With the progressive aging of the population and the evolving spectrum of aortic valve disease, bioprosthetic valve has gained widespread clinical adoption owing to their reduced requirement for lifelong anticoagulation and impact on patients’ postoperative quality of life. Consequently, the long-term durability of bioprosthetic valve has become a central focus in contemporary valvular research. The Avalus valve, representing a new generation stented bovine pericardial valve, incorporates optimized leaflet configuration, stent geometry, and anti-calcification treatment to achieve a balance between superior hemodynamic performance and structural durability. The recently reported 7-year outcomes of the PERIGON trial demonstrated excellent mid- and long-term outcomes, a remarkably low incidence of valve-related adverse events and sustained hemodynamic stability throughout follow-up. Importantly, no cases required reintervention for structural valve deterioration, underscoring the outstanding durability profile of the Avalus valve in surgical aortic valve replacement. This article reviews PERIGON trial clinical outcomes and discusses significance of the Avalus valve, as well as the future directions for bioprosthetic valve therapy in Chinese patients.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo investigate the lower limb muscle synergy patterns during jumping in patients after anterior cruciate ligament reconstruction (ACLR). MethodsFrom March to November, 2022, 23 patients after ACLR were enrolled as observation group, and 24 healthy ones matched in height, body mass and exercise level were recruited as control group at Wuhan Sports University. Surface electromyography (sEMG) data of lower limb muscles were collected during a single-leg vertical jump task. Non-negative matrix factorization was applied for synergy analysis. The number of synergies, variance accounted for, synergy structure (muscle weight) and activation coefficient were extracted. ResultsThree types of muscle synergy patterns were identified on the affected side and contralateral side of the observation group, and the control group. For Synergy 1, the weight of biceps femoris was higher on both the affected and contralateral sides than in the control group (P < 0.01); the weight of semitendinosus was higher on the affected side than on the contralateral side (P < 0.05). For Synergy 2, the weight of lateral gastrocnemius and soleus were higher on both sides of the observation group than in the control group (P < 0.05). For Synergy 3, the weight of gluteus maximus was lower on the affected side than on the contralateral side and in the control group (P < 0.05); the weight of tibialis anterior was higher on the affected side than on the contralateral side and in the control group (P < 0.001); the weight of vastus lateralis was lower on the contralateral side than on the affected side and in the control group (P < 0.001). In the observation group, the peak activation time and stop time of Synergy 3 were delayed bilaterally (P < 0.05). ConclusionPatients after ACLR exhibit altered structural and temporal characteristics of lower limb muscle synergy during jump task. The hamstrings show increased participation during the pre-activation phase, and calf muscles undertake more stabilizing functions during the landing phase.

[摘 要] 目的：以MG-63球形细胞作为骨肉瘤干细胞（OSC）富集模型，探讨靶向细胞膜表面HSP90β的单抗2G1对其生物学特征的影响及其与Wnt信号相关蛋白变化的关系。方法：采用无血清悬浮培养人骨肉瘤MG-63细胞获得MG-63球形细胞。通过免疫荧光共定位和免疫共沉淀实验鉴定单克隆抗体2G1识别的靶抗原；采用流式细胞术检测MG-63亲本细胞和MG-63球形细胞膜表面HSP90β的表达水平；通过甲基纤维素成球实验、Transwell迁移和侵袭实验评价单抗2G1对MG-63球形细胞成球、迁移和侵袭能力的影响；采用裸鼠皮下移植瘤模型观察单抗2G1对MG-63球形细胞体内成瘤能力的影响；进一步结合转录组测序、京都基因与基因组百科全书（KEGG）通路富集分析及WB检测，分析单抗2G1处理后相关分子通路及干细胞特性、上皮-间充质转化（EMT）、Wnt/β-catenin信号通路相关蛋白表达变化。结果：免疫荧光共定位和免疫共沉淀结果显示，单抗2G1识别的靶抗原为HSP90β。流式细胞术结果显示，MG-63球形细胞膜表面HSP90β阳性表达细胞比例为（20.77 ± 1.29）%，显著高于MG-63亲本细胞的（2.87 ± 0.33）%（P < 0.001）。与对照组相比，单抗2G1处理后MG-63球形细胞成球数由82.67 ± 4.70降至42.67 ± 4.00，迁移细胞数由117.00 ± 5.57降至78.33 ± 5.03，侵袭细胞数由130.70 ± 5.03降至89.33 ± 5.03（均P < 0.001）。裸鼠移植瘤实验显示，单抗2G1组移植瘤生长受到抑制，瘤质量抑制率和瘤体积抑制率分别为（31.83 ± 16.36）%和（22.00 ± 15.48）%。转录组测序共筛选出698个差异表达基因，其中329个基因上调，369个基因下调；KEGG富集分析显示差异表达基因涉及Wnt信号通路。WB法检测结果显示，与对照组相比，单抗2G1组SOX2、OCT4、N-cadherin、p-β-catenin和c-Myc表达下调，E-cadherin表达上调（均P < 0.001）。结论：细胞膜表面HSP90β在MG-63球形细胞中高表达，靶向HSP90β的单抗2G1可抑制MG-63球形细胞的成球、迁移、侵袭及体内成瘤能力，并影响其干细胞标志物、EMT相关标志物及Wnt/β-catenin信号通路蛋白的表达水平，提示HSP90β可能参与调控MG-63球形细胞的OSC样特征，可作为骨肉瘤靶向治疗的潜在研究靶点。

