Objective:To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy (HCM) families.Methods:A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from February 2014 to July 2018, and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands. The probands carrying the MYH7-R453C mutation were screened out, and their family members carrying the mutation were verified using Sanger sequencing. Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls. Clinical data such as echocardiography, 12-lead electrocardiogram, and cardiac magnetic resonance imaging of the probands and their family members were collected, and the correlation between patient genotype and clinical phenotype was analyzed. Endpoint or key events were recorded through hospital re-examination or telephone follow-up.Results:The MYH7-R453C mutation was detected in 5 HCM probands, and clinical data and genetic results of 20 family members, including probands, were collected. Among them, 13 carried the MYH7-R453C mutation, of which 12 were diagnosed with HCM, and one child (F1Ⅲ 5) experienced early changes of HCM. The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms. Among the 12 patients diagnosed with HCM, 2 experienced (F2Ⅱ 7, F5Ⅰ 2) sudden cardiac death, 2 experienced (F1Ⅲ 1, F3Ⅲ 3) events of sudden cardiac death survival, 2(F1Ⅱ 2, F3Ⅱ 1) died from heart failure during the follow-up period. Combined with the initial visit and follow-up, 4 families (F1, F2, F3, F5) had a family history of sudden death, among which 3 families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival. Conclusions:In the five families with HCM carrying MYH7-R453C mutations, genotype is highly correlated with clinical phenotype, and patients have a high risk of sudden death and poor prognosis. Early diagnosis of individuals carrying the MYH7-R453C gene mutation, both within the patient′s family and in the patients themselves, is crucial for initiating early treatment, preventing sudden death, and assessing prognosis.

Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10^-3 g·kg^-1·（3 d）^-1］， Shenqi Yiliu prescription group （27 g·kg^-1·d^-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Objective:To study the safety and feasibility of application of delayed umbilical cord clamping (DCC) in very preterm and extremely preterm infants.Methods:Based on the previous improvement projects of temperature management and respiratory support, we conducted a prospective study on the effect of umbilical cord clamping quality improvement project using the clinical data of very preterm and extremely preterm infants admitted to Guangdong Maternal and Child Health Hospital. The infants admitted from July to December 2020 who underwent immediate umbilical cord clamping (ICC) were included in the ICC group, and the infants admitted from January to June 2021 who underwent DCC were involved in the DCC group. The incidence of asphyxia, hypothermia, endotracheal intubation within 24 h after birth, endotracheal intubation within 72 h after birth, bronchopulmonary dysplasia and other complications, mechanical ventilation duration and total oxygen therapy duration were compared between the two groups.Results:A total of 45 cases were included in ICC group and 54 cases in DCC group. The gestational age of the two groups was (29.3±1.7) weeks and (29.6±1.4) weeks, and the birth weight was (1 250±332) g and (1 257±306) g. The differences were not statistically significant ( P>0.05). There were no significant differences between the two groups in the incidence of asphyxia, hypothermia, bronchopulmonary dysplasia and other complications related to preterm infants, tracheal intubation rates within 24 and 72 h, and the neonatal temperature at admission to NICU ( P>0.05). Conclusions:Delayed umbilical cord clamping does not increase the risks of asphyxia, hypothermia or invasive respiratory support in very preterm and extremely preterm infants.

