ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

Objective:To investigate the genetic characteristics of fetuses carrying a small supernumerary marker chromosome (sSMC) derived from chromosome 15.Methods:This was a retrospective study involving three fetuses who were diagnosed with microdeletions or microduplications by non-invasive prenatal testing (NIPT) and confirmed to carry sSMC derived from chromosome 15 through prenatal diagnosis at the Center of Prenatal Diagnosis, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University from June to October 2023. Clinical data, including NIPT results and ultrasound findings, were collected. Genetic tests for the fetuses and their parents were performed using genetic karyotype analysis, fluorescence in situ hybridization (FISH), and single nucleotide polymorphisms array (SNP-array). All data were analyzed using descriptive statistics. Results:(1) The mothers of the three fetuses were aged 36, 37, and 41 years, and all of them were multiparous with no family history of genetic disorders. The fetuses exhibited duplications of 8.80, 8.17, and 8.80 Mb in the 15q11.2q13.3 region, respectively. Amniotic fluid karyotyping revealed a 47,XN,+mar karyotype in all three cases. The abnormal sSMC contained two centromeres. One of them was pycnotic, deeply stained, but remained active, while the other was enlarged and formed a band, losing its activity. Both were pseudo-dicentric structures. (2) FISH was not performed on Fetus 1. FISH results for both Fetus 2 and Fetus 3 were ish idic(15)( D15Z1++, SNRPN++, PML-), indicating the presence of two copies of the D15Z1 and SNRPN probes on the sSMC, with no PML probe signal. The D15Z1 probe was located at both ends of the sSMC, while the SNRPN probe was near the center. (3) SNP-array results were arr[GRCh37] 15q11.2q13.2(22 770 422-31 098 691)×4 for Fetus 1, covering 29 OMIM genes including UBE3A and 38 protein-coding genes; arr[GRCh37] 15q11.2q13.3(22 770 422-32 915 723)×4 for Fetus 2, covering 36 OMIM genes including UBE3A and 50 protein-coding genes; and arr[GRCh37] 15q11.2q13.1 (22 770 422-28 560 664)×4 and arr[GRCh37] 15q13.1q13.3(29 009 041-32 444 043)×3 for Fetus 3, covering 24 OMIM genes including UBE3A and 20 protein-coding genes. Additionally, Fetus 3 had a 3.435 Mb duplication in 15q13.1q13.3, covering 11 OMIM genes including CHRNA7 and 20 protein-coding genes. (4) No significant abnormalities were found in the peripheral blood karyotyping for the parents of Fetus 1 or in the SNP-array analysis for the parents of Fetus 3. (5) All three families opted for pregnancy termination. There were no obvious abnormalities in the appearance of Fetus 1 and Fetus 3 after induction, while details of Fetus 2 were unavailable. Conclusion:The three fetuses carried a psu idic(15)(q13)-derived sSMC, leading to increased copy numbers in the 15q11q13 region.

Non-functioning pituitary adenomas(NFPAs)are relatively common.Apart from hyperprolactinemia caused by pituitary compression,they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects.Previously considered a uniform entity,NFPAs are actually a highly heterogeneous group of tumors,including aggressive subtypes like silent corticotroph adenomas(SCA)and null cell adenomas.The 2022 WHO new classification of pituitary tumors employs transcription factors[e.g.,pituitary-specific transcription factor 1(PIT-1),T-box transcription factor 19(TBX19,also known as TPIT),steroidogenic factor 1(SF-1)]for detailed categorization,allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages,including silent gonadotroph adenomas,SCA,and plurihormonal PIT-1-positive adenomas.This helps identify highly invasive subtypes with high recurrence risk,guiding clinical diagnosis and treatment,prognostic assessment,and individualized management.The new classification also provides a theoretical basis for targeted therapies of NFPAs(e.g.,somatostatin analogs and temozolomide).This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications,aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis,treatment,and prognostic assessment.

The active ingredient of WINREVAIR,sotatercept-csrk,is a recombinant activin receptor ⅡA-Fc(ActRⅡA-Fc)fusion protein that improves pro-proliferation(ActRⅡA/Smad2/3-mediated)and anti-proliferation(BMPRⅡ/Smad 1/5/8-mediated)signals,thereby regulating vascular proliferation.In March 2024,WINREVAIR was approved by the U.S.Food and Drug Administration for the treatment of pulmonary arterial hypertension(PAH)in adults.Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84％.Common adverse drugreactions include headache,epistaxis,rash,etc.

