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

Objective:To analyze the status quo of intelligent health management services in health examination institutions in Shanxi Province.Methods:This study is a cross-sectional study. In October 2023, 292 health examination institutions in 11 cities of Shanxi Province were surveyed by convenient sampling with the help of “Questionnaire star” to investigate the health examination (management) institutions to carry out smart health management services from January to December 2022. It was mainly divided into three aspects: pre-inspection, in-inspection and post-inspection, including 6 dimensions, with a total of 21 items. A total of 300 questionnaires were distributed in this survey, and 292 were effectively collected, with an effective recovery rate of 97.33%. The 292 questionnaires were divided and compared according to four regions: the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province.Results:The health examination (management) institutions were distributed in 11 prefectures and cities in Shanxi Province, and there were 56 (19.2%) tertiary health examination (management) institutions. There were 178 government organizations (61.0%) and 114 social organizations (39.0%). There were 256 (87.7%) that carried out smart health management services; among them, 229 (78.4%) had smart management service systems, and 58 (19.9%) had physical examination centers with smart health management clinics. A total of 108 institutions (36.99%) carried out follow-up visits after intelligent screening. The prevalence of intelligent referrals were 63.3%, 59.6%, 78.0% and 85.2% in the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province, respectively ( χ2=14.02, P<0.05). The prevalence of self-service in the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province were 39.2%, 52.3%, 62.0% and 37.0%, respectively ( χ2=9.75, P<0.05). Conclusions:The development of intelligent health management in health examination (management) institutions in Shanxi Province is good, and the service scale continues to grow, but the problem of uneven development among regions is severe. In addition, the proportion of institutions providing services through information technology is not high, and the rate of intelligent management outpatient service, intelligent post-examination follow-up and intelligent physical examination service satisfaction is low.

Objective:The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations ( TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods:Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated.Results:(1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC . A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion:Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Objective:The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations ( TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods:Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated.Results:(1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC . A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion:Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Objective:To observe the protective effect and possible mechanism of stellate ganglion block(SGB)on spatial learning memory function impairment in rapid eye movement sleep deprived(RSD)rats.Methods:Thirty-two rats were randomly assigned to Control group,RSD group,SGB group,and rapid eye movement sleep deprivation with stellate ganglion block intervention(RSD+SGB)group.The rats in RSD group and RSD+SGB group were modeled by modified multi-platform method(MMPM),and the rats in SGB group and RSD+SGB group were intervened by the SGB method.Morris water maze(MWM)was selected to evaluate the spatial learning and memory functions of rats in each group,and the expression levels of glutamate(Glu)and aspartate(Asp)in hippocampal tissues of rats in each group were detected by colorimetric assay,and the expression levels of N-methyl-D-aspartate receptor 1(NR1)and caspase-3 in hippocampal tissues of rats in each group were detected by Western Blot.Results:Compared with the RSD group,rats in RSD+SGB group had a significantly shorter escape latency after SGB intervention(P＜0.05),while the number of passes through the original platform position and the percentage of target quadrant time were significantly in-creased(P＜0.05);at the same time,the hippocampal tissues'expression levels of Glu,Asp,NR1,and caspase-3 were all significantly reduced(P＜0.05).Conclusion:SGB protects against RSD-induced impairment of spatial learn-ing memory capacity by reducing hippocampal tissue excitotoxicity and apoptosis induced by excitatory amino acid hyper-activation in RSD rats.

Objective Tto analyze the spatial distribution and characteristics of the national AIDS/HIV epidemics from 2009 to 2020 to discover its distribution, aggregation, and hot spots, and provide corresponding suggestions for AIDS prevention and control. Methods Spatial autocorrelation analysis, hot spot analysis, and Kriging interpolation prediction were used to describe, analyze, and predicting the spatial distribution of AIDS epidemics across the country. Results The national AIDS incidence and mortality rate increased yearly, but the growth rate shows a downward tendency with uneven spatial distribution,focusing on the southwest and northwest regions; the average annual incidence rate of AIDS ( Moran's I> 0, P < 0. 01) and the average annual mortality rate (Moran's I> 0, P < 0. 01) of the distribution had a positive global spatial correlation, with Sichuan, Yunnan, Guangxi, Chongqing,Hunan and Guizhou being the areas with ^“high-high^” clusters of AIDS incidence; Sichuan, Yunnan, Guangxi,Hunan,Xinjiang and Guizhou were the areas with ^“high-high^” clusters of average annual mortality. The ^“hot spot^” areas were mainly concentrated in the southwestern part of China, and the ^“cold spot^” areas were mainly concentrated in the eastern coastal and northern parts of China; Kriging interpolation predicted that Xinjiang would be the new hot spot area for future epidemics. Conclusion The spatial distribution of AIDS in China is uneven, showing spatial aggregation, hot spots and cold spots coexist, and the high-risk areas will continue to expand in the future.So the prevention and control work should be carried out in a targeted and localized manner.

