1.Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.
Zicheng ZENG ; Qiwen LIAO ; Shiyi GAN ; Xinyu LI ; Tiantian XIONG ; Lezhi XU ; Dan LI ; Yunlu JIANG ; Jing CHEN ; Richard YE ; Yang DU ; Thiansze WONG
Acta Pharmaceutica Sinica B 2025;15(5):2468-2479
Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.
2.Systematic review on medication risk prediction models for hospitalized adult patients
Yang YANG ; Xuefeng SHAN ; Haidong LI ; Yaozheng LI ; Qiwen ZHOU ; Hongmei WANG
China Pharmacy 2025;36(10):1254-1259
OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed, Embase, Web of Science, CNKI, Wanfang data, VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature, extracting data, and evaluating the quality of the literature, descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included, involving 12 models. Nine studies used Logistic regression algorithm for modeling, and the number of included predictive factors ranged from 3 to 11; the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias; 10 studies had high applicability risk. A total of 31 predictive factors were extracted, including 15 items of basic patient information, 3 test indicators, and 5 items of medication information, and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm, with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved, and the overall risk of bias is relatively high.
3.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.
4.Epidemiological Analysis of Pathogens in Acute Respiratory Infections During the 2023-2024 Autumn-Winter Season in Beijing:A Case Series of 5556 Patients at Peking Union Medical College Hospital
Yan CAO ; Yu CHEN ; Jie YI ; Lingjun KONG ; Ziyi WANG ; Rui ZHANG ; Qi YU ; Yiwei LIU ; Maimaiti MULATIJIANG ; Chenglin YANG ; Yujie SUN ; Yingchun XU ; Qiwen YANG ; Juan DU
Medical Journal of Peking Union Medical College Hospital 2025;16(3):680-686
Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7%,with sin-gle-pathogen positivity at 54.0%,dual-pathogen positivity at 8.9%,and triple or more pathogen positivity at 0.7%.The predominant pathogens detected were FluA(16.1%)and RSV(15.7%),followed by ADV(11.1%),MP(11.1%),HRV(10.0%),and FluB(10.0%).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P<0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P<0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P<0.001),and HRV(x2=174.199,P<0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P<0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P<0.001),whereas FluB was more common in young/middle-aged patients(both P<0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.
5.Eating Raw Snails Infected with Angiostrongylus Cantonensis Causes Eosinophilic Meningitis: A Case Report
Mengting HU ; Dong ZHANG ; Peiyao JIA ; Minya LU ; Menglan ZHOU ; Jiayu GUO ; Huiting SU ; Yi GAO ; Jingyuan XI ; Huadong ZHU ; Qiwen YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1463-1467
We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.
6.Eating Raw Snails Infected with Angiostrongylus Cantonensis Causes Eosinophilic Meningitis: A Case Report
Mengting HU ; Dong ZHANG ; Peiyao JIA ; Minya LU ; Menglan ZHOU ; Jiayu GUO ; Huiting SU ; Yi GAO ; Jingyuan XI ; Huadong ZHU ; Qiwen YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1463-1467
We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.
7.Mechanism of action of traditional Chinese medicine in treatment of nonalcoholic fatty liver disease based on intestinal microecology
Xue YANG ; Xu ZHANG ; Jin XIAN ; Qiwen TAN ; Huijuan YU
Journal of Clinical Hepatology 2024;40(4):804-809
Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease associated with obesity, insulin resistance, and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD, and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota, the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD, and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota, in order to provide new ideas for the treatment of NAFLD.
8.Application of knowledge distillation technology for fine segmentation of three-vessel and trachea views in fetal echocardiographic images
Min DI ; Qiwen CAI ; Mingming MA ; Yuanshi TIAN ; Yang CHEN ; Bowen ZHAO ; Ran CHEN
Chinese Journal of Ultrasonography 2024;33(1):21-26
Objective:To explore the application value of fetal heart ultrasound image segmentation network model based on knowledge distillation technology in the fine segmentation of fetal heart ultrasound image at three-vessel and trachea (3VT) views.Methods:One thousand and three hundred fetals were retrospectively collected from Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2016 to December 2021, the two-dimensional grayscale ultrasound images of fetal heart at 3VT views were analyzed and then divided into training, validation, and test sets. The training and validation sets were used to construct the auxiliary diagnostic network models, and the test set was used to test the reliability of different network models (U-Net, DeepLabv3+ ). The 3VT views were collected and annotated by an experienced doctor as the reference standard. The intersection over union (IoU), pixel accuracy (PA) and Dice coefficient (Dice) were used as the 3 indexes to evaluate the segmentation accuracy, and the diagnostic efficiency of the training model was evaluated. The training model and the most commonly used segmentation models were identified, and the results were compared. A total of 101 images were randomly selected and assigned to junior doctors, AI and junior doctors assisted AI interpretation. Bland-Altman images were drawn to evaluate their consistency with the reference standard, and the results were compared.Results:The training model of knowledge distillation algorithm achieved better results than U-Net, DeepLabv3+ models on all evaluation indexes, and the average IoU, PA and Dice were 68.6%, 81.4% and 81.3%, respectively. Compared with the U-Net model and DeepLabv3+ model, more accurate segmentation boundaries were obtained by the knowledge distillation algorithm training model, and the quantitative evaluation indexes were improved. With the aid of the model, the diagnostic accuracy of junior doctors was improved.Conclusions:The knowledge distillation algorithm training model segmentation method can identify the anatomical structure of the fetal heart in the 3VT view of the fetal heart ultrasound image, and the recognition result is obviously better than other related methods, and can improve the accuracy of image recognition for doctors with low experience.
