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

Objective:To investigate the relationship between the Palatopharyngeal Arch Staging System（PASS） and the severity of Obstructive Sleep Apnea（OSA）, as well as the patterns of airway collapse, while further assessing its clinical applicability. Methods:A total of 98 patients diagnosed with OSA at the Department of Otorhinolaryngology Head and Neck Surgery, Shenzhen University Affiliated Shenzhen Hospital, were recruited for this study. Data collected included basic demographic information, oropharyngeal laryngoscopy videos, results from awake laryngoscopy Muller tests, and indicators from sleep respiratory monitoring. The distribution of each PASS stage among patients with varying severities of OSA was compared. Additionally, both objective and subjective sleep indicators along with occurrences of airway collapse in OSA patients across different PASS stages were analyzed. Results:In total, 98 patients participated in this study. Statistically significant differences were observed in neck circumference, weight, Body Mass Index（BMI）, tongue position, and PASS stage when comparing mild-to-moderate OSA patients to those with severe OSA（P<0.05）. Furthermore, there were statistically significant variations in Apnea-Hypopnea Index（AHI）, minimum blood oxygen saturation levels, average blood oxygen saturation levels, oxygen desaturation index values, and total oxygen desaturation indices among OSA patients categorized by different PASS stages. Multiple comparisons revealed statistically significant differences in AHI as well as minimum and average blood oxygen saturation levels between patients at PASS 1 versus those at PASS 3（P<0.05）. Additionally, notable differences regarding oropharyngeal collapse rates among OSA patients across various PASS stages were identified; specifically between those at PASS stage 1 and those at PASS stage 3. Conclusion:The proportion of PASS stages for OSA varies across different severity levels. The severity of OSA and the degree of airway collapse in patients with varying PASS stages also exhibit significant differences. Patients classified as PASS 3 demonstrate a more severe form of OSA compared to those at PASS 1, with stage 3 being more susceptible to oropharyngeal collapse than its stage 1 counterpart. This assessment system is anticipated to address the current limitations in evaluating the lateral pharyngeal wall within the oropharynx.
Humans ; Sleep Apnea, Obstructive/pathology* ; Male ; Severity of Illness Index ; Female ; Middle Aged ; Polysomnography ; Adult ; Pharynx/physiopathology* ; Aged

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the dosimetry optimization strategy based on filter thickness and shape selection for the bulb superficial X-ray radiotherapy unit.Methods:Monte Carlo code TOPAS was used to model tubular equipment, and the dose distribution from six X-ray energies (50-150 kV) and five conventional aluminum filters (0.5-3.0 mm) with different thickness were simulated in the water model. The percentage depth dose (PDD) curve along the central axis, the center-axis profile dose at different depths, and the lateral dose distribution were analyzed. The dose distribution of three different designs of aluminum filters (conventional cylindrical, conical and oblique cylindrical filters) was compared to evaluate the effect of dosimetric optimization of different filter shapes.Results:Under the same energy, increasing the thickness of the filter can optimize the superficial skin dose, and the optimization effect of depth dose uniformity can be increased by 26% at a depth of 5.5 mm at 70 kV energy. The raised, flat and inclined dose distribution modes can be achieved by using conventional cylindrical, conical and inclined aluminum filters.Conclusions:By selecting the appropriate X-ray energy and filter thickness, an ideal dose distribution matching the tumor depth can be achieved. The application of personalized filters is also of great significance for diverse target areas.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective Cheng's Juanbi Decoction(CSJBD)is a classic traditional Chinese medicine formula for treating rheumatoid arthritis(RA),exhibiting significant clinical efficacy,but the underlying mechanisms remain unclear.We investigated whether CSJBD inhibited RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis using a collagen-induced arthritis(CIA)mouse model and fibroblast-like synoviocytes(FLSs)derived from RA patients(RA FLSs)and examined the underlying mechanisms.Methods We conducted in vivo experiments.Male C57BL/6 mice weighing 17 to 20 g were used to establish the CIA model.The mice were assigned to 6 groups,including the normal group,the model(CIA)group,the model+CSJBD-L(8.1 g/kg)group,the model+CSJBD-M(16.2 g/kg)group,the model+CSJBD-H(32.4 g/kg)group,and the model+leflunomide(LEF)(0.05 mg/10 g)group,with 10 mice in each group.CSJBD was administered twice daily via gastric gavage,while LEF was administered once daily via gastric gavage,for a duration of 28 days.We also conducted in vitro experiments.RA FLSs were assigned to 4 groups,including the RA FLSs+CSJBDS-L group receiving 10%CSJBDS-containing serum,the RA FLSs+CSJBDS-M group receiving 15%CSJBDS-containing serum,the RA FLSs+CSJBDS-H group receiving 20%CSJBDS-containing serum,and the RA FLSs+NC group(negative control).To study whether WTAP regulated Wnt7b,RA FLSs were divided into the RA FLSs group,the RA FLSs+si-WTAP#3 group,the RA FLSs+si-WTAP#3+Wnt7b-OE group,and the RA FLSs+si-WTAP#3+Wnt7b-NC group.To study the underlying mechanism by which CSJBT affected RA FLSs,RA FLSs were divided into the RA FLSs group,the RA FLSs+CSJBDS-M group,the RA FLSs+CSJBDS-M+Wnt7b-OE group,and the RA FLSs+CSJBDS-M+NC group.We used ultra-high performance liquid chromatography(UPLC)to identify and quantify key monomer compounds from CSJBD as quality criteria for CSJBD preparation.Bioinformatics,CCK-8,RT-qPCR,Western blot,immunofluorescence,and related methods were employed to assess the therapeutic efficacy and underlying mechanisms of CSJBD in treating RA.Results According to the UPLC analysis,ferulic acid,osthole,mulberroside A,notopterol,and gentiopicroside were identified as quality control standards for the preparation of CSJBD formula.CSJBD improved RA pathology in CIA mice,reduced the levels of interleukin(IL)-6,IL-1β,IL-8,and tumor necrosis factor-α(TNF-α)in their serum,and decreased the expression of RA pathological genes MMP3 and fibronectin,with the difference between groups being statistically significant.Bioinformatics analysis suggested that CSJBD might inhibit RA pathology by suppressing the Wnt/β-catenin signaling pathway through Wnt7b.Experimental results showed that the expression of WTAP and Wnt7b was significantly increased in RA.After knocking down WTAP,the expression of Wnt7b was significantly reduced,and the Wnt/β-catenin signaling pathway was also inhibited,with the difference between groups being statistically significant(P<0.05),confirming that WTAP regulated the pathway via Wnt7b.According to experimental verification,CSJBD significantly inhibited the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs.Wnt7b overexpression reversed the inhibitory effect of CSJBD on the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs,indicating that Wnt7b is the direct target of CSJBD.Conclusion CSJBD inhibits RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis,with Wnt7b identified as a direct therapeutic target of CSJBD.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.