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.

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 analyze the influencing factors of failed induction of labor(IOL)in full-term singleton pregnant women,and to establish a prediction model for failed IOL.Methods:This study retrospectively analyzed the clinical data of 1483 pregnant women with full-term singleton of IOL in the Department of Obstetrics and Gy-necology,Heping Branch of General Hospital of Northern War Zone from January 1,2019 to December 31,2019.According to the outcome of IOL,the pregnant women were divided into the successful group(1108 cases)and the failed group(375 cases)of IOL.The influencing factors of failed IOL were screened to establish the prediction model through multivariate Logistic regression analysis.The receiver operating characteristic(ROC)curves and Hosmer-Lemeshow test were used to assess the predictive performance and fitting degree of the model.Results:Multivariate Logistic regression analysis showed that there were risk factors for failed IOL(OR>1,P<0.05),in-cluding elderly primiparous delivery,with no history of vaginal delivery,education level≤12 years,gestational age<40 weeks,pre-pregnancy overweight or obesity,excessive gestational weight gain,height<160 cm,cervical Bishop score before IOL<4 points,neonatal weight≥3750 g,combined IOL,suspected fetal distress,and the time from IOL to onset of labor≥24 hours,and height≥165 cm,IOL with dinoprostol suppositories were protective fac-tors for failed IOL(OR<1,P<0.05).Antepartum factors and antepartum factors combined with intrapartum fac-tors were separately used to establish model for predicting failed IOL.The area under the ROC curve(AUC)were 0.914 and 0.940,and the Youden index were 0.660 and 0.733,respectively.The prediction accuracy were 87.5%and 88.9%,respectively.Conclusions:This study screened the significant influencing factors of failed IOL,providing a theoretical basis for clinical measures to improve the success rate of IOL and constructing a pre-diction model of failed IOL,which is helpful for obstetricians and pregnant women to decide the mode of delivery together,and ensure the safety of mother and baby;on the other hand,it aims to enhance everyone′s awareness of pregnancy health care and improve the vaginal delivery rate.

Objective:To explore the factors leading to communication disorders in ICU patients during mechanical ventilation from the perspective of both patients and medical staff, and to use the theoretical framework of acceptability to identify the barriers that can be improved by intervention.Methods:Using the method of descriptive phenomenology from July to August 2022, 11 patients with mechanical ventilation and 8 medical staff in the comprehensive ICU of a Yuhuangding Hospital in Yantai were selected for interviews by the purpose sampling method, combined with participatory observation. The interviews of patients were conducted off ventilator. With Nvivo12.0 Plus software, the seven-step analysis method of Colaizzi phenomenology was adopted to summarize the theme and the theoretical framework of acceptability was used to identify the obstacle factors that could be improved by intervention.Results:The age of 11 patients was 18-46 years old, the duration of mechanical ventilation was 9.5-312.3 h. The age of 8 medical staff was 26-54 years old, the length of service in ICU was 2-30 years. A total of 14 themes were extracted. For patients: defensive mood, difficulty in presenting information, introverted personality, communication tools are hard to use, emergency treatment conflict, deny the ability to communicate, thought slowness. For medical staff: defensive mood, cognitive load, high time cost, lack of humane communication strategies, poor training, other priorities, loss of confidence in effective communication, awareness of the importance of communication was not enough.Conclusions:There are many factors that can be improved for patients with mechanical ventilation in ICU. It is suggested to speed up the research and development of high-tech and personalized alternative communication tools in China, reduce negative communication between doctors and patients and nurses and patients, and implement evidence-based multi-mode and progressive communication intervention strategies.

Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.

Cystic echinococcosis, a zoonotic disease that poses a significant threat to human health and animal husbandry development, is prevalent across the world and predominantly occurs in agricultural and pastoral regions. However, cystic echinococcosis cases are rare in non-endemic areas, which is likely to cause misdiagnosis or missing diagnosis, resulting in delay in treatment. This report presents an overseas imported cystic echinococcosis case misdiagnosed as pulmonary and hepatic cysts, so as to provide insights into diagnosis and treatment of cystic echinococcosis in non-endemic areas.

Aging has become an increasingly important topic in the field of geriatrics, with the exploration of aging-related biomarkers providing a foundation for interventions aimed at delaying and reversing aging.Over the years, numerous biomarkers have been developed at both the cellular level(aging mechanisms, histology)and individual level(composite biomarkers, functional biomarkers).This article systematically discusses the characteristics and application scenarios of significant biomarkers at these two levels, and also outlines comparative studies conducted on aging biomarkers.Future research should consider synthesizing multidimensional aging biomarkers at all levels to achieve a more accurate and reliable assessment of aging.Furthermore, there is great potential for further exploration of aging biomarkers through the analysis of histologic data.

Objective:To compare the effectiveness of the Moses holmium laser and the traditional holmium laser in the treatment of kidney stones using flexible ureteroscopy.Methods:The data of 425 patients with kidney stones treated with flexible ureteroscopic holmium laser lithotripsy at Hebei University Affiliated Hospital from January 2017 to January 2023 were retrospectively analysed. Among them, 136 cases were treated with traditional holmium laser (traditional group), and 289 cases were treated with Moses holmium laser (Moses group). To minimize selection bias due to non-random allocation, 1∶1 propensity score matching (PSM) was employed, ensuring comparability between the two groups in baseline characteristics (age, gender) and stone characteristics (stone location, number, diameter, CT value, and stone composition). The differences in operation time, laser action time, stone clearance rate (SFR), postoperative complications and secondary treatment rate were compared between the two groups after matching. The risk factors affecting SFR were analyzed by multivariate logistic regression. The efficacy of Moses group and traditional group in treating kidney stones with diameter ≥20 mm was also compared.Results:After PSM, 108 patients were selected from each group for data analysis. Traditional group and Moses group demonstrated good consistency in baseline characteristics, including age [57.0(49.0, 65.0) years old vs. 58.5(51.8, 66.0) years old], male gender [58.3% (63/108) vs. 60.2% (65/108)], stone location(upper calyx / mid calyx / lower calyx / pelvis: 33/35/38/42 cases vs. 35/33/40/42 cases), multiple stones [33.3% (36/108) vs. 35.2% (38/108)], diameter [14.0(11.0, 16.0)mm vs. 14.0(12.0, 17.0)mm], CT value [1 115.5(993.2, 1 228.2) HU vs. 1 114.5(1 000.2, 1 216.5) HU], and the presence of calcium stones [83.3% (90/108) vs. 79.6% (86/108)], and all showing absolute standardized mean difference(ASMD) <0.1. The Moses group had shorter operation time [48.5(36.0, 56.0)min vs. 60.0(48.8, 68.0)min, P<0.01], higher post-operative stone-free rate (SFR) [88.9%(96/108) vs. 67.6(73/108), P<0.01], and lower rate of secondary surgery [1.8%(2/108) vs. 9.3%(10/108), P=0.04], indicating advantages in surgical efficiency and post-operative outcomes. Multivariable logistic regression analysis revealed that using Moses holmium laser ( OR=0.029, P<0.01), stone diameter ( OR=1.492, P<0.01), stone CT value ( OR=1.007, P<0.01), presence of calcium stones ( OR=1.551, P<0.01), holmium laser application time ( OR=0.863, P<0.01), preoperative placement of a double-J stent ( OR=0.193, P<0.01), and preoperative moderate to severe hydronephrosis ( OR=1.651, P<0.01) were significant factors affecting SFR. In treating stones with a diameter of 20-30 mm, the surgery time of Moses group was shorter than that of traditional group [50.5(43.8, 58.3)min vs. 72.0(68.0, 78.0)min, P<0.05], and the laser application time of Moses group was also shorter [29.5(22.8, 36.0)min vs. 36.0(32.0, 41.0)min, P<0.05]. The post-operative SFR of Moses group was higher than that of traditional group [65.6%(42/64) vs. 35.3%(6/17), P<0.05], and the rate of secondary surgery was lower[7.8%(5/64) vs. 29.4(5/17), P<0.05]. Conclusions:Flexible ureteroscopy combined with Moses holmium laser lithotripsy demonstrated significant advantages over traditional holmium laser in enhancing stone clearance rate, reducing operation time, and lowering the need for secondary surgeries in the treatment of kidney stones. Flexible ureteroscopy combined with Moses holmium laser lithotripsy also proves its efficacy and clinical value in managing complex kidney stone cases.