OBJECTIVE To establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Objective To observe the value of MR T2WI intratumoral and peritumoral CT radiomics for predicting von Hippel-Lindau(VHL)gene mutation in renal carcinoma.Method Totally 150 patients with renal carcinoma were retrospectively enrolled and divided into training set(n=105)and validation set(n=45)at the ratio of 7∶3,and furtherly assigned into mutation subgroup and wild subgroup according to with VHL gene mutation or not.Multivariate logistic regression analysis was performed to screen the independent risk factors of VHL gene mutation in renal carcinoma,then a clinical model was constructed.The optimal radiomics features were extracted and screened based on intratumoral+peritumoral 2 mm regions shown on MR T2WI.Logistic regression algorithm was used to construct radiomics model,and finally a combined model was established based on radiomics model and clinical model.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting VHL gene mutation in renal carcinoma.Result Patients'age,smoking history,hypertension history,other family histories and β2-microglobulin were all independent clinical risk factors for VHL gene mutation in renal carcinoma(all P＜0.05).The efficacy of clinical model,radiomics model and combined model for predicting VHL gene mutation in renal carcinoma increased successively(all P＜0.05),with AUC of 0.758,0.831 and 0.952 in training set,0.729,0.803 and 0.896 in validation set,respectively.Conclusion MR T2WI intratumoral and peritumoral CT radiomics had good efficacy for predicting VHL gene mutation in renal carcinoma.Combining with clinical features could further improve predicting efficacy of model.

Objective::To compare the analgesic effects of ibuprofen administered orally via two modes combined with a conventional, patient-controlled intravenous analgesia pump on maternal pain after cesarean section (CS).Methods::This prospective, randomized, controlled study enrolled females who underwent CS from August 2022 to August 2023 at Peking University First Hospital, Beijing, China. Participants were randomly assigned to either an as-needed ibuprofen group (300 mg orally upon request) or a scheduled ibuprofen group (300 mg every 12 hours for 48 hours). The primary outcomes assessed were postoperative pain levels using the Wong-Baker Faces Pain Scale-Revised and cumulative oxycodone consumption at multiple time points up to 48 hours post-delivery. Secondary outcomes included recovery parameters (time to first flatus, ambulation, and lactation initiation), patient satisfaction with pain control, and postpartum depression scores evaluated by the Edinburgh Postnatal Depression Scale on postoperative day 3. Normally distributed data analyzed with t-tests; non-normal data with Mann-Whitney U tests; categorical variables with chi-square or Fisher’s exact tests (SPSS 26.0, P < 0.05). Results::After excluding 61 non-eligible cases, 339 patients were included (171 as-needed vs. 168 scheduled). The scheduled group showed significantly better pain control at 12 hours (4.00 (2.00-5.50) vs. 4.00 (4.00-6.00), P < 0.001), 24 hours (4.00 (2.00-4.00) vs. 4.00 (2.00-6.00), P < 0.001), and 36 hours (2.00 (2.00-4.00) vs. 4.00 (2.00-4.00), P < 0.001), and 48 hours (2.00 (2.00-4.00) vs. 2.00 (2.00-4.00), P = 0.004) post-delivery and lower levels of oxycodone consumption at 36 hours (10.20 (8.20-13.35) vs. 11.00 (8.80-14.40), P = 0.042) and 48 hours (12.40 (10.40-15.95) vs. 13.80 (11.00-16.00), P = 0.020) postpartum compared with those in the as-needed group. Additionally, the time to the return of bowel movements was shorter in the scheduled group than in the as-needed group (23.50 (16.94, 31.47) vs. 27.00 (19.88, 35.97), P = 0.004). Differences in post-delivery ambulation, lactation initiation, satisfaction levels, and depression scores were not significantly different between the two groups. Conclusion::The results of this study promote the use of ibuprofen (scheduled oral administration) combined with a conventional, patient-controlled intravenous analgesia pump for achieving better post-CS pain control than an as-needed dosage regimen.Registration::Chinese Clinical Trial Registry, ChiCTR2400082474.

Objective: To identify the risk factors for pulmonary arterial hypertension(PAH) in maintenance peritoneal dialysis(MPD) patients and to develop and validate a nomogram-based risk-prediction model. Methods: A total of 168 hospitalized MPD patients from the Department of Nephrology were enrolled.Body-fluid composition was measured by bioelectrical impedance analysis,and pulmonary-artery systolic pressure(PASP) was assessed by echocardiography.Patients were randomly allocated into a training set and a validation set at 1:1 ratio.Variables with P< 0. 05 in multivariable Logistic regression in the training set were incorporated to construct a nomogram .The validation set was used to test the model ’s predictive performance . ROC curves , calibration curves , and decision-curve analysis were applied to evaluate accuracy , consistency , and clinical usefulness of the model . Results: Dialysis vintage ( OR : 1 . 038 , 95% CI: 1 . 008 - 1 . 069 , P = 0. 012) , hemoglobin level ( OR : 0. 961 , 95% CI: 0. 929 - 0. 994 , P = 0. 021) , and extracellular water/intracellular water ratio (E/I) (OR : 1 . 069 , 95% CI: 1 . 024- 1 . 115 , P = 0. 002) were independent risk factors for PAH . ROC analysis yielded area under curve as 0. 867 (95% CI: 0. 782 - 0. 953) and 0. 808 (95% CI: 0. 714 - 0. 902) in the training and validation sets , respectively .Calibration plots showed that the predicted curves for both the training and validation sets closely overlapped with the ideal reference line , indicating that the nomogram risk-prediction model had good predictive performance . Decision-curve analysis demonstrated that , within threshold ranges of 0. 13 - 0. 76 ( training set ) and 0. 20 - 0. 76 (val- idation set ) , clinical net benefit was substantial when interventions were guided by the nomogram . Conclusion Dialysis vintage , hemoglobin level , and fluid-overload index (E/I) are independent risk factors for PAH in MPD patients . The nomogram based on these parameters reliably predicts PAH risk and may aid clinical decision-making.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

