Objective To observe the clinical effect of treating diabetic nephropathy with Shengqidihuang decoction combined with metformin. Methods 54 cases with diabetic nephropathy were randomly divided into two groups by means of random number table. Both groups were given diabetic routine treatment. The control group was treated with metformin, 0.25 mg each time, three times a day, based on the diabetic routine treatment for 8 weeks, and the treatment group was treated with Shengqidihuang decoction, once a day, 4 weeks as a course, continuously treated for 2 courses based on the control group. 24 h urinary protein (24hUAE) , serum creatinine (SCr) , blood urea nitrogen (BUN) and fasting blood glucose (FBG) were detected before and after the treatment. The clinical effect was observed between the two groups after the treatment. Results The total effective rate of the treatment group and the control group was 85.2% and 66.7% respectively, showing a significant difference (λ2=3.376, P<0.05). Compared with the control group, 24 hUA ,SCr, BUN and FBG in the treatment group decreased significantly (λ2=4.231, P<0.05) after the treatment.24hUAE, SCr, BUN and FBG decreased significantly after the treatment, especially in the treatment group, also showing a significant difference (λ2= 3.754, P<0.05). Conclusion The therapy of mefformin combined with Shengqidihuang decoction on diabetic nephropathy was better than metformin only.

OBJECTIVE: To reported on two fetuses diagnosed with 17q12 microdeletion syndrome. METHODS: The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems. RESULTS: In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified. CONCLUSION Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.
Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 17 ; Female ; Fetus ; Genetic Counseling ; Genetic Testing ; Humans ; Polyhydramnios/genetics* ; Pregnancy ; Prenatal Diagnosis

Objective:To re-evaluate the quality of methodology and outcome indicators for systematic reviews/meta-analysis about the effectiveness of non-pharmacological interventions for chemotherapy-related nausea and vomiting(CINV).Methods:The Cochrane Library, PubMed, Embase, Web of Science, CNKI, Wanfang, VIP and CBM for systematic reviews/meta-analysis on the effectiveness of non-pharmaceutical intervention in the prevention or treatment of CINV from inception to May 2021 were searched. The methodological quality of the included literature was evaluated by the AMSTAR 2 quality evaluation tool, and the quality of the evidence for the outcome indicators was evaluated by GRADE system.Results:A total of 24 articles were included, 7 of the AMSTAR 2 quality evaluation results were low-level, and the remaining 17 were all very low-level. The main defects were the lack of preliminary study design scheme, incomplete search strategy, no list of excluded literature, and no report of included research funding sources, etc. Only 1 of the outcome indicators was classified as high quality, 7 were classified as intermediate, and the rest were low or very low quality.Conclusions:Methodological quality and strength of evidence of systematic reviews/meta-analysis on the effectiveness of non-pharmaceutical intervention for CINV are generally low, and the reliability of research results is poor. It is necessary to design scientific and rigorous high-quality RCTs and systematic reviews to further verify the effectiveness of non-pharmaceutical interventions in the future.

Objective:To retrieve, appraise and summarize the best evidence to prevent accidental extubation of peripheral venous catheters in adults.Methods:According to the "6S" evidence model, computer evidence retrieval was carried out. Search relevant domestic and foreign guideline networks and databases to collect relevant evidences, including clinical decision, guidelines, evidence summary, systematic reviews, etc. The retrieval time was from the establishment of the database to September 2021. Two researchers conducted independent literature search, quality evaluation, evidence extraction and summary. If there is a disagreement between the two, the third party shall be invited to make a ruling.Result:A total of 8 articles were included, including 1 clinical decision, 1 guideline, 2 evidence summaries, 3 RCTs and 1 expert consensus. The 35 best evidences were summarized from six aspects: education and training, catheter placement selection, dressing selection, catheter fixation, catheter maintenance and timing of extubation.Conclusion:This summary of evidence provided evidence-based evidence for the standardized management of clinical prevention of accidental extubation of peripheral venous catheters. However, some of evidence is lacking and of poor quality. In the future, the evidence should be used cautiously according to the clinical situation and patient conditions.

