1.Construction and practice of application model for localized large language model in preoperative medication reconciliation for gastric cancer
Yuxuan ZHU ; Jizhong ZHANG ; Yuhao SUN ; Jiayu WEN ; Xin LIU ; Jifu WEI ; Lingli HUANG
China Pharmacy 2026;37(8):1062-1067
OBJECTIVE To construct a preoperative medication reconciliation model assisted by a localized large language model (LLM) for gastric cancer and evaluate its clinical efficacy. METHODS A total of 249 gastric cancer patients with a history of continuous medication before admission in the Gastric Surgery Department of Jiangsu Cancer Hospital were retrospectively enrolled. Patients were divided into training set (154 cases) and validation set (95 cases) based on the order of time. Based on guidelines, drug package inserts, and other evidence, a standardized medication reconcili ation process and a structured knowledge base were constructed. DeepSeek-V3 LLM was deployed privately in the hospital, combined with retrieval-augmented generation technology, to achieve automated integration of medication information, risk screening, and generation of personalized recommendations. The quality of LLM-generated recommendations was evaluated using automatic metrics (BERT Score and ROUGE-1, 2, L) and manual scoring [seven-dimensional index (7DI) ] . Spearman correlation analysis was performed to explore the correlation between automatic scores and manual scores. Cronbach’s α coefficient was used to test the internal consistency of manual scoring results. The time consumed by manual and LLM-assisted medication reconciliation was compared across tasks of different difficulty levels (simple, moderate, and high). RESULTS A structured knowledge base covering 8 major drug categories was finally established, covering common and high-risk preoperative medication scenarios and providing structured retrieval support for the LLM. For automatic evaluation, the precision, recall, and F1-score of BERT Score were 0.783±0.033, 0.811±0.038, and 0.796±0.028, respectively. The F1-scores of ROUGE-1, ROUGE-2 and ROUGE-L were 0.566±0.067, 0.338±0.076 and 0.468±0.082, respectively. The 7DI scores from three manual raters ranged from 32.06 to 33.45. The F1-score of automatic scoring was significantly positively correlated with the 7DI score of manual scoring (maximum coefficient of determination=0.611, P <0.001), and the internal consistency of manual scoring was good (Cronbach’s α = 0.876). In terms of efficiency, LLM-assisted medication reconciliation reduced time consumption by more than 90% compared with manual reconciliation in the simple, moderate, and high-difficulty groups ( P <0.001). CONCLUSIONS The medication reconciliation model constructed based on a localized LLM and structured knowledge base shows high accuracy, consistency, and clinical applicability in complex preoperative medication scenarios for gastric cancer. It can improve the efficiency of medication reconciliation and reduce potential medication risks.
2.Influence of two methods of smear layer removal on the surface properties of dentin.
Lingli ZHU ; Lin TANG ; Bowen LI ; Mei WANG ; Yuhua LIU
Journal of Peking University(Health Sciences) 2025;57(2):340-346
OBJECTIVE:
To explore the effects of two methods of smear layer removal on the surface properties of dentin.
METHODS:
Sixty extracted sound third molars were collected in this study, and were prepared as uniform dentin specimens with smear layer. All specimens were randomly divided into three groups: Control group, ultrasonic treatment (UT) group and etched treatment (ET) group. Scanning electron microscope (SEM) were used to observe the surface micromorphology of all three groups. Then, the surface elements, mineral phases and functional groups were analyzed by energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and flourier transformed infrared spectrometer (FTIR) respectively. The mechanical properties, hydrophilicity and biocompatibility were also further evaluated.
RESULTS:
It was revealed that dentin tubules of UT and ET groups were exposed, but lots of dentin debris piled up on the surface of the control one which covered up dentin tubules on the surface. The EDX results should that the weaker peak value of calcium and phosphorus in ET group than control and UT groups. Characteristic peaks of hydroxyapatite could be seen by XRD in all of the three groups, but lower distinctive peaks of amide Ⅰ, Ⅱ and Ⅲ bands of collagen of the dentin surface in control group than in ET and UT groups. The microhardness results showed that ET group was lower than control and UT groups, the difference was significant (P < 0.05). Better hydrophilicity of ET group was investigated (P < 0.05) than control group and UT group. Cells could be observed to adhere normally to dentin surface of each group which meant that all of the three groups had good biocompatibility.