Objective:To study the risk factors of failure using nasal high frequency oscillatory ventilation (nHFOV) as initial therapy in the treatment of respiratory distress syndrome (RDS) in very low birth weight infants (VLBWIs).Methods:From January 2018 to December 2021, VLBWIs with RDS initially supported by nHFOV in NICU of our hospital were retrospectively analyzed. They were assigned into success and failure groups according to the ventilation efficacy. Demographic data and clinical outcomes of the two groups were compared. Risk factors of initial nHFOV failure were analyzed using binary Logistic regression method.Results:A total of 135 infants were included, including 103 in the success group and 32 in the failure group. The initial nHFOV failure rate was 23.7%. The failure group had lower pH (7.26±0.09 vs. 7.33±0.08) and PaO 2 [61.0 (49.6, 77.2) mmHg vs. 83.6 (64.4, 99.0) mmHg] than the success group ( P<0.05) and higher PaCO 2 than the success group [49.0 (42.3, 58.1) mmHg vs. 43.4 (36.0, 50.0) mmHg] ( P<0.05). Using PaCO 2 as predictor, the area under the curve (AUC) was 0.682 (95% CI 0.575-0.788) and the cut-off value was 44.8 mmHg for nHFOV failure and the AUC was 0.716 (95% CI 0.615-0.817) and the cut-off value was 67.1 mmHg for nHFOV success. The incidences of early onset sepsis (EOS), shock within 3 d and hemodynamically significant patent ductus arteriosus (hsPDA) in the failure group were significantly higher than the success group (40.6% vs. 7.8%, 53.1% vs. 2.9%, 31.3% vs. 13.6%, P<0.05, respectively). Binary logistic regression analysis found that PaO 2<67.1 mmHg ( OR=5.458,95% CI 1.730-17.220) on the first blood gas analysis and shock within 3 d ( OR=26.585,95% CI 3.854-183.396) were independent risk factors for initial nHFOV failure ( P<0.05). Conclusions:The failure of initial nHFOV is correlated with the first blood gas parameters, EOS, hsPDA and shock within 3 d. Shock within 3 d and low PaO 2(<67.1 mmHg) were independent risk factors for initial nHFOV failure.

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane (CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol (PEG) was used to modifying magnetic graphene oxide (MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine (TCM). With this strategy, the constructed PEGylated MGO (PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of HeLa cell membrane (HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity (116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin, and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surface engineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.

Objective:To study the effects of quality improvement project of respiratory support in delivery room on the short-term clinical outcomes of very/extremely low birth weight infant (VLBWI/ELBWI).Methods:The clinical data of VLBWI/ELBWI before and after the implementation of the quality improvement project of respiratory support in delivery room in our hospital were retrospectively analyzed. The incidences of endotracheal intubation in delivery room, total endotracheal intubation within 72 h after birth, mechanical ventilation duration, total oxygen therapy duration, bronchopulmonary dysplasia (BPD) and other complications were compared between pre-improvement group (from January to October 2019) and post-improvement group (from January to December 2020).Results:A total of 85 cases were included in pre-improvement group and 85 in post-improvement group. The gestational age of the two groups were (29.2±1.4) weeks and (29.1±1.5)weeks and the birth weight were (1 180±195) g and (1 186±207) g, without significant differences ( P>0.05). After the implementation of the quality improvement project, the incidence of endotracheal intubation in the delivery room decreased from 32.9% to 2.4%, and the total incidence of endotracheal intubation within 72 h after birth decreased from 58.8% to 27.1%. The usage of pulmonary surfactant significantly decreased from 54.1% to 38.8% ( P<0.05) and the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) also significantly decreased from 17.6% to 5.9% ( P<0.05).No significant differences existed among other complications ( P>0.05). Conclusions:The quality improvement project of respiratory support in the delivery room can significantly reduce the incidence of endotracheal intubation in VLBWI/ELBWI without increasing short-term adverse outcome.

