Objective:Screening factors that might influence rheumatoid arthritis (RA) complicating interstitial lung diseases (ILD) by constructing and validating a model for early diagnostic.Methods:The study subjects were composed of 712 RA patients in the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University during December 2019 to October 2022. Fifty-two variables such as their demographic data, clinical symptoms, and laboratory indexes were collected. Patients were categorized into RA-only group and RA-ILD group with or without the occurrence of ILD disease. After data preprocessing, subjects were randomly assigned to the modeling and validation groups in a 7:3 ratio.Univariate analysis comparing baseline characteristics of the two groups of patients. Feature selection was performed using LASSO and SVM-RFE regression algorithms.Screening indicators were analyzed by logistic regression and the results were used to develop a nomograms model for the early diagnosis of RA complicating interstitial lung disease; and the modeling group was evaluated for its performance for internal assessment of the model and internal validation using data from the validation group.Results:A total of 712 subjects participated in the study, of which 498 in the modeling group and 214 in the validation group. Univariate analysis showed that the differences between the two groups were statistically significant ( P<0.05) in 18 characteristic indexes, including male, gender, age, smoking history, drinking history, number of swollen joints, number of painful joints, use of prednisone, WBC, ESR, CRP, IL-2, IL-10, IL-17, TNF-α, INF-γ, AFA family, APF, and serum albumin. The LASSO algorithm identified 13 risk variables for RA-ILD, the SVM-RFE algorithm identified 12 variables for RA-ILD, and the intersecting risk variables were male, age, history of alcohol consumption, number of painful joints, prednisone acetate, IL-2, AFA family, TNF-α, serum albumin, and IL-10. The results of multifactorial logistic regression analysis confirmed that the differences between males [ OR(95% CI)=3.61(2.11, 6.18)], gender, age [ OR(95% CI)=1.05(1.03, 1.08)], number of painful joints [ OR(95% CI)=1.03(1.01, 1.06)], IL-2 [ OR(95% CI)=0.91 (0.84, 0.99)], and TNF-α[ OR (95% CI)=1.06 (1.02, 1.10)] were statistically significant ( P<0.05) and were independently influences on ILD complicated by RA. The modeling and validation groups that were used to construct early diagnostic Nomograms had high calibration curve accuracies, and the model had a high diagnostic power, which was mainly demonstrated by the receiver operating characteristic (ROC) area under the curve (AUC) and decision curve analysis(DCA), the model modeling group had an AUC of 0.76 (95% CI=0.71, 0.81), with net benefit rates of 3%~82% and 93%~99%, whereas the model validation group had an AUC of 0.71 (95% CI=0.64, 0.79), with net benefit rates of 5%~11%, 14%~60% and 85%~89%. Conclusion:Male, gender, age, number of painful joints, IL-2, and TNF-α are independent factors for RA complicated with ILD, and the Nomogram model constructed has good performance in early diagnosis of the disease.

