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

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To investigate the impacts of conscious sedation and general anesthesia on the functional outcome after endovascular therapy (EVT) in elderly patients with acute ischemic stroke with large vessel occlusion (AIS-LVO).Methods:The clinical and imaging data of elderly patients with AIS-LVO (≥80 years) underwent EVT at the Affiliated Hospital of Nantong University from January 2020 to January 2023 were collected retrospectively. They were divided into conscious sedation group and general anesthesia group according to anesthesia modality, and divided into good outcome group (0-2 points) and poor outcome group (>2 points) based on the modified Rankin Scale score at 90 d after onset. The multivariate logistic regression analysis was used to investigate the impact of anesthesia modality on functional outcome after EVT. Results:A total of 77 elderly patients with AIS-LVO were enrolled, including 35 males (45.5%) and 42 females (54.5%); median age of 82.0 years (interquartile range, 80.0 to 84.0 years); the median baseline NIHSS score was 16.0 (interquartile range, 10.0-20.0). Conscious sedation was used in 21 cases (27.3%) and general anesthesia was used in 56 cases (72.7%); 17 (22.1%) had good outcome, while 60 (77.9%) had poor outcome. Compared with the general anesthesia group, the conscious sedation group had a longer procedure time (110.0 min vs. 89.0 min; P=0.049), but a higher rate of good outcome at 90 d (38.1% vs. 16.1%; P=0.038), a lower incidence of stroke-associated pneumonia (33.3% vs. 58.9%; P=0.045), and a lower proportion of patients who underwent tracheostomy after procedure (4.8% vs. 25.0%; P=0.046). Compared with the poor outcome group, the good outcome group had shorter procedure time (75 min vs. 99 min; P=0.033), lower incidence of stroke-associated pneumonia (29.4% vs. 58.3%; P=0.035), lower tracheotomy rate (0% vs. 25%; P=0.022), and a lower proportion of patients who received conscious sedation (47.1% vs. 21.7%; P=0.038). Multivariate logistic regression analysis showed that conscious sedation was an independent predictor of good outcome (odds ratio 0.090, 95% confidence interval 0.010-0.771; P=0.028). Conclusion:Conscious sedation may be more appropriate for elderly patients with anterior circulation AIS-LVO undergoing endovascular treatment.

Objective: To explore the relationship between adolescents physical fitness and depressive symptoms, and to provide reference for the early prevention and intervention of depressive symptoms and improvement of physical fitness in Chinese adolescents. Methods: From September to December 2021, a total of 8 102 adolescents were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Center for Epidemiologic Studies Depression Scale(CES-D) was used to investigate the depressive symptoms, and completed grip strength, standing long jump, 50 m running, modified sitting forward flexion, 20 s repeated traverse, 30 s sit ups, 20 m round trip running (20 m SRT) test. χ 2 test, Goodman Kruskal Gamma and Logistic regression analysis were used to analyze the relationship between physical fitness index(PFI) and depressive symptoms. Results: The overall detection rate of depressive symptoms in adolescents with high level PFI was 23.4%, and the detection rate of low level adolescents was 26.3%, with a statistically significant difference ( χ 2=6.73, P =0.01). There was a significant positive correlation between PFI and depressive symptoms in the high school group ( G=0.09, P <0.05) and the boy group ( G=0.12, P < 0.05 ), and there was no significant association between PFI and depressive symptoms in the junior high school group and the girl group ( P >0.05). After adjusting for gender and age in the Logistic regression model, compared with those with high PFI, the risk of depressive symptoms in those with low PFI was 1.18 times (95% CI =1.05-1.33). Conclusion There is a correlation between physical fitness and depressive symptoms in adolescents. Adolescents with low PFI are at higher risk of developing depressive symptoms than those with high PFI.

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.

OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia （ALL）in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ，Embase，Web of Science，the Cochrane Library ，CNKI，Wanfang database and CBM during the inception to February 3，2022，randomized controlled trials （RCTs）and cohort studies of blinatumomab （experimental group ） versus conventional chemotherapy （control group ）in the treatment of ALL were collected. After literature screening and data extraction ，the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0，and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale （NOS）. Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ，involving 3 RCTs and 5 cohort studies ，with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR ＝1.30，95％CI（1.14，1.48），P＜0.000 1]，relapse-free survival rate [RR ＝1.78，95％CI（1.50，2.12），P＜0.000 01]，complete remission rate [RR ＝1.42，95％CI（1.11，1.82），P＝0.006]，the incidence of tremor [RR ＝16.98，95％CI（2.17，133.12），P＝0.007]，and the incidence of cytokine release syndrome [RR ＝14.11， 95％CI（3.43，58.01），P＝0.000 2] in trial group were all significantly higher than control group ，but there was no statistical significance in the incidence of headache between two groups [RR ＝1.31，95％CI（0.66，2.59），P＝0.44]. The incidence of adverse events with grade more than or equal to 3，infection，stomatitis，thrombocytopenia，febrile neutropenia ，anorexia， constipation，diarrhea，abdominal pain ，hypokalemia in trial group were significantly lower than control group （P＜0.05）. The incidence of cough ，rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in the total incidence of adverse events ，sepsis，anemia，leucopenia，neutropenia， lymphopenia，nausea，vomiting，hyperglycemia，hypotension，hypertension，elevated transaminase or epistaxis between two groups（P＞0.05）. Results of subgroup analysis by study type showed that the overall survival rate ，relapse-free survival rate and complete response rate （except for cohort studies ）of patients in trial group were significantly higher than control group in both RCTs and cohort studies （P＜0.05）. The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ，with low incidence of infection and adverse events of digestive system ，but high incidence of tremor ，cough，rash，fever，hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .

In order to explore the effect of peptidoglycan hydrolase on the viable cell counts of Bacillus amyloliquefaciens and the yield of alkaline protease, five peptidoglycan hydrolase genes (lytC, lytD, lytE, lytF and lytG) of B. amyloliquefaciens TCCC111018 were knocked out individually. The viable cell counts of the bacteria and their alkaline protease activities before and after gene deletion were determined. The viable cell counts of the knockout mutants BA ΔlytC and BA ΔlytE achieved 1.67×10⁶ CFU/mL and 1.44×10⁶ CFU/mL respectively after cultivation for 60 h, which were 32.5% and 14.3% higher than that of the control strain BA Δupp. Their alkaline protease activities reached 20 264 U/mL and 17 265 U/mL, respectively, which were 43.1% and 27.3% higher than that of the control strain. The results showed that deleting some of the peptidoglycan hydrolase genes effectively maintained the viable cell counts of bacteria and increased the activity of extracellular enzymes, which may provide a new idea for optimization of the microbial host for production of industrial enzymes.
Bacillus amyloliquefaciens/genetics* ; Bacterial Proteins ; Cell Count ; Endopeptidases/genetics* ; N-Acetylmuramoyl-L-alanine Amidase/genetics*

Objective:To explore the level of tibial growth plate chondrocyte mitophagy in young rats with chronic renal failure (CRF) and its effect on chondrocyte apoptosis.Methods:Male 4-week-old Sprague-Dawley rats were randomly divided into two groups according to random number table method: normal control group ( n=20, intragastric administration with distilled water) and CRF group ( n=20, given adenine suspension 150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of tibia was measured on X ray film, the width of tibia growth plate was measured and compared on histological section, and the apoptosis rate of chondrocytes in growth plate was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The growth plate chondrocytes of two groups were isolated and cultured to the third generation in vitro, and the apoptosis rate of chondrocytes was detected by TUNEL assay. The co-localization of mitochondria and autophagy lysosomes in chondrocytes was observed by double fluorescence staining. Western blotting was used to detect the level of mitochondrial marker protein translocate of the outer mitochondrial membrane-20 (Tom-20) and autophagy marker light chain-3 protein (LC-3). The mitophagy of growth plate chondrocytes was observed by transmission electron microscope. Results:Compared with the normal control group, the tibia length of CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], and the relative width of growth plate in histological section was narrower (0.56±0.19 vs 1.00±0.21, t=6.744, P<0.001). The apoptosis rate of chondrocytes in growth plate in CRF group was higher than that in the normal control group (17.2%±4.8% vs 5.1%±3.4%, t=6.505, P<0.001). The apoptosis rate of chondrocytes cultured in vitro in CRF group was higher than that in the normal control group (11.8%±6.2% vs 3.1%±1.2%, t=4.357, P<0.001). The result of double influorescence staining showed that there was co-localization between mitochondria and autophagy lysosomes in CRF group. Western blotting results showed that the levels of LC-3 protein ( t=8.944, P<0.001) and Tom-20 protein ( t=6.708, P<0.001) in CRF group were lower than those in the normal control group. Conclusion:The level of tibial growth plate chondrocyte mitophagy in young rats with CRF increases, which will lead to a decrease in the number of mitochondria, an increase in the apoptosis and a decrease in the number of chondrocytes, and eventually lead to dysplasia of tibia.

OBJECTIVE To systematically evaluate the efficacy and safety of oral Janus kinase （JAK） inhibitor in the treatment of alopecia areata （AA）in order to provide evidence -based reference for clinical use . METHODS PubMed，Embase， Web of Science ，the Cochrane Library ，CNKI，Wanfang and CBM were searched from the inception to March 29，2022. Randomized controlled trials （RCTs）of oral JAK inhibitors （trial group ）versus placebo （control group ）in the treatment of AA were collected . Two researchers independently screened the literature ，extracted the data ，and evaluated the quality of the included studies. RevMan 5.4 software was used for meta -analysis and analysis of publication bias . RESULTS A total of 2 170 patients were enrolled in 5 RCTs，including 1 619 in the trial group and 551 in the control group . Meta-analysis results showed that ：compared with control group ，the ratio of the patients with the Severity Alopecia Tool （SALT）score ≤20 at 24th week [RR＝6.10，95%CI （3.86，9.63），P＜0.000 01] and 36th week [RR＝6.59，95%CI（4.16，10.43），P＜0.000 01] were both higher ；Hospital Anxiety and Depression Scale -Anxiety （HADS-A） score [RR＝0.35， 95%CI （0.07，0.64），P＝0.02] and Hospital Anxiety and 1009） Depression Scale -Depression （HADS-D） score [RR＝0.50， 95%CI（0.22，0.77），P＝0.000 4] were more decreased at 24th week . HADS-A score [RR＝0.55，95%CI（0.21，0.89）， 话：0371-66913047。 P＝0.001] and HADS -D score [RR＝0.50， 95%CI （0.16，0.84），P＝0.004] were also significantly decreased at 36th week . The incidence of acne [RR＝4.07，95%CI（1.83，9.08），P＝0.000 6] and low density lipoprotein （LDL）elevation [RR＝1.66，95%CI（1.21，2.28），P＝0.002] in trial group were incr eased significantly （P＜0.05）. There were no significant differences in the incidence of urinary tract infection，upper respiratory tract infection ， headache，nasopharyngitis and creatine phosphokinase elevation between 2 groups （P＞0.05）. There was little possibility of publication bias in this study based on the publication bias analysis . CONCLUSIONS Oral JAK inhibitor can significantly improve AA patients ’hair regrowth ，anxiety and depression . Acne and LDL elevation are the main adverse events .

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.