BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To summarize Chinese materia medica with estrogen-activity based on data mining and analyze their characteristics.Methods:Literature was retrieved from CNKI, Wanfang Data, Chongqing VIP, CBM, PubMed and Web of Science from the establishment of the databases to June 30, 2024, and Chinese materia medica with estrogenic activity were screened. Excel 2021 and KH Coder 3.0 software were used to perform statistical and network co-occurrence analysis on the efficacy classification of Chinese materia medica, properties, tastes and meridians, screening methods for estrogen activity, and applications.Results:Totally 121 kinds of Chinese materia medica with estrogen-activity were included in total. The efficacy classifications were mostly tonic medicines, heat-clearing medicines and blood circulation promoting drugs. The properties were mainly warm and neutral, the tastes were mainly sweet and bitter, and the meridians were mainly the liver, kidney and spleen meridians. The network co-occurrence analysis of the efficacy classification, properties, tastes and tropism meridians showed that the clustering relationship of tonic medicine-neutral-sweet-liver-kidney was the most obvious. The screening methods mainly included MCF-7 cell proliferation and uterine weight gain experiments. Their applications mainly covered osteoporosis, perimenopausal syndrome, lipid metabolism disorder, and premature ovarian failure, etc.Conclusions:Chinese materia medica with estrogen-activity or their components act on estrogen target cells or organs to exert estrogen-like or antagonistic estrogenic effects. This kind of Chinese materia medica can regulate the body's qi, blood, yin and yang, the function of organs and the fullness of Tiangui, as well as the Chong meridian and Conception Vessel, thus improving human growth and development, reproduction and aging. In the future, it is suggested to explore their effective components, mechanisms, bidirectional effect and safety on the basis of guiding clinical medication with the theory of TCM, combining with modern medical research techniques and evidence-based medical research.

Objective: To assess the efficacy and safety of combining traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), with Western medicine (WM), compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis (BCET-OP) by meta-analysis. Methods: Thirty-eight randomized controlled trials involving 2170 participants were analyzed. Eight databases were searched for articles published between inception and December 2023. Quality assessment was performed using the Risk of Bias 2 tool. Results: Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density (BMD) (P < .001, mean difference (MD) = 0.07, 95% confidence interval (CI): 0.06 to 0.08), lumbar vertebrae T-score (P = .0005, MD = 0.21, 95%CI: 0.09 to 0.33) and collum femoris BMD (P = .01, MD = 0.10, 95%CI: 0.02 to 0.19). No significant difference was observed between the groups in the collum femoris T-score and estradiol levels. Bone gla-protein levels were significantly increased in the TCM-WM group (P = .0002, MD = 0.52, 95%CI: 0.25 to 0.79). Beta-CrossLaps decreased significantly in the TCM-WM group (P = .0008, MD = −0.10, 95%CI: −0.16 to −0.04). No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase, in procollagen type I N-terminal propeptide, and in the Kupperman index. The visual analog score (VAS) was decreased in the TCM-WM group compared to the WM group (P < .001, MD = −1.40, 95%CI: −1.94 to −0.87). No significant difference in adverse events was observed between the two groups. Conclusion Combining CHM with WM in patients with BCET-OP significantly improved BMD, T-score, and certain bone turnover markers and reduced the VAS score, indicating potential benefits for bone health and related pain. Adverse event analysis revealed no differences between the groups, supporting the feasibility of the combination therapy. However, further research, particularly in diverse populations, is required.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Humans ; Immunologic Deficiency Syndromes/genetics*

