Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

In this study, Saccharomyces cerevisiae R0 was used as the chassis cell to synthesize oleanolic acid from scratch through the heterologous expression of β-amyrin synthase(β-AS) from Glycyrrhiza uralensis, cytochrome P450 enzyme CYP716A154 from Catharanthus roseus, and cytochrome P450 reductase AtCPR from Arabidopsis thaliana. The engineered strain R1 achieved shake flask titres of 5.19 mg·L~(-1). By overexpressing enzymes in the pentose phosphate pathway(PPP)(ZWF1, GND1, TKL1, and TAL), the NADH kinase gene in the mitochondrial matrix(POS5), truncated 3-hydroxy-3-methylglutaryl-CoA reductase(tPgHMGR1) from Panax ginseng, and farnesyl diphosphate synthase gene(SmFPS) from Salvia miltiorrhiza, the precursor supply and intracellular reduced nicotinamide adenine dinucleotide phosphate(NADPH) supply were enhanced, resulting in an 11.4-fold increase in squalene yield and a 3.6-fold increase in oleanolic acid yield. Subsequently, increasing the copy number of the heterologous genes tPgHMGR1, β-AS, CYP716A154, and AtCPR promoted the metabolic flow towards the final product, oleanolic acid, and increased the yield by three times. Shake flask fermentation data showed that, by increasing the copy number, precursor supply, and intracellular NADPH supply, the final engineered strain R3 could achieve an oleanolic acid yield of 53.96 mg·L~(-1), which was 10 times higher than that of the control strain R1. This study not only laid the foundation for the green biosynthesis of oleanolic acid but also provided a reference for metabolic engineering research on other pentacyclic triterpenoids in S. cerevisiae.
Oleanolic Acid/biosynthesis* ; Saccharomyces cerevisiae/metabolism* ; Industrial Microbiology ; Microorganisms, Genetically-Modified/metabolism* ; Plants/enzymology* ; Fermentation ; Metabolic Engineering

OBJECTIVE: To explore the immunophenotypic characteristics of bone marrow granulocytes (G) and their clinical significance in patients with multiple myeloma (MM). METHODS: The granulocyte immunophenotypes of bone marrow in 70 MM patients (MM group) and 40 anemia patients (control group) were detected by flow cytometry, and its correlation with clinical characteristics was further analyzed. Univariate and multivariate regression analysis were used to screen factors that affected prognosis. RESULTS: The CD56⁺G%, CD13⁺G%, CD22⁺G% and CD117⁺G% in MM group were higher than those in the control group (all P <0.05). CD56⁺G% and CD117⁺G% in CR⁺VGPR group were significantly lower than those in PR+MR+PD group (both P <0.05). The CD10⁺G% in RISS Ⅲ stage and Ca²⁺ ≥2.65 mmol/L groups were increased (both P <0.05). The CD56⁺G% in elevated lactate dehydrogenase, β₂-microglobulin≥5.5 mg/L and hemoglobin <85 g/L groups were increased (all P <0.05), while the CD117⁺G% in high-risk cytogenetic positive group was decreased (P <0.05). The expression rate of CD molecules on granulocytes was divided into low (L) and high (H) groups according to the median value. The overall survival (OS) of the LCD56⁺G%, LCD13⁺G% and LCD22⁺G% groups was significantly prolonged (all P <0.05). CD13⁺G% and CD22⁺G% were independent risk factors for OS in MM patients (HR=0.443, 0.410, both P <0.05). CONCLUSION The CD56⁺G%, CD10⁺G% and CD117⁺G% are closely correlated with clinical features in MM patients, while CD13⁺G% and CD22⁺G% are closely correlated with prognosis. Detection of CD molecules expression on granulocytes may be used to evaluate prognosis and guide treatment.
Humans ; Multiple Myeloma/immunology* ; Granulocytes/immunology* ; Prognosis ; Immunophenotyping ; Male ; Bone Marrow ; Female ; Flow Cytometry ; Middle Aged ; Aged ; Clinical Relevance

