ObjectiveTo investigate the anti‑pancreatic fibrosis mechanism of Klotho‑derived peptide 7 （KL7） by observing its effect on a mouse model of chronic pancreatitis （CP） induced by cerulean， and to provide a basis for clinical medication. MethodsA total of 40 male BALB/c mice were randomly divided into control group， model group， low-dose KL7 group （2 mg/kg）， and high-dose KL7 group （4 mg/kg）， with 10 mice in each group. All mice except those in the control group were given intraperitoneal injection of cerulean （50 μg/kg） 6 times a day at an interval of 1 hour， twice a week for 4 consecutive weeks to establish a model of CP. The mice in the low-dose KL7 group and the high-dose KL7 group were treated with different doses of KL7 once a day for 4 consecutive weeks. In vivo imaging was used to observe the accumulation of KL7 in the pancreas； molecular docking was used to detect the binding of KL7 to transforming growth factor-β type Ⅱ receptor （TβRⅡ）； the mice were measured in terms of body weight and pancreatic weight； HE staining was used to observe the pathological changes of pancreatic tissue； Masson staining was used to observe the degree of pancreatic fibrosis； immunohistochemical staining was used to measure the expression of α-smooth muscle actin （α-SMA） and type Ⅰ collagen （COL1A1）； Western blotting was used to measure the protein expression levels of α-SMA， TβRII， and phosphorylated small mothers against decapentaplegic homolog 2/3 （p-Smad2/3） in pancreatic tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups. ResultsKL7 was significantly enriched in the pancreatic tissue of CP mice， and there was a strong binding activity between KL7 and TβRⅡ. Compared with the control group， the model group had significant reductions in pancreatic mass and relative pancreatic mass （P<0.000 1）， with disordered structure of pancreatic tissue， an increase in inflammatory cell infiltration， and significant increases in fibrosis degree， the positive areas of α-SMA and COL1A1 （P<0.000 1）， and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.05）. Compared with the model group， the high-dose KL7 group had significant increases in pancreatic mass and relative pancreatic mass （P<0.01）， with alleviation of structural damage of pancreatic tissue and inflammatory cell infiltration， a significant reduction in fibrosis degree， and significant reductions in the positive areas of α-SMA and COL1A1 （P<0.001） and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.01）. ConclusionKL7 has a significant targeted therapeutic effect on pancreatic fibrosis in CP mice through specific binding of KL7 to TβRⅡ， thereby inhibiting the activation of the TGF-β/Smad signaling pathway.

Objective To study the clinical efficacy of buccal acupuncture in the treatment of refractory tinnitus in the elderly.Methods In this study,50 elderly patients with refractory tinnitus were randomly divided into two groups:the experimental group(n=26)received buccal acupuncture therapy on the neck,upper neck,scapula zone,shoulder,back,mastoid process,thoracic plexus,abdominal plexus and pelvic plexus on the affected side,and the control group(n=24)received sound therapy.After 8 weeks of treatment intervention,the two groups were comprehensively evaluated for the changes in the tinnitus evaluation scale(TEQ),self-rating depression scale(SDS),and blood rheological indexes,including whole blood high-cut viscosity(HSV),plasma viscosity(PSV)and fibrinogen in blood(FIB)clotting.Results After treatment,the total effective rate of the experimental group was 84.6％(22/26),higher than 54.2％(13/24)in the con-trol group.The difference in total effective rate and efficacy level between the two groups was statistically significant(P＜0.05).TEQ and SDS were significantly lower in the two groups compared to pre-treatment(P＜0.05),and HSV,PSV and FIB in the experimental group were significantly lower compared to pre-treatment(P＜0.05).The experimental group demonstrated better post-treatment outcomes in TEQ,SDS,HSV,and FIB compared to the control group(P＜0.05).Conclusion Buccal acupuncture treatment is effective in improving the symptoms of refractory tinnitus in the elderly,relie-ving the depression complicated by tinnitus,and is helpful in changing blood flow resistance and reducing blood coagulation probably.