Objective:To study the efficacy of nasal intermittent positive pressure ventilation (NIPPV) and minimally invasive surfactant therapy (MIST) in very preterm infants with respiratory distress syndrome (RDS).Methods:From January to December 2020, very preterm infants (gestation age ≤30 weeks) with RDS born and treated in our hospital were randomly assigned into NIPPV group and nasal continuous positive airway pressure (NCPAP) group. Both groups were treated with MIST technique. The following items were compared between the two groups:adverse reactions during MIST, partial pressure of carbon dioxide (PaCO 2) at 2 h after MIST, the incidences of intubation within 72 h, two or more doses of pulmonary surfactant (PS), frequent apnea, other complications and the parameters of respiratory support treatment. Results:A total of 62 cases were included, with 32 in the NIPPV group and 30 in the NCPAP group. Compared with the NCPAP group, the NIPPV group had lower incidences of bradycardia (6.3% vs. 30.0%), decreased oxygen saturation (12.5% vs. 40.0%) and apnea (6.3% vs. 30.0%) during MIST ( P<0.05). No significant difference existed in the incidence of regurgitation ( P>0.05). PaCO 2 at 2 h after MIST [40.1(38.2,43.8)mmHg vs. 48.3(44.1,50.0)mmHg], the incidences of intubation within 72 h (6.3% vs. 30.0%), two or more doses of PS (6.3% vs. 30.0%)and frequent apnea (6.3% vs. 30.0%) in NIPPV group were lower than NCPAP group ( P<0.05). No significant differences existed between the two groups on the following items: the durations of invasive ventilation, non-invasive ventilation, oxygen therapy, the incidences of bronchopulmonary dysplasia, intraventricular hemorrhage (≥Ⅲ), periventricular leukomalacia, retinopathy of prematurity (≥Ⅱ), necrotizing enterocolitis (≥Ⅱb), nasal injury, air leak and death ( P>0.05). Conclusions:Combining NIPPV and MIST can reduce the incidence of adverse reactions during PS administration without increasing respiratory support duration and common complications in preterm infants. It is recommended for clinical use.

Objective:To identify the differences in clinical manifestations between Chinese giant cell arteritis (GCA) patients and polymyalgia rheumatica (PMR) patients.Methods:Twelve GCA patients were included during September 2010 to September 2019 in our hospital. Clinical and laboratory data were collected. Twenty-four age and sex-matched pure PMR patients were selected as control. Statistical analysis was performed using Statistical product and service solutions (SPSS) software. The categorical variables were tested by chi square test, and the continuous variables were expressed by mean and standard deviation ( ± s). The comparison between groups was conducted by t-test. P<0.05 was considered statistically significant. Results:In these 12 GCA patients, the onset age was 55-70 (67±7) years old, and male to female ratio was 1∶11. The most common initial symptom of GCA was the same as PMR (7/12, 58%) . Compared with PMR patients, the specific clinical manifestations of GCA patients were scalp pain ( P=0.031), mandibular claudication ( P=0.031) and migraine ( P=0.000). The creatine kinase of GCA (60±27) U/L patients was higher than that in PMR (41±15) patients ( t=1.098, P=0.029). There was no significant difference in other laboratory tests including erythrocyte sedimentation rate, C reactive protein level. Seven of 12 GCA patients were first diagnosed with PMR, then were diagnosed with GCA during follow-up. No obvious differences could be found in clinical manifestations between these 7 patients and 24 pure PMR patients. Through imaging examinations, we found that 9 of the 12 GCA patients had arterial stenosis, 5 had thickened vascular walls, 5 had atherosclerosis, and 2 had rough endometrium. Conclusion:GCA patients and PMR may have similar clinical presentations. The presence of scalp pain, mandibular claudication and migraine during the course of the disease implies that GCA is more likely. Vascular ultrasound, arterial CTA, and positron emission tomograph (PET)/CT play an increasingly important role in the diagnosis of GCA.

Objective To explore the correlation between pregnancy-related anxiety and serum 25 (OH)D level during early pregnancy. Methods A radioimmunoassay was used to determine the serum 25 (OH)D levels of 2 122 early pregnant women in Maanshan Maternal and Child Health Care Hospital, from June 2015 to 2016. Data were collected using a questionnaire. Results The mean serum 25(OH)D level was(29.71±32.27)nmol/L.About 15.2% of the subjects had adequate,22.6% had insufficient,45.1% had deficient,and 17.1% had severely deficient serum 25(OH)D levels.The type of housing and testing seasons were significantly associated with the serum 25(OH)D level.Single factor logistic regression analysis results show that pregnancy-related anxiety incidence in the group deficient in 25(OH)D was higher than that in the adequate group, which has a statistically significant difference (P<0.05). After adjusting for the maternal age,BMI,and educational level,multivariate logistic regression analysis results showed that the difference was statistically significant. Conclusion The serum 25(OH)D level in early pregnant women was inadequate. Furthermore, lack of serum 25(OH)D in early pregnancy and pregnancy-related anxiety were negatively correlated.