Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To explore the predictive value of preoperative pelvic floor electromyography(EMG)parameters for the risk of urinary incontinence after prostate cancer surgery.Methods:This study retrospectively analyzed the medical records of 271 patients who underwent radical prostatectomy in the urology department of Peking University First Hospital from January 2020 to October 2022.The data included patient age,body mass index(BMI),international prostate symptom score(IPSS),prostate-specific antigen(PSA)levels,Gleason score,type of surgery,urethral reconstruction,lymph node dis-section,nerve preservation,catheterization duration,D'Amico risk classification,American Society of Anesthesiologists(ASA)score,Charlson comorbidity index,postoperative duration,prostate volume,and pelvic floor EMG parameters(pre-resting mean,fast muscle mean,and slow muscle mean scores).Independent risk factors affecting early postoperative urinary incontinence were identified through multiva-riate Logistic regression analysis.The predictive efficacy of pelvic floor EMG results was evaluated by cal-culating the area under the receiver operating characteristic(ROC)curve,and the optimal threshold for early postoperative urinary incontinence was determined based on the Youden index and clinical signifi-cance.Results:The study included 271 prostate cancer patients,with an 81.9％rate of voluntary urinary control post-surgery.The median score for fast pelvic floor muscles was 23.5(18.2,31.6),and for slow muscles,it was 12.5(9.6,17.3).Among the patients,179(66.1％)did not preserve nerves,and 110(40.6％)underwent urethral reconstruction.Advanced age and low fast muscle scores were identified as independent risk factors for urinary incontinence.Patients aged ≤60 had 5.482 times the voluntary urinary control rate compared with those aged ≥70(95％CI:1.532-19.617,P＜0.05).There was a significant correlation between fast muscle scores and urinary incontinence recovery(OR=1.209,95％CI:1.132-1.291,P＜0.05).When the optimal threshold for preoperative fast muscle score was set at 18.5,the ROC sensitivity and specificity were 80.6％and 61.2％,respectively.Con-clusion:Preoperative pelvic floor EMG parameters show good predictive accuracy and clinical applicabili-ty for the risk of urinary incontinence after prostate cancer surgery.These parameters can be used for ear-ly identification of urinary incontinence risk,with age and fast muscle scores being important predictors.

Objective:To explore the influencing factors of the poor sustainability of the evidence-based practice project for irritant dermatitis around urostomy.Methods:This is a qualitative study. From April to May 2020, 12 nurses working in the Urology Surgery of Peking University First Hospital were selected by purposive sampling for the semi-structured interview. The integrated-Promoting Action on Research Implementation in Health Services framework (i-PARIHS framework) was applied to analyze and extract the obtained data.Results:The interview results found that, in terms of transform (evidence) , the localization and continuity of evidence for the evidence-based practice project of irritant dermatitis around urostomy needed to be improved, including the high matching between evidence and practice environment, and the insufficient continuity of evidence application. In terms of transform recipients, the leadership of project practitioner needed to be improved, including the conflict between the roles of practitioners and researchers, the lack of knowledge reserves of practitioners, and the conflict among the values of practitioners. In terms of organizational environment, the leadership of managers and the imformatization degree of project needed to be improved, including insufficient support from leaders and insufficient facilities.Conclusions:At the initial stage of formulating the nursing evidence-based practice project, the project implementer should fully incorporate the opinions of stakeholders for localization debugging, and consider the sustainability of the project. In addition, the leadership of managers, nurses and interns should be increased, the use and training of urostomy talents should be strengthened, the training of urostomy knowledge should be continued, the information-based follow-up system should be improved, and the intervention strategy should be continuously adjusted to ensure the project is carried out.

Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.
Carboxylic Acids/metabolism* ; Metabolic Engineering ; Synthetic Biology ; Yarrowia/metabolism*

Objective:To investigate the correlation between cognitive function and living ability of older adult patients living in a mining community.Methods:A total of 180 older adult patients living in a mining community who received treatment during July-October 2019 were included in this study. They were randomly divided into the low-age group (< 68 years old, n = 94) and the high-age group (≥ 68 years old, n = 86). Cognitive function and living ability were evaluated using the Mini-Mental State Examination (MMSE), The Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL). The relationship between cognitive function and living ability was investigated using hierarchical analysis and Pearson correlation analysis. Results:The proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA were 39.4% and 66.0%, respectively in the low-age group, and they were 32.6% and 61.6%, respectively in the high-age group. The MoCA had a greater performance in identifying abnormal cognitive function in each group than the MMSE ( χ2 = 26.69, 10.18, both P < 0.001). There were no significant differences in proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA between low-age and high-age groups ( χ2 = 0.90, 0.36, both P > 0.05). The proportion of older adult patients with abnormal living ability was not significantly different between low-age and high-age groups (4.3% vs. 10.5%, χ2 = 2.58, P > 0.05). Compared with patients negative for MMSE items, living ability and instrumental activity of daily living increased by 7.0% and 9.4% in low-age patients positive for MMSE items (both P < 0.05). Compared with patients negative for MoCA items, living ability increased by 3.5% in low-age patients positive for MoCA items ( P < 0.05). Correlation analysis revealed that total scores of MMSE and MoCA were significantly negatively correlated with ADL score ( r = -0.26, -0.27, both P < 0.001) and instrumental activity of daily living score ( r = -0.27, -0.27, P < 0.001). Conclusion:Cognitive function and living ability are correlated in older adult patients living in a mining community. We should pay attention to the screening results of cognitive disorder in older adult patients and improve their living ability by improving their cognitive function.

