Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Objective To construct a predictive model for cerebral small vessel disease (CSVD) MRI burden based on β2-microglobulin (β2-MG) and lipoprotein(a) [Lp(a)], analyze its predictive value, and validate the model. Methods A total of 138 CSVD patients admitted to Anhui No.2 Provincial People’s Hospital from February 2023 to August 2024 were enrolled. Patients were divided into a low-burden group (n=63) and a moderate/severe burden group (n=75) according to the CSVD MRI burden scoring criteria. The related clinical data were compared between the two groups. Binary logistic regression analysis was used to identify independent factors for CSVD moderate/severe MRI burden. A nomogram predictive model was constructed based on these factors and its performance was evaluated. Results The proportions of male patients, as well as those with a history of diabetes or hypertension, were significantly higher in the moderate/severe burden group than those in the low burden group. Additionally, the age of patients in the moderate/severe burden group was significantly older, and the levels of β2-MG, Lp(a), and homocysteine (Hcy) were higher than those in the low burden group (P＜0.01). Binary logistic regression analysis revealed that hypertension, diabetes, β2-MG, and Lp(a) were independent factors for CSVD moderate/severe MRI burden (P＜0.05). The nomogram predictive model based on these four factors had a cut-off value of 0.467 0, with an area under curve (AUC) of 0.838 7 (95%CI 0.760 8-0.916 6) in the training set (n＝97) and 0.854 1 (95%CI 0.742 1-0.966 1) in the internal validation set (n＝41) . The calibration curve demonstrated good agreement between predicted and observed values. Decision curve analysis (DCA) indicated that the nomogram model had good clinical utility. Conclusions The nomogram model based on β2-MG and Lp(a) has high predictive performance in assessing the risk of CSVD moderate/severe MRI burden, with good discrimination and calibration.

Objective:To explore the mechanism of Yiqi Jiedu Huayu Recipe(YQJDHY)on ulcerative colitis model rats based on the negative regulation of JAK2/STAT3 pathway by SOCS.Methods:The rats with ulcerative colitis were cloned by TNBS/ethanol method,and randomly divided into normal group,model group,SASP group,YQJDHY high-dose,medium-dose and low-dose groups.Serum IL-21 and IL-22 were detected by ELISA.Real-time quantitative polymerase chain assay(RT-PCR)was used to detect IL-23,IL-6,IL-17A,cytokine signaling inhibitor 1(SOCS1),SOCS3,tyrosine protein kinase 2(JAK2),transcription activa-tor 3(STAT3),retinoic acid-associated orphan receptorγ antibody(RORγt)mRNA expressions.Results:Pathological examination of rats in model group showed obvious inflammation and ulceration,indicating successful modeling.Compared with normal group,IL-21 and IL-22 contents in model group were significantly increased(P<0.05);the down-regulation of IL-21 and IL-22 in YQJDHY groups and SASP group were statistically different(P<0.05,P<0.01).Compared with model group,IL-23,IL-6,JAK2,STAT3 and IL-17A mRNA levels in intestinal mucosa and serum of YQJDHY groups and SASP group were significantly down-regulated(P<0.01),the ex-pressions of SOCS1 and SOCS3 mRNA in intestinal mucosa were increased in YQJDHY groups(P<0.01).The levels of RORγt mRNA in serum and intestinal mucosa of YQJDHY high-dose group and SASP group were increased(P<0.01).Compared with SASP group,the mRNA levels of JAK2 and STAT3 in YQJDHY high-dose group were increased(P<0.05).Conclusion:YQJDHY can increase the levels of SOCS1 and SOCS3 in ulcerative colitis model rats,and then inhibit JAK2/STAT3 signaling pathway,down-regulate the pro-duction of inflammatory factors,and reduce immune inflammatory response.

Objective:To evaluate the effectiveness of amplification intervention with hearing aids for restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss. Methods:This study selected 30 patients with normal hearing in one ear and moderate to severe sensorineural hearing loss in the other ear. They were fitted with hearing aids for the worse ear and underwent more than half a year and one year of adaptation training. The Chinese translation of the Twelve-item version of SSQ（C-SSQ12）, angle identification test, speech recognition score（SRS） at different signal-to-noise ratios（SNR=5 and SNR=10） and audiometric thresholds were used to compare the results before and after hearing aid use to evaluate the effectiveness of the unilateral hearing loss intervention. Results:The results of the audiometric thresholds, C-SSQ12 scores, angle identification test, and SRS at SNR=5 and SNR=10 in the worse ear of the unilateral hearing loss patients after hearing aid use were all statistically significant compared to before hearing aid use（P<0.01）. Conclusion:Amplification intervention with hearing aids has significant effects on restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss.
Humans ; Hearing Aids ; Hearing Loss, Unilateral/therapy* ; Middle Aged ; Hearing Loss, Sensorineural/rehabilitation* ; Adult ; Female ; Male ; Auditory Threshold ; Young Adult ; Aged