Objective:To investigate the influential factors of lung function injury in occupational exposure workers in carbon industry.Methods:In January 2024, a judgment sampling method was employed, with 230 occupational exposure workers in the carbon industry as the study subjects. They were divided into abnormal group and normal group according to whether there was lung function injury in occupational health examination. The basic information of workers in carbon industry was collected by questionnaire, their lung function was measured, urine and blood samples were collected after work, and 1-hydroxypyrene, 1-hydroxynaphthalene and 2-hydroxynaphthalene concentrations and the percentage of DNA in the comet tail and Olive tail distance in peripheral blood lymphocytes were determined. The differences in indicators of lung function, urine and blood samples between the two groups were compared by Mann-Whitney test and t-test. The influencing factors of lung function injury were analyzed by logistic regression. Results:The forced vital capacity (FVC) %[88% (86%, 92%) ], forced expiratory volume in the first second (FEV 1) %[92% (88%, 95%) ] and FEV 1.0/FVC%[96% (91%, 102%) ] of occupational exposure workers in the carbon industry in the normal lung function group ( n=118) were significantly higher than those in the abnormal lung function group [ n=112, 83% (80%, 87%), 84% (80%, 88%), 86% (79%, 91%) ], the differences were statistically significant ( P<0.05). 1-Hydroxypyrene[9.28 (2.96, 25.94) μg/g], 1-hydroxynaphthalene[2.48 (1.47, 4.37) μg/g], percentage of DNA in the comet tail [11.83% (5.30%, 21.45%) ] and Olive tail distance [2.30 (0.82, 4.77) μm] in the abnormal lung function workers was significantly higher than those in the normal group[2.57 (1.17, 9.34) μg/g, 1.70 (0.94, 2.89) μg/g, 6.75% (2.55%, 12.60%), 1.25 (0.43, 2.34) μm], and the differences were statistically significant ( P<0.05). Logistic regression analysis showed that sex, working age, job type, percentage of comet tail DNA in peripheral blood, Olive tail distance and 1-hydroxypyrene were all factors influencing lung function injury in occupational exposure workers in carbon industry ( P<0.05) . Conclusion:The percentage of DNA in the comet tail, Olive tail distance in peripheral blood lymphocytes and 1-hydroxypyrene may be markers of lung function injury in workers exposed to carbon industry. Working age and job type are occupational factors affecting lung function injury. Occupational protection should be strengthened and a reasonable operating system should be established to ensure the health of occupational workers.

To explore the understanding of the target population regarding the Get Active Questionnaire for Pregnancy(GAQ-P)and the Companion Health Care Provider Consultation Form for Prenatal Physical Activity(cHCP-CF-PPA)in the Chinese context,and to verify the consistency of the Chinese version of the prenatal physical activity dual screening questionnaire with the original version in terms of language expression,27 pregnant women and 12 healthcare providers were selected from Obstetrics and Gynecology Hospital,Fudan University during Aug and Oct 2023,and were interviewed using purposive sampling.Two rounds of cognitive interviews were conducted.The first round revealed that some respondents experienced ambiguities in understanding the meanings of 5 items in the questionnaire.Following modifications,the second round indicated that the revised items were consistent in meaning with the original questionnaire.Cognitive interviews can facilitate the adaptation of the prenatal physical activity dual screening questionnaire to the Chinese cultural context,improve the understanding of the questionnaire items among the target population,and promote the localization of the screening tool.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVES: To investigate the expression of the long non-coding RNA maternally expressed gene 3 (LncRNA Meg3) in patients with the Wilson disease (WD) and its correlation with the severity of liver fibrosis and autophagy-related markers. METHODS: A total of 100 WD patients and 50 healthy individuals were enrolled from the First Affiliated Hospital of Anhui University of Chinese Medicine. Serum biomarkers, including platelet count, hyaluronic acid (HA), laminin (LN), type III procollagen N-terminal peptide (PIIINP), type IV collagen (C‑IV), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were measured, and the non-invasive indices APRI and FIB-4 were calculated. Peripheral blood levels of LncRNA Meg3, Beclin-1 and LC3B were detected using RT-qPCR, and liver stiffness (LSM) and shear wave velocity (SWV) were evaluated using two-dimensional shear wave elastography (2D-SWE). The liver tissues from 10 WD patients and 10 patients with hepatic hemangioma were examined using histochemical staining, transmission electron microscopy, and RT-qPCR. RESULTS: The expression level of LncRNA Meg3 was significantly lower, while the levels of AST, ALT, HA, LN, PIIINP, C‑IV, APRI, FIB-4, LSM and SWV were significantly higher in WD patients than in the healthy individuals (all P<0.01). LncRNA Meg3 was negatively correlated with LSM, SWV, APRI, FIB-4, Beclin-1 and LC3B (P<0.05). ROC analysis demonstrated that LncRNA Meg3 effectively discriminated >F4 stage fibrosis (AUC=0.902) with a sensitivity of 92.9% and a specificity of 83.7% at the optimal cut-off value, outperforming APRI (AUC=0.746) and FIB-4 (AUC=0.661). The liver tissues from WD patients exhibited characteristic histopathological changes and lowered expression of LncRNA Meg3, which was negatively correlated with Beclin-1 and LC3B expressions (P<0.05). Liver fibrosis staging (7 S4 cases and 3 S3 cases) was significantly associated with LSM and SWV levels (P<0.05). CONCLUSIONS The expression level of LncRNA Meg3 is significantly decreased in WD patients, which is negatively correlated with the severity of liver fibrosis and closely related to the level of autophagy.
Humans ; RNA, Long Noncoding/metabolism* ; Liver Cirrhosis/metabolism* ; Adult ; Female ; Male ; Hepatolenticular Degeneration/metabolism* ; Case-Control Studies ; Young Adult ; Adolescent ; Middle Aged