9.Epidemiological Analysis of Pathogens in Acute Respiratory Infections During the 2023—2024 Autumn-Winter Season in Beijing: A Case Series of 5556 Patients at Peking Union Medical College Hospital
Yan CAO ; Yu CHEN ; Jie YI ; Lingjun KONG ; Ziyi WANG ; Rui ZHANG ; Qi YU ; Yiwei LIU ; MULATIJIANG MAIMAITI ; Chenglin YANG ; Yujie SUN ; Yingchun XU ; Qiwen YANG ; Juan DU
Medical Journal of Peking Union Medical College Hospital 2024;16(3):680-686
To analyze the epidemiological characteristics of acute respiratory infections (ARIs) during the autumn-winter season in Beijing, providing evidence for the prevention, control, diagnosis, and treatment of ARIs. A convenience sampling method was employed, enrolling patients who visited Peking Union Medical College Hospital (PUMCH) between September 2023 and February 2024 due to ARIs. Nasopharyngeal swabs were collected, and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus (FluA), influenza B virus (FluB), human rhinovirus (HRV), A total of 5556 eligible patients were included. The overall positivity rate for the six common respiratory pathogens was 63.7%, with single-pathogen positivity at 54.0%, dual-pathogen positivity at 8.9%, and triple or more pathogen positivity at 0.7%. The predominant pathogens detected were FluA(16.1%) and RSV(15.7%), followed by ADV(11.1%), MP(11.1%), HRV(10.0%), and FluB(10.0%).No significant difference in overall pathogen positivity was observed between genders.However, significant differences were found between autumn and winter( The prevalence of respiratory pathogens in Beijing is associated with age and season. Targeted preventive measures should be implemented in different seasons and for key populations.
10.The Mechanism of Brucea javanica Regulating Hela Cell Apoptosis Through TLR9-MyD88 Signaling Pathway
Juan YANG ; Weiqi WU ; Xiuyi LU ; Liuyan WEN ; Shaoping YUAN ; Yan BAI ; Qiwen WU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1481-1489
Objective To investigate the molecular mechanism of Brusatol(BRU)regulating apoptosis of Hela cells through TLR9-MyD88 signaling pathway.Methods Hela cells preserved in our laboratory were treated with Brucea javanica at different concentrations(0,5.0,10.0,20.0,40.0,80.0 nmol·L-1).Hela cells were divided into Control group(normal cultured Hela cells),BRU-L group(treated with 10.0 nmol·L-1 Brucea javanica)and BRU group-H(treated with 20.0 nmol·L-1 Brucea javanica)Cells were treated with nmol·L-1 of Brucea javanica),BRU+pcDNA-NC group(transfected with pcDNA-NC+20.0 nmol·L-1 of Brucea javanica),BRU-H+pcDNA-TLR9 group(transfected with pcDNA-TLR9+20.0 nmol·L-1 of Brucea javanica).Cell proliferation was detected by CCK-8 and EdU methods.Apoptosis was detected by TUNNEL staining and flow cytometry.The protein expression levels of TLR9,MyD88,Bax,Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were detected by Western blot.Cell apoptosis and mitochondrial membrane potential detection kit(JC-1)were detected by flow cytometry,and the contents of adenosine triphosphate(ATP)and reactive oxygen species(ROS)were detected by ELISA.Results Compared with 0 nmol·L-1 group,the survival rate and IC50 value of 10 nmol·L-1 group were significantly decreased(P<0.05).After stimulation of BRU with different concentrations,the proliferation ability of cells was significantly decreased in a dose-dependent manner(P<0.05).Compared with control group,the 5-ethynyl-2'-deoxyuracil(EDU)positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein of cells in BRU-L,BRU-H and pcDNA-NC groups were significantly decreased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly increased(P<0.05).In control group,BRU-L,BRU-H group/BRU-H+pcDNA-NC,there was a continuous decreasing trend(P<0.05).Compared with the BRU-H+pcDNA-NC group,the EDU positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein in the BRU-H+pcDNA-TLR9 group were significantly increased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly decreased(P<0.05).Compared with Control group,JC-1 level and ATP content in BRU-L,BRU-H and BRU-H+pcDNA-NC groups were significantly decreased,while ROC content and mitotracker positive cell level were significantly increased(P<0.05).Compared with BRU-L group,JC-1 level and ATP content in BRU-H group and BRU-H+pcDNA-NC group were further decreased,while ROC content and mitotracker positive cell level were further increased(P<0.05).Compared with the BRU-H+pcDNA-NC group,the levels of JC-1 and ATP in the BRU-H+pcDNA-TLR9 group were increased,while the levels of ROC,mitotracker staining positive cells were decreased(P<0.05).Conclusion Brucea javanica can produce Hela cell proliferation by regulating TLR9-MyD88 signaling pathway.

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