Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

A 1-year and 9-month-old male proband presented with clustered rice grain-sized flat smooth red papules on the face, trunk and limbs for 1.5 years, without fever, joint swelling, or pain. The proband′s sister aged 7 years ever experienced swelling and pain in the finger joints of both hands at the age of 2 years, and had intermittent fever and papules all over the body at the same time, and the papules gradually regressed with the subsidence of fever. The proband′s mother aged 27 years suffered from swelling and pain in the finger joints of both hands when she was young, gradually leading to finger deformities, and experienced intermittent knee swelling and pain at the age of 12 years without obvious skin lesions on the body. No abnormality was found in ophthalmological and systemic physical examinations of the 3 patients. Whole-exome sequencing showed that the proband, his sister and mother all had a heterozygous missense mutation c.1001G>A (p.R334Q) in exon 4 of the NOD2 gene. A diagnosis of Blau syndrome was made. The proband was treated with topical moisturizing cream all over the body; during the 52-week follow-up, no joint swelling and pain or eye symptoms were found in the proband, while erythema and depressed scars were observed on the face, trunk and limbs. The proband′s sister and mother were treated with subcutaneous injections of adalimumab at initial doses of 40 mg and 80 mg respectively, followed 1 week later by injections at 20 mg and 40 mg respectively, and then treated with injections at 20 mg and 40 mg respectively every 2 weeks; after 12-week treatment, the joint swelling and pain were markedly relieved in the proband′s sister and mother, and most skin lesions subsided in the proband′s sister; at week 52 during the follow-up, there was no joint swelling, pain or skin lesions in the proband′s sister, and there was no swelling or pain in the knee joints of the proband′s mother, while no improvement was observed in her finger deformities. During the treatment, no eye symptoms or adverse reactions were observed neither in the proband′s sister nor in his mother.

Pregnancy with autoimmune diseases is a challenging area that involves multidisciplinary management of immunology, rheumatology, and obstetrics. During pregnancy, the maternal immune system dynamically regulates the balance between maintaining immune tolerance to the fetus and autoimmune. However, for women with common systemic autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis, this balance can be upset, leading to exacerbation or recurrence of the disease and significantly increasing the risk of pregnancy complications. This paper describes the adaptive changes of the immune system during pregnancy and the effects of systemic autoimmune diseases on pregnancy outcomes, proposes multidisciplinary management strategies and challenges in perinatal pregnancy, and aims to provide references for optimizing clinical practice and improving pregnancy outcomes.

Preeclampsia is a serious threat to maternal and fetal health and safety, and is an important cause of maternal death. At present, there is no effective treatment except termination of pregnancy. It is an important measure to identify high-risk groups for standardized management and early prevention to reduce the incidence of preeclampsia and maternal and fetal mortality. Chronic patients are at high risk of preeclampsia, and their morbidity and mortality have increased significantly. It is of great significance for chronic patients to regulate preconception guidance and formulate preconception management strategies to reduce the incidence of preeclampsia and improve maternal and infant outcomes.

Obstetric antiphospholipid syndrome (APS) is an autoimmune disease that leads to adverse pregnancy outcomes. In the past decade, the diagnosis and treatment of obstetric APS has been based on the Sapporo classification standard revised in 2006. Considering the limitations of this standard, the American College of Rheumatology (ACR) and the European League against Rheumatic Diseases (EULAR) developed a new APS classification standard in 2023. The new standard has high specificity, greatly reduces the misdiagnosis of obstetric APS, and provides clinical basis for further standardized treatment.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objectives:To investigate the risk factors and short-term prognosis of early pulmonary hypertension (PH) in preterm infants.Methods:A retrospective case-control study was performed in preterm infants (gestational age <32 weeks) in the neonatal intensive care unit (NICU) of the Children′s Hospital, Zhejiang University School of Medicine from January 2012 to December 2019. Eighty preterm infants with a diagnosis of PH between 3 and 14 days (early PH group) were matched in gestational age and sex with the controls (1∶2) of the same period in NICU. Perinatal clinical records, complications, echocardiography and early outcomes were collected. Characteristics and outcomes were compared between the two groups with t-test, nonparametric test or Chi-square test. Multivariate Logistic regression was used to analyze the predictive factors of early PH. Results:The gestational age of the early PH group and the control group were both (27.9±1.4) weeks, and 52 (65.0%) and 104 (65.0%) were males in each group, respectively. Univariate analysis showed that birth weights were lower in the early PH group than those in the control group (1 030 (850, 1 200) vs. 1 110 (1 000, 1 278) g, Z=-3.27, P=0.001). The early PH group had higher rates of pregnancy-induced hypertension, prolonged rupture of membranes (PROM) >1 week, born by caesarean, small for gestational age (SGA), 1 and 5 min Apgar score ≤7 scores, neonatal respiratory distress syndrome (RDS) and hemodynamic significant patent ductus arteriosus (hsPDA) (12.5% (10/80) vs. 3.8% (6/160), 11.2% (9/80) vs. 3.8% (6/160), 48.8% (39/80) vs. 28.8% (46/160), 10.0% (8/80) vs. 1.9% (3/160), 70.8% (51/72) vs. 51.7% (74/143), 50.0% (36/72) vs. 20.3% (29/143), 88.8% (71/80) vs. 59.4% (95/160), 85.0% (68/80) vs. 22.5% (36/160), χ 2=6.56, 5.12, 3.31, 8.05, 7.17, 20.05, 21.58, 84.84, all P<0.05). Multivariate Logistic regression analysis showed that the independent predictive factors of early PH were PROM >1 week, SGA, 5 min Apgar score ≤7 scores, nenonatal RDS and hsPDA ( OR=10.40, 18.61, 4.47, 4.13, 20.10, 95% CI 1.93-56.12, 2.82-122.76, 1.91-10.46, 1.50-11.39, 8.28-48.80, all P<0.05),respectively. Infants with early PH had higher incidence of bronchopulmonary dysplasia (BPD), BPD associated PH, severe intraventricular hemorrhage (IVH), extrauterine growth retardation (EUGR), laser treatment for retinopathy of prematurity (ROP) and mortality than the controls (all P<0.05). The duration of invasive mechanical ventilation was also longer in the early PH group than that in the control group ( P<0.05). Conclusions:Risk of early PH will be increased in preterm infants with PROM >1 week, SGA, 5 min Apgar score ≤7 scores, and comorbidities of nenonatal RDS and hsPDA. Early PH is associated with increased mortality, BPD, BPD associated PH, severe IVH, EUGR and laser treatment for ROP.

