Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

Exosomal-microRNAs Improve Islet Cell Survival and Function In Islet Transplantation.

Exosomal-microRNAs (Exo-miRNAs) are key regulators of islet cell function, including insulin expression, processing, and secretion. Exo-miRNAs have a significant impact on the outcomes of islet transplantation as biomarkers for evaluating islet cell function and survival. Furthermore, they have been linked to vascular remodeling and immune regulation following islet transplantation. Mesenchymal stem cell-derived exosomes have been shown in preliminary studies to improve islet cell viability and function when injected or transplanted into mice. Overall, Exo-miRNAs have emerged as novel agents for improving islet transplantation success rates. The role of islet-derived Exo-miRNAs and mesenchymal stem cells-derived Exo-miRNAs as biomarkers and immunomodulators in islet regeneration, as well as their role in improving islet cell viability and function in islet transplantation, are discussed in this review.

An Updated Comprehensive Pharmacovigilance Study of Drug-Induced Thrombocytopenia Based on FDA Adverse Event Reporting System Data.

Drug-induced thrombocytopenia (DIT) deserves both clinical and research attention for the serious clinical consequences and high prevalence of the condition. The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with thrombocytopenia events. A disproportionality analysis of DIT was conducted using reports submitted to FARES from January 2004 to December 2022. Both the information component (IC) and reporting odds ratio (ROR) algorithms were applied to identify an association between target drugs and DIT events. A total of 15,940,383 cases were gathered in FAERS, 168,657 of which were related to DIT events. The top 50 drugs ranked by number of cases and ranked by signal strength were documented. The top 5 drugs ranked by number of cases were lenalidomide (10,601 cases), niraparib (3726 cases), ruxolitinib (3624 cases), eltrombopag (3483 cases), and heparin (3478 cases). The top 5 drugs ranked by signal strength were danaparoid (ROR 37.61, 95%CI 30.46-46.45), eptifibatide (ROR 34.75, 95%CI 30.65-39.4), inotersen (ROR 34.00, 95%CI 29.47-39.23), niraparib (ROR 30.53, 95%CI 29.42-31.69), and heparin (ROR 28.84, 95%CI 27.76-29.97). The top 3 involved drug groups were protein kinase inhibitors, antimetabolites, and monoclonal antibodies and antibody-drug conjugates. The current comprehensive pharmacovigilance study identified more drugs associated with thrombocytopenia. Although the mechanisms of DIT have been elucidated for some drugs, others still require further investigation.

Mechanism and treatment of mucous hypersecretion in chronic obstructive pulmonary disease / 中国临床药理学与治疗学

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection / 中国血吸虫病防治杂志

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Role of salidroside in a mouse model of non-alcoholic fatty liver disease： A study based on nicotinamide phosphoribosyltransferase / 临床肝胆病杂志

ObjectiveTo investigate the protective effect of salidroside against nonalcoholic fatty liver disease （NAFLD） and its mechanism of action. MethodsA total of 24 male KM mice were randomly divided into normal group， HFD group， HFD+blank control group， and HFD+salidroside group， with 6 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given high-fat diet. After 14 weeks of modeling， the mice were given salidroside 100 mg/kg/day by gavage， and related samples were collected at the end of week 22. Enzyme-linked immunosorbent assay was used to measure the serum levels of related biochemical parameters including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）； HE staining and NAFLD activity score （NAS） were used to observe the liver histopathology of mice； Western blot was used to measure the changes in the expression of NAMPT， Sirt1， AMPKα， and SREBP1 in liver tissue. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the HFD group had obvious steatosis and extensive large lipid droplets in liver tissue， with significant increases in NAS score （P<0.01） and the content of AST， ALT， TG， TC， and LDL-C in peripheral blood （all P<0.05） and a significant reduction in the content of HDL-C （P<0.05）， as well as significant reductions in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant increase in the expression level of SERBP1 （P<0.01）. Compared with the HFD group and the HFD+blank control group， the HFD+salidroside group had reductions in the distribution of vacuolar lipid droplets and intralobular inflammation in liver tissue， alleviation of the ballooning degeneration of hepatocytes， significant reductions in NAS score （P<0.01） and the content of AST， ALT， TG， and LDL-C in peripheral blood （all P<0.05）， and a significant increase in the content of HDL-C （P<0.05）， as well as significant increases in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant reduction in the expression level of SERBP1 （P<0.01）. ConclusionSalidroside can significantly improve the pathological state of mice with NAFLD induced by high-fat diet and exert a protective effect against NAFLD by increasing the expression of NAMPT， Sirt1， and AMPKα and reducing the expression of SERBP1.

