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*

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Objective To explore the intervention effect and mechanism of Zhiwei Fuwei pills on precancerous lesions of gastric cancer(PLGC)model rats based on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods PLGC model rats were established by the combination of N-methyl-N'-nitro-N-nitrosoguanidine and ammonia drinking,hunger and satiation disorder,ethanol gavage and ranitidine feeding,and were randomly divided into model group,control group and experimental-H,-M,-L groups,with 8 rats in each group.Another 8 healthy rats were selected as blank group.Experimental-H,-M,-L groups were given 1.67,0.84 and 0.42 g·kg-1 Zhiwei Fuwei pills solution by intragastric administration,respectively;control group was given 2.00 × 10-3g·kg-1 folic acid solution by intragastric administration;blank group and model group were given 0.9％NaCl by intragastric administration,once a day for 4 weeks.The structural changes of gastric microvessels were detected by transmission electron microscopy,and the expression levels of HIF-1α,VEGF,vascular endothelial growth factor receptor-2(VEGFR-2)and Angiopoietin-2(Ang-2)were detected by western blot.Results Compared with the model group,the abnormality of gastric microvascular structure in experimental-H,-M,-L groups was improved to some extent,and the effect of high dose experimental group was the most obvious.The relative expression levels of HIF-1 α protein in experimental-H,-M groups and control group,model group and blank group were 0.43±0.03,0.66±0.04,0.77±0.01,0.80±0.02 and 0.37±0.02;the relative expression levels of VEGF protein were 0.97±0.06,1.21±0.06,1.51±0.07,1.54±0.05 and 0.88±0.02;the relative expression levels of VEGFR-2 protein were 1.03±0.06,1.18±0.04,1.37±0.05,1.45±0.02 and 0.70±0.02;the relative expression levels of Ang-2 protein were 0.51±0.03,0.61±0.02,0.71±0.01,0.78±0.03 and 0.34±0.01,respectively.Compared with the model group,the above indexes in the experimental-H,-M groups were statistically significant(all P＜0.01).Conclusion Zhiwei Fuwei pills may inhibit the abnormal activation of HIF-1α/VEGF signaling pathway,improve hypoxia microenvironment,reduce angiogenesis,and then effectively interfere with the progression of PLGC.

Objective To explore the intervention effect and mechanism of Zhiwei Fuwei pills on precancerous lesions of gastric cancer(PLGC)model rats based on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods PLGC model rats were established by the combination of N-methyl-N'-nitro-N-nitrosoguanidine and ammonia drinking,hunger and satiation disorder,ethanol gavage and ranitidine feeding,and were randomly divided into model group,control group and experimental-H,-M,-L groups,with 8 rats in each group.Another 8 healthy rats were selected as blank group.Experimental-H,-M,-L groups were given 1.67,0.84 and 0.42 g·kg-1 Zhiwei Fuwei pills solution by intragastric administration,respectively;control group was given 2.00 × 10-3g·kg-1 folic acid solution by intragastric administration;blank group and model group were given 0.9％NaCl by intragastric administration,once a day for 4 weeks.The structural changes of gastric microvessels were detected by transmission electron microscopy,and the expression levels of HIF-1α,VEGF,vascular endothelial growth factor receptor-2(VEGFR-2)and Angiopoietin-2(Ang-2)were detected by western blot.Results Compared with the model group,the abnormality of gastric microvascular structure in experimental-H,-M,-L groups was improved to some extent,and the effect of high dose experimental group was the most obvious.The relative expression levels of HIF-1 α protein in experimental-H,-M groups and control group,model group and blank group were 0.43±0.03,0.66±0.04,0.77±0.01,0.80±0.02 and 0.37±0.02;the relative expression levels of VEGF protein were 0.97±0.06,1.21±0.06,1.51±0.07,1.54±0.05 and 0.88±0.02;the relative expression levels of VEGFR-2 protein were 1.03±0.06,1.18±0.04,1.37±0.05,1.45±0.02 and 0.70±0.02;the relative expression levels of Ang-2 protein were 0.51±0.03,0.61±0.02,0.71±0.01,0.78±0.03 and 0.34±0.01,respectively.Compared with the model group,the above indexes in the experimental-H,-M groups were statistically significant(all P＜0.01).Conclusion Zhiwei Fuwei pills may inhibit the abnormal activation of HIF-1α/VEGF signaling pathway,improve hypoxia microenvironment,reduce angiogenesis,and then effectively interfere with the progression of PLGC.

OBJECTIVE: This study was designed to provide the evidences on the toxicokinetics of microplastics (MPs) and nanoplastics (NPs) in the bodies of mammals. METHODS: 100 nm, 3 μm, and 10 μm fluorescent polystyrene (PS) beads were administered to mice once by gavage at a dose of 200 mg/kg body weight. The levels and change of fluorescence intensity in samples of blood, subcutaneous fat, perirenal fat, peritesticular fat, cerebrum, cerebellum, testis, and epididymis were measured at 0.5, 1, 2, and 4 h after administration using an IVIS Spectrum small-animal imaging system. Histological examination, confocal laser scanning, and transmission electron microscope were performed to corroborate the findings. RESULTS: After confirming fluorescent dye leaching and impact of pH value, increased levels of fluorescence intensity in blood, all adipose tissues examined, cerebrum, cerebellum, and testis were measured in the 100 nm group, but not in the 3 and 10 μm groups except in the cerebellum and testis at 4 h for the 3 μm PS beads. The presence of PS beads was further corroborated. CONCLUSION After a single oral exposure, NPs are absorbed rapidly in the blood, accumulate in adipose tissues, and penetrate the blood-brain/testis barriers. As expected, the toxicokinetics of MPs is significantly size-dependent in mammals.
Male ; Animals ; Mice ; Microplastics ; Plastics ; Genitalia ; Adipose Tissue ; Polystyrenes/toxicity* ; Nerve Tissue ; Mammals

OBJECTIVE: To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS: The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34 RESULTS: In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.
Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Myelodysplastic Syndromes ; Platelet Transfusion ; Retrospective Studies

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.
Dissection ; Humans ; Lymph Node Excision ; Lymph Nodes ; Prognosis ; Rectal Neoplasms/surgery* ; Treatment Outcome

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.
Cohort Studies ; Colorectal Neoplasms ; Diverticulitis, Colonic ; Diverticulum ; Humans ; Male ; Middle Aged ; Retrospective Studies