Objective:To investigate the characteristic of mild cognitive impairment (MCI) in the adults aged 48 years and over in a coal mine community, and to analyze its associated risk factors.Methods:From July to October 2019, a questionnaire survey for basic information was conducted among 180 middle-aged and elderly adults who met the inclusion criteria in the Datong coal mine community. The cognitive function was evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The effects of gender, age, years of education, sleep, living alone, physical exercise, social activities, smoking and drinking status, body mass index and chronic diseases on cognitive level were analyzed by single factor stratification and multiple linear regression.Results:There was no significant difference in the positive rate of MCI screened by MMSE and MoCA in the age groups of 48-<64, 64-<72 and 72-90 (original and corrected P>0.05); The positive rate of MCI in MoCA screening (64.4%, 66.7%, 60.9%) was significantly higher than that in MMSE (35.6%, 45.6%, 28.1%) (all P<0.05); MMSE was positively correlated with MoCA score ( r=0.762, P<0.001). With the increase of age, the scores of memory, execution and visual space detected by MoCA decreased significantly (all P<0.05), while the scores of attention, language and orientation did not change significantly (all P>0.05). Univariate stratification showed that the significant influencing factors of MMSE or MoCA scores were gender, age, years of education and sleep status (all P<0.05). Multiple linear regression analysis showed that gender ( βMMSE=-0.192; βMoCA=-0.140), years of education ( βMMSE=0.209; βMoCA=0.328) and sleep status( βMMSE=-0.162; βMoCA=-0.136) were risk factors affecting MMSE and MoCA scores ( P<0.05). Conclusions:More middle-aged and elderly adults with MCI might be observed in a coal mine community, and the main characteristics of MCI are impaired memory, executive function and visual space. To prevent and reduce the occurrence of dementia, early interventions of MCI should be carried out among the adults with female, old age, low years of education and poor sleep quality.

Objective:To explore the effects of the LEARNS model in health education of urinary incontinence for patients undergoing laparoscopic radical prostatectomy.Methods:From September 2019 to August 2020, totally 60 patients who underwent laparoscopic radical prostatectomy in the Department of Urinary Surgery, Peking University First Hospital were selected by convenience sampling and divided into a control group and an intervention group according to the time of admission, with 30 cases in each group. Patients in the control group underwent conventional health education, while patients in the intervention group received nursing using the LEARNS model, with specific steps including listen (L), establish (E), adopt (A), reinforce (R), name (N), and strengthen (S). The mastery of knowledge about pelvic floor muscle before discharge was compared between the two groups, and the urinary continence of the two groups at 1 and 3 months after discharge was observed.Results:The knowledge level and correctness of pelvic floor muscle in the intervention group were higher than those in the control group, and the differences were statistically significant ( P<0.01). At 3 months after surgery, the urinary incontinence score of the intervention group was lower than that of the control group; the number of urine pads used was less than that of the control group; the rate of continence was higher than that of the control group, with statistically significant differences ( P<0.01) . Conclusions:The LEARNS mode can effectively improve the mastery of knowledge about pelvic floor muscle in patients undergoing laparoscopic radical prostatectomy, and improve their postoperative urinary continence.

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Objective:To build a comprehensive clinical management of outpatient with orthotopic neobladder based on doctor-nurse cooperation to provide overall service to patients.Methods:The comprehensive clinical management was established in October 2018, 32 patients were collected retrospectively from January 2009 to before the establishment of the clinic, and 14 patients were collected from the establishment of the clinic to January 2020. After the establishment of the clinic, the comprehensive management mode was adopted, including the medical team implementing management from the aspects of implementing doctor-patient joint decision-making, guiding patients to carry out pelvic floor muscle rehabilitation training, teaching family members to carry out new bladder irrigation, and establishing patients′ records. Before the establishment of the clinic, there was no specialized personnel for unified management, and the doctor for new bladder irrigation and so on.Results:The rate of complete urinary control in the 46 patients with orthotopic neobladder was 82.6%(38/46) in the day and 71.7%(33/46) in the night. The rates of complete urine control of patients in the day and night were 12/14 and 9/14 after the establishment of the clinic. The length of stay which was (13.36 ± 9.44) d, and feeding time which was (5.00 ± 2.11) d of the patients after the establishment of the clinic were both less than those of the patients before the establishment of the clinic, which were (17.28 ± 9.98) d and (5.78 ± 2.90) d, but the differences were not statistically significant ( t values were -1.247 and -0.905 respectively, both P>0.05). However, for diurnal and night-time urine control, the proportion of people with more than one diaper was better after the establishment of outpatient clinic than before. Conclusions:The establishment of the comprehensive clinical management meets the needs of patients with orthotopic neobladder, enables patients to get the function of continence and urination sooner, and contributes to improve the clinical outcome of patients.