Retinal ganglion cells encode differently in the myopic mouse retina?

The etiology of myopia remains unclear. This study investigated whether retinal ganglion cells (RGCs) in the myopic retina encode visual information differently from the normal retina and to determine the role of Connexin (Cx) 36 in this process. Generalized linear models (GLMs), which can capture stimulus-dependent changes in real neurons with spike timing precision and reliability, were used to predict RGCs responses to focused and defocused images in the retinas of wild-type (normal) and Lens-Induced Myopia (LIM) mice. As the predominant subunit of gap junctions in the mouse retina and a plausible modulator in myopia development, Cx36 knockout (KO) mice were used as a control for an intact retinal circuit. The kinetics of excitatory postsynaptic currents (EPSCs) of a single αRGC could reflect projection of both focused and defocused images in the retinas of normal and LIM, but not in the Cx36 knockout mice. Poisson GLMs revealed that RGC encoding of visual stimuli in the LIM retina was similar to that of the normal retina. In the LIM retinas, the linear-Gaussian GLM model with offset was a better fit for predicting the spike count under a focused image than the defocused image. Akaike information criterion (AIC) indicated that nonparametric GLM (np-GLM) model predicted focused/defocused images better in both LIM and normal retinas. However, the spike counts in 33% of αRGCs in LIM retinas were better fitted by exponential GLM (exp-GLM) under defocus, compared to only 13% αRGCs in normal retinas. The differences in encoding performance between LIM and normal retinas indicated the possible amendment and plasticity of the retinal circuit in myopic retinas. The absence of a similar response between Cx36 KO mice and normal/LIM mice might suggest that Cx36, which is associated with myopia development, plays a role in encoding focused and defocused images.

DEGENERATED LEMMA (DEL) regulates lemma development and affects rice grain yield.

In grass, the lemma is a unique floral organ structure that directly determines grain size and yield. Despite a great deal of research on grain enlargement caused by changes in glume cells, the importance of normal development of the glume for normal grain development has been poorly studied. In this study, we investigated a rice spikelet mutant, degenerated lemma (del), which developed florets with a slightly degenerated or rod-like lemma. More importantly, del also showed a significant reduction in grain length and width, seed setting rate, and 1000-grain weight, which led to a reduction in yield. The results indicate that the mutation of the DEL gene further affects rice grain yield. Map-based cloning shows a single-nucleotide substitution from T to A within Os01g0527600/DEL/OsRDR6, causing an amino acid mutation of Leu-34 to His-34 in the del mutant. Compared with the wild type, the expression of DEL in del was significantly reduced, which might be caused by single base substitution. In addition, the expression level of tasiR-ARF in del was lower than that of the wild type. RT-qPCR results show that the expression of some floral organ identity genes was changed, which indicates that the DEL gene regulates lemma development by modulating the expression of these genes. The present results suggest that the normal expression of DEL is necessary for the formation of lemma and the normal development of grain morphology and therefore has an important effect on the yield. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01297-6.

Transplantation of insulin-producing cells derived from human MSCs to treat diabetes in a non-human primate model.