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

ObjectiveTo introduce the basic design， development plan and objectives of a population-based birth cohort in Shanghai， and further present the main data and baseline characteristics of enrolled participants in the cohort， and to provide key information for reproductive health-related studies. MethodsThe Shanghai population-based birth cohort initiated on January 1， 2005， included newborns born in Shanghai every year and their parents， and collected information on reproductive health， reproductive treatment， birth characteristics， growth and development status， as well as the incidence， treatment and death of diseases by employing data linkage technology and investigations. This formed a birth cohort spanning the entire life cycle. ResultsAs of October 2022， a total of 2 978 538 newborns and their parents were included in the cohort. Among them， 2 905 135 （97.54%） were naturally conceived （NC）， and 73 403 （2.46%） were born through assisted reproductive technologies （ART）. The average age of parents was （32.56±4.12） years old for females and （34.62±5.34） years old for males in the ART group， which was higher than （28.02±4.71） years and （30.07±5.54） years for parents in the NC group. Among parents， females and males aged 30 and above accounted for 77.12% and 85.08%， respectively， which were higher than that of parents （35.28% for females and 49.66% for males） in the NC group. Furthermore， the percentage of parents with a college degree or above in the ART group was 73.23% for females and 73.66% for males， which were higher than those in the NC group （49.98% and 50.91%， respectively）. The multiple births rate in the ART group was 33.81%， which was higher than that in the NC group （1.88%）. The incidence of premature birth and low birth weight in the ART group were 24.47% and 19.08%， respectively， which was higher than that in the NC group （5.47% and 3.73%）. ConclusionThe comprehensive collection of reproductive health-related information in the birth cohort in Shanghai can provide essential resources to determine the influence of genetics， environment， reproductive treatment and other related factors on the health of offspring after birth.

