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*

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To explore the effects of Bushen Jiedu Formula combined with auricular pressure by coxherb seeds on cancer pain and quality of life in patients with advanced colorectal cancer. Methods A total of 120 patients with advanced colorectal cancer admitted to our hospital from June 2019 to May 2023 were included in the study, and were randomly divided into two groups. The control group (60 cases) received routine nursing care and the "three-step" analgesic method to intervene pain, while the observation group (60 cases) received treatment with Bushen Jiedu Formula combined with auricular pressure by coxherb seeds on the basis of the control group. Both groups were treated for one month. The Numerical Rating Scale (NRS) score, the therapeutic effect, the quality of life (QOL) score and the occurrence of adverse reactions were compared between the two groups before and after treatment, and the levels of substance P (SP), β-endorphin (β-EP) and prostaglandin E₂(PGE₂) of the two groups before and after treatment in serum were detected. Results After treatment, the NRS score and the levels of SP, β-EP and PGE₂ in the observation group were (2.23±0.64), (11.51±2.64) ng/mL, (78.64±9.46) ng/L and (41.90±6.32) ng/L, respectively, which were lower than (2.87±1.25), (15.64±2.42) ng/mL, (101.29±11.26) ng/L and (78.63±10.17) ng/L, respectively of the control group (P < 0.05). The total effective rate and QOL score of the observation group were 90.00% and (51.92±5.66), which were higher than 75.00% and (43.58±5.12), respectively of the control group (P < 0.05).There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The combination of Bushen Jiedu Formula and auricular pressure by coxherb seeds can obviously improve the cancer-induced pain of patients with advanced colorectal cancer, improve their quality of life, and have good safety.

The 2 patients were both aged females with medical history of diabetes mellitus. The chief complaints were both hyperpyrexia. Laboratory tests presented markedly elevated white blood cells and C-reactive protein, indicating severe systemic infections. Urine culture confirmed the growth of Escherichia coli. CT scan revealed thickened bladder wall with intraluminal and interstitial collections of gas. After the diagnosis of emphysema cystitis was established, conservative treatments including bladder drainage, strict glycemic control and sensitive antibiotics were administered timely. Both of the 2 patients got fully recovery after standard treatment.

A large spontaneous mass on the dorsal abdomen near the hip joint was found in an aged female Tupaia belangeri subsp. yaoshanensis after 5 years of routine feeding. The tumor in the diseased tree shrew was huge, with an intact surface and no ulceration; however, it caused inconvenience in movement while maintaining a good mental state. After inhalation anesthesia with isoflurane (2%-4%), the tree shrew was euthanized after the tree shrew entered deep anesthesia. Anatomical dissection of the tumor, the tumor boundary was unclear and infiltrated into surrounding tissues. HE staining showed that small focal pleomorphism and large areas of adipocytes were seen in the tumor tissue. The pleomorphic sarcoma area was mainly composed of atypical epithelioid cells with easily visible nuclear divisions. The size of the adipocytes was significantly different, and more pleomorphic adipocytes were seen. The cell volume was large, the nucleus was deeply stained and deformed, the edge was impressed, and the cytoplasm was seen with multiple vesicular lipid droplets. Immunohistochemical results showed that the tumor cells were positive for Vimentin, the small focal polymorphic adipocyte nucleus was positive for S-100, and Ki-67 exhibited a higher proportion of positivity. Combined with HE staining and immunohistochemical results, the spontaneous tumor in this tree shrew was comprehensively diagnosed as pleomorphic liposarcoma.

Objective:To explore the influences of times of venous thromboembolism (VTE) drug prophylaxis in formation of deep vein thrombosis (DVT) in patients with severe craniocerebral injury after surgical treatment.Methods:Ninety patients with severe craniocerebral injury, admitted to our hospital from February 2021 to December 2021, were chosen in our study; they were divided into early group ( n=47, less than 48 h from the time of admission) and late group ( n=43, more than 48 h from the time of admission) according to the times of initiation for VTE drug prophylaxis (low molecular weight heparin calcium injection [LMWH] 100 IU/Kg was injected subcutaneously once a d). One week after injection, the DVT formation in the lower limbs, intracranial rebleeding, gastrointestinal bleeding and death were compared in the two groups. Results:The times of initiation for drug prophylaxis in the early group and late group were (28.91±4.50) h and (71.56±8.89) h. The DVT formation in the early group was significantly lower than that in the late group (12.8% vs. 34.9%, P<0.05). There was no difference in the incidence of intracranial rebleeding, mortality or gastrointestinal bleeding between the two groups ( P>0.05). Conclusion:Early initiation of VTE drug prophylaxis can significantly reduce the incidence of DVT in patients with severe craniocerebral injury after surgical treatment, enjoying high safety.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*