Objective:To compare the efficacy and safety of different dosages of new drugs in the treatment of PsA by using network meta-analysis.Methods:Three medical databases (PubMed, Web of Science, Cochrane Library) were searched for the studies that compared the efficacy and safety of 4 new drugs (secukinumab, ixekizumab, apremilast, tofacitinib) with different dosages in the treatment of PsA. Data from included studies were analyzed by Stata 15.0.Results:A total of 16 RCTs were included. The results of the network meta-analysis showed that: (1) Among the overall patients, in terms of ACR20 response rate, the larger the surface under the cumulative ranking (SUCRA), the more effective it is. Secukinumab 300 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q4W(79.0%), ixekizumab 80 mg Q2W(75.1%), secukinumab 150 mg Q4W(73.2%), apremilast 30 mg BID(50.6%), apremilast 20 mg BID(38.6%), tofacitinib 5 mg BID(18.1%), tofacitinib 10 mg BID(17.7%) and placebo(2.0%). (2) In terms of PASI75 response rate, the larger the area under the SUCRA curve, the more effective it is. Ixekizumab 80 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q2W(88.7%), secukinumab 300 mg Q4W(75.6%), secukinumab 150 mg Q4W(63.3%), apremilast 30 mg BID(44.5%), apremilast 20 mg BID(38.4%), tofacitinib 10 mg BID(30.0%), tofacitinib 5 mg BID(12.5%) and placebo(1.0%). (3) Among the overall patients, in terms of safety, the smaller the area under the SUCRA curve, the higher the safety it is. Secukinumab 300 mg Q4W (17.3%) has the best safety. (4) The results of subgroup analysis showed that in terms of ACR20 response rate, ixekizumab 80 mg Q2W(85.3%) had the best efficacy in bDMARDs-na?ve patients, while in bDMARDs-IR patients, secukinumab 300 mg Q4W(83.9%) had the best efficacy.Conclusion:Among all patients, secukinumab 300 mg Q4W is the best in terms of ACR20 response rate and safety, but ixekizumab 80 mg Q4W is more effective in improving PsA lesions comparing yo other drugs.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective:To explore the prenatal ultrasound manifestations of fetal congenital right aortic arch and its diagnostic significance.Methods:The characteristics of prenatal ultrasound images (focusing on the three vessel trachea section) and clinical data of 128 cases of fetal congenital right aortic arch diagnosed in Dalian Women and Children′s Medical Center(Group) from January 2014 to January 2019 were analyzed retrospectively.Results:Among 128 cases of fetal congenital right aortic arch, 111 cases were right aortic arch and leftductus arteriosus with aberrant left subclavian artery (RAA-LDA-ALSA), 1 case was diagnosed as left aortic arch atresia of double aortic arch by operation after birth; 9 cases were right aortic arch and right ductus arteriosus (RAA-RDA); 6 cases were mirror-image right active aortic arch and left ductus arteriosus connected to descending aorta (RAA-BAMB-LDA-DAO); 2 cases were mirror-image right aortic arch and left ductus arteriosus connected to the left innominate artery (RAA-BAMB-LDA-LINA). The three vessels and trachea view (3VT) had characteristic sonographic features.If necessary, coronary section of the upper thoracic aorta and / or stic were added - HD live flow technology assisted the diagnosis of 3vt section.Conclusions:Three vessel trachea view is a sensitive and effective view for prenatal detection and diagnosis of congenital right aortic arch. Upper thoracic aorta coronal section and combined stic - HD live flow technology can make up for its shortcomings. Prenatal ultrasound diagnosis of right aortic arch hasguiding significance for prenatal prognosis consultation.

A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson's disease (PD). However, the mechanisms underlying these links remain to be defined. Here, we investigated the impact of deregulation of intestinal dopamine D2 receptor (DRD2) signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration. Dopamine/dopamine signaling in the mouse colon decreased with ageing. Selective ablation of Drd2, but not Drd4, in the intestinal epithelium, caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge, and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota. Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential. This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival. These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects* ; Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Parkinson Disease ; Pyrrolidines ; Receptors, Dopamine D2/metabolism* ; Substantia Nigra ; Succinates

[摘 要] 目的：探索南蛇藤提取物齐墩果烷型五环三萜（28-hydroxy-3-oxoolean-12-en-2-oic acid）协同miR-451对人胃癌AGS细胞增殖、迁移的影响及其可能的分子机制。方法：用miR-451过表达慢病毒感染AGS细胞，并用盐酸多西环素（DOX）10或100 ng/ml诱导24 h，构建过表达miR-451的细胞AGS/miR-451+。采用10、20、40、80、160 μmol/L的齐墩果烷型五环三萜处理AGS/miR-451+细胞，MTT法、划痕实验分别检测细胞增殖和迁移能力的变化，WB法检测细胞中mTOR通路及凋亡相关蛋白表达水平的变化。结果：成功构建过表达miR-451的AGS/miR-451+细胞。与未加药对照组相比，齐墩果烷型五环三萜处理后AGS/miR-451+细胞的增殖抑制率均呈时间和浓度依赖性升高（P<0.05或P<0.01），细胞迁移率均显著降低（P<0.05或P<0.01）。齐墩果烷型五环三萜处理组细胞中，mTOR 信号通路相关蛋白的表达量均有所降低（P<0.05或P<0.01）；凋亡相关蛋白中，Bcl2的表达量下降，BAX、caspase-3、caspase-1及细胞色素c的表达量升高（P<0.05或P<0.01）。结论：齐墩果烷型五环三萜能够协同miR-451抑制人胃癌AGS细胞的增殖与迁移，其机制可能与影响凋亡和mTOR信号通路相关蛋白的表达有关。

