With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

This study retrospectively analyzed data from 25 patients with paroxysmal nocturnal hemoglobinuria (PNH) admitted to Peking Union Medical College Hospital and Dongfang Hospital of Beijing University of Chinese Medicine from January 2023 to June 2024. Patients receiving sufficient eculizumab treatment for at least 3 months and who completed hemolytic complex (CH50) level testing pre- and post-treatment for 3 and 6 months were selected. Blood routine, biochemistry, and the 50% CH50-related indicators were monitored pre- and post-treatment. Among these patients, 24 completed 6 months of treatment and CH50 testing. After 3 and 6 months of eculizumab treatment, all patients with PNH showed significant improvement in symptoms, with lactate dehydrogenase (LDH) levels decreasing from a baseline of (1 814.4 ± 924.8) U/L to (248.5 ± 61.0) U/L and (239.3 ± 44.8) U/L. Hemoglobin levels increased from a baseline of (73.9±14.4) g/L to (99.9 ± 21.3) g/L and (99.6 ± 19.8) g/L. The baseline CH50 level was (32.4±14.7) %, which decreased to 2.0% (1.0% –8.0% ) and 1.0% (1.0% –4.0% ) at 3 and 6 months posttreatment, respectively. At baseline, a linear correlation was found between CH50 and LDH levels ( P<0.001), and the trend of CH50 changes was significantly lower than LDH at 3 and 6 months post-treatment with eculizumab, with similar trends. However, no linear correlation was observed between CH50 and LDH levels or other parameters at 3 and 6 months of medication. Our case demonstrates that eculizumab is effective for PNH hemolysis treatment. The serum CH50 level may be a biomarker for complement blockade induced by eculizumab, which can, to some extent, reflect the intravascular hemolysis of PNH and the efficacy of eculizumab.

Photoacoustic imaging (PAI), an emerging hybrid imaging modality, integrates the high spatial resolution of optical imaging with the deep-tissue imaging capability of ultrasound. Emerging evidence from recent studies in dental medicine has demonstrated the unique potential of PAI in screening, diagnosis, and therapeutic monitoring of oral pathologies, including periodontal diseases, oral cancers, and pulpal disorders. However, its clinical translation remains contingent upon addressing multiple technical barriers, particularly signal attenuation induced by optical scattering in biological tissues and limitations in real-time imaging efficiency. Therefore, investigating the advancements and challenges of PAI technology in the diagnosis of oral diseases will contribute to advancing further research and clinical applications, thereby providing practical support for improving the accuracy of early diagnosis and the efficacy of treatment for oral diseases.

Objective:To evaluate the therapeutic efficacy of an upper limb rehabilitation robot on the recovery of elbow function recovery following arthroscopic elbow joint release.Methods:Seventy-two patients who underwent arthroscopic elbow joint release at Shanghai Sixth People’s Hospital from December 2022 to December 2023 were recruited. All patients were randomly assigned to either the conventional group (n=36; 16 males, 20 females; age 34.39±9.04 years, range 24-56; fractures: 4 intercondylar humerus, 18 olecranon, 8 radial head, 6 other) which received conventional rehabilitation postoperatively, or the robot-assisted group (n=36; 18 males, 18 females; age 33.78±9.98 years, range 20-59; fractures distribution identical to the conventional group) receiving conventional rehabilitation combined with robot-assisted upper limb rehabilitation therapy. The active range of motion (ROM) of elbow joint, Mayo elbow performance score (MEPS), visual analogue scale (VAS) of elbow joint were recorded preoperatively and at 4 weeks and 3 months postoperatively. The surface electromyography were analyzed at 3 months postoperatively.Results:All patients completed the 3-month rehabilitation program. At 4 weeks postoperatively, the conventional group exhibited a mean active ROM of 106.78°±9.91°, MEPS of 67.78±7.68, VAS of 2.11±0.74; the robot-assisted group showed active ROM of 113.72°±7.06°, MEPS of 73.33±9.28, VAS of 21.89±0.46. By 3 months postoperatively, the conventional group achieved a mean active ROM of 118.11°±6.75°, MEPS of 85.00±8.66, VAS of 0.67±0.67; robot-assisted achieved a mean active ROM of 127.61°±6.61°, MEPS of 91.11±6.57, VAS of 0.39±0.49. Both groups exhibited significant improvements in active ROM and MEPS, and significant reductions in VAS scores at 4 weeks and 3 months postoperatively compared with preoperatively values ( P<0.05). The robot-assisted group demonstrated significantly higher active ROM and MEPS at both 4 weeks and 3 months postoperatively, and a significantly lower VAS score at 3 months postoperatively, compared with the conventional group ( P<0.05). Surface electromyography at 3 months revealed significantly higher biceps brachii root mean square and significantly lower co-contraction index in the robot-assisted group compared to the conventional group ( P<0.05). No adverse symptoms were reported in the treated elbows of either group during the operation and follow-up period. Conclusion:The integration of upper limb rehabilitation robot-assisted therapy and conventional rehabilitation program significantly enhances the recovery of elbow range of motion and functional outcomes at 3 months following arthroscopic elbow joint release.

Objective To explore the clinical value of energy-spectrum CT single-energy imaging in enhancing the image quality and stent display of stent placement CT angiography(CTA)in lower extremity atherosclerotic occlusive disease.Methods Twenty patients[mean(65.61±9.65)years;male/female,16/4]who underwent stenting for chronic occlusive disease of the lower extremity arteries by lower extremity arterial energetic spectral CTA were retrospectively recruited at our hospital.The original images were reconstructed into seven sets of single energy(40-100 keV),120 kVp,virtual unenhanced images(VUE)and metal artifact reduction(MAR)technique images.Images were debossed and then scaffolded for display with volumetric reconstruction(VR),maximum density projection(MIP)and curve planar reconstruction(CPR),and were objectively and subjectively assessed and compared using one-way analysis of variance(ANOVA).Results The 80 keV and MAR images had the highest scores compared to the other reconstruction group images(P＜0.01).Conclusion 80 keV single-energy imaging and de-metallization artifacts MAR improve the image quality of lower extremity arterial stent lumen and structure display;therefore,they have higher diagnostic value for clinicians.

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.