Objective:To assess cognitive impairment in children with obstructive sleep-disordered breathing (OSDB) using event-related potentials (ERPs).Methods:This case-control study analyzed data from 143 OSDB children[94 males, 49 females, aged 9.0(7.0-11.0) years] scheduled for adenotonsillectomy at the Department of Otolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, between June 2023 and September 2024, along with 17 healthy controls [control group: 10 males, 7 females, aged 10.0 (7.5-12.0) years]. Based on polysomnography results, OSDB children were divided into a mild group [obstructive apnea-hypopnea index (OAHI)≤5 events/hour, 49 males, 29 females, aged 9.0 (7.0-10.0) years] and a moderate-to-severe group [OAHI>5 events/hour, 45 males, 20 females, aged 9.0 (8.0-10.0) years]. All children completed a face perception integration task. The occipital P100 and parietal, central and frontal P300 components of incomplete face stimuli (S1) and complete face stimuli (S2) were recorded. Amplitude and latency differences across groups were analyzed. Intergroup comparisons were performed using ANOVA, while independent samples t-tests were used for pairwise comparisons. Non-normally distributed data were analyzed using the Mann-Whitney U test. Results:(1) P100: Both the mild group [occipital P100 amplitude: O1-S1(12.44±5.96) μV, O2-S1(14.19±6.39) μV, O2-S2(30.34±11.30) μV] and moderate-to-severe group [O1-S1 (12.12±5.58) μV, O2-S1 (14.08±5.48) μV, O2-S2(29.12±10.89) μV] showed significantly higher amplitudes than the control group [O1-S1(8.46±4.74) μV,O2-S1(9.68±3.70) μV,O2-S2(23.09±9.16) μV] ( F=3.501, 4.486, 3.072; all P<0.05). No significant differences were found between the two OSDB subgroups ( P>0.05), suggesting compensatory neuronal hyperactivity maintaining normal perceptual function. The moderate-to-severe group exhibited significantly prolonged P100 latency [O2-S1 (134.52±13.42) ms] compared to controls [O2-S1 (125.18±15.31) ms] ( F=3.156 , P<0.05), while no significant difference was observed between the mild group and either the control or moderate-to-severe groups ( P>0.05), indicating delayed visual processing in severely affected children. (2) P300: The mild group exhibited significantly higher P300 amplitudes in parietal regions [P4-S1(8.22±4.32) μV, P4-S2(17.67±9.42) μV] compared to controls [P4-S1 (4.84±2.89) μV, P4-S2 (13.19±7.23) μV] ( F=7.19, 4.771; both P<0.05), whereas no significant differences were observed between the moderate-to-severe group and either the control or mild groups ( P>0.05), indicating mild group reduced alertness. The latency of P300 in the central region showed an increase in the mild group, although not significantly ( P>0.05), indicating a potential decrease in attentional response speed. However, the moderate-to-severe group demonstrated significantly shorter P300 latencies [CZ-S1(394.18±89.12) ms] compared to the mild group [CZ-S1 (433.33±100.33) ms] ( F=3.145, P<0.05), possibly reflecting compensatory enhancement of attentional engagement in more severe cases. Conclusion:Children with OSDB exhibit impairments in primary visual processing and attentional regulation, as evidenced by altered ERP components such as P100 and P300. These findings suggest that OSDB may affect neural mechanisms underlying sensory integration and executive functioning.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

