ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

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:The clinical significance of aural fullness in patients with vestibular migraine（VM） remains unclear, and it is yet to be determined whether VM with aural fullness represents a distinct subtype of VM; this study aimed to compare differences in demographic characteristics, clinical manifestations, audiological findings, and vestibular function tests between VM patients with and without aural fullness, and explore whether the former is a subtype of VM and whether it requires differentiated treatment. Methods:A total of 174 VM patients were enrolled, including 75 with aural fullness（aural fullness group） and 99 without aural fullness（non-aural fullness group）; demographic data, vertigo characteristics, medical history, family history, pure-tone audiometry, and vestibular function tests were thoroughly recorded, and independent samples t-test and chi-square test were used for inter-group comparisons. Results:①Regarding demographic characteristics, the age of the aural fullness group was significantly lower than that of the non-aural fullness group[（44.08±13.97） years vs. （49.45±16.05） years, P=0.020）, while the two groups showed consistent gender distribution（more females than males） with no statistically significant difference. ②For aural fullness characteristics, unilateral aural fullness accounted for 65.0% in the aural fullness group, significantly higher than bilateral aural fullness（35.0%, P<0.001）. ③In terms of vertigo characteristics, there were no statistically significant inter-group differences in the nature of attacks（rotational vertigo: 36.0% vs. 41.4%, P=0.463; dizziness: 21.3% vs. 11.1%, P=0.064; rotational vertigo or dizziness: 29.3% vs. 25.3%, P=0.548; dizziness with unsteady gait: 9.3% vs. 11.1%, Fisher P=0.806; visual oscillation with unsteady gait: 4.0% vs. 11.1%, Fisher P=0.086）, duration（several hours: 34.7% vs. 33.3%, P=0.841; several minutes: 22.7% vs. 21.2%, P=0.808; several seconds: 5.3% vs. 8.1%, Fisher P=0.557; several days: 9.3% vs. 9.1%, Fisher P=1.000; multiple combined patterns: 17.3% vs. 15.2%, P=0.686）, or incidence of nausea and vomiting（84.0% vs. 72.7%, P=0.071, no statistical significance）. ④No statistically significant inter-group differences were found in medical history and family history, including motion sickness history（8.0% vs. 4.0%, Fisher P=0.337）, headache history（22.7% vs. 34.3%, P=0.084）, and family history of dizziness（12.0% vs. 14.1%, P=0.666）. ⑤For audiological characteristics, 21.3%（16/75） of patients in the aural fullness group had low-frequency hearing loss, significantly higher than 5.1% in the non-aural fullness group（χ²=10.66, P=0.001）; among patients with unilateral aural fullness, 28.6%（14/49） had ipsilateral low-frequency hearing loss, significantly higher than 7.7%（2/26） of those with bilateral aural fullness（χ²=4.41, P=0.036）; however, there was no statistically significant difference in the rate of bilateral high-frequency hearing loss between the two groups（54.7%[41/75]vs. 50.5%[50/99], χ²=0.30, P=0.586）. ⑥In vestibular function tests, no statistically significant inter-group differences were observed in smooth pursuit type Ⅲ/Ⅳ（12.5% vs. 13.1%, P=0.913）, caloric test with CP>25%（31.2% vs. 37.4%, P=0.411）, abnormal video head impulse test（vHIT） rate（30.8% vs. 32.6%, P=0.865）, or abnormal vestibular evoked myogenic potential（VEMP） rate（53.8% vs. 38.9%, Fisher P=0.484）. Conclusion:VM patients with aural fullness have an earlier age of onset, with nearly 1/4 accompanied by low-frequency hearing loss; VM patients with and without aural fullness are highly consistent in gender distribution, nature/duration of vertigo, vestibular function impairment, and presence of bilateral high-frequency hearing loss, suggesting that the core clinical phenotypes of the two groups are consistent, while the former has an earlier age of onset and a higher proportion of unilateral hearing loss, which may be related to the pathological mechanism of VM and inner ear microcirculation disorders.
Humans ; Female ; Male ; Middle Aged ; Adult ; Migraine Disorders/classification* ; Young Adult ; Vertigo ; Age of Onset ; Aged ; Hearing Loss