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*

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

Objective:To explore the surgical treatment strategies for Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures.Methods:A retrospective analysis was performed on the clinical data of 25 adult patients with Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures, admitted to the Upper Extremity Orthopaedics Department of Zhengzhou Orthopaedic Hospital from June 2013 to June 2023. There were 15 males and 10 females, with an average age of 43.5±14.7 years (range: 20-67 years). Among them, 5 cases were complicated with humeroulnar joint dislocation. The patients were divided into two groups: 17 cases were treated with open reduction and internal fixation (ORIF) of radial head fractures combined with ORIF of proximal ulnar fractures (open reduction group), and 8 cases were treated with radial head replacement combined with ORIF of proximal ulnar fractures (radial head replacement group). At the last follow-up, elbow joint range of motion was recorded, and pain, elbow function, and subjective upper limb function were evaluated using the Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), and Disabilities of the Arm, Shoulder and Hand (DASH) scale. The incidence of complications was also recorded.Results:All 25 patients were followed up for an average of 25.6±9.0 months (range: 12-45 months). At the last follow-up, the affected elbows in the open reduction group had a flexion of 124.47°±12.59° (range, 90°-140°), extension of 21.12°±10.07° (range, 10°-50°), pronation of 48.59°±11.62° (range, 20°-61°), and supination of 48.53°±8.43° (range, 30°-60°). In the radial head replacement group, the affected elbows showed flexion of 128.75°±13.17° (range, 100°-140°), extension of 14.00°±7.71° (range, 0°-25°), pronation of 61.25°±10.26° (range, 60°-80°), and supination of 71.88°±10.33° (range, 60°-80°). The MEPS score in the open reduction group was 82(75, 85) points (range, 55-90 points), the VAS pain score was 1(1, 2) points (range, 0-3 points), and the DASH score was 9(8, 14) points. In the radial head replacement group, the MEPS score was 90(85, 90) points (range, 85-90 points), the VAS pain score was 1(0, 1) points (range, 0-1 points), and the DASH score was 5(5, 6) points. Complications included 5 cases of heterotopic ossification, 1 case of incision infection, 1 case of nonunion, 1 case of ulnar nerve injury combined with traumatic arthritis, and 1 case of proximal radioulnar bone bridge formation.Conclusions:Both radial head replacement and open reduction internal fixation combined with proximal ulnar fracture fixation can effectively treat Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures. There was no significant difference in postoperative flexion and extension, but the radial head replacement group demonstrated better forearm rotation and DASH scores postoperatively.

The mother formula of Ruyizhenbao formula was the 25-flavor Zhumu Fang recorded in the Four Medical Codes,which was called Ruyi 25-flavor Zhumu Fang in the 16th century book Tibetan Medicine Ruyi Daquan.Later,in the book Qianwan Sheli,licorice was added to the formula,forming a 26-flavor basic formula of Ruyizhenbao.With the development of Tibetan medicine history,various doctors added and subtracted medicinal flavors to the basic formula.Finally,it was developed by Qinrenorbu into Ruyizhenbao formula composed of 30 herbs,which was published in the Treasure Source of Tibetan Medicine Secrets and was included in the Drug Standard of the Ministry of Health(Tibetan medicine)in 1995,becoming the formula standard of Ruyizhenbao formula.Through systematically sorting out Tibetan medicine literature from past dynasties,the formula name,medicinal taste composition,and changes of Ruyizhenbao formula recorded in different literature was comprehensively analyzed.Through primary literature research,the various claims about the origin of Ruyizhenbao formula published to date have been verified one by one to clarify its past and present,and to clarify its origin.The mother formula of Ruyizhenbao is the 25-flavor mother powder recorded in the Four Medical Codes.The basic formula is the Ruyizhenbao formula composed of 26 herbs in Qianwan Sheli,and the standard formula is the Ruyizhenbao formula composed of 30 herbs in the Treasure Source of Tibetan Medicine Secrets.