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 analyze the mediating effect of professional identity between teacher's support and student's learning engagement in nursing students.Methods:A total of 409 nursing students were enrolled in this cross-sectional study. Their professional identity, teacher's support, learning engagement were evaluated by Professional Identification Scale (PIS), Nursing Students' Perceptions of Instructor Caring (NSPIC), and Utrecht Work Engagement Scale-Student (UWES-S). A mediating model was proposed and the impacts of professional identity on teacher's support and learning engagement were observed.Results:The average score of NSPIC was (4.60±0.67) points, that of PIS was (3.58±0.63) points, and that of UWES-S was (4.79±0.97) points. The scores of NSPIC and PIS were a highly positive correlation ( r=0.504, P<0.001). The scores of NSPIC was positively correlated with the scores of UWES-S ( r=0.362, P<0.001). The scores of PIS was positively correlated with the scores of UWES-S ( r=0.315, P<0.001). Multiple linear regression analysis showed that learning engagement of nursing students was associated with the total score of PIS and supportive learning atmosphere, which accounted for 16.6% of the total variability. Professional identity had a mediating effect between teacher's support and learning engagement, with statistic significance among all coefficients of each path ( P<0.05), and all the fitting indexes were good. Teachers support had direct effect (0.31) on learning engagement and indirect effect (0.11) on learning engagement through professional identity. Conclusion:Teacher's support can directly predict student's learning engagement and professional identity plays an mediating role between them.

Objective:To investigate the effects of esketamine on the behavior of post-traumatic stress disorder(PTSD).Methods:Thirty-six adult male SD rats were randomly divided into three groups. The mouse craniocerebral trauma model was established by cortical impact injury method. The Sham group ( n=12) only opened the bone window without craniocerebral trauma. The TBI group( n=12) and the TBI+ ES group( n=12) were subjected to cortical trauma; Immediately after trauma, the TBI+ ES group was intraperitoneally injected with esmketamine (10 mg/kg, once every two hours, three times in total), and the TBI group and Sham group were intraperitoneally injected with equal volume 0.9% sodium chloride solution. The results of sugar water preference test, open field test on day 16 and elevated cross maze test on day 17 were collected to analyze PTSD like behavior changes, and Morris water maze test was used to evaluate the learning and memory ability of rats in each group from day 18 to 23 after craniocerebral trauma. After the experiment, the rats were euthanized and the brain tissues were taken. The expression levels of brain-derived neurotrophic factor (BDNF), synaptic protein PSD95 and synaptophysin (Syp) were analyzed by Western blot. The measurement data of normal distribution were expressed as mean ± standard deviation ( ± s). One way ANOVA was used for multi group comparison, SNK- q test was used for post pairwise comparison, and LSD method was used for repeated measurement data. Results:In the TBI group, the preference rate of sugar water, the number of moving grids, the number of standing upright, the residence time of open arm, the number of open arm entry, the escape latency and the number of crossing platform [(75.8±4.9)%, (30.9±4.1) grids, (12.4±2.6) times, (40.3±8.5) s, (6.8±2.3) times, (30.0±4.6) s and (7.0±2.5) times] were significantly lower than Sham group [(85.3±4.4)%, (40.5±5.4) grid, (17.3±2.7) times, (95.8±12.4) s, (15.3±3.1) times, (18.3±7.8) s, (15.7±2.6) times] ( P< 0.05); In TBI+ ES group, the sugar water preference rate, the number of moving grids, the number of upright times, the time of open arm stay, the number of open arm entry, the number of escape latency and the number of crossing platform position [(82.9±5.5)%, (35.5±5.5) grids, (15.1±2.4) times, (68.4±9.7) s, (12.1±3.2) times, (22.3±8.8) s and (12.5±4.1) times] were significantly higher than those in TBI group ( P<0.05). The expression levels of BDNF, PSD95 and Syp in TBI+ ES Group [0.43±0.08), (0.22±0.02), (0.31±0.04)] were higher than those in TBI group [0.19±0.02), (0.20±0.02), (0.24±0.01)], the difference was significant ( P<0.05), and they were lower than those in Sham group [0.89±0.11), (0.45±0.12), (0.57±0.15)], and the difference was significant ( P<0.05). Conclusion:Esticketamine significantly reduce PTSD-like behavior in TBI rats and play a neuroprotective role, which may be a potential medicinefor PTSD treatment.

OBJECTIVE: To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS). METHODS: Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing. RESULTS: The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2). CONCLUSION The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.
Child ; Facies ; Hirschsprung Disease/genetics* ; Humans ; Infant ; Intellectual Disability/genetics* ; Male ; Microcephaly/genetics* ; Mutation

OBJECTIVE: To explore the clinical feature, diagnosis and phenotype of Majeed syndrome. METHODS: Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed. RESULTS: The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur. CONCLUSION Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.
Anemia, Dyserythropoietic, Congenital/genetics* ; Child ; Genetic Testing ; Humans ; Immunologic Deficiency Syndromes/genetics* ; Infant ; Male ; Osteomyelitis/genetics*

【Objective】 To discuss the influence of direct reimbursement of blood expenses in hospitals on the recruitment of blood donors in Xianyang City. 【Methods】 Blood donors or reimbursers, who reimbursed blood expenses either at hospitals or at our blood center were investigated, and these two kinds of blood expense reimbursements were compared in terms of convenience, the impact on the enthusiasm of blood donation, as well as the impact of the awareness of hospital reimbursement on the recruitment of blood donors. 【Results】 The direct reimbursement of blood expenses at hospitals took 22 minutes per person, without any round trips nor transportation costs. The rate of satisfaction, long-term intention to blood donation, and voluntary mobilization of others were 98.11%, 91.89%, and 82.56%, respectively, higher than those in the reimbursers at blood station(P<0.01). 35.16%, 38.90%, 98.56%, 94.24% and 93.37% of the blood donors, who were aware of benefits of hospital reimbursement, had donated for 2~3 times, donated more than 3 times, satisfied with the way of reimbursement, intended to redonate and mobilize others, which were higher than those who were unaware of the the hospital reimbursement(P<0.05). 【Conclusion】 Direct reimbursement of blood expenses at hospitals not only improved the convenience, but also increased the enthusiasm of blood donors by improving their satisfaction, which was conductive to blood donation recruitment.

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.

Adoptive T-cell therapy is the administration of tumor cytotoxic T-cells derived from either patient himself or donors, which were induced or genetically engineered and expanded, and then injected into patients. Several strategies for adoptive T-cell therapy have been developed since last 30 years. From lymphokine-activated killer cells, tumor-infiltrating lymphocytes, cytokine-induced killer cells, to gene-modified T-cells and tumor associated antigen (TAA)-specific cytotoxic T-cells, the adoptive T-cell therapy has been moving forward to more precise tumor targeting and more effective in elimination of cancer cells. This article reviewed the advances of therapeutic approaches of adoptive T-cell therapy for cancer patients.