BACKGROUND: Islet cell transplantation is an emerging therapy in the treatment of diabetes mellitus. Differentiation of islet cells from mesenchymal stem cells (MSCs) is a potential solution to the challenge of insufficient donor sources. This study investigated whether human umbilical cord-derived MSCs could effectively differentiate into insulin-producing cells (IPCs) and evaluated the therapeutic efficacy of IPCs in treating diabetes. METHODS: IPCs were induced from MSCs by a two-step protocol. IPC expression products were evaluated by western blot and real-time PCR. IPC insulin secretion was evaluated by ELISA. The viability of IPCs was measured by FDA/PI and dithizone staining. The non-human primate tree shrew was used as a diabetes model. After a single STZ induction into a diabetes model, a single intraportal transplantation of IPCs, MSCs, or normal saline was performed (n = 6 per group). Blood glucose was monitored for 3 weeks, then the animals were euthanized and the distribution of IPCs in the liver was examined pathologically. RESULTS: After about 3 weeks of in vitro induction, IPCs formed microspheres of 100-200 µm, with >95% viable cells that were dithizone stain positive. IPCs expressed islet-related genes and proteins and secreted high levels of insulin whether stimulated by low or high levels of glucose. After transplantation of IPCs into diabetic tree shrews, blood glucose levels decreased rapidly to near normal and were significantly lower than the MSC or saline groups for 3 weeks thereafter. CONCLUSION: We present the novel discovery that IPCs derived from human umbilical cord MSCs exert a therapeutic effect in a non-human primate model of diabetes. This study provides a preliminary experimental basis for the use of autologous MSC-derived IPCs in the treatment of human diabetes.

Prenatal Diagnosis of Structural Anomaly Among Singletons and Twins: Eight-Year Experience in a Chinese Tertiary Center.

OBJECTIVES: This study was designed to reveal structural abnormalities in singleton and twin pregnancies in the Chinese population. METHODS: This retrospective study spanned 8 years and included 1228 singleton pregnancies (112,919 examinees) and 49 twin pregnancies (1865 examinees) with structural anomalies diagnosed by ultrasound. Detailed descriptions of anomalies, gestational weeks at diagnosis, and maternal age were recorded. The odds ratio was evaluated in twin pregnancies with detectable structural anomalies. RESULTS: The annual average "ultrasound prevalence of fetal anomalies" among singleton and twin pregnancies were 1.09 and 3.06%, respectively. Mothers with twin anomalies were older (P < .001), and twin pregnancies were diagnosed with anomalies in earlier gestational weeks than singleton (P = .011). No differences were found in the types of anomalies between singleton and twin pregnancies. Central nervous system anomaly was the most common type in singleton and twin pregnancies. Twin pregnancies had higher rates of major anomalies than singleton (total OR 2.45), especially cardiovascular, central nervous, and gastrointestinal systems and ear/eye/face/neck disorders. CONCLUSIONS: Compared with singleton, twin pregnancies had higher odds of detectable structural anomalies. Twin pregnancies with structural anomalies were diagnosed at earlier gestational age and associated with older maternal age. Central nervous system anomaly was the most common type in singleton and twin pregnancies.

Safflor yellow injection combined with anti-vascular endothelial growth factor drugs in the treatment of non-ischemic central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the efficacy and safety of safflor yellow injection combined with anti-vascular endothelial growth factor(VEGF)drug in the treatment of non-ischemic central retinal vein occlusion(CRVO).METHODS: A total of 91 patients(91 eyes)with non-ischemic CRVO complicated with macular edema who were treated in the Affiliated Eye Hospital of Nanchang University from April 2017 to December 2021 were selected. They were randomly divided into observation group, with 47 cases(47 eyes)treated with safflor yellow injection combined with intravitreal injections of ranibizumab, and control group with 44 cases(44 eyes)who were treated with intravitreal injections of ranibizumab. Followed-up for 11mo, the best corrected visual acuity(BCVA)and macular central retinal thickness(CRT)of the two groups were observed and the cases of complete absorption of retinal hemorrhage, the times of anti-VEGF drug injections, the cases of ischemic CRVO, and the occurrence of systemic or ocular complications were recorded.RESULTS: At 1, 2, 3, 5, 7, 9 and 11mo after treatment, the BCVA and CRT in both groups were significantly improved compared with those before treatment, and BCVA and CRT in the observation group were superior to the control group at 3, 5, 7, 9 and 11mo after treatment(all P&#x003C;0.05). At 5, 7, 9 and 11mo after treatment, the complete absorption rate of retinal hemorrhage in the observation group was higher than that in the control group(P&#x003C;0.05). During the follow-up period, the anti-VEGF drug injection in the observation group was significantly less than that in the control group(4.83±1.05 vs. 5.75±1.01, P&#x003C;0.05), and the incidence of ischemic CRVO was significantly lower than that in the control group(21% vs. 86%, P&#x003C;0.05), and there were no treatment-related systemic and ocular complications in both groups.CONCLUSION: Safflor yellow injection combined with anti-VEGF drugs is a safe and effective method for the treatment of non-ischemic CRVO, which can significantly improve vision and reduce CRT. It can increase the complete absorption rate of retinal hemorrhage, reduce the times of anti-VEGF drug injections and the incidence of ischemic CRVO compared with monotherapy of anti-VEGF drug.