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Objective To construct a prediction model for coronal malalignment of lower limb in middle-aged and young people in China based on body surface big data in order to provide a faster and more accurate tool for predicting the malalignment in clinical practice.Methods A cross-sectional trial was adopted on 915 patients with knee meniscus tears admitted to the Sports Medical Center of our hospital from May 2022 to December 2023.The coronal force line of lower limb was measured,and according to the lower limb force line grading standards,the patients were divided into neutral force line group and malalignment lower limb group,and assigned randomly into training set and validation set in a ratio of 7∶3.Seven indicators,such as gender,age,and body surface big data (including BMI,lower limb length,distance between both knee joints,distance between both ankle joints,and subcutaneous fat thickness)were used to analyze the training set to predict the value of malalignment force line.Logistic regression model and nomogram model were constructed to visualize our prediction model. Then calibration curves,receiver operating characteristic (ROC)curve,and decision curve analysis (DCA)were applied to evaluate the diagnostic efficacy of the constructed model.Results In the training set of 640 cases,there were 299 males and 341 females,with a median age of 41 .5 years old,and for the validation set,there are 275 patients,including 128 males and 147 females,with a median age of 41 .0 years old.Significant differences were observed in above mentioned 7 indicators between the 2 groups in the training set (P<0.01 ).Based on the results of multiple logistic regression analysis,a prediction model for malalignment of lower limb was constructed,including BMI (24.31±3.58 kg/m2,OR=1 .12,95％CI:1 .06～1 .19,P<0.001 ),lower limb length[82.00 (78.00～87.00)cm,OR=0.95,95％CI:0.92～0.98,P=0.002],distance between both knee joints[30.00 (16.00～45.25)cm,OR=1 .06,95％CI:1 .05～1 .07,P<0.001],distance between both ankle joint[23.00 (8.00～30.00)mm,OR=0.98,95％CI:0.96～1 .00,P=0.078]and gender[man 299 (46.72％),OR=0.70,95％CI:0.46～1 .06,P=0.089].The area under the subject curve (AUC)value of our constructed model for predicting malalignment of lower limb was 0.808 and 0.770,respectively,in the training and validation sets.Conclusion Based on body surface big data,we primarily construct a prediction model for malalignment of lower limb for middle-aged and young people in China,which shows a good diagnostic performance on malalignment of lower limb.

Objective To explore the characteristics and correlation of the chin and airway in females with skeletal Class Ⅱ mandibular retraction for reference for clinical diagnosis and therapy.Methods This study was approved by the hospital Medical Ethics Committee.Forty cases of skeletal Class Ⅱ mandibular retraction adult females with aver-age angle were selected as the research group,and sixty cases of skeletal Class Ⅰ patients with average angle were se-lected as the control group.Cone-beam computed tomography(CBCT)images for all subjects were analyzed using three-dimensional modeling software.Measurements included the chin morphology,position,and upper airway morphology.Results Compared with skeletal Class Ⅰ patients,patients with skeletal Class Ⅱ mandibular retraction had smaller an-terior chin thickness,base bone volume,chin total volume,and larger chin angle,chin depression,chin curvature,and alveolar area with statistically significant differences(P＜0.05).Gn-V,Gn-H,Po-NB distance,and facial angle were smaller,and the Y-axis angle was larger in patients with skeletal Class Ⅱ mandibular retraction with statistically signifi-cant differences(P＜0.05).Upper airway total volume,transverse and sagittal diameter of the glossopharynx upper boundary were smaller in patients with skeletal Class Ⅱ mandibular retraction with statistically significant differences(P＜0.05).The correlation analysis between the morphology and position of the chin and the morphology of the upper airway in patients with Class Ⅱ mandibular retraction showed that there was a negative correlation between chin angle and laryngopharynx length in patients with Class Ⅱ mandibular retraction(r=-0.277,P＜0.01).There was a negative correlation between Po-NB distance and palatopharyngeal length(r=-0.222,P＜0.05).Chin height(r=-0.261,P＜0.01)and basal bone area(r=-0.225,P＜0.05)were negatively correlated with the transverse diameter of the palato-pharyngeal upper boundary.The minimum chin thickness(r=0.245,P＜0.05),chin angle(r=0.249,P＜0.05),and al-veolar area(r=0.213,P＜0.05)were positively correlated with the sagittal diameter of the palatopharyngeal upper boundary.Gn-V(r=0.217,P＜0.05)and Po-NB distance(r=0.208,P＜0.05)were positively correlated with the trans-verse diameter of the glossopharynx upper boundary.Anterior chin thickness was negatively correlated with the sagittal diameter of the laryngopharynx upper boundary(r=-0.211,P＜0.05).Chin depression was negatively correlated with the sagittal diameter of the laryngopharynx lower boundary(r=-0.237,P＜0.05).Chin curvature was positively corre-lated with the transverse diameter of the laryngopharynx lower boundary(r=0.231,P＜0.05).Conclusion Patients with skeletal Class Ⅱ mandibular retraction exhibit thinner chins.The sagittal position of the chin is backward,and the vertical position is upward.Patients with skeletal Class Ⅱ mandibular retraction have a narrow glossopharyngeal airway.There is a correlation between the morphology and position of the chin and the morphology of the upper airway in pa-tients with Class Ⅱ mandibular retraction.

