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

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To analyze the efficacy of gasless unilateral axillary endoscopic approach, transoral vestibular endoscopic approach and open thyroidectomy for papillary thyroid carcinoma (PTC).Methods:A retrospective analysis was made on 98 PTC patients who underwent surgical treatment at our hospital from Aug 2020 to Dec 2022,including 29 cases of transaxillary non pneumatic endoscopic surgery (group A), 33 cases of oral vestibular non pneumatic endoscopic surgery (group B), and 36 cases of traditional open neck surgery (group C). The operation related indicators, neck function, immune function, scar condition and postoperative complications of the three groups were compared.Results:The intraoperative blood loss (18.3±2.8),(30.2±4.2)ml in group A and group B was lower than that in group C (37.0±13.6)ml, the operation time (126.4±9.2) min,(191.0±60.1) min was longer than that in group C (73.8±6.3)min, and the drainage volume (91.8±5.4)ml,(85.2±6.1)ml was higher than that in group C (52.7±7.3)ml ( F=37.431, 94.144, 357.922, all P<0.05). The scores of dysphagia index (6.8±2.5,7.0±2.6) in group A and B were lower than those in group C (12.6±3.5) ( P<0.05). After treatment, surface antigen differentiation cluster 4 + (35.5±7.3,35.0±7.3,31.6±5.4), surface antigen differentiation cluster 4 +/surface antigen differentiation cluster 8 +level(1.4±0.4, 1.4±0.4, 1.0±0.3) decreased, and surface antigen differentiation cluster 8 +level (26.4±3.4 ,26.8 ±3.4, 29.5 ±3. 8) increased in the three groups,and the change amplitude in groups A and B was higher than that in group C ( P<0.05). At 3 months after operation, the VSS scores in group A and group B (6.0±1.0, 6.4±1.0) were lower than those in group C (8.5±1.2) ( F=18.925, P<0.05). Conclusions:Compared with open thyroidectomy for PTC, application of endoscopic thyroidectomy via gasless unilateral axillary or transoral vestibular approach has the advantage of a less swallowing impact and better patient satisfaction with cosmetic appearance, making it a safe and effective surgical procedure for clinical treatment of PTC.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

