Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.

Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.

Objective:To investigate the risk factors for new adjacent vertebral fracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fracture (OVCF) and their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 476 OVCF patients admitted to The Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 2018 to December 2024, including 74 males and 402 females, aged 49-91 years [71(65, 79)years]. Among them, 397 patients underwent single-level PKP, while 79 received multi-level PKP. Surgical segments involved T 6 in 9 patients, T 7 in 9, T 8 in 14, T 9 in 12, T 10 in 9, T 11 in 50, T 12 in 110, L 1 in 173, L 2 in 77, L 3 in 46, L 4 in 31, and L 5 in 13. The patients were divided into adjacent vertebral fracture group ( n=55) and non-adjacent vertebral fracture group ( n=421) according to whether adjacent vertebral fracture was observed during the follow-up. The following data were collected in both groups: gender, age, body mass index (BMI), bone mineral density T-value, underlying diseases (hypertension, diabetes, coronary heart disease), prior cerebral infarction, history of OVCF, long-term glucocorticoid use, thoracolumbar fracture, number of operated vertebrae, cement injection approach (unilateral or bilateral), mean cement dose, postoperative vertebral height restoration rate, postoperative Cobb angle correction, postoperative thoracolumbar kyphosis angle correction, and cement distribution score. Univariate and multivariate Logistic stepwise regression analysis were performed to assess and identify independent risk factors for adjacent vertebral fracture in OVCF patients after PKP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the risk factors′ predictive performance for adjacent vertebral fracture in OVCF patients after PKP. Results:Univariate analysis revealed significant differences in age, bone mineral density T-value, history of OVCF, long-term glucocorticoid use, number of operated vertebrae, and cement distribution score between the two groups ( P<0.05). The multivariate Logistic stepwise regression analysis showed that the bone mineral density T-value ( OR=0.68, 95% CI 0.48, 0.95, P<0.05) and cement distribution score ( OR=0.61, 95% CI 0.49, 0.76, P<0.01) were significantly correlated with new adjacent vertebral fractures after PKP. The ROC curve analysis showed that bone cement distribution score showed better predictive performance (AUC=0.72, 95% CI 0.64, 0.79), compared with bone mineral density T-value (AUC=0.62, 95% CI 0.54, 0.70), while the combined predictive performance of the two factors was the best (AUC=0.75, 95% CI 0.68, 0.81). Conclusions:Bone mineral density T-value and cement distribution score are independent risk factors for new adjacent vertebral fracture in OVCF patients after PKP. The predictive performance of cement distribution score is proved to be good and can be better in combination with bone mineral density T-value.

Objective:To investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective To analyze the effects of adalimumab treatment on serum micro ribonucleic acid-141(miR-141),micro ribonucleic acid-335-5p(miR-335-5p),and bone metabolism indexes in patients with rheumatoid arthritis(RA),and to provide a basis for the rational development of clinical treatment plans.Methods 82 cases of patients with RA admitted to our hospital from April 2021 to March 2024 were selected as study subjects,and they were divided into the methotrexate group(41 cases)and the adalimumab group(41 cases)by randomized numerical table method.The methotrexate group was treated with methotrexate tablets orally,and the adalimumab group was treated with adalimumab injection subcutaneously on the basis of methotrexate group,and both groups continued the treatment for 3 months.The efficacy after 3 months of treatment,symptom improvement and adverse reactions during the treatment period were counted;enzyme-linked immunosorbent assay detected the levels of inflammatory response,serum ACPA,RF and bone metabolism indexes before and after 3 months of treatment;and fluorescence quantitative PCR assay detected serum miR-141,miR-335-5p before and after 3 months of treatment.Results The total effective rate after 3 months of treatment was higher in the adalimumab group(90.24％)than in the methotrexate group(73.17％)(P＜0.05).Compared with before treatment,the duration of morning stiffness was shorter in both groups after 3 months of treatment,and it was shorter in the adalimumab group than in the methotrexate group(P＜0.05);pressure pain,number of swollen joints,scores of visual analog score(VAS),28 joints disease activity(DAS28),levels of serum interleukin-22(IL-22),interleukin-17(IL-17),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),miR-141,anti-cyclic citrullinated peptide antibody(ACPA),rheumatoid factor(RF)decreased in both groups,and decreased in the adalimumab group compared with the methotrexate group(P＜0.05);levels of serum miR-335-5p,25 hydroxyvitamin D,osteocalcin(BGP),osteocalcin N-terminal intermediate molecular fragment(N-MID),and bone alkaline phosphatase(B-ALP)were elevated in both groups,and increased in the adalimumab group compared with the methotrexate group(P＜0.05).The overall incidence of adverse reactions during treatment was lower in the adalimumab group(7.32％)than in the methotrexate group(24.39％)(P＜0.05).Conclusion Adalimumab could regulate the levels of inflammatory response indicators,serum miR-141,miR-335-5p,ACPA,RF,and bone metabolism indicators in patients with RA,and promote the improvement of symptoms,which in turn contributes to the improvement of therapeutic efficacy and had a high safety profile.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Abstract Breastfeeding has an irreplaceable effect on the growth and development of premature infants and the reduction of complications during hospitalization. In recent years, with the opening of China′s birth policy, the incidence of premature babies has increased, and the corresponding complications have also gradually increased. Breast milk not only carries a rich supply of nutrients, including rich proteins, lipids, sugars to support the normal growth and development of infants, but also contains a large number of immunoglobulins, hormones and other bioactive substances to promote the improvement of body immune function and the development of nervous system. In recent years, many studies have been carried out on the current situation of breast milk operation in breast milk bank, the collection and influencing factors of breast milk, the strategies of breast milk enrichment and its effects on the growth and development of premature infants and complications. Therefore, breast-feeding and intensive breast-feeding can effectively promote the growth and development of premature infants, and reduce the occurrence of complications.

Objective:To explore the clinical efficacy of the splenic vessel-oriented anatomical plane priority strategy in Da Vinci robotic Kimura distal pancreatectomy.Methods:A retrospective analysis was conducted on 26 patients who underwent robotic-assisted distal pancreatectomy at Zhejiang Provincial People’s Hospital from January 2019 to September 2024. The cohort included 7 male and 19 female patients, aged (49.3±16.7) years. Surgical outcomes, including operative time, intraoperative blood loss, postoperative complications, and hospital stay, were analyzed, and surgical techniques were summarized.Results:All 26 patients successfully completed the surgery. Pathological diagnoses included 5 cases of intraductal papillary mucinous neoplasm, 5 serous cystadenomas, 1 pancreatic neuroendocrine tumor, 6 solid pseudopapillary neoplasms, 4 mucinous cystic neoplasms, and 5 neuroendocrine tumors. The maximum tumor diameter was (2.3±1.1) cm, and the operative time was (183.2±77.4) min. The spleen preservation rate was 100% (26/26). Intraoperative blood loss was 50.0 (17.5, 125) ml, and postoperative hospital stay was (10.1±3.7) d. No Clavien-Dindo grade III or higher complications occurred. The post-operative pancreatic fistula (POPF) rate was 53.8% (14/26), including 38.5% (10/26) biochemical leak and 15.3% (4/26) grade B POPF, with no grade C POPF.Conclusion:The splenic vessel-oriented anatomical plane priority strategy in robotic-assisted spleen-preserving distal pancreatectomy (Kimura technique) is safe and feasible, significantly improving the spleen preservation rate.

Background:Acute pancreatitis(AP)is a common clinical gastrointestinal emergency with a high mortality rate.Intestinal dysfunction is one of the common complications of AP and can aggravate the disease condition.Therefore,early and accurate assessment of the disease severity and intestinal dysfunction of AP is of great significance for improving the prognosis of patients.Aims:To investigate the correlation of early serum levels of interleukin-1β(IL-1β),C-reactive protein(CRP),endotoxin(ET),D-lactic acid(D-LA),and diamine oxidase(DAO)with disease severity and intestinal dysfunction in AP patients.Methods:A total of 52 AP patients admitted to the Second Affiliated Hospital of Baotou Medical College from September 2023 to September 2024 were enrolled,and 10 healthy individuals recruited during the same period were served as the control group.AP patients were classified into mild acute pancreatitis(MAP),moderately severe acute pancreatitis(MSAP)and severe acute pancreatitis(SAP)groups according to the severity of the disease.Intestinal function was evaluated using the acute gastrointestinal injury(AGI)grading system.ELISA was used to detect the early serum levels of IL-1β,CRP,ET,D-LA,and DAO,and the correlation of these indicators with the severity of AP and AGI grade were analyzed by Spearman correlation coefficient.Results:Serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MAP,MSAP,and SAP groups were significantly higher than those in the control group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MSAP group were significantly higher than those in the MAP group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the SAP group were significantly higher than those in the MAP and MSAP groups(all P<0.05).Compared with AGI grade 0-Ⅰ subjects,serum levels of IL-1β,CRP,ET,D-LA,and DAO in patients with AGI grade Ⅱ,Ⅲ and Ⅳ were significantly increased(all P<0.05).Compared with AGI grade Ⅱ patients,serum D-LA level in patients with AGI grade Ⅲ was significantly increased(P<0.05).Compared with AGI grade Ⅲ patients,serum D-LA level in patients with AGI grade Ⅳ was significantly increased(P<0.05).Serum levels of IL-1β,CRP,ET,D-LA,and DAO were positively correlated with the severity of AP and AGI grade(all P<0.05).Conclusions:Early serum levels of IL-1β,CRP,ET,D-LA,and DAO in AP patients are significantly increased and closely related to the disease severity and intestinal dysfunction.