Objective:To explore the risk factors for postoperative adverse events in older persons with gastrointestinal malignancies and thus provide reference for selection of surgery and evaluation of such patients.Methods:An observational study design was employed, the study cohort comprising patients aged 65 years and over with gastrointestinal malignancies who underwent elective surgery in Peking University Cancer Hospital from 2008 to 2022. In this study, we compared the clinical characteristics (disease type, tumor stage), surgical safety (combined organ resection, operation duration, comorbidities), and treatment outcomes (postoperative complications, unplanned reoperation, and perioperative mortality) of these patients. Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse outcomes.Results:The study cohort comprised 10,135 patients, of whom 74.7% (7,568) were 65–75 years old (excluding 75 years old), 23.6% (2,391) 75–85 years old (excluding 85 years old), and 1.7% (176) ≥85 years old. The type of cancer was colorectal in 63.4% (6,427 patients) and gastric in 36.6% (3,708); 62.0% (6,284/10,135)of the patients had stage II or III disease. The proportion of stage III and stage IV tumors was higher in patients aged over 85 years (47.4% [73/154) and 11.0% [17/154]), respectively, than in those aged 75–85 years (41.6% [854/2 051) and 8.2% [168/2 051]), respectively, and those aged 65–75 years (40.1% [2,576/6,431) and 10.9% [700/6,431]); these differences are statistically significant (χ 2=27.95, P<0.01). Comorbidity was present in 50.6% (5,128/10,135) of the whole study cohort, comprising 58.0% (102/176) of those aged over 85 years, this being significantly higher than the 56.3% (1,346/2,391) in those aged 75–85 years and 48.6% (3,678/7,568) of those aged 65–75 years. The main comorbidities were hypertension (37.3%), diabetes (16.4%), and cardiovascular and cerebrovascular diseases (14.0%). Minimally invasive surgery was performed on 36.9% (3,740/10,135) of the whole study cohort, the 38.4% in 65–75 years old patients being significantly higher than the 32.5% in those aged 75–85 years and the 29.0% in those aged over 85 years; these differences are statistically significant (χ 2=31.97, P<0.01). Preoperative neoadjuvant therapy was administered to 9.1% (924/10,135) of the whole study cohort, the proportion of patients receiving preoperative neoadjuvant therapy being significantly higher in those aged 65–75 years (11.1%) than in those aged 75–85 years (3.4%) and over 85 years (0.6%); these differences are statistically significant (χ 2=148.98, P<0.01). Combined organ resection was performed in 4.9% (496/10,135) of the whole study cohort, the proportion undergoing combined organ resection being significantly lower in those aged over 85 years (2.3%) than in those aged 65–75 years (5.3%) and 75–85 years (3.8%); these differences are statistically significant (χ 2=11.20, P<0.01). The mean operating time was (182.2±76.8) minutes, being significantly higher in those aged 65–75 years (186.6±78.3 minutes) than in those aged 75–85 years (169.4±71.3 minutes) and over 85 years (153.2±53.7 minutes); these differences are statistically significant ( F=46.85, P<0.01). The overall incidence of postoperative complications was 10.9% (802/7,384); the incidence did not differ significantly between the three groups ( P>0.05). The incidence of unplanned reoperation was 1.9% (193/10,135) and of death during hospitalization 0.3% (32/10,135). The perioperative mortality in the three groups was 1.1%, 0.5% and 0.2% in those aged over 85, 75–85, and 65–75 years, respectively. These differences are statistically significant (χ 2=9.71, P<0.01). Among the patients with postoperative complications, 15.0% (120/802) underwent unplanned reoperation, which had a perioperative mortality of 1.0% (8/802), these rates being significantly higher than those for unplanned reoperation (1.1%, 73/6,582) and perioperative mortality (0.4%, 24/6,582) in patients without complications (all P<0.01). The median length of hospital stay was 11 days in patients aged over 85 years; this is significantly longer than the 9 days in those aged 65–75 years and 10 days in those aged 75–85 years (H=37.00, P<0.01). Multivariate logistic regression analysis showed that tumor stage IV (OR=1.56, 95%CI: 1.24–1.96, P<0.01), comorbidities (OR=1.26, 95%CI: 1.08–1.47, P<0.01), open surgery (OR=1.33, 95%CI: 1.13–1.56, P<0.01), and operation time >180 minutes (OR=1.82, 95%CI:1.53–2.15, P<0.01) were risk factors for adverse outcomes. Conclusion:Older patients with gastrointestinal tumors who have comorbidities and stage IV disease and undergo open surgery with a longer operation time are at higher risk of adverse outcomes than patients without these characteristics.