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective To analyze the status quo and existing problems of radiation protection for veterinary X-ray facilitiesin Beijing-Tianjin region, China, and to provide a basis for improving radiation protection management level. Methods According to the requirements of the Technical guidelines for status quo assessment of occupational hazard of the employing unit (AQ/T 4270—2015), the study performed status quo assessment on the workplaces of veterinary X-ray facilities in 16 pet hospitals in Beijing-Tianjin region, and comprehensively analyzed the impact of the workplaces on the health of radiation workers and the public. Results In terms of personnel management, the pass rates of occupational health management post setting, personnel training, personal protective equipment, individual monitoring of occupational external exposure, notification of occupational hazards, and occupational health surveillance were 100%, 81.3%, 100%, 75%, 37.5%, and 25%, respectively. In terms of workplace management, most workplaces had reasonable layout and zoning and complete protection and emergency devices. However, there were some problems in some places, such as non-standard radiation warning signs, no notice board of occupational hazards, and no radiation protection testing. In terms of document management, all institutions had imperfect system documents. Conclusion The workplaces of veterinary X-ray facilities in 16 institutions basically meet the requirements for radiation protection, but there are also some problems, such as inadequate management of personnel and workplace radiation protection, and imperfect system documents. Institutions should strengthen the study of radiation protection knowledge. The competent authorities should strengthen supervision, formulate corresponding standards for radiation protection, enhance training, and improve the professional level of staff.

Objective To evaluate the current status of radioactive occupational hazards in the construction of some medical institutions in Tianjin, discover existingproblems and deficiencies, and provide a technical basis for radiation protection management. Methods Based on the requirements of relevant regulations and standards, we comprehensivelyevaluated the results of the pre-evaluation and control effect evaluation of 81 radioactive occupational hazards in Tianjin. Results Among the 35 proposed protective measures for pre-evaluation of radiation occupational hazards constructionprojects, the lowest compliance rate is warning signs and personal protective equipment. Among the 46 construction projects of radioactive occupational hazard control evaluation, the pass rate of protective measures was between 73.9% and 100%, with the lowest pass rate for personal protective equipment. Besides, the pass rate of radiation protectionmanagement evaluation was 95.7% ～ 100%, with the lowest pass rate for the protection management system.The initial inspectionpass rateof the equipment quality control acceptancewas 98.6%, while the pass rate was 97.1% for the relevant workplace radiation protection during the initial inspection. Conclusion The pre-evaluation completion rate of radiological occupational hazard evaluation in Tianjin medical institution construction project, unilateral and area of construction room, workplace layout and zoning, ventilation, shielding measures, personal dose management and occupational health inspection all meet the requirements of regulations and standards. However, there are still some deficiencies in the personal protective equipment, warning signs and the radiation protection management system. Therefore, the regulatory department should further strengthen the evaluation of medical institutions, especially the key supervision and management of non-conformities.

Objective:To understand the current status of quality control of medical X-ray diagnostic equipment in Tianjin, discuss the problems existing in the process of quality control, and provide technical basis for the relevant regulatory agencies.Methods:Using stratified random sampling, a total of 401 pieces of medical X-ray diagnostic equipment distributed over 111 medical institutions in Tianjin was used for this study. X-ray multifunctional dosimeters and other types of equipment were used to perform quality control testing and evaluation under the relevant health industry standards.Results:The initial testing pass rate of these equipment was 90.0%, with the pass rates of X-ray imaging equipment lower than those of X-ray fluoroscopy equipment, digital subtraction angiography (DSA) and X-ray computed tomography (CT) ( χ2=9.203, 3.383, 5.754, P<0.05). Among the imaging equipment, the screen X-ray equipment had the lowest pass rate, followed by the breast X-ray equipment and medical digital radiography (DR). The main unqualified items were output repeatability, deviation of tube voltage indication and limit spatial resolution. DR accounted for the highest percentage of X-ray equipment that were below testing condition. The unqualified proportion of X-ray imaging equipment was higher than that of X-ray fluoroscopy equipment ( χ2=8.216, P <0.05). Among the imaging equipment, the screen X-ray equipment was seen to have the highest unaqualified proportion, followed by computed radiography (CR). Among the 401 devices in this study, the initial testing pass rates of private medical institutions was not statistically different from those of public medical institutions ( P>0.05). The initial pass rates of domestic equipment was lower than those of imported equipment ( χ2=4.576, P<0.05). Conclusions:The performance of medical X-ray diagnostic equipment in Tianjin needs to be further improved. Medical institutions should pay attention to the quality control testing of medical X-ray diagnostic equipment. The relevant regulatory agencies should strengthen oversight and management of equipment that contains unqualified items, no baseline values and below the testing conditions.