ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective:To explore the clinical and genetic characteristics of three children with Leguis syndrome.Methods:Three children suspected as Legius syndrome at the Henan Children′s Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c. 751C>T (p.Arg251Ter194) in child 1, c. 229A>T (p.Lys77Ter368) in child 2, and c. 1044_1046delinsC (p.R349fs *11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. Conclusion:All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Objective:To evaluate the clinical efficacy and safety of hematoporphyrin monomethyl ether (HMME) -mediated photodynamic therapy (PDT) in the treatment of facial port-wine stains (PWS) in children with Sturge-Weber syndrome (SWS) .Methods:A retrospective analysis was conducted based on the clinical data from SWS children treated with HMME-PDT at the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from December 2020 to January 2022. HMME was intravenously injected at a dose of 5 mg/kg, followed by the irradiation of SWS lesions with a 532-nm light-emitting diode light source, and the treatment interval was 8 weeks. The efficacy of HMME-PDT for SWS was evaluated based on the subsidence of erythema and changes in the number and density of blood vessels under a dermoscope before and after treatment; adverse events after treatment were recorded. Fisher's exact test was used to analyze differences in efficacy.Results:A total of 15 children with SWS were included, comprising 7 males and 8 females, with an average age of 4.74 years (range, 1 - 14 years). There were 10 cases of clinical phenotype Ⅰ and 5 cases of type Ⅱ; 10 patients were accompanied by glaucoma, 6 by epilepsy, and 10 showed abnormalities on craniocerebral imaging. After HMME-PDT treatment, 4 out of 15 patients achieved complete remission of SWS lesions, 3 showed marked improvement, and 5 achieved improvement. Among 8 cases receiving 2 sessions of treatment, 1 achieved marked improvement and 4 showed improvement; among 7 cases receiving 3 or more sessions of treatment, 4 achieved complete remission, 2 achieved marked improvement, and 1 showed improvement; the proportions of patients achieving complete remission and marked improvement were significantly higher among those receiving 3 or more sessions of treatment than those receiving 2 sessions (both P < 0.05). Among 7 patients with pink-type PWS, 1 recovered completely, 2 achieved marked improvement, and 4 showed improvement; among 4 patients with purplish-red-type PWS, 3 recovered completely and 1 showed marked improvement; among 4 patients with thickened-type PWS, 1 achieved improvement; there was a significant difference in the proportions of patients achieving marked improvement or improvement among the patients with different types of PWS (both P < 0.05). Among 14 patients with lesions involving the central face region, 4 achieved marked improvement and 2 showed improvement; among 15 with lesions involving the lateral face region, 5 recovered completely, 3 achieved marked improvement, and 4 showed improvement; the recovery rate of lesions was higher in the lateral face region than in the central face region ( P < 0.05). Under a dermoscope, the skin lesions showed 4 vascular patterns: short rod-shaped vessels in 3 cases, linear vessels in 4, reticular vessels in 5, and mixed-type vessels in 3. The 3 patients with short rod-shaped vessels all recovered completely; among the 4 patients with linear vessels, 2 achieved marked improvement, and 2 showed improvement; among the 5 patients with reticular vessels, 1 recovered completely, 1 achieved marked improvement, and 3 showed improvement; the 3 patients with mixed-type vessels all showed poor response to the treatment; the proportions of patients who recovered completely and those who achieved improvement significantly differed among the patients with 4 different vascular patterns (both P < 0.05). All the children experienced varying degrees of pain, swelling, purpura, and crusting after treatment, but none exhibited exacerbation of ocular or neurological complications. Conclusion:HMME-PDT was safe and effective in the treatment of PWS in children with SWS, and its efficacy was related to the number of treatment sessions, lesion types and locations.

Objective To investigate the relationship between serum leucine-rich a-2 glycoprotein-1(LRG1),transforming growth factor-β1(TGF-β1)and the carotid intimal middle layer thickness(IMT)and short-term poor prognosis in acute cerebral infarction(ACI).Methods A total of 123 patients with ACI who were treated in Guangji Hospital of Suzhou from January 2020 to January 2023 were selected,and the patients were divided into normal group(23 cases),thickened group(30 cases)and plaque group(70 cases)according to the IMT,and 35 healthy physical examiners in Guangji Hospital of Suzhou during the same period were se-lected as the health control group,and the serum LRG1,TGF-β1 levels and IMT of 4 groups were compared.The patients were followed up for 3 months and divided into good prognosis group(75 cases)and poor prog-nosis group(48 cases)according to the prognosis.The correlation between serum LRG1,TGF-β1 and IMT was analyzed by Pearson method.Univariate and multivariate Logistic regression were used to analyze the risk factors of short-term poor prognosis in ACI patients.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of serum LRG1 and TGF-β1 for the short-term poor prognosis of ACI.Re-sults The serum LRG1 level in health control group,normal group,thickened group and plaque group in-creased sequentially,and TGF-β1 level decreased sequentially(P＜0.05).Pearson correlation analysis showed that serum LRG1 was positively correlated with IMT,while TGF-β1 was negatively correlated with IMT(P＜0.05).Age,proportion of patients with diabetes,the National Institutes of Health Stroke Scale(NIHSS)score at admission,low-density lipoprotein cholesterol(LDL-C),fasting plasma glucose(FPG),white blood cell count(WBC),C-reactive protein(CRP)and serum LRG1 levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05),time from onset to thrombolysis was longer than that in the good prognosis group(P＜0.0.05),while the serum TGF-β1 level was lower than that in the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score,long time from onset to thrombolysis,elevated serum LRG1 level and decreased TGF-β1 level were risk factors for short-term poor prognosis in ACI patients(P＜0.05).ROC curve results showed that the area under the curve of the sin-gle and combined detection of serum LRG1 and TGF-β1 for predicting the short-term prognosis of ACI pa-tients were 0.824,0.708 and 0.902,respectively.Conclusion ACI patients have elevated serum LRG1 levels and decreased TGF-β1 levels.Serum LRG1 and TGF-β1 levels are closely related to the IMT and the short-term prognosis of ACI patients,and the combined detection of serum LRG1 and TGF-β1 levels have high ref-erence value for predicting the short-term poor prognosis of ACI patients.

