Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective:To compare the efficacy and safety of a domestic hair follicle extraction system versus traditional follicular unit excision (FUE) in extracting hair follicles for the treatment of androgenetic alopecia (AGA) .Methods:A multicenter, randomized, self-controlled clinical trial was conducted on AGA patients aged 18 - 59 years who were recruited from the Huashan Hospital, Fudan University, the Affiliated Hangzhou First People's Hospital, and the China-Japan Friendship Hospital between June 2023 and September 2024. Each patient's scalp was randomly divided into two sides (experimental side vs. control side) using an envelope method. The experimental side underwent robotic hair transplantation with a domestic hair follicle extraction system, and the control side underwent traditional FUE. Hair follicles were extracted from the safe donor area in the occipital region, and implanted into the ipsilateral hair loss area. The primary outcome was the hair transection rate which was calculated immediately after follicular extraction. The secondary outcomes included the hair follicle unit loss rate and the change in hair density at the recipient site on postoperative day 14. Safety was evaluated by assessing the incidence of folliculitis at the donor site on postoperative day 14 and the overall incidence of adverse events. Surgical outcomes were evaluated at 9 months after surgery. Comparisons of evaluation indicators among groups were performed by using a paired t test or Wilcoxon signed-rank test. Results:A total of 55 patients with AGA (51 males and 4 females, aged 32.71 ± 5.75 years) completed the hair follicle transplantation and postoperative follow-up. The hair transection rate ( M[ Q1, Q3]) was 6.65% (4.56%, 10.16%) in the experimental group and 5.28% (3.04%, 8.89%) in the control group (difference = 1.24%, 95% CI: -0.24%, 2.65%) . The hair follicle unit loss rate was 2.00% (1.00%, 3.50%) in the experimental group and 0.50% (0, 2.00%) in the control group, with a significant difference between the two groups ( P = 0.008) . On postoperative day 14, there was no significant difference in the hair density between the experimental group and control group (72.20 ± 25.95 per cm 2vs. 76.49 ± 30.84 per cm 2, P = 0.173) . At 9-month follow-up, both groups showed improvement in the investigator's overall score in the recipient areas. Seven adverse events occurred in 7 subjects (12.72%) in each group, and all were mild folliculitis. Conclusion:The domestic hair follicle extraction system demonstrated comparable efficacy and safety to the traditional FUE in hair transplantation.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

The theory of yin-yang is a foundational concept in traditional Chinese medicine (TCM) and has been refined through millennia of clinical practice and theoretical development. This theory remains central to syndrome differentiation and therapeutic decision-making. With rapid advances in modern biomedicine and information sciences, this review synthesizes recent interdisciplinary progress linking yin-yang concepts to cellular metabolism, redox balance, gene regulation, and immunomodulation. We outline how pathological states historically described as “yin deficiency” or “yang hyperactivity” correspond to alterations in cellular energy conversion, molecular signaling networks, and systemic homeostasis, and we critically evaluate current evidence for mechanistic pathways. Notwithstanding promising correlations, major gaps persist in mechanistic clarity and the establishment of quantitative metrics, limiting the rigorous integration of yin-yang theory into evidence-based frameworks. To address these gaps, we propose a research roadmap that leverages modern biotechnology, mathematical modeling, and artificial intelligence for quantitative multiscale analysis. By integrating molecular, cellular, and systemic datasets, this approach can clarify the biological connotations of yin-yang balance for physiology, disease mechanisms, and clinical outcome assessment.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