Objective:To explore the value of the Pfirrmann grading standard for disc degeneration in the quantification of heterotopic ossification (HO) after artificial cervical disc replacement (ACDR).Methods:Data of 120 patients who underwent ACDR from January 2009 to December 2016 were retrospectively analyzed. There were 88 males and 32 females with an average age of 43.86±8.69 (range, 27-67) years old. There were 100 single-level replacements (9 Hybrid cases) and 20 double-level replacements (3 Hybrid cases). The occurrence of HO was observed by lateral radiographs of the cervical spine. The HO severity was assessed using the McAfee rating system. Degeneration degrees of cervical intervertebral discs were evaluated by the Pfirrmann grading standard based on the preoperative cervical MRI. The weighted Kappa test was used to analyze the consistency of evaluations between different observers of the Pfirrmann scoring system and the McAfee grading system. Pfirrmann scores for preoperative disc degeneration in the HO and non-HO groups were compared using the t-test. The chi-square test was used to analyze the effect of the Pfirrmann score on the incidence of postoperative segmental HO. The correlation between Pfirrmann score and McAfee grade, as well as postoperative ROM of HO group were analyzed by the Spearman rank-sum test. Quantitative indicators for risks of HO after ACDR surgery were proposed based on the incidence of segment HO in different Pfirrmann score groups. Results:One hundred and twenty patients were followed up for an average of 74.08±28.05 (range, 31-125) months. Based on statistics of cases 2 years after surgery, the overall HO incidence was 31.67% (38/120). The HO incidence was 27% (27/100) and 55% (11/20) for single-level and double-level replacements, respectively. There were 46 replacement segments in the HO group and 94 replacement segments in the non-HO group. The Pfirrmann score of HO group (3.17±1.08) was 25.80% significantly higher than that of the non-HO group (2.52±0.98) ( t=3.46, P=0.01). The incidence of HO in the replacement segment increased significantly with the preoperative Pfirrmann score ( χ2=12.44, P=0.01). The Pfirrmann score of the intervertebral disc in the HO group had a significant positive correlation with the McAfee grade ( R=0.54, P=0.01) and a significant negative correlation with the ROM ( R=-0.75, P=0.01). At 2 years after the operation, when the Pfirrmann score of the intervertebral disc was less than 3, the incidence of HO in the replacement segment was 20.55%(15/73); when the Pfirrmann score was equal to 3, the incidence of HO was 38.46% (10/26); when the Pfirrmann score was greater than 3, HO incidence was 51.22% (21/41). Conclusion:The Pfirrmann score of cervical disc degeneration was significantly related to the incidence of HO, McAfee grade, and ROM in the postoperative replacement segment. The Pfirrmann score of cervical disc degeneration can be used as a quantitativeindicator of HO risk in ACDR.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.

Objective: To investigate the sonographic findings of fetal congenital absence of the ductus venosus (ADV) and its effect on the prognosis of fetus. Methods: The ultrasonographic features of 11cases of fetal ADV deficiency diagnosed from December 2013 to June 2017 were retrospectively analyzed, and the fetal prognosis was followed up. Results: Of the 11 cases, umbilical vein flew directly back to the right atrium in 7 cases; umbilical vein connected with the inferior vena cava in 1 case; umbilical vein directly flowed into the iliac vein in 1 case; umbilical vein and portal vein connection in the other 2 cases. Of the 11 cases, 4 cases were solitary and had no abnormality after birth; 5 cases were complicated with abnormal structure of intracardiac and extracardiac system; 2 cases were only followed with abnormal extracardiac system. Of the 5 complicated cases, 1 case was double chorionic twin amniotic membrane pregnancy (the second fetuse had no obvious abnormality) and died after birth; the other 4 cases were terminated before 28 weeks of gestation. Of the 2 complicated cases, 1 case was followed with severe digestive tract abnormalities and died after birth, and the other one was followed with single umbilical artery and hydramnion. Conclusions Color Doppler ultrasonography is an important means for prenatal screening of fetal ADV.The prognosis of patients with solitary ADV without fetal cardiac dysfunction is good.The prognosis is poor to patients with severe intracardiac and extracardiac abnormality. There is a correlation between the ADV and fetal chromosomal abnormalities. If pregnancy is necessary, fetal chromosome examination should be recommended first and cardiac function should be followed up closely by ultrasound.