OBJECTIVE To provide reference for medical institutions to establish the record management mode and review rules of off-label use of 5-aminolevulinic acid （ALA） in photodynamic therapy based on the level of evidence. METHODS All ALA-containing outpatient prescriptions in the rational drug use system in our hospital from January 1， 2024 to December 31， 2025 were retrospectively collected. Based on the drug instructions， the current status of off-label use of ALA in photodynamic therapy was identified . The relevant studies in Micromedex， PubMed， CNKI， Wanfang Data and other databases were systematically searched as the relevant evidence-based evidence of ALA off-label use. According to the Off-label Drug Use Filing Standard of the hospital，the evidence-based evaluation method was used to evaluate the evidence-based evidence of ALA off-label use and carry out hierarchical management. RESULTS A total of 1 803 effective prescriptions were included， of which 676 （37.49%） were off-label use， distributed in the dermatology department （564 prescriptions，83.43%） and the plastic surgery department （112 prescriptions，16.57%）. All 676 prescriptions were off-indications medication， involving ten types of skin diseases， primarily including moderate to severe acne （39.94%）， skin warts （25.44%）， Bowen’s disease （11.98%）， and others. According to evidence-based evidence，off-label uses such as moderate to severe acne， actinic keratosis， and Bowen’s disease were managed according to the evidence categoryⅠ orⅡ.The uses of extramammary Paget’s disease and rosacea were managed according to the evidence category Ⅲ.The uses of lichen sclerosus and keloids were managed according to the evidence category Ⅳ.The results of evidence-based evaluation showed that 92.01% of off-label use in our hospital had high-level evidence-based support （ evidence category was gradeⅠ-Ⅱ）. CONCLUSIONS Off-label uses supported by high-level evidence， such as moderate to severe acne， skin warts， and Bowen’s disease， can be managed under filing category Ⅰ or Ⅱ. For the use of lichen sclerosus and keloids， evidence-based evidence is insufficient and should be strictly restricted.The vast majority of ALA off-label use in our hospital has sufficient evidence-based basis.

OBJECTIVE To construct and evaluate a perioperative pharmaceutical care model for orthopedic joint replacement based on clinical pharmacy specialty collaboration and medication therapy management （MTM）， so as to provide a reference for improving the level of clinical rational drug use and reducing medical costs.METHODS Patients undergoing orthopedic joint replacement were taken as the research subjects. A specialized collaboration group was established， consisting of the head of the clinical pharmacy group， ward-based clinical pharmacists， and multi-specialty clinical pharmacists. The practice path， service contents，and workflow of MTM for the perioperative period of orthopedic joint replacement were clarified，and a perioperative pharmaceutical care model for orthopedic joint replacement was developed. Data of patients in the orthopedic diagnosis-related groups （DRG）-IC29 group of the department of orthopedics in Daping Hospital，Army Medical University were collected from July 2022 to June 2023 （pre-intervention， 581 cases） and from July 2023 to June 2024 （post-intervention， 843 cases）. The work-implementation indicators in the post-intervention period were counted， and the efficiency indicators and pharmaceutical management indicators were compared between the pre- and post-intervention periods. Meanwhile，200 patients were randomly selected from the pre-intervention and post-intervention groups， respectively， to evaluate the rate of rational medical orders.RESULTS From July 2023 to June 2024， the collaboration group implemented MTM for 843 patients undergoing orthopedic joint replacement via the established perioperative pharmaceutical care model. A total of 1 163 drug‑related problems （DRPs） were identified， and 79 patients with high medication‑related risks were screened out. The most common types of DRPs included （possible） adverse drug events/reactions （48.93%）， unnecessary drug therapy （21.58%）， and ineffective drug therapy （16.25%）. Among the 1 163 DRPs， 895 （76.96%） were completely resolved. Compared with the pre‑intervention period， the post‑intervention period showed reductions in average hospitalization cost per case， average drug cost per case， average length of hospital stay， proportion of drug cost， utilization rate and use intensity of antibacterial agents， and per‑capita drug cost of six main drug categories. The rate of rational medical orders increased from 78.25% to 98.11%.CONCLUSIONS The perioperative pharmaceutical care model for orthopedic joint replacement based on clinical pharmacy specialty collaboration and MTM can help pharmacists identify and resolve DRPs during the perioperative period of orthopedic joint replacement，improve the level of clinical rational drug use，and reduce treatment costs.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective:To explore the feasibility and clinical outcomes of transperineal prostate multimodal image fusion-targeted biopsy under the day surgery model.Methods:Clinical data of 258 patients who underwent transperineal prostate biopsy at the Second Affiliated Hospital of Xi’an Jiaotong University between December 2022 and June 2024 were retrospectively analyzed. Patients were divided into two groups，and the experimental group（ n = 141）underwent transperineal prostate multi-modal image-fusion targeted biopsy in the day-surgery mode，with age of（70.0 ± 8.8）years，median prostate-specific antigen（PSA）level of 11.10（7.63?17.06）ng/ml，and median Prostate Imaging Reporting and Data System（PI-RADS）score of 4（3，5）. The control group（ n = 117）underwent traditional transperineal systematic biopsy，with age of（69.3 ± 7.4）years，median PSA of 25.20（16.18-54.40）ng/ml，and median PI-RADS score of 4（3，5）. The experimental group was given the day surgery mode：preoperatively，multiparametric magnetic resonance imaging（mpMRI）of the prostate was multimodally fused with ultrasound images，the location of target lesions in the prostate was manually mapped，and a targeted biopsy plan was developed. Intraoperatively，under ultrasound guidance，precise puncture was performed at the lesion sites，followed by systematic biopsy. After the operation，the patients were observed for 4-6 hours，and could be discharged if there were no obvious abnormalities，with the total hospitalization time within 24 hours. For the control group，the conventional biopsy mode was used. Intraoperatively，under ultrasound guidance，the standard 12-core transperineal systematic biopsy protocol was adopted，and sampling was conducted according to the anatomical regions of the prostate（base，midportion，apex，transition zone，and peripheral zone）to cover the entire gland. Patients in this group required routine hospitalization，with a hospital stay of 3-5 days. Operative time，intraoperative pain Numerical Rating Scale（NRS）score，complications within one week postoperatively，treatment costs，overall prostate cancer detection rate，and clinically significant prostate cancer（csPCa，defined as Gleason score ≥ 7 or pathological stage ≥ T 2b）detection rate were compared between the two groups. Results:All procedures were successfully completed without special incidents. The operative time was（13.49 ± 2.00）min in the experimental group and（13.05 ± 2.89）min in the control group，showing no significant difference（ P > 0.05）. The intraoperative pain NRS scores were（3.01 ± 1.17）and（3.10 ± 1.25）in the experimental and control groups，respectively，with no significant difference（ P > 0.05）. Pathological examination revealed that the overall prostate cancer detection rates were 46.8%（66/141）in the experimental group and 42.7%（50/117）in the control group，while the csPCa detection rates were 35.5%（50/141）and 31.6%（37/117），respectively. The differences were not statistically significant（ P > 0.05）. The complication rate was 6.4%（9/141）in the experimental group（including 2 cases of acute urinary retention，3 hematuria，3 fever，and 1 sepsis）and 6.0%（7/117）in the control group（including 3 acute urinary retention，1 hematuria，2 fever，and 1 sepsis），with no significant difference（ P > 0.05）. All complications improved after symptomatic treatment. The treatment costs were（4 063.25 ± 67.26）yuan in the experimental group and（5 185.14 ± 469.15）yuan in the control group，demonstrating a statistically significant difference（ P < 0.05）. Conclusions:Transperineal prostate multimodal image fusion-targeted biopsy can be safely performed under the day surgery model，offering advantages including a relatively high detection rate for csPCa，low complication rate，and better cost-effectiveness.

Objective To investigate the value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)for predicting high-risk coronary plaques in elderly males.Methods A retrospective study was conducted on 46 elderly males aged ≥60 years undergoing health check-ups and coro-nary computed tomography angiography in our hospital between May and July 2024.Their general clinical data were collected.Artificial intelligence software was used to analyze coronary calcium scores and plaque characteristics.The participants were divided into a high-risk plaque group(n=15)and a non-high-risk plaque group(n=31).The differences were compared between the two groups.Multivariate logistic regression analysis was used to identify the influencing factors for high-risk coronary plaques.ROC curve was plotted to determine the predictive value of serum Lp-PLA2 for high-risk plaques,and its AUC value was calculated.Results The high-risk plaque group had significantly larger proportions of smoking history and hyperlipidemia,and higher level of homocysteine and Lp-PLA2 than the non-high-risk plaque group(P＜0.05,P＜0.01).Multiva-riate logistic regression analysis indicated that Lp-PLA2 was an independent risk factor for high-risk coronary plaques(HR=1.030,95％CI:1.008-1.053,P＜0.05).ROC curve analysis revealed that the AUC value of Lp-PLA2 in predicting high-risk coronary plaques was 0.833(95％CI:0.694-0.927,P＜0.01),with a sensitivity of 93.3％,a specificity of 71.0％,a positive predictive value of 62.5％,and a negative predictive value of 100％.Conclusion Serum Lp-PLA2 is of signif-icant value in predicting high-risk coronary plaques in elderly men.

Objective:To design a special device for limiting position of boat-shape headrest of breast brackets,and explore its application value in radiotherapy post-radical mastectomy.Methods:1 cm plex glass plate was cut as T-shape base plate,and the top of the T-shape base plate was drilled to obtain four holes for limiting position.A 2 mm acrylic plate was cut as horse hoof-shape and strip-shape pieces for limiting position,which were adhered respectively to the top and bottom of the T-shape base plate to form a boat-shape headrest with groove structure for limiting position.Self-made pillars with limiting position were used to connect the T-shape base plate with the backplane of breast bracket,so as to realize rigid connection between conventional boat-shape headrest and breast bracket.A total of 60 female patients who received radiotherapy after radical mastectomy for breast cancer at Changzhou Cancer Hospital during January and December 2023 were selected.They were randomly divided into an observation group and a control group(with 30 cases in each group)by using a random number table.The observation group adopted breast bracket combined with self-made boat-shape headrest for limiting position device+boat-shape headrest to conduct fixation,while the control group adopted rotundity headrest of breast bracket to conduct fixation.Both groups adopted hybrid intensity-modulated radiotherapy(IMRT)technique to formulate plan,and the exposure dose was 50Gy/25 fractions,and patients received radiotherapy as 5 times per week,and the treatment course was 5 weeks.Cone-beam computed tomography(CBCT)was used to conduct verification for position before the first 3 treatments.During the treatment duration between the 2nd and the 5th week,CBCT verification for position was conducted in each week.The positioning error and positioning time on left-right direction(x),head-foot direction(y)and abdomen-back direction(z)at each time between two groups were compared.Results:The positioning errors on x,y,z direction of three dimension at each time in observation group were lower than those in control group,and the differences were significant(Z=-7.666,-11,672,-6.311,P<0.05).The average positioning time at first time and the total average positioning time were respectively(222.4±12.9)s and(212.2±15.1)s in observation group,all of which were lower than(262.9±12.5)s and(254.0±15.7)s in control group,and the differences were significant(t=12.364,27.783,P<0.05).Conclusion:The combination of breast bracket and self-made device with boat-shape for limiting position can increase precision and efficiency of positioning,and improve comfort through individually chooses the type of boat-shape headrest,and set the position of headrest,which has favorable clinically application value.

AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P＜0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P＜0.01)and decreased TG,TC,LDL-C(P＜0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P＜0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P＜0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P＜0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.