OBJECTIVE: To explore the application effect of self-developed anatomical main nail insertion guide in proximal femoral nail antirotation (PFNA) internal fixation for the treatment of intertrochanteric fractures (IFF) in elderly patients. METHODS: A retrospective analysis was performed on 62 patients with AO31-A2 intertrochanteric fractures who underwent PFNA surgery and met the inclusion criteria from January 2022 to December 2024. They were divided into the conventional PFNA insertion group (conventional operation group) and the anatomical main nail insertion guide-assisted PFNA insertion group(guide group). The conventional operation group (PFNA) included 31 patients, 14 males and 17 females, the age ranged from 64 to 90 with an average of (75.2±11.6) years old;the guide group (PFNA) included 31 patients, 10 males and 21 females, the age ranged fron 67 to 97 with an average of (78.6±13.4) years old. The incision length of the main nail entry, the number of fluoroscopies from satisfactory reduction to before main nail insertion, operation time, intraoperative blood loss, 3-day postoperative VAS score, postoperative hip function Harris score, complications, etc. were observed and compared between the two groups. RESULTS: All patients were followed up for a period ranging from 4 to 12 months, with an average follow-up duration of (6.8±1.6) months. Compared with the guide group, the conventional operation group showed significant differences in the following parameters:the entrance length of the main screw was (6.74±3.77) cm vs. (5.13±1.31) cm, the number of fluoroscopies before the insertion of the main screw was (10.32±3.08) times vs. (7.71±2.41) times, the operation time was (150.45±53.47) minutes vs. (127.48±30.37) minutes, and the intraoperative blood loss was (196.77±121.06) ml vs. (140.97±86.00) ml, with P<0.05 indicating statistical significance.There was no statistically significant difference in 3-day postoperative VAS between the two groups (P>0.05). There was a statistically significant difference in the Harris scores between the conventional operation group and the guided operation group one month post-surgery (60.61±6.60) vs. (65.48±5.19) points (P<0.05). and there was no statistically significant difference in hip Harris scores between the two groups at 3 months after operation (P>0.05). During the 3-month follow-up after operation, neither group had incision infection, screw loosening, cutting, pressure sores, deep vein thrombosis, etc., and there was no statistically significant difference in the complication rate between the two groups. CONCLUSION It is quickly and accurately to implant PFNA assisted by the anatomical major nail implant guide in treatment of osteoporotic intertrochanteric fracture in the elderly.Compared with the traditional operation, it can shorten the operation time and reduce the surgical and X-ray trauma, and beneficial to the rapid rehabilitation of patients.
Humans ; Male ; Female ; Aged ; Hip Fractures/surgery* ; Bone Nails ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/instrumentation*

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*

Infertility, defined as the inability to conceive after 1 year of regular unprotected intercourse, impacts 10%-20% of couples globally. Both male and female factors contribute equally to this condition. Azoospermia, particularly nonobstructive azoospermia (NOA), which affects 10%-15% of infertile men, represents a significant challenge in male infertility. The advent of assisted reproductive technology (ART), specifically microdissection testicular sperm extraction (micro-TESE) followed by intracytoplasmic sperm injection (ICSI), offers a possibility for men with NOA to father biological children. Recent studies have focused on the predictors of sperm retrieval in NOA patients, such as age, testicular volume, and follicle-stimulating hormone (FSH) level. This review aims to explore the limited data on the anatomical characteristics of NOA patients and provide surgical considerations for micro-TESE, thereby enhancing understanding and improving outcomes for this challenging condition.
Humans ; Azoospermia/surgery* ; Male ; Testis/pathology* ; Sperm Retrieval ; Scrotum/pathology* ; Sperm Injections, Intracytoplasmic ; Microdissection

Oncological microdissection testicular sperm extraction (onco-micro-TESE) represents a significant breakthrough for patients with nonobstructive azoospermia (NOA) and a concomitant in situ testicular tumor, to be managed at the time of sperm retrieval. Onco-micro-TESE addresses the dual objectives of treating both infertility and the testicular tumor simultaneously. The technique is intricate, necessitating a comprehensive understanding of testicular anatomy, physiology, tumor biology, and advanced microsurgical methods. It aims to carefully extract viable spermatozoa while minimizing the risk of tumor dissemination. This review encapsulates the procedural intricacies, evaluates success determinants, including tumor pathology and spermatogenic tissue health, and discusses the implementation of imaging techniques for enhanced surgical precision. Ethical considerations are paramount, as the procedure implicates complex decision-making that weighs the potential oncological risks against the profound desire for fatherhood using the male gametes. The review aims to provide a holistic overview of onco-micro-TESE, detailing methodological advances, clinical outcomes, and the ethical landscape, thus offering an indispensable resource for clinicians navigating this multifaceted clinical scenario.
Humans ; Male ; Azoospermia/therapy* ; Testicular Neoplasms/pathology* ; Sperm Retrieval ; Microdissection/methods* ; Testis/surgery*

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*