Objective:To investigate the effect of astragaloside IV (AS-IV) on the secretion of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4) by high glucose injured human umbilical vein endothelial cells (HUVECs), so as to lay a foundation for further study on AS-IV improving angiogenesis by regulating SDF-1 α/CXCR4 axis of endothelial cells.Methods:HUVECs were isolated and cultured from the umbilical vein of full-term healthy newborns and identified by von Willebrand factor (vWF) combined with 4-diamino-2-phenylindole (DAPI) nuclear staining. The obtained HUVECs was cultured in EGM-2 medium with 30 mmol/L glucose for 120 h to obtain high glucose damaged HUVECs. After intervention with different concentration gradients (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L, 400 mg/L) AS-IV for 72 hours, the contents of SDF-1α and CXCR4 were detected by enzyme linked immunosorbent assay (ELISA) method to determine the best concentration of AS-IV. The supernatant of damaged HUVECs were collected at 6, 12, 24, 48 and 72 hours after intervention with the best concentration of AS-IV, and the contents of SDF-1α and CXCR4 were detected by ELISA method to determine the best action time of AS-IV. The damaged HUVECs was randomly divided into experimental group and control group, and the blank group was set up at the same time. The experimental group was treated with the best concentration of AS-IV and the best time, the control group and the blank group were treated with the same volume of phosphate buffered saline (PBS) solution, and the contents of SDF-1α and CXCR4 in each group were detected by ELISA method.Results:The vWF factor on the cell membrane was green fluorescence, and the nucleus was blue after DAPI staining. When the fusion image showed green fluorescence, HUVECs were identified by blue fluorescence. The expression of SDF-1α in damaged HUVECs was the best when treated with AS-IV of 100 mg/L for 24 hours (1 642.87 pg/ml), and the expression of CXCR4 in damaged HUVECs was the best when treated with AS-IV of 50 mg/L for 48 hours (8.44 ng/ml). Compared with the control group, the contents of SDF-1α and CXCR4 in the experimental group were significantly increased, and the difference was statistically significant ( P<0.05). While the contents of SDF-1α and CXCR4 in the experiment group were slightly less than those in the blank group and there was no statistically significant difference ( P>0.05). Conclusions:AS-IV can promote the expression of SDF-1α and CXCR4 in HUVECs damaged by high glucose to return to normal physiological level, so as to play the role of vascular repair and neovascularization.

With the continuous elucidation of the molecular mechanism of primordial follicle activation, clinical in vitro activation (IVA) has gradually become a clinical treatment for premature ovarian insufficiency (POI) and reduced ovarian reserve (DOR). This article will review the mechanism of phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K), hippo signal and mammalian target of rapamycin complex 1 (mTORC1) signal involved in the activation of primordial follicles, and the application of IVA in patients with POI and DOR.

Objective:The correlation between in vitro fertilization-embryo transfer (IVF-ET) pregnancy and preeclampsia was studied by the propensity score matching. Methods:4 823 pregnant women with delivery gestational weeks >24 weeks were selected, including 481 in IVF group and 4 342 in natural pregnancy group. The propensity score model was established by using 16 maternal covariates, and the propensity score matching samples (924 cases) were obtained to evaluate the correlation between IVF-ET and preeclampsia.Results:⑴ Before matching, the incidence of preeclampsia in the IVF group was higher than that in the natural pregnancy group (9.8% vs 3.3%, P<0.05). Multivariate regression analysis showed that IVF-ET was a risk factor for preeclampsia (a OR=1.887; 95% CI: 1.23-2.89, P=0.003); After matching propensity score, OR was 2.067 (95% CI: 1.24-3.44, P=0.005), confirming that there was a significant association between IVF-ET and preeclampsia. ⑵ Before matching, the incidence of preeclampsia in IVF group was significantly higher than that in natural pregnancy group in singleton pregnancy (9.0% vs 3.1%, a OR=2.530, 95% CI: 1.63-3.94, P>0.05); In twin pregnancy, there was no significant difference in the incidence of preeclampsia between the two groups (12.7% vs 7.5%, a OR=1.004, 95% CI: 0.35-2.87, P=0.994); The result of propensity score matching is consistent with that before matching. Conclusions:Propensity score matching analysis showed that the risk of preeclampsia increased after IVF-ET pregnancy, IVF-ET was an important risk factor for preeclampsia in singleton pregnancy, and IVF-ET did not increase the risk of preeclampsia in twin pregnancy. It is suggested that the correlation between IVF and preeclampsia may be disturbed by twin pregnancy.