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 explore the relationship of course and recurrence after norms antiviral treatment for patients with chronic hepatitis B. Methods All cases were confirmed by standard use of nucleos drug treatment,after treatment,followed up for 104 weeks; patients after stopping the treatment and contiued to conslidate 1 year, set the control group,patients after stopping the treatment and tiued to consolidate 3 years, as observation group,the recurrence rates and recurrence time were compared. Results The relapse rate of observation group was significantly lower than the control group(χ2=3.877,P<0.05). Control group of 38 cases,31 cases of recurrence after treatment,included 2 cases of recurrence within 2 weeks,25 cases of recurrence within 24 weeks; 4 cases relapsed after 24 weeks.Observation group of 30 cases,18 cases of relapse after discontinuation,1 case relapsed in two weeks,15 cases of recurrence within 24 weeks,2 cases relapsed after treatment 24 weeks. Conclusion The prolonged antiviral therapy can reduce the recur-rence rate of the time,but did not extend the time to recurrence,we recommend patients with chronic hepatitis B nu-cleoside (acid) drug treatment medication should be strictly in accordance with the relevant guidelines,emphasizing long-term medication to maintain efficacy,And standardize management with antiviral treatment.

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 investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical 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.