Objective:To search, evaluate and summarize the best evidence for non-pharmaceutical therapy of cancer-related fatigue in cancer patients.Methods:According to the "6S" evidence model, systematically searched relevant domestic and foreign guideline networks and databases to collect relevant evidences, including clinical decision support, guidelines, evidence summaries, and systematic reviews. Retrieval time from the establishment of the database to August 2021. After evaluating the quality of the literature, we extracted and summarized relevant evidence.Results:A total of 18 articles were included in this study, including 1 clinical decision support, 4 clinical practice guidelines, 5 evidence summarie and 8 systematic reviews. 25 pieces of best evidence were summarized, involving non-pharmacological interventions in 7 aspects: health education, exercise intervention, psychosocial intervention, traditional Chinese medicine therapy, nutritional support, sleep therapy and bright white light therapy.Conclusions:It is recommended that medical staff should combine clinical practice, scientifically select the best evidence and use evidence-based management scheme for cancer-related fatigue to reduce cancer-related fatigue and improve patients′ life quality.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

OBJECTIVE: Through a retrospective large sample analysis of copy number variants in single center, we explored the technical standards for the interpretation and reporting of constitutional copy-number variants (CNVs) jointly proposed by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) in 2019, analyzing its impact on CNVs ratings and the improvement in the consistency of the classification of CNVs in clinical laboratories. METHODS: 236 CNVs that assessed as pathogenic, uncertain significant (including likely pathogenic, uncertain and likely benign) by the 2011 ACMG guidelines between August 2018 and December 2019 in our center were re-analyzed. Four working group members of the center reclassified and evaluated 235 CNVs according to 2019 ACMG guidelines. RESULTS: The consistency of clinical significance classification of CNVs was 91% and the α test coefficient was 0.98 among four working group members. Compared with the 2011 and 2019 ACMG technical standards for the CNVs classification, evaluation of pathogenicity and uncertain significant is basically consistent. 90% (45/50) of likely pathogenic and likely benign CNVs were Re-evaluated as variants of uncertain significance, and the difference is significant. CONCLUSION The new version ACMG/ClinGen guidelines for the evaluation of CNVs developed semi-quantitative point-based scoring system and help to improve the consistency in clinical classifications. It can also make the interpretation of CNVs more standardized and transparent.
DNA Copy Number Variations ; Genetic Testing ; Genetic Variation ; Genome, Human ; Humans ; Mutation ; Retrospective Studies

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

OBJECTIVE: To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL). METHODS: Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members. RESULTS: The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.
Child ; Humans ; Family ; Genetic Counseling ; Language ; MEF2 Transcription Factors/genetics* ; Muscle Hypotonia/genetics* ; Neurodevelopmental Disorders

OBJECTIVE: To explore the types of NF1 gene variants and clinical characteristics among patients with Neurofibromatosis type I (NF1). METHODS: Clinical data of 12 patients diagnosed at Ningbo Women and Children's Hospital between December 2019 and May 2022 were retrospectively analyzed. The probands and their family members were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing and chromosome microarray analysis. RESULTS: The 12 patients had ranged from 4 months to 27 years old, with a male-to-female ratio of 2 : 1. Cafè-au-lait spots were found in all patients. 83.3% of them also had axillary and/or inguinal freckling, 58.3% had neurofibromas, and 16.7% had congenital pseudarthrosis of the tibia. Five types of NF1 gene variants were identified in the patients, including 5 nonsense variants, 4 frameshift variants, 1 missense variant, 1 splice variant, 1 large deletion involving the whole gene. Six patients were found to harbor de novo variants, 2 had inherited the variants from their parents, and 4 were not verified for their parental origin. The c.3379del (p.Thr1127Glnfs*15) and c.6628_6629del (p.Glu2210Thrfs*10) variants were unreported in literature and databases. CONCLUSION Most NF1 patients may present with Cafè-au-lait spots initially and are due to pathogenic variant of the NF1 gene. High-throughput sequencing can efficiently identify such variants among the patients and enable the definite diagnosis.
Child ; Humans ; Female ; Male ; Neurofibromatosis 1/diagnosis* ; Cafe-au-Lait Spots/diagnosis* ; Genes, Neurofibromatosis 1 ; Retrospective Studies ; Frameshift Mutation