Objective To evaluate the efficacy and safety of neoadjuvant arterial interventional chemotherapy(NAIC)and neoadjuvant intravenous chemotherapy(NIVC)for the treatment of locally advanced cervical cancer(LACC).Methods Randomized controlled trials(RCTs)which fit the theme were included by searching PubMed,Web of Science,Embase,CNKI,and Wanfang databases.After study quality assessment and data extraction,statistical analysis was performed using Stata 17.0,and outcome quality was assessed using the GRADE system.Results A total of 14 RCTs were included,with 1 063 LACC patients.The results of the Meta-analysis showed that NAIC and NIVC had a positive effect on the effectiveness indicators:complete response(CR)[RR=1.23,95％CI(0.91,1.67),P=0.174],partial response(PR)[RR=1.10,95％CI(0.86,1.20),P=0.874],total response(TR)[RR=1.10,95％CI(0.95,1.25),P=0.212],no change(NC)[RR=0.62,95％CI(0.33,1.16),P=0.137]and progressive disease(PD)[RR=1.43,95％CI(0.41,4.99),P=0.574]were not statistically significant.Differences in safety indicators:gastrointestinal reactions[RR=0.96,95％CI(0.76,1.23),P=0.755],hepatic and renal impairment[RR=0.71,95％CI(0.41,1.23),P=0.226]were not statistically significant.While in the incidence of myelosuppression[RR=0.62,95％CI(0.45,0.86),P=0.04],NAIC was superior to NIVC.In addition,the GRADE score results showed CR,PR,TR,and NC were high-quality evidence.Conclusion For LACC patients,the incidence of myelosuppression after treatment with NAIV is lower and safer than that with NIVC,and no significant difference was found between the two in terms of other efficacy and safety indicators.Clinicians should choose the appropriate neoadjuvant chemotherapy regimen based on a comprehensive assessment of the patient's actual condition.

Objective:To evaluate the safety and efficacy of ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique for the treatment of complex encapsulated lesions.Methods:A total of 48 patients(48 lesions) with complex encapsulated lesions who underwent ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique at Xi′an Chest Hospital from January to October 2023 were retrospectively enrolled, including 39 cases of encapsulated abscess, 7 cases of encapsulated effusion, and 2 cases of encapsulated haematoma; the distribution of the bacterial flora of the abscesses were as follows: 24 cases of tuberculous abscess, 14 cases of bacterial abscess, 1 case of bacterial combined bacterial-fungal abscess, and 7 cases of encapsulated effusion were tuberculous pleurisy, and the clinical data were analysed retrospectively. The maximum upper and lower diameters, right and left diameters, and anterior and posterior diameters of the lesions were measured by ultrasound before and after the operation. The patients′ various biochemical indicators (C-reactive protein, white blood cell count, neutrophil count, erythrocyte sedimentation rate) were detected. The intraoperative and postoperative complications, postoperative outcomes, and postoperative clinical symptoms were recorded.Results:Of the 48 patients, 39 were cured and discharged after negative pressure suction and rotatory excision technique, and 9 patients were cured and discharged after surgical incision and drainage of the lesions. The overall effective rate of negative pressure suction and rotatory excision treatment reached 81.25%, and the average number of days of tube placement was (11.81±7.22) days, and the average number of days of follow-up was (35.77±19.39) days. Compared with preoperative values, the upper and lower diameters, the left and right diameters, and the anterior and posterior diameters of the lesions were all reduced after operation [5.80 (4.95, 7.95)cm vs 8.00 (6.00, 11.82)cm, 4.00 (3.25, 5.00)cm vs 5.85 (4.52, 7.65)cm, 1.80 (1.00, 2.90)cm vs 3.40 (2.50, 6.15)cm, all P<0.01]; and postoperative C-reactive protein, white blood cell count and neutrophil count all decreased (all P<0.05). Before operation there were 31 cases of local swelling, 16 cases of pain, 12 cases of activity limitation, 12 cases of fever, 7 cases of chest tightness, and 6 cases of shortness of breath, and during postoperative follow-up, there were 4 cases of local swelling, 5 cases of pain, and 4 cases of activity limitation. The symptoms of fever, chest tightness, and shortness of breath all disappeared, and there was a statistically significant difference between preoperation and postoperation (all P<0.05). There were no adverse events or complications associated with the intraoperative and postoperative follow-up of negative pressure suction and rotatory excision treatment. Conclusions:Ultrasound-guided percutaneous negative pressure suction and invasive rotatory excision technique for the treatment of complex encapsulated lesions can significantly reduce lesion size, reduce inflammatory response and improve patient symptoms, which is a safe, effective and minimally invasive technique.