Background: The global rise in visual impairment, driven by population aging, the increasing prevalence of lifestyle-related chronic diseases, and environmental factors, has made it a critical public health concern, highlighting the urgent need for effective preventive strategies and eye health maintenance. Cuscutae Semen (CS), a traditional Chinese herbal medicine long regarded for its vision-enhancing properties, has been widely used to support ocular health. However, its underlying molecular mechanisms and bioactive constituents remain poorly understood, limiting its modernization and broader clinical application. Objective: This study aims to investigate the restorative effects of CS on visual impairment, elucidate its underlying mechanisms, and identify potential active components. Methods: A zebrafish model of visual impairment was established using mepanipyrim to simulate retinal structural damage and visual dysfunction. The therapeutic effects of CS were systematically evaluated through behavioral analyses and histomorphological observations. To elucidate the underlying mechanisms, an integrated approach was employed, combining transcriptome sequencing (RNA-seq), reverse transcription quantitative polymerase chain reaction validation, and immunofluorescence staining to identify critical genes and pathways involved. Furthermore, macroporous resin column chromatography was employed for the fractionation and screening of potential active components. Results: CS treatment significantly alleviated mepanipyrim-induced ocular abnormalities in zebrafish, restoring approximately 82% of the observed morphological defects. Behavioral assessments revealed that CS-treated zebrafish exhibited markedly increased swimming speed and distance, indicating enhanced visual light sensitivity. Histopathological analysis demonstrated that CS effectively repaired the structure of retinal cell layers. RNA-seq revealed that CS broadly reversed mepanipyrim-induced gene expression disturbances, suggesting a restorative effect on transcriptomic homeostasis. Gene Ontology enrichment analysis identified the phototransduction pathway as a key mediator of CS’s therapeutic effects. This was further supported by reverse transcription quantitative polymerase chain reaction validation of critical genes and immunofluorescence staining, which confirmed the restored expression of Pde6a and Gnat2, key proteins involved in photic signal transmission. Active component screening indicated that high-polar constituents, including chlorogenic acid, may constitute one of the major bioactive fractions responsible for the observed therapeutic effects. Conclusion: This study provides evidence of the vision-protective effects of CS in a zebrafish model, demonstrating that its therapeutic mechanism involves modulation of the phototransduction pathway. Chlorogenic acid was identified as one of the key bioactive constituents contributing to this effect. These findings not only provide scientific validation for the traditional use of CS in ocular protection but also present promising therapeutic prospects for the prevention and treatment of visual impairment.