Objective:To investigate the effects and mechanism of exosomes secreted by human umbilical cord-derived mesenchymal stem cells （hUC-MSCs） in repair of tendon cell injury.Methods:The hUC-MSCs which were stably subcultured were isolated and purified by a tissue block adherent method，and the immunophenotype of hUC-MSCs was detected by flow cytometry. The induction media was employed to induce the differentiation of hUC-MSCs to osteoblasts，chondroblasts and adipocytes，and cell identification was performed subsequently. The secreted exosomes of MSCs （MSCs-exosomes） were extracted using an ultracentrifugation method. The exosomes were detected by Western blot and electron microscopy，and the fusion ability of the exosome membrane was detected by PKH67 staining fluorescence. Forty Wistar rats were divided into tendon injury group （ n = 20） and normal group （ n = 20） according to the random number table. In tendon injury group，the rats were sacrificed with 100 mg/kg pentobarbital sodium one week after Achilles tendon transection，and the injured tendon cells were obtained following digestion of the Achilles tendon. In normal group，the rats were sacrificed without any treatment and the normal tendon cells were obtained concurrently. After the exosomes were co-cultured with tendon cells in vitro for 12，24，48，72 hours，the proliferation of tendon cells was detected by CCK-8 assay. After the tendon cells were treated with hUC-MSCs exosomes for 24 hours，the effects of exosomes on transforming growth factor β （TGF-β），bone morphogenetic protein （BMP），vascular endothelial growth factor （VEGF），fibroblast growth factor （FGF），interleukin（IL）-1β and tumor necrosis factor-α （TNF-α） were detected by Western blot，qPCR and immunofluorescence. Results:The hUC-MSCs were identified and hUC-MSCs-exosomes were isolated successfully. The cultured MSCs were fusiform and positive for Alanine aminopeptidase （CD13），integrin β-1 （CD29），ECTO-5'-nucleotidase （CD73），thymocyte surface antigen （CD90） and endothelin （CD105），but negative for human leukocyte DR antigen （HLA-DR），hematopoietic progenitor cell antigen （CD34） and leukocyte common antigen （CD45）. The exosomes isolated showed a round disc shape and a diameter of 30-100 nm with a depressed internal structure under the electron microscope which was verified via PKH67 staining and the motility-related protein-1 （CD9） and lysosomal associated membrane protein 3 （CD63） were highly expressed. The CCK-8 assay showed the cell viability in tendon injury group was markedly higher than that in normal group at 12 h，24 h，48 h，and 72 h following treatment of tendon cells （ P < 0.01）. The results of qPCR revealed that the mRNA expressions of TGF-β （1.850 ± 0.127），BMP （2.133 ± 0.398），FGF （1.610 ± 0.223） and VEGF （2.207 ± 0.059） in tendon injury group were markedly higher than those in normal group（1.004 ± 0.105，1.007 ± 0.145，1.007 ± 0.140，1.001 ± 0.065，respectively） （ P < 0.05）. However，the mRNA expressions of IL-1β （0.102 ± 0.009） and TNF-α （0.130 ± 0.013） in tendon injury group was markedly lower than those in normal group （1.004 ± 0.113，1.006 ± 0.134） （ P < 0.01）. The results of Western blot were consistent with those of qPCR. Conclusions:The exosomes secreted by hUC-MSCs can promote the growth of tendon cells and repair of tendon cell injury by up-regulating the expression of growth factors TGF-β，BMP，VEGF and FGF，and inhibiting the expression of inflammatory factors IL-1β and TNF-α.

Objective:To understand the current status of HIV self-testing reagent use in pre-exposure prophylaxis (PrEP) and related factors in men who have sex with men (MSM).Methods:From December 2018 to December 2019, "Gold data" online platform (www.jinshuju.com) was used to conduct multicenter PrEP studies in Shenyang, Beijing, Chongqing and Shenzhen of China.Results:A total of 1 222 MSM PrEP users were included in the multicenter study. The average age of the participants was (31.5±8.7) years, and the number of sexual partners in the past three months was 3 ( P 25, P 75:2,6). The proportions of those who did not use condoms in anal sex with fixed, casual and commercial partners were 62.7% (456/727), 56.3% (440/781) and 41.0% (16/39), respectively. Up to 74.5% (910/1 222) of participants had used HIV self-testing reagents, and the number of HIV self-testing during last year was 3 ( P 25, P 75:2,5). The multivariate logistic regression analysis indicated that compared with age group >40 years, those with education level of junior high school or below, those with psychological identity as female, event driven PrEP users, those never using new type drugs in past 3 months, the participants aged 18- years (a OR=2.06, 95% CI: 1.35-3.14), 26- years (a OR=2.72, 95% CI: 1.77-4.17), 31- years (a OR=1.76, 95% CI: 1.19-2.59), undergraduates (a OR=2.18, 95% CI: 1.35-3.49), graduate students and above (a OR=3.06, 95% CI: 1.69-5.54), those with psychological identity as male (a OR=3.22, 95% CI: 1.55-6.70), daily PrEP users (a OR=1.35, 95% CI: 1.03-1.78), and new type drug users in the past three months (a OR=1.72, 95% CI: 1.30-2.28) had higher proportions of HIV self-testing behaviors. Conclusions:The proportion of HIV self-testing in MSM PrEP users was high, while it was relatively low in older age group, event driven PrEP users and MSM never using new type drugs. To assess and improve the effectiveness and compliance of PrEPs, it is necessary to provide better HIV self-testing service for MSM with low HIV self-testing rate.