Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

OBJECTIVE: To explore the early clinical outcomes of 3D printed individualised customised prostheses for in hip revision in patients with combined severe bone defects. METHODS: Twenty-two patients from January 2021 to May 2023 underwent hip revision using 3D printed personalised customised prostheses were retrospective analyzed, including 10 males and 12 females, age 28 to 78 with a mean of (58.9±12.8) years old. All of patients were combined with severe bone defects (Parprosky type Ⅲ). Among of them, 9 patients had periprosthetic infections and 13 patients had aseptic prosthesis loosening. All patients were treated with a 3D printed personalised prosthesis protocol, patients with the periprosthetic infection received a second stage revision after infection control. The operation time, preoperative waiting time, intraoperative and postoperative complications were recorded, and the clinical efficacy were evaluated at the final follow-up using the visual analogue scale (VAS) for pain, the Harris hip score. RESULTS: One patient was lost to follow-up and the remaining 21 patients were followed up for 10 to 15 with a mean of (12.91±1.44) months after surgery. All patients completed surgery as planned, with an operative time of 135 to 390 with a mean of (165.4±39.3) minutes and a preoperative waiting time of 7 to 16 with a mean of (10.5±3.3) days. Regarding patient complications:one patient had a severe intraoperative periprosthetic femoral fracture due to the combination of severe osteoporosis; one patient had an intraoperative greater trochanteric femur fracture. At the latest follow-up, all patients had good position of the custom-made prosthesis and no loosening of the prosthesis;all patients had good wound healing and no local redness or swelling. The total Harris score at the final follow-up (85.86±7.04) was significantly improved compared to the preoperative (44.86±2.36), P<0.001. The VAS at the last follow-up (2.19±0.87) was significantly improved compared with preoperative (7.41±0.96), P<0.001. CONCLUSION The clinical efficacy of 3D-printed personalised customised prosthesis in combined severe bone defect hip revision is satisfactory, but due to the increased preoperative waiting time of the patients and certain risks, certain indications should be mastered when applying in the clinic.
Humans ; Male ; Female ; Printing, Three-Dimensional ; Middle Aged ; Aged ; Adult ; Retrospective Studies ; Hip Prosthesis ; Arthroplasty, Replacement, Hip ; Reoperation ; Prosthesis Design ; Treatment Outcome

OBJECTIVE: Investigation on the clinical application of HURWA robot and Smith & Nephew Cori robot in total knee arthroplasty(TKA). METHODS: A retrospective analysis was performed on 84 patients with knee osteoarthritis who underwent robotic-assisted TKA (RATKA) between June 2023 and March 2025. According to the different robotic systems used, the patients were divided into the domestic HUARUN robotic-assisted total knee arthroplasty group (HRATKA group) and the Smith & Nephew Cori robotic-assisted total knee arthroplasty group (CRATKA group). There were 42 patients in the HRATKA group, including 16 males and 26 females; the age ranged from 56 to 73 years old, with an average of (64.70±8.30) years old;the body mass index (BMI) was (25.10±2.30) kg·m^-2;21 cases were on the right side and 21 cases on the left side;in terms of Kellgren-Lawrence(K-L) classification, there were 15 cases of Grade Ⅲ and 27 cases of Grade Ⅳ;the disease duration ranged from 3 to 25 years, with an average of (15.5±7.5) years. The CRATKA group also included 42 patients, with 14 males and 28 females;the age ranged from 58 to 74 years old, with an average of (65.60±7.50) years old;the BMI was (24.50±2.70) kg·m^-2; 20 cases were on the right side and 22 cases on the left side;regarding K-L classification, there were 11 cases of Grade Ⅲ and 31 cases of Grade Ⅳ;the disease duration ranged from 2 to 26 years, with an average of (16.5±8.8) years. Collect general data of all patients, including age, gender, height, weight, surgical site, K-L classification, incision length, and operation time. To evaluate prosthesis position, compare the frontal tibia component (FTC) angle, lateral femoral component (LFC) angle, lateral tibia component (LTC) angle, and frontal femoral component angle between the two groups of patients after surgery. Measure the deviation of the hip-knee-ankle (HKA) angle to assess lower limb alignment. Additionally, compare the following indicators between the two groups:Knee Society Score (KSS), Visual Analogue Scale (VAS) for pain, knee range of motion (ROM), hemoglobin (HB) level, hematocrit (HCT) level, complication rate, and in-hospital satisfaction. RESULTS: All patients successfully completed the surgery as scheduled, and all were followed up after the operation. The follow-up period ranged from 5 to 17 months with an average of (11.2±6.1) months. There were 4 cases of venous thrombosis in the HRATKA group and 3 cases in the CRATKA group;each group had 2 cases of wound exudation. No mechanical-related complications, pulmonary embolism, or other severe complications occurred. Comparison of the incision length and hospital stay between the HRATKA group and the CRATKA group showed no statistically significant difference (P>0.05). The operation time in the HRATKA group was (96.80±7.10) minutes, which was longer than that in the CRATKA group (90.10±8.80) minutes, and the difference was statistically significant (P<0.05). In the HRATKA group, the HKA angle was (178.93±1.11) degree, the FFC angle was (89.00±0.91)°, and the LFC angle was (7.31±2.17) degree;the corresponding values in the CRATKA group were (178.05±1.34)°, (87.88±1.74)°, and (10.60±2.84) degree respectively. The differences in these three indicators between the two groups were all statistically significant (P<0.05). However, there were no statistically significant differences in the FTC angle or LTC angle between the two groups (P>0.05). There was also no statistically significant difference in the total perioperative blood loss between the two groups (P>0.05). At 3 days after surgery, the VAS score for movement in the HRATKA group (5.95±1.45) points was higher than that in the CRATKA group (4.50±0.97) points, with a statistically significant difference (P<0.05);at 90 days after surgery, there was no statistically significant difference in the movement VAS score between the two groups (P>0.05). Additionally, no statistically significant differences were observed between the two groups in the KSS, ROM at 3 and 90 days after surgery, or satisfaction degree during hospitalization (all P>0.05). CONCLUSION The domestic HURWA robot demonstrates excellent performance in osteotomy efficiency and lower limb alignment recovery. The Smith & Nephew Cori robot has a significant advantage in soft tissue assessment and joint stability optimization. Both robotic systems offer high-quality surgical treatments that significantly improve short-term knee function.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/instrumentation* ; Aged ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Osteoarthritis, Knee/surgery*

Aortic regurgitation and mitral regurgitation are more common in elderly heart valve disease,and both may be present in some patients.Severe aortic regurgitation complicated with severe mitral regurgitation often requires surgical valve replacement,but in patients at high risk of surgery,the risk of perioperative mortality is significantly increased.Therefore,for such patients,minimally invasive interventions can significantly improve long-term patient outcomes while reducing surgical risk.This article report a case of transcatheter aortic valve replacement combined with transcatheter edge-to-edge repair in the treatment of severe aortic regurgitation combined with mitral valve prolapse,in order to explore new treatment ideas for similar cases.

Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Neurogenic bladder(NB)is one of the most challenging urinary system disorders,with spinal cord injury(SCI)being an important etiological factor.Animal models provide crucial tools for investigating the pathogenesis,therapeutic strategies,and novel drug screening for NB subsequent to SCI.We reviewed and synthesized recent literature on NB animal models after SCI from both domestic and international sources.This review summarizes and analyzes research advancements using these models in terms of animal species,SCI segments,modeling techniques,and evaluation indicators,with the aim of offering insights and guidance for future experimental research based on animal models of NB following SCI.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.