Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency. METHODS: The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members. RESULTS: Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant. CONCLUSION Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

Objective:To explore the performance and clinical application value of a rapid detection method for the hematopoietic stem/progenitor cell of peripheral blood using the automated hematology analyzer.Methods:Methodology validation and retrospective study. Collected sample from Fujian Medical University Union Hospital from January 2015 to December 2018, the peripheral blood of 4 patients with acute myeloid leukemia was first treated, and one healthy donor′s peripheral blood stem cell collection 5 times diluent, for the methodology validation. And the peripheral venous blood and 5-fold dilutions of peripheral blood stem cell collection, from 23 patients with hematopoietic stem cell transplantation and 22 healthy donors of allogeneic peripheral blood stem cell transplantation, used for consistency retrospective analysis. In the linear test, each of the peripheral blood and HPC collecting solutions from blood cell separator, which known CD34 +cell concentration, that was high-value samples for the expected upper limit (H) . Another low-value sample is normal saline (L) . According to the multiple proportion dilution, HPC was detected and regressed consistency test specimens were 126, EDTA-K 2 anticoagulant venous blood 78 and peripheral blood stem cell 48. Venous blood was collected at the same time, one tube of blood routine and HPC detection, the other tube flow cytometry (FCM) detection of CD34 +cells. Stem cell collection was diluted 5 times with sterilized saline and divided into two tubes. One tube was used to count whole blood cells and HPC, the other tube was used to detect CD34 +cells by FCM. The test results of the two instruments were compared, and the deviation was evaluated. Results:The background counting was 0×10 9/L and the carryover rate was 0.1%, conformed to the quality requirements of hematology analyzer, and the repeatability study imprecision ranged between 4.7%-18.8%. HPC of peripheral venous blood linear range (0-27.201×10 9/L), Stem cell collection was diluted 5 times linear range (0-0.878×10 9/L). The results of 126 samples detected by the hematology analyzer and FCM were compared. The correlation coefficient r2=0.960 1. When WBC>10×10 9/L, the results of the two instruments have a good consistency. The slope is between 0.95 and 1.05, and the relative bias is less than 30%. Conclusions:This study suggests that the hematology analyzer has a good linear range for detecting HPC, and has a good correlation with FCM. The hematology analyzer has the advantages of no pretreatment, convenient operation, a wide range of applications in detecting HPC specimens.

OBJECTIVE： To study the relationships of polymorphism of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus with drug concentration of methotrexate （MTX） and high-dose MTX （HD-MTX）-induced ADR in acute lymphoblastic leukemia （ALL） children. METHODS： From Oct. 2015 to Sept. 2018， 70 ALL hospitalized children of Han nationality in Sichuan area who received HD-MTX treatment and were in consolidation chemotherapy were selected retrospectively from Sichuan People’s Hospital. The blood concentration of MTX at 48 and 72 hours after administration was measured by EMIT. The genetic typing of MTRR gene rs1801394 locus and SLCO1B1 gene rs11045879 locus were detected with real-time PCR. The relationships of the polymorphism of MTRR gene and SLCO1B1 gene with MTX blood concentration [dose-corrected concentration （c48 h/D，48 h）， the proportion of children with different concentration of MTX （≤0.1， ＞0.1 μmol/L）] and ADR （such as myelosuppression， liver function damage， gastrointestinal response， mucosal damage， rash， etc.） were analyzed. Binary Logistic regression analysis for the correlation of ADR with different influencing factors （gene polymor- phism， blood concentration of MTX， immunophenotyping， body mass index， etc.） was carried out by Wald method. RESULTS： Totally 31， 32， 7 children with MTRR gene AA， AG and GG genotype， while 23， 37， 10 children with SLCO1B1 gene TT， TC and CC genotype were detected. The distribution of each genotype in 70 children conformed to Hardy-Weinberg equilibrium （P＞0.05）. There was no significant difference in c48 h/D（48 h） of children and the proportion of children with different concentration of MTX （72 h） among difterent genotypes of MTRR and SLCO1B1 gene （P＞0.05）. There was statistical significance in the incidence of liver function injury in children with different genotypes of MTRR gene （P＜0.05）， and the AA genotype was significantly higher than the AG+GG genotype （P＜0.05）. There was no correlation of MTRR gene polymorphism with the incidence of other ADR， neither SLCO1B1 gene polymorphism with the incidence of ADR （P＞0.05）. The results of Binary Logistic regression analysis showed that liver function damage in ALL children was related to the gene polymorphism of MTRR； gastrointestinal reaction was related to whether the plasma concentration was more than 0.1 μmol/L at 72 h； mucosal damage was related to the immune type and BMI of children； the occurrence of skin allergy was correlated with body weight of children（P＜0.05）. CONCLUSIONS： Gene polymorphism of MTRR rs1801394 locus may associated with the occurrence of HD-HTX-induced liver function injury in ALL children， but its polymorphism and gene polymorphism of SLCO1B1 rs11045879 locus are not related to MTX blood concentration in ALL children.