Objective:To explore the risk factors for postoperative adverse events in older persons with gastrointestinal malignancies and thus provide reference for selection of surgery and evaluation of such patients.Methods:An observational study design was employed, the study cohort comprising patients aged 65 years and over with gastrointestinal malignancies who underwent elective surgery in Peking University Cancer Hospital from 2008 to 2022. In this study, we compared the clinical characteristics (disease type, tumor stage), surgical safety (combined organ resection, operation duration, comorbidities), and treatment outcomes (postoperative complications, unplanned reoperation, and perioperative mortality) of these patients. Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse outcomes.Results:The study cohort comprised 10,135 patients, of whom 74.7% (7,568) were 65–75 years old (excluding 75 years old), 23.6% (2,391) 75–85 years old (excluding 85 years old), and 1.7% (176) ≥85 years old. The type of cancer was colorectal in 63.4% (6,427 patients) and gastric in 36.6% (3,708); 62.0% (6,284/10,135)of the patients had stage II or III disease. The proportion of stage III and stage IV tumors was higher in patients aged over 85 years (47.4% [73/154) and 11.0% [17/154]), respectively, than in those aged 75–85 years (41.6% [854/2 051) and 8.2% [168/2 051]), respectively, and those aged 65–75 years (40.1% [2,576/6,431) and 10.9% [700/6,431]); these differences are statistically significant (χ 2=27.95, P<0.01). Comorbidity was present in 50.6% (5,128/10,135) of the whole study cohort, comprising 58.0% (102/176) of those aged over 85 years, this being significantly higher than the 56.3% (1,346/2,391) in those aged 75–85 years and 48.6% (3,678/7,568) of those aged 65–75 years. The main comorbidities were hypertension (37.3%), diabetes (16.4%), and cardiovascular and cerebrovascular diseases (14.0%). Minimally invasive surgery was performed on 36.9% (3,740/10,135) of the whole study cohort, the 38.4% in 65–75 years old patients being significantly higher than the 32.5% in those aged 75–85 years and the 29.0% in those aged over 85 years; these differences are statistically significant (χ 2=31.97, P<0.01). Preoperative neoadjuvant therapy was administered to 9.1% (924/10,135) of the whole study cohort, the proportion of patients receiving preoperative neoadjuvant therapy being significantly higher in those aged 65–75 years (11.1%) than in those aged 75–85 years (3.4%) and over 85 years (0.6%); these differences are statistically significant (χ 2=148.98, P<0.01). Combined organ resection was performed in 4.9% (496/10,135) of the whole study cohort, the proportion undergoing combined organ resection being significantly lower in those aged over 85 years (2.3%) than in those aged 65–75 years (5.3%) and 75–85 years (3.8%); these differences are statistically significant (χ 2=11.20, P<0.01). The mean operating time was (182.2±76.8) minutes, being significantly higher in those aged 65–75 years (186.6±78.3 minutes) than in those aged 75–85 years (169.4±71.3 minutes) and over 85 years (153.2±53.7 minutes); these differences are statistically significant ( F=46.85, P<0.01). The overall incidence of postoperative complications was 10.9% (802/7,384); the incidence did not differ significantly between the three groups ( P>0.05). The incidence of unplanned reoperation was 1.9% (193/10,135) and of death during hospitalization 0.3% (32/10,135). The perioperative mortality in the three groups was 1.1%, 0.5% and 0.2% in those aged over 85, 75–85, and 65–75 years, respectively. These differences are statistically significant (χ 2=9.71, P<0.01). Among the patients with postoperative complications, 15.0% (120/802) underwent unplanned reoperation, which had a perioperative mortality of 1.0% (8/802), these rates being significantly higher than those for unplanned reoperation (1.1%, 73/6,582) and perioperative mortality (0.4%, 24/6,582) in patients without complications (all P<0.01). The median length of hospital stay was 11 days in patients aged over 85 years; this is significantly longer than the 9 days in those aged 65–75 years and 10 days in those aged 75–85 years (H=37.00, P<0.01). Multivariate logistic regression analysis showed that tumor stage IV (OR=1.56, 95%CI: 1.24–1.96, P<0.01), comorbidities (OR=1.26, 95%CI: 1.08–1.47, P<0.01), open surgery (OR=1.33, 95%CI: 1.13–1.56, P<0.01), and operation time >180 minutes (OR=1.82, 95%CI:1.53–2.15, P<0.01) were risk factors for adverse outcomes. Conclusion:Older patients with gastrointestinal tumors who have comorbidities and stage IV disease and undergo open surgery with a longer operation time are at higher risk of adverse outcomes than patients without these characteristics.

Purpose/Significance Based on the typical use scenario of sensitive personal information in medical and health institu-tions,the implementation of the secure use of sensitive personal information is explored.Method/Process For user registration,internal utilization and interaction,medical device/wearable device collection and information disclosure and other scenarios,the paper analyzes the risk of sensitive personal information leakage,explores the application scenarios,advantages and disadvantages of various technical means such as identity authentication,access control,data encryption,data desensitization and detection audit.Result/Conclusion The application of technical means can assist medical and health institutions to further protect the security of patients'personal information.