{L-End}Objective To investigate the role and mechanism of Toll-like receptor 2 (TLR2)/nuclear factor-κB(NF-κB) signaling pathway in the inflammatory response induced by aluminum in the rat GMI-R1 microglia cells. {L-End}Methods GMI-R1 cells in logarithmic growth phase were randomly divided into the control group, positive control group, and low-, medium-, and high-dose groups. The cells in the three dose groups were stimulated with maltolol aluminum at concentrations of 100, 200, and 400 μmol/L, respectively. The cells in the positive control group were stimulated with lipopolysaccharide at a mass concentration of 20 mg/L, while the cells in the control group were not treated. The morphological changes of cells were observed, and the cell survival rate was evaluated by CCK-8 method after 24 hours of culture. The secretion levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -12 and IL-4 were detected by enzyme-linked immunosorbent assay. The relative protein expression of TLR2, NF-κB P65, cluster of differentiation (CD) 68 and CD206 of cells was detected by Western blotting, and the expression of CD68 and CD206 of cells was detected by immunofluorescence method. {L-End}Results The results of cell morphology showed that the number of GMI-R1 cells decreased, the number of activated cells increased, the degree of cell cytoplasm filling decreased, and the cell protrusions elongated with the increase of exposure dose, showing a dose-response relationship. The cell viability of the positive control group and the medium- and high-dose groups were significantly lower than those of the control group (all P<0.05). The secretion levels of TNF-α, IL-12 and the relative expression of TLR2 and CD68 proteins increased (all P<0.05) while the secretion level of IL-4 decreased (all P<0.05) in the cells of positive control group compared with the control group. The secretion levels of TNF-α and IL-12 increased (all P<0.05) while the secretion levels of IL-4 decreased in the cells of the three doses groups (all P<0.05), compared with the control group, and all showed a dose-effect relationship. The relative expression of TLR2 protein in the cells of the three doses groups increased (all P<0.05) compared with the control group. The relative expression of NF-κB p65 and CD68 protein in the cells of the medium- and high-dose groups increased (all P<0.05), but the relative expression of CD206 protein decreased (all P<0.05) compared with the control group. The relative expression of TLR2 and NF-κB p65 protein increased (all P<0.05) while the relative expression of CD206 protein decreased (all P<0.05) in cells of the high-dose group, compared with the low- and medium-dose groups. The average fluorescence intensity of CD68 increased (all P<0.05) while the average fluorescence intensity of CD206 decreased in the cells of high-dose group and the positive control group (all P<0.05), compared with the control group. {L-End}Conclusion Aluminum participated in and promoted the inflammatory response of GMI-R1 cells through the TLR2/NF-κB signaling pathway.

Under the background of " Internet+ medical treatment" and the continuous deepening of face recognition technology research, the face recognition industry has continued to mature, and face recognition has been initially applied in medical fields such as hospital management, auxiliary medical care, and epidemic prevention and control. At the same time, face recognition technology brings problems including error risk, technical cracking risk, privacy risk, equality risk, abuse risk, and other issues in practice, which seriously threaten the personal and property rights and interests of the public. On the basis of summarizing the specific application direction of face recognition technology in hospitals, the authors sorted out the legal regulation of face recognition in China, and proposed that it should be based on technology research and development, strengthen the " gatekeeper" responsibility of medical institutions, improve legal system and recommendations for strengthening judicial leadership in order to improve the legal regulations of face recognition technology, reduce the risk of infringement by medical institutions in the application of face recognition technology, and protect the legitimate rights and interests of citizens.

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.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis