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.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

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.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

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 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

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.