Objective:To prepare PLGA electrospinning membranes doped with hollow mesoporous silica nanoparticles loaded with metformin and investigate their biological properties.Methods:PLGA(Control group)and PLGA/HMSN/Met electrospun membranes(Experimental group)were prepared by electrospinning technology.The microscopic morphology of the 2 groups of electrospun mem-branes was observed by SEM.The hydrophilicity,elemental composition and in vitro drug release were detected by contact angle meas-urement,EDS,and drug release test,respectively.SEM and laser scanning confocal microscope(LSCM)were used to observe the growth of periodontal ligament stem cells(PDLSCs)on the 2 groups of electrospun membranes,and CCK-8 assay was used to detect the cell proliferation.Results:Both electrospun membranes had extracellular matrix(ECM)-like fiber structures.The PLGA/HMSN/Met electrospun membranes could slowly release Met for up to 35 days,and the hydrophilicity of PLGA membranes was improved by HMSN-Met doped.The composite electrospun membranes had good cell biocompatibility in vitro,and could promote cell proliferation.Conclu-sion:Modification of PLGA with HMSN-Met can improve the hydrophilicity of PLGA electrospun membranes,continuously release Met,and have good cell biocompatibility.

[Objective[ To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

Objective:To investigate the clinical features and risk factors of left ventricular systolic dysfunction in children with septic shock.Methods:A retrospective analysis was performed on the clinical data of children diagnosed with septic shock in the Department of Critical Care Medicine of Children’s Hospital, Capital Institute of Pediatrics from February 2016 to June 2021. Inclusion criteria: (1) patients met the diagnostic criteria of septic shock; (2) Cardiac ultrasound was performed within 48 h after shock treatment and was dynamically monitored during shock treatment. Exclusion criteria: (1) Previous history of chronic cardiac insufficiency, cardiomyopathy, or organic heart disease; (2) patients with acute cerebral infarction, cerebral hemorrhage and necrotizing encephalopathy; (3) congenital genetic metabolic diseases; and (4) incomplete information. Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) <50% and a ≥10% decrease in the patient’s initial LVEF assessed on admission. Patients with left ventricular systolic dysfunction and without left ventricular systolic dysfunction were compared. Comparisons between groups were performed with unpaired Student’s t test, or Mann-Whitney U test, or chi-square test. Multivariate logistic regression analysis was used to analyze the correlation factors of left ventricular systolic dysfunction. Results:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0% with the lowest LVEF of (42±8)%. Left ventricular systolic dysfunction occurred on (2.4±1.3) days after shock onset, and the LVEF returned to normal on (6.7±3.3) days. Hematogenous infection was more frequent (77.8% vs. 40.5%, P=0.018), ventilator application (83.3% vs. 50.0%, P=0.033) and inotropes and vasopressor drugs (100.0% vs. 64.3%, P=0.009) were used more frequently in patients with left ventricular systolic dysfunction(n =18), compared with patients without left ventricular systolic dysfunction(n =42). Patients with left ventricular systolic dysfunction had a lower LVEF [(42±8)% vs. (67±5)%, P<0.001], a lower pediatric critical illness score [(64±13) vs. (76±14), P=0.003], a lower resuscitation success rate at 6 h (38.9% vs. 73.8%, P=0.010), a higher lactate at admission [3.80 (3.15, 5.88) mmol/L vs. 2.70 (1.85, 3.80) mmol/L, P=0.001) and a higher 28-d mortality (38.9% vs. 12.8%, P=0.025) compared with patients without left ventricular systolic dysfunction. Hematogenic infection ( OR=7.358, 95% CI: 1.198~45.197, P=0.031) and lactate at admission ( OR=1.743, 95% CI: 1.041~2.917, P=0.034) were independent risk factors for left ventricular systolic dysfunction. Conclusions:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0%. Left ventricular systolic dysfunction usually occurred on (2.4±1.3) days after shock onset and resolved within 7 days, which was associated with 28-d mortality. Hematogenous infection and high lactate value were independent risk factors for left ventricular systolic dysfunction.

Objective: To evaluate the indications and outcomes of thoracoscopic repair with hernia-ring pin (TRHP) applied in neonates with congenital diaphragmatic hernia (CDH). Methods: Fifty-six cases diagnosed as CDH were collected from Department of Neonatal Surgery or Cardiothoracic Surgery in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2013 to September 2018.Patients were divided into thoracoscopic repair (TR) group and TRHP group, and the data, including birth weight, pregnant weeks, ages at operation, hospital stay postoperatively and the number of recurrence cases were compared, between the 2 groups.The size of defect was coded into A, B, C and D grades.Status of patients was grouped into Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴstages according to the defect size and complicated congenital heart disease. Results: There were 7 cases in TRHP group, including 3 boys and 4 girls.Four cases belonged to A-class defect and 3 cases were of B-class defect, respectively.The contents of the hernia included small intestine, colon, kidney and spleen.Six cases presented left CDH and 1 case presented right CDH.One of the left CDH cases and the 1 right CDH case had hernia sac.The right CDH neonate presented haematuria in the first day and the second day postoperatively, whose symptom disappeared after treatment.The follow-up time was (12.17±3.41) months, and no recurrent cases were found.All the cases in TRHP group belonged to Ⅰ or Ⅱ stage.There were 49 cases in the TR group.Among them, 29 cases belonged to class-A defect, 18 cases class-B defect, and 4 cases class-C defect, respectively.Cases classified into A and B defects were in stageⅠorⅡ, and cases classified into C defect were in stage Ⅲ.In those 45 cases belonged to A or B defect, 40 cases presented left CDH and 5 case presented right CDH.Among them, 5 neonates had hernia sac.The contents of the hernia included small intestine, colon, kidney and spleen.There were significant differences in the operative time [(83.47±10.28) min vs.(54.29±17.09) min, P<0.05] and length of stay postoperatively [(12.76±5.89) d vs.(7.86±2.03) d, P<0.05] in both groups.TRHP was carried out by the same surgeon, and he also operated on other 18 cases in TR group.Compared with the operative time of cases operated by the same surgeon in both groups, significant diffe-rence was found [(83.47±10.28) min vs.(54.29±17.09) min, P<0.05]. The cases were followed up for (46.17±6.92) months postoperatively and 4 recurrent cases were tracked.One A defect and 1 B defect patients had recurrence 1 month or 2 months postoperatively.Two C defect cases were found to have recurrence postoperatively in 2 months or 6 months, respectively.All 4 cases mentioned above recovered by reoperation.The risk of recurrence in C defect CDH cases existed as high as 21.5 times compared with the A or B defect cases. Conclusions It is safe to repair CDH by THRP in neonates with CDH A or B defect, for their operative time may be shorter.TRHP should be highly recommend for CDH cases with A or B defect.

