Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

OBJECTIVE To explore the clinical efficacy of Fuxin Mixture in the treatment of patients with heart failure of yang deficiency and water inundation type after myocardial infarction and its effect on serum myocardial injury and ventricular remodeling re-lated indicators.METHODS A total of 92 patients with heart failure of yang deficiency and water inundation type after myocardial infarction were randomly divided into an observation group and a control group(n=46).The control group was given basic western medicine treatment,and the observation group was given Fuxin Mixture on the basis of the control group's treatment.The TCM syn-drome scores,ultrasound cardiogram indices[left ventricular ejection fraction(LVEF),left ventricular Tei index,and stroke volume(SV)],serum myocardial injury indices[serum N-terminal pro-B-type natriuretic peptide(NT-ProBNP)level,serum high-sensitiv-ity cardiac troponin I(hs-cTnI)level,and creatine kinase isoenzyme(CK-MB)level],serum ventricular remodeling indices[hypoxi-a-inducible factor 1α(HIF-1α),soluble growth-stimulated gene expressed 2 protein(sST2),and angiotensin Ⅱ(AngⅡ)],and changes in the Minnesota Living with Heart Failure Questionnaire(MLHFQ)were evaluated before and after treatment.The two groups were followed up for 1 year after treatment to observe the occurrence of major adverse cardiovascular events.RESULTS After treat-ment,the TCM syndrome scores of both groups were significantly reduced(P＜0.01),the observation group was better than the control group(P＜0.05,P＜0.01),and the total effective rate of TCM in the observation group was better than that of the control group(P＜0.05);the serum ultrasound cardiogram indexes,myocardial injury,ventricular remodeling indexes and MLHFQ scores of the two groups were significantly reduced(P＜0.01),and the observation group was better than the control group(P＜0.01).During the fol-low-up period,the all-cause mortality,malignant arrhythmia rate and acute heart failure rate of the observation group after treatment were significantly lower than those of the control group(P＜0.05,P＜0.01).CONCLUSION Fuxin Mixture has significant clinical efficacy in the treatment of patients with heart failure of yang deficiency and water inundation type after myocardial infarction,and the efficacy mechanism may be related to its reduction of myocardial injury and inhibition of ventricular remodeling.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal copy number variations (CNVs) in addition to trisomies 21, 18, and 13. METHODS: A total of 37 306 pregnant women underwent the NIPT test. For those with fetal CNVs indicated by NIPT and accepted invasive prenatal diagnosis, amniotic fluid samples were obtained for chromosomal karyotyping analysis and chromosome microarray analysis (CMA). All cases were followed up. RESULTS: Among the 37 306 cases, 78 (0.209%) were predicted to have fetal CNVs. Among these, 52 pregnant women accepted invasive prenatal diagnosis, and 15 of them (28.85%) obtained a consistent result. Follow up of 26 women who refused invasive prenatal diagnosis have found 2 cases with spontaneous abortion, 2 with induced labor for fetal malformation indicated by ultrasonography, and 1 had multiple malformations and a consistent result by CMA, which yielded an abnormal rate of 19.23%. CONCLUSION NIPT can signal fetal chromosomal abnormalities through detection of gain and/or loss of fetal DNA copies. Combined chromosomal karyotyping and CMA can increase the detection rate for common chromosomal aneuploidies and CNVs, thereby provide a basis for genetic counseling for the affected families.

Objective To explore the mutation characteristics of DMD gene in patients with Duchenne or Becker muscular dystrophy and female carriers, to provide effective prenatal diagnosis. Methods Samples were collected from 94 male patients clinically diagnosed with Duchenne or Becker muscular dystrophy and 121 corresponding female relatives from Qingdao Women and Children′s Hospital from June 2011 to October 2018. Multiplex ligation-dependent probe amplification (MLPA) was used to detect their DMD gene, and 23 high risk pregnants were performed prenatal diagnosis. Any candidate of DMD gene single-exon deletion was validated by further PCR amplification. The sample with whole DMD gene deletion was confirmed by chromosomal microarray analysis (CMA) to detect copy number variations and break site. Results Among 94 clinical Duchenne or Becker muscular dystrophy patients, 66(70.2%, 66/94) were detected gene mutation; 56 cases were exon deletion mutation and 10 cases were duplication mutation. In 121 female relatives, 48 cases (39.7%, 48/121) were diagnosed as carriers. The mutation carrying rate, was 64.5% (40/62) identified in 62 mothers of Duchenne or Becker muscular dystrophy patients. Five Duchenne or Becker muscular dystrophy fetuses and 5 carrier fetuses were prenatally diagnosed in 23 high risk pregnants. Two children with the entire DMD gene deletion were identified more deletions at Xp21, with deletions of 6.66 Mb and 10.64 Mb respectively. Conclusions MLPA may be an important method to detect DMD gene mutation of deletion and duplication. Therefore, the diagnosis of probands, female carriers and making an effective prenatal diagnosis are essential to reduce the birth of children with Duchenne or Becker muscular dystrophy.

OBJECTIVETo assess the value of combined chromosome karyotype analysis and multiplex ligation probe amplification (MLPA) assay for the prenatal diagnosis of fetuses with abnormalities detected by ultrasonography.

METHODSWith informed consent obtained, 72 pregnant women with ultrasound detected fetal structural abnormalities underwent percutaneous umbilical cord blood sampling. Routine karyotype analysis and MLPA assay were used to detect potential chromosomal deletions and duplications.

RESULTSFive cases were found with an abnormal karyotype. In addition, the MLPA has detected 2 chromosomal microdeletions and 1 microduplication. Together the two methods have yielded a detection rate of 11.11%.

CONCLUSIONFor fetal abnormalities revealed by ultrasonography, combined karyotype analysis and MLPA assay can provide a better option for its efficiency and simplicity.

Adult ; Chromosomes ; genetics ; Female ; Fetus ; abnormalities ; Humans ; Karyotyping ; methods ; Ligation ; methods ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; methods ; Young Adult

OBJECTIVETo characterize the clinical feature of a child with infantile spasm, karyotype and molecular cytogenetic analyses were performed to investigate the cause of disease and choose a suitable prenatal diagnostic method for the couple with the child.

METHODRoutine G-banding was performed to analyze the karyotype of the patient and her parents, and molecular karyotyping was performed using SNP array. Confirmation and segregation studies were performed by fluorescence in situ hybridization (FISH).

RESULTThe patient presented with severe psychomotor retardation, epilepsy, muscular hypotonia, stereotypic behavior and facial phenotype characterized by bulging forehead, cupid-bow upper lip, large ears with prominent lobes and pronounced occipital protuberance. Subdural collection of fluid was shown in cranial CT scan, and frequent interictal epileptiform discharges and hypsarrhythmia was shown in EEG monitoring. Routine G-banding revealed a normal female karyotype. A 2.03 Mb deletion in 5q14.3 including MEF2C gene was revealed using SNP array, and the patient's molecular karyotype was arr 5q14.3 (87 538 430-89 565 757) ×1. FISH with locus-specific probe RP11-293L20 from the deleted region on metaphase preparations of the patient and her parents confirmed the de novo occurrence of the deletion.

CONCLUSIONThe microdeletion of 5q14.3 was the cause of infantile spasm in the patient. FISH confirmed the de novo occurrence of the microdeletion. SNP array should be chosen as prenatal diagnostic method for the couple with the child.

Child ; Chromosome Deletion ; Chromosome Structures ; Chromosomes ; Cytogenetic Analysis ; Epilepsy ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Karyotyping ; Phenotype ; Pregnancy ; Prenatal Diagnosis ; Spasms, Infantile ; genetics ; Syndrome