To combine more than 20 years of experience in clinical practice skills teaching of laboratory medicine, with the characteristics of laboratory medicine, the theory system of formative assessment has been constructed, to guide the clinical practice of the students.Based on the construction of network question bank, students make use of the network question bank self testing, to know whether they had got the stage goal, existing problems and future plan through self testing, so as to mobilize their enthusiasm and initiative to enhance their self-confidence.Under the formative assessment teaching system, students establish internship file information, including practice notes, weekly practice, group discussion, self testing results, the teacher and peer assessment information.Teachers set up QQ group, WeChat group with their students, the timely to get the question from students and to take appropriate measures improve teaching.Teachers had established and improved the long-term after graduation feedback mechanism, and formative assessment improved the teaching quality of the whole practice teaching benefits teachers as well as students.

Objective To explore the short and long-term efficacy of extralevator abdominoperineal excision (ELAPE)vs.conventional abdominoperineal excision (APE)on distal rectal cancer.Methods Relevant studies were identified by search of Medline,EMBASE,and Web of Science published between January 1,2008 and February 28,2015,and included in the systematic review and meta-analysis with Stata software (version 12.0). Results Our Meta-analysis included 14 studies involving 3278 patients,of whom 1843 (56.2%)underwent ELAPE and 1435 (43.8%)underwent APE.Compared with patients undergoing APE,those undergoing ELAPE had a significantly reduced risk of intraoperative bowel perforation (IBP)involvement (OR=0 .55 ,95% CI= 0 .37-0 .85 ),but no significant reduction in the occurrence of CRM positivity (OR=0 .81 ,95% CI=0 .52-1 .25 ), local recurrence (LR)(OR=0.49,95% CI=0.18-1.30),wound complications (WCs)(OR=0.93,95% CI=0.65-1.35)or in-hospital death (IHD)(OR=0.89,95% CI=0.47-1.71).Conclusion ELAPE can reduce the risk of IBP but not for CRM positivity or LR when compared with APE.Therefore,more higher-quality studies are needed to verify the short-and long-term effects of ELAPE procedure on distal rectal cancer.

Aim To study the effects of Triptolide (TPL) on HL-60 cells in vitro and in vivo.Methods MTT was used to examine the effects of TPL on proliferation of HL-60 cells;TUNEL assay was used to detect apoptotic cells.The effect of TPL on xenograft growth of HL-60 cells was evaluated by tumor inhibition rate.Results In vitro TPL inhibited the proliferation and induced apoptosis of HL-60 cells in a dose-dependent manner.In vivo TPL inhibited xenograft growth of HL-60 cells with the highest inhibition rate of 53.5%.Conclusion TPL is able to inhibit the proliferation of HL-60 cells and induce apoptosis of HL-60 cells in vitro and in vivo.