In the context of aging population, the issue of polypharmacy among elderly patients with mental disorders has become increasingly prominent.Cognitive decline and depressive symptoms render these patients more vulnerable to medication-related risks, while poorly managed physical illnesses further complicate their treatment.To address these challenges, this paper proposes a series of management strategies that emphasize the critical role of pharmacists in conducting medication reviews.A comprehensive assessment of drug risks, benefits, and patient adherence is essential.The proposed strategies not only require careful consideration of patients' clinical needs and individual preferences but also highlight the importance of multidisciplinary team collaboration to reach a consensus on medication therapy.The use of clinical decision support systems as an auxiliary tool is recommended to enhance the scientific rigor of medication decision-making.Furthermore, pharmacists can optimize medication regimens through scientifically validated methods and promote patient or family involvement in self-management to improve acceptance and adherence to treatment adjustments.

Objective::To compare the analgesic effects of ibuprofen administered orally via two modes combined with a conventional, patient-controlled intravenous analgesia pump on maternal pain after cesarean section (CS).Methods::This prospective, randomized, controlled study enrolled females who underwent CS from August 2022 to August 2023 at Peking University First Hospital, Beijing, China. Participants were randomly assigned to either an as-needed ibuprofen group (300 mg orally upon request) or a scheduled ibuprofen group (300 mg every 12 hours for 48 hours). The primary outcomes assessed were postoperative pain levels using the Wong-Baker Faces Pain Scale-Revised and cumulative oxycodone consumption at multiple time points up to 48 hours post-delivery. Secondary outcomes included recovery parameters (time to first flatus, ambulation, and lactation initiation), patient satisfaction with pain control, and postpartum depression scores evaluated by the Edinburgh Postnatal Depression Scale on postoperative day 3. Normally distributed data analyzed with t-tests; non-normal data with Mann-Whitney U tests; categorical variables with chi-square or Fisher’s exact tests (SPSS 26.0, P < 0.05). Results::After excluding 61 non-eligible cases, 339 patients were included (171 as-needed vs. 168 scheduled). The scheduled group showed significantly better pain control at 12 hours (4.00 (2.00-5.50) vs. 4.00 (4.00-6.00), P < 0.001), 24 hours (4.00 (2.00-4.00) vs. 4.00 (2.00-6.00), P < 0.001), and 36 hours (2.00 (2.00-4.00) vs. 4.00 (2.00-4.00), P < 0.001), and 48 hours (2.00 (2.00-4.00) vs. 2.00 (2.00-4.00), P = 0.004) post-delivery and lower levels of oxycodone consumption at 36 hours (10.20 (8.20-13.35) vs. 11.00 (8.80-14.40), P = 0.042) and 48 hours (12.40 (10.40-15.95) vs. 13.80 (11.00-16.00), P = 0.020) postpartum compared with those in the as-needed group. Additionally, the time to the return of bowel movements was shorter in the scheduled group than in the as-needed group (23.50 (16.94, 31.47) vs. 27.00 (19.88, 35.97), P = 0.004). Differences in post-delivery ambulation, lactation initiation, satisfaction levels, and depression scores were not significantly different between the two groups. Conclusion::The results of this study promote the use of ibuprofen (scheduled oral administration) combined with a conventional, patient-controlled intravenous analgesia pump for achieving better post-CS pain control than an as-needed dosage regimen.Registration::Chinese Clinical Trial Registry, ChiCTR2400082474.

AIM To analyze the dynamic change patterns of aflatoxin B1,aflatoxin B2,aflatoxin G1,aflatoxin G2,T-2 toxin and deoxynivalenol contents during the fermentation of Massa Medicata Fermentata.METHODS The analysis was performed on a 40 ℃ thermostatic Waters ACQUITY UPLC HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.01％formic acid-[acetonitrile-methanol(1∶1)]flowing at 0.3 mL/min,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.RESULTS Six mycotoxins showed good linear relationships within their own ranges(R2＞0.998 0),whose average recoveries were 76.1％-119.3％with the RSDs of 0.49％-9.27％,and except for deoxynivalenol,their contents demonstrated the trends of growing out of nothing and gradually increasing.CONCLUSION The risk of mycotoxin infection exists in the fermentation of Massa Medicata Fermentata.This simple,efficient,rapid and sensitive method can provide a reference for whole-process monitoring the fermentation process for Massa Medicata Fermentata.