Application of MassARRAY genotyping assay in the diagnosis of neonatal genetic metabolic diseases / 中华检验医学杂志

Objective:To investigate the accuracy, effectiveness and feasibility of MassARRAY genotyping assay in the diagnoses of neonatal genetic metabolic diseases.Methods:This is a retrospective study. From December 2016 to January 2020, newborns were screened by tandem mass spectrometry at the Zhejiang Newborn Screening Center, among which the data of 7 922 suspected positive cases of genetic metabolic diseases were collected. These patients were then tested for the common variants of 27 genetic metabolic diseases by MassARRAY genotyping assay, along with further testing using Sanger or next-generation sequencing used to verify and/or further search for potential variants.Results:A total of 1 408 cases were tested with MassARRAY. Among these, 307 cases were confirmed with certain genetic metabolic diseases. The detection rate of hyperphenylalaninemia was the highest, followed by primary carnitine deficiency, short acyl-coA dehydrogenase deficiency and methylmalonic acidemia. With these cases, the consistency of Sanger sequencing and MassARRAY was 100% (307/307). Another 287 cases were identified as carriers by MassARRAY with a 49.1% (141/287) consistency in reference to Sanger sequencing, mainly involving SLC22A5 and MCCC1 genes. Meanwhile, 50.8% (146/287) of these cases were found to have another variant mainly involving PAH, PTS and ACADS genes. The remaining 814 cases have no variants; 158 cases out of these patients have continuously abnormal amino acids, acyl carnitines, urine organic acid and/or other biochemical indices, and were tested by next-generation sequencing, among which 38% (60/158) were detected with two variants. In this study, a total of 513 patients with genetic metabolic disease were diagnosed, and the detection rate of MassARRAY was 59.8% (307/513). Conclusions:MassARRAY genotyping assay can be used as an early molecular screening method for neonatal genetic metabolic diseases. The detection rate is particularly high in diseases with a high concentration of hotspot variants, such as hyperphenylalaninemia and primary carnitine deficiency. The future application value of MassARRAY should be further improved by continuously optimizing its ability to identify new disease genes and potential variable sites.

Influence of effective liver drainage volume on overall survival in patients with malignant hilar biliary obstruction: a multicenter study / 中华消化内镜杂志

Objective:To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction.Methods:Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence.Results:The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95% CI: 1.8-7.2) months, 5.6 (95% CI: 5.0-6.2) months and 6.6 (95% CI: 5.2-8.0) months. The overall survival time was 2.4 (95% CI: 1.8-3.0) months, 4.0 (95% CI: 3.4-4.6) months and 4.9 (95% CI:4.4-5.4) months, respectively. The clinical success rate ( χ 2=8.28, P=0.012), median stent patency period ( χ 2=18.87, P=0.015) and overall survival time ( χ 2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95% CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95% CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95% CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L ( HR=1.35, 95% CI:1.14-1.60, P<0.001),metal stents ( HR=0.67, 95% CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95% CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95% CI:0.41-0.81, P=0.002) and anti-tumor therapy ( HR=0.51, 95% CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion:When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.

