levels of phosphorylate（p）-Akt/Akt and HIF-1α by OVA sensitization in mice （P<0.05， P<0.01）， which was consistent with the results of network pharmacology. ConclusionUPLC-MS combined with network pharmacology was used to preliminarily clarify the chemical composition of Loki Zupa and its underlying mechanism in intervention in airway remodeling in asthma. Specifically， Loki Zupa presumably synergistically intervened in airway remodeling in asthma through key targets represented by Akt1 and HIF-1α， and multiple pathways represented by the PI3K/Akt and HIF-lα pathways， which is expected to provide ideas for further research on Loki Zupa.

Objective:To investigate the influencing factors of post-dialysis hypertension in maintenance hemodialysis (MHD) patients.Methods:This study was a cross-sectional and retrospective study. The patients receiving hemodialysis from January 9, 2017 to January 14, 2017 in 5 hemodialysis centers of Beijing area were selected. Post-dialysis hypertension was defined as an event characterized by an average increase of more than 15 mmHg in post-dialysis mean artery pressure (MAP) compared to intradialytic 3 h MAP during 3 consecutive hemodialysis sessions. Post-dialysis stable blood pressure was defined as an event characterized by an increase of less than 15 mmHg or a decrease of less than 10 mmHg in post-dialysis MAP compared to intradialytic 3 h MAP, with the exception of patients with post-dialysis hypertension and post-dialysis hypotension. The patients were divided into hypertension group and stable blood pressure group based on whether they had post-dialysis hypertension, and the differences of clinical data between the two groups were compared. The influencing factors of post-dialysis hypertension were analyzed by multivariate unconditional logistic regression.Results:A total of 491 MHD patients were enrolled in this study, including 65 patients (13.2%) in the hypertension group, 406 patients (82.7%) in the stable blood pressure group and 20 patients (4.1%) in the hypotension group. The age, blood calcium before dialysis and the proportion of patients using 1.75 mmol/L Ca 2+ dialysate in the hypertension group were higher than those of the stable blood pressure group, and pre-dialysis serum intact parathyroid hormone and pre-dialysis serum uric acid in the post hypertension group were lower than those of the stable blood pressure group (all P<0.05). The age, pre-dialysis serum intact parathyroid hormone, pre-dialysis serum calcium, pre-dialysis serum uric acid, dialysate Ca 2+ concentration of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and post-dialysis serum calcium, pre-dialysis total serum cholesterol, application of β receptor blocker, gender of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. Multivariate logistic regression analysis showed that using 1.75 mmol/L Ca 2+ dialysate was the independent influencing factor of post-dialysis hypertension (with using 1.50 mmol/L Ca 2+ dialysate as reference, OR=2.930, 95% CI 1.282-6.694, P=0.011). The age and pre-dialysis serum calcium of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and pre-dialysis serum sodium and pre-dialysis serum uric acid of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. The older age ( OR=1.046, 95% CI 1.000-1.093, P=0.049) and higher pre-dialysis serum calcium ( OR=21.847, 95% CI 2.111-226.075, P=0.010) were the independent influencing factors of post-dialysis hypertension when the 1.50 mmol/L Ca 2+ dialysate was used. Conclusions:The independent influencing factor of post-dialysis hypertension is using 1.75 mmol/L Ca 2+ dialysate, while the independent influencing factors of post-dialysis hypertension are the older age and the higher pre-dialysis serum calcium level when the dialysate Ca 2+ concentration was 1.50 mmol/L.