Objective To develop and validate a"quick self-assessment questionnaire for cochlear implant out-come(QSACI)".Methods A research team,composed of audiologists,otolaryngologists,data analysis experts,and cochlear implant(CI)recipients,was formed to establish objectives,research subject criteria,and framework of the QSACI.An item pool was creaed through literature review and brainstorming.Question items were evaluated and screened,and the framework and answer options of the questionnaire were established.The comprehensibility,etc.,was analyzed and refined through pilot test,interviews,and expert consultation,leading to the development of the final version.A total of 39 post-lingually deafened adults with known stable outcomes completed the question-naire.The split-half and test-retest reliabilty of the questionnaire was analyzed,and the validity was quantitatively analyzed by comparing scores with the categories of auditory performance(CAP)scores.Results The initial item pool of the questionnaire had 18 items,and the final questionnaire consisted of 12 questions in four dimensions:com-munication status,audiological status,medical factors,and other factors.The average score of 39 recipients was 88.81±6.17 and CAP was 6.19±0.94.The questionnaire showed good reliability and validity,with a Cronbach's alpha coefficient of 0.71 and a test-retest reliability of 0.824(P＜0.05).The criterion-related validity,assessed by the correlation between the self-assessment questionnaire scores and CAP scores,showed a significant moderate pos-itive correlation(r=0.512,P＜0.05).The correlation coefficient between self-assessment and professional assess-ment was 0.720(P＜0.05),indicating a significant correlation.The area under the receiver operating characterstic(ROC)curve was 0.82(P＜0.05),the cutoff values corresponding to the maximal Youden index were 82.5 and 88.6,therefore score of 85 was taken as the median threshold score of judgement.Conclusion The QSACI reflects the post-imlplant outcomes,and it can serve as a tool for people with postlingually deafness and their families to un-derstand the eligbility of CI and the expected outcomes,helping to establish realistic expectations before CI surgery.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

Drug development remains a critical issue in the field of biomedicine.With the rapid advancement of information technologies such as artificial intelligence(AI)and the advent of the big data era,AI-assisted drug development has become a new trend,particularly in predicting drug-target associations.To address the challenge of drug-target prediction,AI-driven models have emerged as powerful tools,of-fering innovative solutions by effectively extracting features from complex biological data,accurately modeling molecular interactions,and precisely predicting potential drug-target outcomes.Traditional machine learning(ML),network-based,and advanced deep learning architectures such as convolutional neural networks(CNNs),graph convolutional networks(GCNs),and transformers play a pivotal role.This review systematically compiles and evaluates AI algorithms for drug-and drug combination-target predictions,highlighting their theoretical frameworks,strengths,and limitations.CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions.GCNs provide deep insights into molecular interactions via relational data,whereas transformers increase prediction accu-racy by capturing complex dependencies within biological sequences.Network-based models offer a systematic perspective by integrating diverse data sources,and traditional ML efficiently handles large datasets to improve overall predictive accuracy.Collectively,these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy.This review summa-rizes the application of AI in drug development,particularly in drug-target prediction,and offers rec-ommendations on models and algorithms for researchers engaged in biomedical research.It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.

Traditional Chinese medicine (TCM) is characterized by complex, multicomponent herbal formulations that challenge the conventional“one drug, one target” paradigm. Network pharmacology, through the construction of multilayered drug-target-disease networks, provides a systematic framework for unraveling TCM’s multitarget and multipathway mechanisms. Recent advancements in artificial intelligence, particularly large language models (LLMs), further enhance data integration, target identification, and clinical decision-making. This review synthesizes current progress in the application of network pharmacology and LLMs in TCM, highlighting their potential to deepen mechanistic insights and optimize drug discovery. By bridging traditional medical wisdom with modern computational tools, this integrative approach aims to advance the scientific validation of TCM and foster innovative healthcare solutions.

Objective To explore the efficacy of hypofractionated radiotherapy at different time intervals after surgery for keloid,and to analyze the factors affecting the efficacy.Methods A total of 76 patients who underwent 20 Gy/5 postoperative radiotherapy regimen in the Fifth Affiliated Hospital of Zhengzhou University from January 2021 to June 2023 were selected as study subjects,and a total of 100 keloids were divided into effective group(n=79)and recurrence group(n=21).Regular follow-up and record of the patients after radiotherapy treatment effect and adverse effects,and multivariate Logistic was used to analyze factors of recurrence in keloid patients.Results Multivariate Logistic regression analysis found that postoperative radiotherapy time and scar incision length were related to recurrence after treatment,radiotherapy within 7h of surgery was an independent risk factor for recurrence after treatment(OR＞1,P=0.022),and scar incision≤5cm was an independent protective factor for recurrence after treatment(OR＜1,P=0.028).Conclusion Surgical excision combined with hypofractionated radiotherapy is one of the effective measures to prevent and treat keloid recurrence,though keloids on the trunk may need more effective treatment options.The recurrence rate of radiotherapy initiated 7-48h after surgery is relatively the lowest,and it is worthy of clinical promotion and application.