Relationship between cardiometabolic index and hyperuricemia in health examination population / 中华健康管理学杂志

Objective:To investigate the relationship between cardiometabolic index (CMI) and hyperuricemia (HUA) in the health examination population.Methods:It was a cross-sectional study. A total of 21 720 individuals who received health examinations in Xiangya hospital, Central South University between 2020 and 2021 were recruited in this study. Multivariate logistic regression analysis was used to determine the independent correlation between CMI and HUA, and stratified analysis was applied to check whether there were population differences. Then the predictive value of CMI for hyperuricemia in the health examination population was evaluated with the area under the receiver operator characteristic (ROC) curve.Results:Among the 21 720 subjects, 4 418 (20.34%) were detected with HUA. In the HUA group, the body mass index (BMI), waist-to-hip ratio, CMI, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, fasting blood glucose, 2-hour postprandial blood glucose, and blood creatinine levels were all significantly higher than those in the normal uric acid group, while high-density lipoprotein and epidermal growth factor receptor (eGFR) were significantly lower (all P<0.05). Multiple logistic regression analysis showed that after adjusting for relevant factors, CMI was significantly positively correlated with HUA ( OR=1.16, 95% CI: 1.129-1.192); and with the increase of CMI, the risk of HUA increased gradually. Stratified analysis and interaction test according to gender, age, BMI, hypertension, abnormal blood glucose and glomerular filtration rate indicated that CMI was positively associated with the occurrence of HUA in all populations. Compared with that in people with abnormal blood glucose, the correlation between CMI and HUA was more obvious in people with normal blood glucose. The area under the ROC curve (AUC) for CMI to predict HUA was 0.723(95% CI: 0.715-0.731), with a specificity of 0.636 and a sensitivity of 0.698, and the cut-point was 0.693. Conclusion:There was a significant positive correlation between CMI and HUA in the health examination population, which has good predictive value for HUA.

Fascia lata autograft bridging repair reinforced with artificial ligament as an internal brace for arthroscopic management of irreparable massive rotator cuff tears / 中华骨科杂志

Objective:To compare the clinical and imaging outcomes of fascia lata autograft bridging repair reinforecd with an artificial ligament as the internal brace with the autograft bridging repair for the treatment of irreparable massive rotator cuff tears (IMRCTs).Methods:The data of 26 patients with IMRCT who underwent fascia lata autograft bridging repair augmented with artificial ligament as the internal brace (internal brace group) and of 24 patients with IMRCT who underwent bridging autograft repair alone (control group) were retrospectively evaluated preoperatively and at 2-year follow-up. Clinical outcomes were assessed using shoulder activity, the American Shoulder and Elbow Surgeons (ASES) Score, University of California Los Angeles (UCLA) Score, and visual analogue scale (VAS) for pain. Imaging outcomes were evaluated using acromiohumeral distance (AHD), Goutallier grade, and status of fascia lata grafts according to radiographs or magnetic resonance imaging results.Results:All 50 cases were followed up for 34.2±7.2 months (range 24-45 months). Compared to the control group, the internal brace group showed better ASES score (93.5±5.3 vs. 89.5±5.7, P<0.05), UCLA score (31.7±3.8 vs. 28.5±5.6, P<0.05), improvement in UCLA score (19.6±4.2 vs. 15.9±5.7, P<0.05), active elevation (167.3°±8.4° vs. 159.4°±13.6°, P<0.05), abduction strength (8.9±1.2 vs. 8.2±1.2, P<0.05), improvement in abduction strength (4.1±1.2 vs. 3.3± 1.0, P<0.05), AHD (7.0±1.4 mm vs. 5.9±1.0 mm, P<0.05), improvement in AHD (3.3±1.5 mm vs. 2.0±0.6 mm, P<0.05), and healing rate of fascia lata autografts (92% vs. 54%, P<0.05) at 2-year follow-up. Conclusion:Fascia lata autograft bridging repair reinforced with an artificial ligament as the internal brace improves healing rate of bridging graft and postoperatively short-term clinical outcomes of patients with IMRCT.