OBJECTIVE： To predict the anti-inflammatory active components and mechanism of couplet medicine of Notopterygium incisum-Angelica pubescens. METHODS： According to the principle of oral bioavailability≥30％ and drug- likeness≥0.18， active components of N. incisum and A. pubescens were screened； TCMSP was used to predict and screen the potential target of them. Using “Anti-inflammatory” as keyword， inflammatory related target genes were retrieved from human gene database Genecards. Common target was screened by mapping the target genes of active ingredients from couplet medicine of N. incisum-A. pubescens. The active ingredient-target network was established by using Cytoscape 3.5.1 software. The screened targets were used to construct the target protein interaction （PPI） network on the STRING V 10.5 platform. Its anti-inflammatory mechanism was studied by KEGG signaling pathway and GO biological enrichment analysis. RESULTS： Totally 15 active components such as coumarin， beta-sitosterol， ammidin， nodakenin were selected from couplet medicine of N. incisum-A. pubescens. Acting on 49 targets such as transcription factor AP-1， PI3-kinase subunit gamma， estrogen receptor， they mainly involved 19 signaling pathways such as hepatitis B and cell apoptosis， and were involved in 47 biological processes such as regulating inflammatory response and prostaglandin biosynthesis. CONCLUSIONS： The anti-inflammatory mechanism of active components of couplet medicine of N. incisum-A. pubescens on multi-target， multi-channel and multi-biological processes is predicted， and it points out the direction for further anti-inflammatory mechanism study.

OBJECTIVE: To analyze genetic variant in a pedigree affected with congenital high myopia. METHODS: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. RESULTS: WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). CONCLUSION A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.
Collagen Type XI ; genetics ; Genetic Testing ; Heterozygote ; Humans ; Myopia ; genetics ; Pedigree ; Whole Exome Sequencing

Objective: To analyze genetic variant in a pedigree affected with congenital high myopia. Methods: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. Results: WES has identified a novel splice site heterozygous variant (c.2556+ 1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+ 1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+ PM2). Conclusion A novel splice variant (c.2556+ 1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients′ overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

Objective To understand the epidemiological characteristics and clinical features of Zika virus disease,and to improve its prophylaxis and treatment.Methods The first case with imported Zika virus disease in China was retrospectively reported and analyzed.The literature of Zika virus infection in human was reviewed.Results This patient was the first case with imported Zika virus disease in China who presented with typical clinical characteristics and had clear epidemiological history.All the contacts were test negative for Zika virus nucleic acid.Literature retrieval showed evidence of Zika virus propagation in more than 40 countries in Africa,Asia,and Americas.The majority of patients presented with mild symptoms and the main prevention measures included mosquito control and improved awareness of personal protection.Conclusions Human infected with Zika virus often shows recessive infection.Only a small part develop disease and have generally good prognosis with supportive treatment.

Objective To summarize the experiences of surgical treatment for aortic coarctation and/or aortic hypoplasty associated with intracardiac anomalies in infants.Methods The clinical data of 51 cases with aortic coarctation and/or aortic hypoplasty hospitalized in Wuhan Children's Hospital between Jan.2010 and Jun.2013 were analyzed retrospectively.Thirty-two patients had received a expanded end-to-end anastomosis and 19 patients had got a end-to-side anastomosis.Autologous pericardial patch,bovine pericardial patch or autologous pulmonary patch was taken according to the circumstances during surgery.Results There were 2 intraoperative deaths because of serious low cardiac output syndrome,and 2 postoperative deaths,which could not take off long-term respiratory assistance after surgery in aortic one child and low cardiac output syndrome in the other.Three patients appeared trachyphonia but recovered basically after 3 months follow-up.Forty-seven patients were followed up for 2 months-3 years,among them,3 patients had significant upper to lower extremity systolic blood pressure gradient[＞20 mmHg(1 mmHg =0.133 kPa)],and a second operation was proposed recently for 1 of them,while the other 2 children were in follow-up.The other 44 patients did not appear obvious restenosis.The 47 cases of children had no neurologic symptoms.Conclusions There have to be positive diagnoses and strictly surgery indications for aortic coarctation and/or hypoplasty associated with intracardiac anomalies in infants.Selective antegrade cerebral perfusion or deep hypothemic circulatory arrest depends on the surgon's discretion.Both expanded end-to-end anastomosis and end-to-side anastomosis can achieve good operation effects.