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*

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.

ObjectiveMolecular docking plays a critical role in predicting binding modes and affinity between molecules, serving as a pivotal method in structural biology and computer-aided drug design research. Our research team has recently developed a novel template-based docking method called FitDock, which outperforms commonly used molecular docking methods in terms of accuracy and speed, particularly when approximate protein-ligand templates are available. To enhance the accessibility of the FitDock method and promote its broader application in the field of molecular simulation, the development of a graphical software tool is imperative. MethodsUtilizing Python-based graphical programming, we have created FitDockApp, a plugin software for the molecular visualization software PyMOL. ResultsFitDockApp enables template-based molecular docking and ligand structure alignment through an interactive graphical interface, providing real-time visualization of predicted three-dimensional structures. It also offers the convenience of uploading docking files to a laboratory server to obtain the optimal template. Additionally, FitDockApp includes batch docking functionality. ConclusionFitDockApp simplifies the docking process through its user-friendly interface and provides robust functionality to assist researchers in obtaining precise docking results. FitDockApp is a free software compatible with both Windows and Linux systems and can be downloaded from http://cao.labshare.cn/fitdock/.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objective To investigate the clinical efficacy of modified Fuzheng Yiliu Decoction(composed of Astragali Radix,Codonopsis Radix,Ligustri Lucidi Fructus,Hedyotis Diffusae Herba,Moutan Cortex,Visci Herba,etc.)combined with XELOX regimen(Oxaliplatin plus Capecitabine)for the treatment of postoperative patients with advanced gastric cancer of qi and yin deficiency type.Methods A total of 80 postoperative patients with advanced gastric cancer of qi and yin deficiency type were randomly divided into the Chinese medicine group and the control group,with 40 cases in each group.Both groups received chemotherapy with XELOX regimen,while the Chinese medicine group was given modified Fuzheng Yiliu Decoction.Three weeks constituted a course of treatment,the medication of Chinese medicine decoction lasted for two weeks or more in each course of treatment,and a total of 8 courses of treatment were performed.The incidence of adverse reactions during chemotherapy was monitored and changes in serum tumor markers of serum carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and alpha-fetoprotein(AFP)were observed in the two groups before and after treatment.Moreover,the patients'quality of life was assessed by the scores of Karnofsky's Performance Status(KPS)and World Health Organization Quality of Life Measurement Scale(WHOQOL-100).Long-term follow-up was carried out for the evaluation of the prognostic indicators such as overall survival and one-year and 2-year overall survival rates.Results(1)Patients in the two groups were all followed up,and the median follow-up time was 27 months(95%CI:23.59-27.86).(2)After treatment,the levels of serum CEA and AFP in the Chinese medicine group were significantly lower than those before treatment(P＜0.05 or P＜0.01),while serum CA199 tended to decrease compared with those before treatment,but the difference was not statistically significant(P＞0.05);in the control group,the levels of serum CEA,CA199,and AFP were not significantly decreased after treatment(P＞0.05).The intergroup comparison showed that the decrease of serum CEA,CA199 and AFP levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The adverse reactions during chemotherapy in the two groups mainly involved bone marrow suppression,gastrointestinal reactions and liver function abnormalities,etc.The incidences of all adverse reactions in the Chinese medicine group tended to be lower than those in the control group,but the differences were not statistically significant(P＞0.05).(4)After treatment,the KPS scores of patients in both groups were improved compared with those before treatment(P＜0.01),and the improvement in the Chinese medicine group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the scores of the four dimensions of WHOQOL-100 such as health status,mobility,life feelings,and other activities of daily life in the Chinese medicine group were significantly improved compared with the pre-treatment(P＜0.05),whereas there was no significant improvement in the control group(P＞0.05).The intergroup comparison showed that the improvement of the scores of each dimension of the WHOQOL-100 in the Chinese medicine group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(6)The median survival in the Chinese medicine group was 29.0 months(95%CI:25.95-31.70)and that in the control group was 22.0 months(95%CI:19.67-25.58),indicating that the median survival was significantly prolonged in Chinese medicine group(P＜0.01).The one-year and 2-year postoperative survival rates were 97.5%and 77.5%in the Chinese medicine group and 92.5%and 47.5%in the control group,respectively.The intergroup comparison showed that the one-year and 2-year postoperative survival rates in the Chinese medicine group were higher than those in the control group(P＜0.01).Conclusion Modified Fuzheng Yiliu Decoction can effectively alleviate the adverse reactions during adjuvant chemotherapy for postoperative patients with advanced gastric cancer of qi and yin deficiency type,improve the quality of life of patients,and prolong the survival time of patients.

Objective To establish a renal cell co-culture system to simulate the renal barrier system,and to test its responsiveness to different glucose concentrations,and to investigate the regulatory effect of miR-29b-3p on osteopontin(OPN)/transforming growth factor β(TGF-β)pathway and the changes of this pathway under high glucose condition.Methods The three-cell co-culture system consisting of human renal podocytes,human glomerular mesangial cells and human renal tubular epithelial cells was established to test the cell viability and glucose consumption value at glucose concentrations of 5,8,12 and 16 mmol/L.The content of TGF-β and OPN in cell supernatant was measured.The recombinant plasmid and siRNA of OPN were transfected,and the expressions of TGF-β and OPN were detected by Q-PCR and Western blot.Results The mRNA expressions of OPN,TGF-β and miR-29b were significantly increased at 12 mmol/L glucose conditions.Western blot results showed that the protein expression of OPN increased in high glucose conditions,while the protein expression of TGF-β did not change significantly.After adding miR-29b-3p activator,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly increased.After adding miR-29b-3p inhibitor,the mRNA levels of OPN and TGF-β in the cell supernatant were significantly decreased.Western blot results showed that compared with 5 mmol/L glucose,the protein expressions of OPN and TGF-β were increased by miR-29b-3p activator,and the protein expressions of OPN and TGF-β were decreased by miR-29b-3p inhibitor.After transfection with OPN recombinant plasmid,the content of TGF-β in the cell supernatant was significantly increased,and the mRNA expressions of OPN and TGF-β in the cells were significantly increased.After transfection with OPN siRNA,the content of TGF-β in the cell supernatant was decreased,and the expression of OPN mRNA in the cells was significantly decreased,but the expression of TGF-β mRNA was not significantly increased.Conclusion The renal cell co-culture system can mimic the complex renal environment in vivo.When induced by high glucose,cell proliferation is inhibited,glucose consumption is increased,and the content of TGF-β in the cell supernatant is increased,and miR-29b-3p has a regulatory effect on OPN/TGF-β signaling pathway in the co-culture system.

Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.