Preoperative breast MRI combined with axillary ultrasound for the prediction of lymphovascular invasion in invasive ductal carcinoma of the breast / 中华放射学杂志

Objective:To investigate the value of preoperative breast MRI combined with axillary ultrasound in predicting lymphovascular invasion (LVI) of breast invasive ductal carcinoma.Methods:The clinical, pathological and imaging features of 160 female patients [age 25-74(49±10)years] with breast invasive ductal carcinoma from March 2014 to December 2017 in Shanxi Cancer Hospital were retrospectively analyzed. According to the LVI status determined by postoperative pathology, 160 patients were divided into LVI positive group (56 cases) and LVI negative group (104 cases). The clinical characteristics, pathological characteristics and imaging features of LVI positive group and LVI negative group were compared by the independent t test, Mann-Whitney U test or χ 2 test. Multivariate logistic regression analysis was performed to identify independent predictors for predicting LVI and construct a predictive model. The receiver operating characteristic (ROC) curve and area under the curve (AUC) was used to evaluate the discrimination of the prediction model, and the Hosmer-Lemeshow test was used to evaluate its calibration. Results:There was no significant difference in age, menopausal status, estrogen receptor, progesterone receptor, human epidermal growth factor 2, Ki67 index and molecular subtype between LVI positive group and negative group ( P>0.05). Tumor size, peritumoral edema, adjacent vessel sign, multifocality or multicentricity, peritumoral maximum-apparent diffusion coefficient (ADC), peritumour-tumour ADC ratio, MRI axillary lymph node status and ultrasound axillary lymph node status between LVI positive group and LVI negative group showed significantly statistical difference ( P<0.05). Variables with significant difference in the univariate analysis were entered into multivariate logistic regression analysis to explore predictors for LVI. Peritumoral edema (OR=3.367, 95%CI 1.382-8.201, P=0.008), multifocality or multicentricity (OR=4.026, 95%CI 1.268-12.776, P=0.018), high peritumoral-tumor ADC ratio (OR=7.321, 95%CI 2.226-24.079, P=0.001) and positive ultrasound axillary lymph node (OR=6.779, 95%CI 2.819-16.303, P<0.001) were independent predictors for predicting LVI. A logistic regression model was constructed using the above four indicators, and ROC showed AUC of this model for predicting LVI was 0.882, superior to any of the single indicator ( P<0.05); its sensitivity was 80.36% and specificity was 84.62%. Hosmer-lemeshow test showed that the prediction model had good calibration ( P=0.503). Conclusion:The combined prediction model constructed by preoperative breast MRI and axillary ultrasound could help to predict the LVI status of breast invasive ductal carcinoma.

Arthroscopic side-to-side repair of transtendinous rotator cuff tears with remnants preserved / 中华创伤骨科杂志

Objective:To evaluate the clinical efficacy of arthroscopic side-to-side suture with remnants preserved in repair of transtendinous rotator cuff tears.Methods:A retrospective study was conducted to analyze the data of 17 patients who had been treated by arthroscopic side-to-side suture with remnants preserved for transtendinous rotator cuff tear caused by trauma at Sports Medicine Center, The Second Hospital Affiliated to Inner Mongolia Medical University from January 2017 to January 2020. There were 11 males and 6 females with an age of (47.9±8.3) years and a duration from injury to surgery of (50.4±21.3) d. Recorded were range of motion and muscle strength of the shoulder, University of California at Los Angeles (UCLA) shoulder function score, Constant-Murley shoulder function score, visual analogue scale (VAS) pain score, re-tears and complications before operation and at the last follow-up.Results:The 17 patients were followed up for (16.5±3.5) months after operation. Retear of the rotator cuff occurred in 2 patients after operation while MRI showed good healing of the rotator cuff in the other patients with no such postoperative complications as infection or wound dehiscence. At preoperation and the last follow-up, respectively, the range of shoulder flexion was 152.9°±8.5° and 172.4°±5.6°, the abductor muscle strength 3.5 (2.6, 4.1) kg and 6.9 (6.3, 8.3) kg, the external rotator muscle strength (3.8±1.0) kg and (5.9±1.6) kg, the internal rotator muscle strength 3.9 (3.4,4.7) kg and 5.2 (4.5,5.9) kg, the UCLA score (13.2±1.9) points and (30.9±2.4) points, the Constant score (40.1±2.8) points and (86.1±4.6) points, and the VAS score (6.7±0.8) points and (0.9±0.6) points, all showing a significant difference between preoperation and the last follow-up ( P<0.05). Conclusion:In repair of transtendinous rotator cuff tears, arthroscopic side-to-side suture with remnants preserved can lead to significantly improved clinical outcomes in range of motion, muscle strength, functional recovery and pain relief.