Objective To explore the clinical and genetic characteristics of 17α-hydroxylase/17,20-lyase deficiency(17OHD)in childhood.Methods The clinical features,laboratory and imaging examination results,gene mutation characteristics of 4 children diagnosed with 17OHD in Children's Hospital Affiliated to Zhengzhou University from January 2016 to December 2022 were retrospectively analyzed,and the literature was reviewed and summarized.Results At the time of diagnosis,the age of 4 children ranged from 11 months and 21 days to 10 years and 6 months.All patients had karyotypes of 46,XY.Social gender:1 male and 3 females.The chief complaints were 1 case of short penis,1 case of inguinal mass,and 2 cases of grade 2 hypertension,and 3 cases of testes were found in scrotum,groin and inguinal annulus,respectively.The levels of cortisol,testosterone,and androstenedione decreased at 8 o'clock in 4 children,while the levels of adrenocorticotropic hormone,progesterone,luteinizing hormone,and follicle stimulating hormone increased.17 hydroxyprogesterone was normal.Mild decrease in blood potassium levels(3.44-3.48 mmol/L)was found in 3 cases.One case of CYP17A1 homozygous mutation and three cases of compound heterozygous mutation were found,among which c.563 A＞G and c.436+1G＞T were new mutation sites that had not been reported in the past,and 3 cases had c.985_987delinsAA mutation.All 4 cases received oral hydrocortisone treatment.Conclusions Abnormal external genitalia,inguinal/labial mass and hypertension are the main features of 46,XY type 17OHD in childhood.Early hydrocortisone replacement therapy can effectively prevent the complications of 17OHD.The CYP17A1 c.985_987delinsAA mutation may be a hot topic mutation in children with 17OHD in China.

Objective:To analyze and determine the clinical and genetic characteristics of children with Helsmoortel-Van der Aa syndrome(HVDAS).Methods:Clinical data of 6 children with HVDAS treated at the First Hospital of Peking University from November 2018 to October 2022 and their family members were collected and analyzed retrospectively.Whole exome sequencing was performed on children and their family members to identify the genetic variants.Genotype and phenotype correlation was analyzed.Results:(1) Clinical analysis results: among the 6 children, there were 5 boys and 1 girl, and their age at diagnosis ranged from 11 months and 17 days to 12 years and 9 months.Six patients all presented with developmental delays/intellectual disabilities; (2) Genetic analysis results: 6 de novo ADNP variants were discovered in 6 children, including 1 initial codon deletion variant c. 1_2del, 2 nonsense variants c. 1175dup, p.(Tyr392*) and c. 2213C>G, p.(Ser738*), and 3 frameshift variants c. 2632dup, p.(Ser878Lysfs*3), c.1695_1696insATGGTATGTATGTATGTATG, p.(Val566Metfs*8) and c. 2120_2123del, p.(Asn707Serfs*8).All variants were classified as pathogenic variants by the American College of Medical Genetics and Genomics.Except the c. 2213C>G, p.(Ser738*), the other 5 variants are all novel variants that have not been reported before. Conclusions:All of the 6 cases of HVDAS showed typical clinical manifestations, and expanded the phenotype spectrum of microcephaly and tall stature.Six de novo mutations were discovered, expanding the ADNP mutation spectrum and providing accurate genetic counseling and prenatal genetic diagnosis of the disease.

Atrial fibrillation (AF) is one of the most common arrhythmias. Studies have shown that there is a significant correlation between inflammation and AF. Pathogenic microbial infection has long been considered the most likely factor to trigger and maintain the inflammatory process. In recent years, with the development of molecular biology technology, more and more evidence shows that some bacteria and viruses can cause AF. The research on AF and pathogens has gradually become a hot topic in recent years.

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
Saccharomyces cerevisiae/genetics* ; Sterols ; Phytosterols ; Biological Transport ; ATP-Binding Cassette Transporters/genetics*

Objective To explore the effects and influencing factors of traditional occupational health training on occupational health literacy (OHL) of employees in micro-, small- and medium-sized enterprises. Methods A total of 540 employees from 154 micro-, small- and medium-sized enterprises, who participated (347 employees) and not-participated (193 employees) in traditional occupational health training, and 171 community residents/students (not-participated in occupational health training) were selected as the research subjects using the convenient sampling method. The OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations. Results The overall OHL level of employees was 43.3% (234/540). Among them, the overall OHL level of untrained and trained employees was 38.9% and 45.8%, respectively, and the overall OHL level of community residents/students was 43.3%. The results of multivariate logistic regression analysis showed that the higher the educational level, the higher the OHL level (all P<0.01). The OHL level of untrained and trained employees was higher than that of untrained community residents/students (all P<0.05). The interaction of education level and training status had no statistical difference on the OHL level of the research subjects (P>0.05). The results of factorial design analysis of variance showed that the overall OHL score rate of untrained employees and trained employees was higher than that of untrained community residents/students (all P<0.05). However, there was no significant difference in overall OHL score rate between untrained and trained employees (P>0.05). Conclusion The role of traditional occupational health training in improving the OHL level of employees in micro-, small- and medium-sized enterprises needs to be improved. The responsibility of enterprise occupational health training should be implemented, and multiple measures should be taken to enrich the ways and approaches of occupational health education for enterprise employees, to effectively improve the OHL of workers.