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.

By consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing methods of Curculiginis Rhizoma（CR） were systematically combed and verified， in order to provide a basis for the development and utilization of famous classical formulas containing CR. The results of herbal textual research showed that the name Xianmao was first recorded in Leigong Paozhilun， the name of CR was used in all dynasties and this name came from its efficacy and morphological characteristics， the mainstream source for CR of the past dynasties was the rhizome of Curculigo orchioides or C. capitulata， since modern times， C. orchioides has been the main source of commodities. In ancient times， most of the places of origin of the description were the western regions and southwest China， while in modern times， Sichuan and Guizhou were regarded as genuine places. Since modern times， its quality has been summarized as the best with thick roots， firm texture and black-brown surface， the harvesting and processing methods recorded in the past dynasties are mainly sun drying after harvest in the second， eighth and ninth months of the lunar calendar， and most of them are harvested in autumn and winter in modern times. In ancient times， there were many processing methods of CR， mainly in processing with rice swill， while in modern times， stir-frying with wine was the main processing method. The nature， taste， meridian tropism， functions and indications of CR are basically consistent from ancient to modern times， the taboos for taking are to avoid iron， cow's milk， and beef. Although there are some differences in the understanding of the toxicity of CR in the past dynasties， most of the materia medica are clear that it has a certain toxicity. Based on the research conclusion， it is suggested that the rhizome of C. orchioides of Lycoris family should be used as its source in the famous classical formulas， and the corresponding processing method should be selected according to the processing requirements in the formulas， while the raw products is recommended to be selected as medicine if the processing requirement is not specified.

Objective This study aims to evaluate the application of BOPPPS teaching model combined with case and problem-based learning(CPBL)and the scenario simulation in cardiovascular internal medicine education.Methods The study included cardiovascular internal medicine graduates from the 2022 and 2023 cohorts.The 2022 cohort(n=12)served as the control receiving traditional teaching methods,while the 2023 cohort(n=16)was the experimental group,which utilized the BOPPPS model combined with CPBL and scenario simulation.The students theoretical examination scores were assessed and a questionnaire survey was conducted to evaluate self-assessment of abilities and teaching satisfaction among the students in the experimental group.Results The examination scores of experimental group were significantly higher(97.94±3.46)as compared to that of control group(69.13±12.88)(P＜0.05).Over 93.75%of the students in the experimental group strongly or somewhat agreed that the combined teaching model stimulated their learning interest,improved learning efficiency,facilitated their capacity building of autonomous learning,theoretical knowledge,helped establish clinical reasoning,and improved their teamwork skills.Additionally,over 93.75%of the students were highly satisfied with the course design,emphasizing key content,pro-moting teacher-student interaction,and expressed willingness to continue with this teaching method in the future.Conclusions The application of the BOPPPS teaching model combined with CPBL and scenario simulation in cardio-vascular internal medicine education achieved excellent teaching outcomes.It effectively stimulated students interest in learning,enhanced autonomous learning abilities,and received high satisfaction ratings from students.

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.

Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

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.