Trajectory and impact factors of cycle threshold values of virus load in respiratory tract in children infected with severe acute respiratory syndrome coronavirus 2 Omicron variants / 中华传染病杂志

Objective:To investigate the clinical characteristics of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, and the impact factors of duration of cycle threshold (Ct) values turning to ≥35 detected by nucleotide test.Methods:Children aged 0 to 14 years with clinical symptoms of Omicron variants infection who admitted to designated hospital in Shanghai City (Renji Hospital, South Branch, Shanghai Jiao Tong University School of Medicine) from April 7 to June 2, 2022 were enrolled. The daily nasopharyngeal swab specimens were used for SARS-CoV-2 nucleic acid detecting by polymerase chain reaction and the results were expressed as Ct values. The T Ct≥ x was defined as from the symptom onset or first positive nucleic acid test results (the earlier data) to Ct≥ x of the open reading frame 1ab ( ORF1 ab) gene, which was the time duration from the initial to a specific Ct value.Clinical data were collected, including age, sex, vaccination and comorbidities.Cox model was performed to analyzed the impact factors of T Ct≥35. Results:A total of 871 pediatric cases with a median age of two years (ranging from one month to 14 years old) were included. Among them, 474 cases (54.4%) were male, and 89 cases (10.2%) had underlying diseases including congenital heart disease, solid tumors and epilepsy. There were 572(65.7%) mild cases, 298(34.2%) common cases, one (0.1%) severe case and no critical cases or deaths. The T Ct≥35 was 12(10, 14) days. Cox model indicated that compared to children aged one to 12 months, children aged 37 to 84 months and 85 to 168 months had shorter T Ct≥35 (hazard ratio ( HR)=1.55 and 1.84, respectively, both P<0.001). After adjusted with age, comparing to unvaccinated patients, patients with one or two shots vaccine had shorter T Ct≥35 (adjected hazard ratio (a HR)=1.49, P=0.011), and common patients had longer T Ct≥35 than mild patients (a HR=0.78, P=0.002), and patients with comorbidities had longer T Ct≥35than patients without comorbidities (a HR=0.38, P<0.001).The duration of T Ct≥28, T Ct≥30, T Ct≥33 and T Ct≥35 in children without underlying diseases were 7(6, 9) d, 9(7, 10) d, 10(8, 11) d and 12(10, 14) d, respectively. Conclusions:Age, vaccination, disease severity and underlying diseases could affect the duration of SARS-CoV-2 nucleotide turning to negative (Ct value≥35) in children infected with Omicron variants.

Primary ciliary dyskinesia in children: a case report and literature review / 中国综合临床

Objective:To explore the clinical features and diagnostic methods of primary ciliary dyskinesia (PCD).Methods:A case of PCD diagnosed by Kunming Children's Hospital was analyzed retrospectively (including general information, clinical characteristics, auxiliary examination results), and the literature was reviewed.Results:The patient, an 8-year-old female, went to hospital for repeated cough and suffered from pneumonia and sinusitis repeatedly in the past. The electron microscope of cilia biopsy showed that the number of cilia was reduced. The mutation of c.7615T>C (p.W2539R) in DNA H5 gene located in chr5-13,809,290 was detected by gene test, so the patient was diagnosed as PCD.The mutation site was a new mutation site.Conclusion:PCD is a rare disease in children. Electron microscopy and genetic examination are helpful to the diagnosis of PCD. Children with recurrent respiratory tract infection and wet cough should be alert to the possibility of PCD.

Quercetin exhibits neuroprotective effect by reduc-ing amyloid precursor protein expression and oxida-tive stress in Neuro2a/APPswe cell model / 中国药理学与毒理学杂志

OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.