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective:To identify the incidence and prevalence of inflammatory bowel disease (IBD) in the northern Chinese population of Jinan, Shangdong Province, along with its temporal trends from 2005 to 2022.Methods:By utilizing the data from the Jinan basic medical insurance system, a population-based IBD cohort was constructed. This facilitated the computation of both the incidence and prevalence rates of IBD, alongside their temporal trends throughout the 2005 to 2022 timeframe. The 95% confidence intervals were estimated using poisson regression.Results:The overall incidence rate of IBD showed a yearly increasing trend, with age-standardized incidence rates rising from 0.03/100 000 in 2005 to 5.39/100 000 in 2022. The age-standardized incidence rate of ulcerative colitis (UC) increased from 0.03/100 000 in 2005 to 4.97/100 000 in 2022. The age-standardized incidence rate of Crohn's disease (CD) rose from 0.05/100 000 in 2011 to 0.44/100 000 in 2022. The crude prevalence of IBD increased from 0.60/100 000 in 2005 to 32.39/100 000 in 2022. Specifically, the crude prevalence of UC increased from 0.60/100 000 in 2005 to 31.44/100 000 in 2022, while the crude prevalence of CD increased from 0.05/100 000 in 2011 to 1.19/100 000 in 2022.Conclusions:Analysis of recent medical insurance data reveals a continuous uptrend in both the incidence and prevalence of IBD in Jinan, a northern city in China. This underscores the urgent need for enhanced medical resources and healthcare guaruntee to ensure the well-being of individuals afflicted with IBD.

Objective:To estimate the radiation dose to caregivers and the public from 177Lu- peptide receptor radionuclide therapy (PRRT) for pediatric neuroblastoma patients and determine the duration of contact restrictions, in order to provide a reference for relevant radiation protection measures. Methods:A retrospective study was conducted by collecting data from 18 pediatric neuroblastoma patients, aged between 3 and 13 (6.72±2.72), who received 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) treatment at the Nuclear Medicine Department of Shandong Cancer Hospital from June 2023 to July 2023. Absorbed dose rate in air at 0, 0.1, 0.5, 1 and 2 m from the patients was measured using a radiation-survey at 1, 4, 24, 48 and 96 h after administration. The whole-body region of interest was delined using HERMES software. Subsequently, curve regression fitting was performed using a biexponential function model. By incorporating hypothesized social contact durations, the effective doses received by family members and the public in contact with patients were estimated. Additionally, MIM software was used to outline the whole-body VOI to obtain the total volume of lesions, and the Pearson or Spearman correlation coefficient was employed to analyze the relationship between the absorbed dose rate in air and clinical indicators as well as the total volume of lesions. Results:The 177Lu-DOTATATE administration dose was (4 353.42±1 451.51) MBq. All patients were discharged from hospital 24 h after 177Lu-DOTATATE administration. At the time of discharge, patients had excreted (76.70±3.99)% of the administered activity, and the absorbed dose rate in air at 0.1, 1 and 2 m from the patients were (32.74±6.98), 3.68(3.01, 4.70) and (1.22±0.51) μSv/h, respectively. After being discharged, the radiation doses to caregivers from children aged 2-5 years and 5-13 years were (2.47±1.80) mSv and (0.88±0.47) mSv, respectively. The contact restriction duration was 2 d for nighttime sleeping with family members and 1 d for contact with other children. On the day of discharge, patients should limit their time on public transportation within 4 h and do not need to restrict private transportation. Conclusions:To ensure the effective dose kept within the safety limits stipulated by current regulations, it is necessary to implement contact restrictions for patients’ family members and the public. After implementing preventive measures, 177Lu-DOTATATE treatment is a safe radionuclide therapeutic option.

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques