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.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.
3.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.
4.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.
5.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.
6.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.
7.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.
8.Defucosylation of anti-West Nile virus NS1 antibody enhances ADCC
Wanlu ZHU ; Lingli WU ; Nan CHEN ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Microbiology and Immunology 2025;45(9):740-745
Objective:To obtain fucose-free anti-West Nile virus nonstructural protein 1 (NS1) antibody and evaluate its antibody-dependent cell-mediated cytotoxicity (ADCC).Methods:The guanosine diphosphate-fucose transporter SLC35C1 in CHO cells was knocked out using CRISPR/Cas9 gene editing technology to obtain the fucose-free cell line CHO SLC35C1 -/-. CHO SLC35C1 -/- cells were used to produce fucose-free anti-West Nile virus NS1 antibodies. The binding abilities of the antibodies to the target antigen of West Nile virus NS1 protein and the human high-affinity IgG Fc receptor hFcγRⅠ (hCD64) were detected by ELISA and flow cytometry, respectively. The ADCC activity of the antibodies was detected by ADCC reporter gene assay. One-way analysis of variance was used for statistical analysis. Results:CHO SLC35C1 -/- cells expressed green fluorescent protein but not Lens culinaris agglutinin. The anti-West Nile virus NS1 antibodies produced by CHO SLC35C1 -/- cells with a fucose content of 0.22% could bind to West Nile virus NS1 protein in a concentration-dependent manner. Compared with the wild-type antibodies, the fucose-free anti-West Nile virus NS1 antibodies showed a stronger binding ability to hFcγRⅠ(hCD64), as indicated by a significant increase in fluorescence intensity. The ADCC reporter gene assay showed that the fucose-free anti-West Nile virus NS1 antibodies had increased activity as compared with the wild-type antibodies ( P<0.001). Conclusion:The fucose-free anti-West Nile virus NS1 antibodies may be used to protect against West Nile virus infection.
9.Defucosylation of anti-West Nile virus NS1 antibody enhances ADCC
Wanlu ZHU ; Lingli WU ; Nan CHEN ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Microbiology and Immunology 2025;45(9):740-745
Objective:To obtain fucose-free anti-West Nile virus nonstructural protein 1 (NS1) antibody and evaluate its antibody-dependent cell-mediated cytotoxicity (ADCC).Methods:The guanosine diphosphate-fucose transporter SLC35C1 in CHO cells was knocked out using CRISPR/Cas9 gene editing technology to obtain the fucose-free cell line CHO SLC35C1 -/-. CHO SLC35C1 -/- cells were used to produce fucose-free anti-West Nile virus NS1 antibodies. The binding abilities of the antibodies to the target antigen of West Nile virus NS1 protein and the human high-affinity IgG Fc receptor hFcγRⅠ (hCD64) were detected by ELISA and flow cytometry, respectively. The ADCC activity of the antibodies was detected by ADCC reporter gene assay. One-way analysis of variance was used for statistical analysis. Results:CHO SLC35C1 -/- cells expressed green fluorescent protein but not Lens culinaris agglutinin. The anti-West Nile virus NS1 antibodies produced by CHO SLC35C1 -/- cells with a fucose content of 0.22% could bind to West Nile virus NS1 protein in a concentration-dependent manner. Compared with the wild-type antibodies, the fucose-free anti-West Nile virus NS1 antibodies showed a stronger binding ability to hFcγRⅠ(hCD64), as indicated by a significant increase in fluorescence intensity. The ADCC reporter gene assay showed that the fucose-free anti-West Nile virus NS1 antibodies had increased activity as compared with the wild-type antibodies ( P<0.001). Conclusion:The fucose-free anti-West Nile virus NS1 antibodies may be used to protect against West Nile virus infection.
10.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.

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