Objective:To analyze the protective effect of neurotracheal catheter monitoring on recurrent laryngeal nerve in patients with bilateral cervical lymph node dissection of thyroid cancer.Methods:The clinical data of 92 patients undergoing bilateral cervical lymph node dissection for thyroid cancer at the First People's Hospital of Shangqiu from Jul 2019 to Aug 2022 were retrospectively analyzed. Patients were divided into control group (routine exposure, 52 cases) and study group (intraoperative neurotrachatic catheter monitoring, 40 cases) The general data, perioperative indicators, parathyroid function, vocal cord function, voice disorder index, quality of life and postoperative complications were compared between the two groups.Results:The intraoperative blood loss in the study group [(12.3±3.3) ml] was less than that in the control group [(16.9±4.0) ml]. The exposure time [(8.7±2.6) min], operation time [(4.0±0.8) h] and postoperative hospitalization time [(3.2±0.9) d] were shorter than those of control group [(14.4±3.6) min, (4.5±1.2) h, (5.7±1.3) d] ( t=5.770, 8.391, 2.387, 10.853, all P<0.05);Amplitude perturbation (4.85%± 0.58%), fundamental frequency perturbation (0.28%±0.17%), standardized noise energy [(-20.3±4.4) dB], VHI-10 score [(1.6±0.5) score], Quality of life scale for cancer patients 1 month after surgery the TG-V4 score [(43.7±4.8) points] was lower than that of control group [(3.05%±0.54%), (0.42%±0.16%), (-14.6±3.3) dB, (3.3±0.4) points, (50.4±5.6) points]. The harmonic noise ratio [(24.9±4.1) dB] was higher than that of the control group [(20.3±4.4) dB] ( t=10.446, 4.049, 7.036, 19.076, 6.116, 5.144, all P<0.001);The incidence of postoperative complications in the study group (8%) was lower than that in the control group (23%) ( χ2=4.020, P=0.045). Conclusion:Neurotracheal catheter monitoring during bilateral cervical lymph node dissection for thyroid cancer can improve vocal cord function, reduce recurrent laryngeal nerve injury, reduce voice disturbance and improve quality of life.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Objective:To analyze the efficacy of gasless unilateral axillary endoscopic approach, transoral vestibular endoscopic approach and open thyroidectomy for papillary thyroid carcinoma (PTC).Methods:A retrospective analysis was made on 98 PTC patients who underwent surgical treatment at our hospital from Aug 2020 to Dec 2022,including 29 cases of transaxillary non pneumatic endoscopic surgery (group A), 33 cases of oral vestibular non pneumatic endoscopic surgery (group B), and 36 cases of traditional open neck surgery (group C). The operation related indicators, neck function, immune function, scar condition and postoperative complications of the three groups were compared.Results:The intraoperative blood loss (18.3±2.8),(30.2±4.2)ml in group A and group B was lower than that in group C (37.0±13.6)ml, the operation time (126.4±9.2) min,(191.0±60.1) min was longer than that in group C (73.8±6.3)min, and the drainage volume (91.8±5.4)ml,(85.2±6.1)ml was higher than that in group C (52.7±7.3)ml ( F=37.431, 94.144, 357.922, all P<0.05). The scores of dysphagia index (6.8±2.5,7.0±2.6) in group A and B were lower than those in group C (12.6±3.5) ( P<0.05). After treatment, surface antigen differentiation cluster 4 + (35.5±7.3,35.0±7.3,31.6±5.4), surface antigen differentiation cluster 4 +/surface antigen differentiation cluster 8 +level(1.4±0.4, 1.4±0.4, 1.0±0.3) decreased, and surface antigen differentiation cluster 8 +level (26.4±3.4 ,26.8 ±3.4, 29.5 ±3. 8) increased in the three groups,and the change amplitude in groups A and B was higher than that in group C ( P<0.05). At 3 months after operation, the VSS scores in group A and group B (6.0±1.0, 6.4±1.0) were lower than those in group C (8.5±1.2) ( F=18.925, P<0.05). Conclusions:Compared with open thyroidectomy for PTC, application of endoscopic thyroidectomy via gasless unilateral axillary or transoral vestibular approach has the advantage of a less swallowing impact and better patient satisfaction with cosmetic appearance, making it a safe and effective surgical procedure for clinical treatment of PTC.

OBJECTIVE To investigate the clinical efficacy and safety of rituximab （RTX） followed by belimumab （BLM） in patients with severe systemic lupus erythematosus（SSLE）. METHODS Nine SSLE patients， who were treated with RTX followed by BLM for more than 6 months in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University from October 2020 to June 2021， were enrolled. Baseline clinical data of patients， laboratory examination results and basic treatment status at weeks 0， 4， 12， and 24 of medication were collected retrospectively. The patients’ systemic lupus erythematosus disease activity index （SLEDAI） score， glucocorticoid dosage and serological indicators （complement C3， complement C4， serum albumin， and 24-hour urine protein quantification） level were analyzed. At the same time， the occurrence of adverse drug reaction was collected. RESULTS All 9 patients completed more than 24 weeks of RTX followed by BLM therapy. All patients suffered from renal impairment， of which 7 （77.8%） had renal pathology support， 3（33.3%） had blood system damage and 2 （22.2%） had nervous system damage. During treatment， with the prolongation of treatment time， the SLEDAI score， 24- hour urinary protein quantification， and glucocorticoid dosage of patients showed a significant downward trend， and ultimately decreased to the normal index level （P＜0.05）； serum albumin， complement C3 and complement C4 all showed a significant upward trend， eventually rose to the normal index level （P＜0.05）. During treatment and follow-up， 1 patient developed herpes zoster， 1 patient developed upper respiratory tract virus infection， and 1 patient developed urinary system bacterial infection. All patients recovered after symptomatic treatment. CONCLUSIONS In sequential use of RTX followed by BLM for SSLE， early administration of RTX can quickly stabilizethe condition， significantly alleviate clinical symptoms， and gradually normalize specific serological indicators； subsequent administration of BLM can reduce the type and dosage of basic treatment drugs； there is no increase in the incidence of adverse drug reactions.