CONCLUSION
Both UT and ET could effectively remove the smear layer on the surface of dentin and had no adverse effect of the dentin micromorphology and biocompatibility. The ultrasonic removal of the smear layer did not influence the mineral structure, hydrophilicity and mechanical properties of dentin surface. Although ET can effectively improve the hydrophilicity of dentin but decreased mechanical properties and the content of calcium and phosphorus.
Dentin/ultrastructure*
;
Humans
;
Surface Properties
;
Smear Layer
;
Molar, Third
;
Microscopy, Electron, Scanning
;
Dental Etching/methods*
3.Multimerization through PEGylation improves properties of a single-chain variable fragment against West Nile virus
Wanlu ZHU ; Lingli WU ; Huihui JIA ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Microbiology and Immunology 2025;45(11):914-919
Objective:To obtain a polyvalent single-chain variable fragment(scFv)against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue(scFvC)was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay,both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group( P<0.000 1). Moreover,the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells( P<0.05),suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study,a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation,which improves the antigen-binding and neutralizing activity of the parental scFv.
4.Application of allergen sIgE test in children′s respiratory diseases and analysis of related factors
Lingli LUO ; Caizhi HUANG ; Xingyuan ZHU
Chinese Journal of Laboratory Medicine 2025;48(6):715-721
Objective:This study aim to explore the distribution patterns of inhalant allergen specific immunoglobulin E(sIgE) positive rates in children with respiratory diseases and its correlation with clinical characteristics, so as to provide reference basis for the prevention and diagnosis of respiratory diseases in children.Methods:A cross-sectional retrospective study was conducted using clinical data from 3 574 children with respiratory tract infections and allergic diseases attending Hunan Children′s Hospital from August 2022 to August 2024.The χ 2 test or Fisher′s test was used for statistical analysis to compare the distribution characteristics of inhaled allergen positive rates among children across different ages, genders, seasons, and diseases. The correlation between allergens and clinical features was analyzed. Results:Of the 3 574 children, 51.4%(1 838) were positive for at least 1 inhalant allergen sIgE, with house dust mite, dust mite, and house dust being the most common allergens with top 3 positive rates. The children had a single sensitization rate of 17.9%(329/1 838) and a multiple sensitization rate of 82.1%(1 509/1 838), with a predominance of two (31.6%, 580/1 838) and three (30.6%, 562/1 838) positive allergens. The total positive rate of allergen sIgE for children in the adolescent group was 70.1%(103/147), higher than that in children in the infant group 24.9%(122/489), the preschool group 49.0%(818/1 669), and the school-age group 62.6%(795/1 269)(all P<0.001). The positive rate of allergen sIgE increased gradually with age (χ 2 trend value=93.70, P<0.001). The overall positive rate of allergen sIgE was higher in male children 52.6%(1 157/2 199) than in female children 49.0%(673/1 375)(χ 2=5.95, P<0.05). The allergic rhinitis subgroup had the highest sIgE positive rate of 60.3%(152/252), followed by the 54.9%(123/224) from the allergic rhinitis with asthma subgroup, and the 52.6%(1 142/2 173) from the asthma subgroup. These differences were statistically significant (χ 2=9.87, P<0.05). The allergen sIgE positive rate of the children was the highest in summer, with 57.8%(786/1 360), and the lowest in winter, with 42.1%(215/511). The difference between the different seasons was statistically significant (χ 2=58.20, P<0.001). Spearman correlation analysis found that the number of positive species of allergens was positively correlated with the sIgE levels ( r=0.51, P<0.001), and there was a positive correlation between sIgE levels of house dust mites and dust mites ( r=0.88, P<0.01). Conclusions:The main allergens of respiratory diseases in children are house dust mite and dust mite. The positive rate of allergen sIgE increases with age, is higher in males than females, has the highest rate of sensitization in summer, and is easy to be multiple sensitized. Early sIgE screening is recommended to guide the prevention and diagnosis of the disease for children.
5.Interpretation of Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024)
Dan JIANG ; Zaiwei SONG ; Yuan GAO ; Daobin ZHOU ; Yue LI ; Lingli ZHANG ; Liyan MIAO ; Qun SHAO ; Jun MA ; Jun ZHU ; Hongmei JING ; Rongsheng ZHAO
Adverse Drug Reactions Journal 2025;27(7):385-396
Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.
6.Retrospective epidemiological analysis of fungal infection of a hospital from 2018 to 2024
Zhihao LIU ; Yali LIU ; Lina GUO ; Yao WANG ; Ying ZHAO ; Xiuli XIE ; Wenjing LIU ; Renyuan ZHU ; Hongli SUN ; Hongtao DOU ; Dingding LI ; Lingli LIU ; Shuying YU ; Menglan ZHOU ; Qiwen YANG ; Yingchun XU ; Li ZHANG
International Journal of Laboratory Medicine 2025;46(21):2588-2594
Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5%(2 576/4 479)]was higher than that of female patients[42.5%(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0%(2 241/4 479)].About 90.0%of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6%of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5%of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8%.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6%).98.6%of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.
7.Effects of deep transcranial magnetic stimulation combined with fluoxetine therapy on the hypothalamic-pituitary-adrenal axis and inflammatory factors in adolescent patients with depression
Chinese Journal of Primary Medicine and Pharmacy 2025;32(5):657-662
Objective:To investigate the efficacy of deep transcranial magnetic stimulation combined with fluoxetine therapy in the treatment of depression in adolescent patients and its effects on the hypothalamic-pituitary-adrenal axis.Methods:A randomized controlled study was conducted, enrolling 108 adolescent patients with depression diagnosed and treated at The Third Hospital of Quzhou from May 2022 to April 2023. The participants were randomly assigned to an observation group and a control group, with 54 patients in each group. The control group received fluoxetine hydrochloride capsules, while the observation group received deep transcranial magnetic stimulation in addition to the treatment provided to the control group. Both groups underwent a treatment course of 4 weeks. The scores of the Hamilton Depression Rating Scale scores and the World Health Organization Quality of Life-BREF were compared before and after treatment. Serum levels of corticotropin-releasing hormone, cortisol, and adrenocorticotropic hormone were measured before and after treatment. Additionally, the expression levels of cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-6 in peripheral blood cells were also detected using western blot assay. The specific regulatory signaling pathways involved in the combined treatment was investigated using transcriptome sequencing.Results:At 2 and 4 weeks after treatment, the Hamilton Depression Rating Scale scores in the observation group [(15.62 ± 1.64), (9.56 ± 1.19)] were significantly lower than those in the control group [(16.69 ± 1.89), (13.47 ± 1.16), t = 3.14, 17.29, both P < 0.01]. The scores of the physiological, psychological, social, and environmental domains in the the World Health Organization Quality of Life-BREF in the observation group were significantly higher than those in the control group ( t = -5.06, -3.86; -2.17, -3.26; -1.99, -2.15; -2.02, -3.55, all P < 0.05). After 4 weeks of treatment, serum levels of cortisol, corticotropin-releasing hormone, and adrenocorticotropic hormone in the observation group were (8.97 ± 2.26) mmol/L, (86.33 ± 13.76) ng/L, and (8.69 ± 2.98) mmol/L, respectively. These values were significantly lower than those in the control group, which were (13.06 ± 2.91) mmol/L, (97.41 ± 15.58) ng/L, and (12.77 ± 3.06) mmol/L ( t = 13.73, 16.75, 36.21, all P < 0.001). The levels of cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha in peripheral blood in the observation group were significantly lower than those in the control group ( t = 8.16, 3.92, 6.16, all P < 0.001). Furthermore, tumor necrosis factor-α levels were positively correlated with serum levels of corticotropin-releasing hormone, cortisol, and adrenocorticotropic hormone ( r = 0.803, 0.846, 0.879, all P < 0.05). Transcriptome sequencing results showed that inflammatory response was a specific regulatory pathway involved in the combined therapy. Conclusions:Deep transcranial magnetic stimulation combined with fluoxetine therapy can effectively improve the clinical symptoms of adolescent patients with depression and further regulate the hypothalamic-pituitary-adrenal axis and micro-inflammatory state. Therefore, this combined therapy is of great clinical application value.
8.Multimerization through PEGylation improves properties of a single-chain variable fragment against West Nile virus
Wanlu ZHU ; Lingli WU ; Huihui JIA ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Microbiology and Immunology 2025;45(11):914-919
Objective:To obtain a polyvalent single-chain variable fragment(scFv)against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue(scFvC)was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay,both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group( P<0.000 1). Moreover,the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells( P<0.05),suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study,a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation,which improves the antigen-binding and neutralizing activity of the parental scFv.
9.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
10.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

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