BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. Methods:A female IP patient with a heterozygous IKBKG c. 1167dup variant but without family genetic data who sought genetic counseling at Women and Children′s Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094). Results:In total seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38 + 6 weeks of gestation. Conclusion:For IP patients with de novo mutation or without family samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.

Objective: To investigate the characteristics and trend of stroke incidence in Yixing City, Jiangsu Province from 2016 to 2023, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke case in Yixing City from 2016 to 2023 were collected from the National Health Information Platform of Yixing City, including sex, age, time of onset, and diagnostic subtypes. Crude incidence was standardized using the data from the 2010 Chinese National Population Census to analyze the characteristics of stroke incidence. The incidence trend of stroke was analyzed by average annual percent change (AAPC). Results: A total of 54 157 stroke cases were reported in Yixing City from 2016 to 2023, with a crude incidence of 629.52/100 000 and a standardized incidence of 299.50/100 000, showing an upward trend (AAPC=9.744% and 5.955%, both P<0.05). The crude and standardized incidence of stroke in males were significantly higher than those in females (695.30/100 000 vs. 565.79/100 000, 328.73/100 000 vs. 270.71/100 000, both P<0.05). Stroke incidence exhibited an age-dependent increase (P<0.05), peaking in the ≥60 years age group (1 820.43/100 000). The crude and standardized incidence of ischemic stroke (555.46/100 000 and 262.26/100 000) were significantly higher than those of hemorrhagic stroke (52.80/100 000 and 28.03/100 000, both P<0.05). From 2016 to 2023, the standardized incidences of stroke in males, females, the 0-<40 years age group, the 40-<60 years age group, the ≥60 years age group, and ischemic stroke all showed an upward trend (AAPC=6.692%, 4.925%, 5.607%, 5.777%, 5.698%, and 8.481%, respectively, all P<0.05). No significant temporal trend was observed for hemorrhagic stroke incidence (P>0.05). Conclusions The incidence of stroke among residents in Yixing City showed an upward trend from 2016 to 2023, with males and elderly individuals being high-risk populations. Ischemic stroke emerged as the predominant subtype, while a concerning trend of increasing stroke incidence among younger adults was observed.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. Methods:A female IP patient with a heterozygous IKBKG c. 1167dup variant but without family genetic data who sought genetic counseling at Women and Children′s Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094). Results:In total seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38 + 6 weeks of gestation. Conclusion:For IP patients with de novo mutation or without family samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

OBJECTIVE To know about the working mode and human resource status of pharmacy intravenous admixture services （PIVAS） in national medical institutions. METHODS Through questionnaire survey， the national PIVAS was invited to fill out questionnaire and statistical analysis was performed on the effective sample data related to PIVAS working mode and human resources in the questionnaire. RESULTS In this study， 761 PIVAS from 722 medical institutions of 29 provinces were involved in the questionnaire survey， with 471 valid questionnaires for working mode and 441 valid questionnaires for human resources survey. In terms of working mode， among 471 PIVAS， 292 PIVAS （62.0%） were in pharmacist-alone mode， and 176 PIVAS （37.4%） were in pharmacist-nurse cooperative mode； there was no significant difference in the types of medical orders received by PIVAS between these two working modes except for the other medical orders （P＞0.05）. In terms of human resource setting， among 441 PIVAS， the average number of total staff of single PIVAS was 24（16，33）， including 11（6，19） pharmacists， 7（2，13） nursing staff， and 3（1，5） workers； there was a statistically significant difference in the number of personnel among three groups （P＜ 0.01）. The per capita income of PIVAS respondents in 2019 was [7.9（4.8，10.7）]×104 yuan， and in 2021 it was [8.8（5.8，11.7）]× 104 yuan， with an increase of 9.0% compared to 2019. The difference between the two groups was statistically significant （P＜ 0.01）. CONCLUSIONS Medical institutions’ PIVAS in China had not fully implemented the pharmacist-alone work model， and some medical institutions had chosen a pharmacist-nurse cooperative mode. It is suggested that relevant departments formulate corresponding qualification requirements and training standards for nursing personnel as soon as possible based on sufficient research on PIVAS’s demand for nursing professionals.