1.Construction and application of the "Huaxi Hongyi" large medical model
Rui SHI ; Bing ZHENG ; Xun YAO ; Hao YANG ; Xuchen YANG ; Siyuan ZHANG ; Zhenwu WANG ; Dongfeng LIU ; Jing DONG ; Jiaxi XIE ; Hu MA ; Zhiyang HE ; Cheng JIANG ; Feng QIAO ; Fengming LUO ; Jin HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):587-593
Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.
2.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
3.Clinical observation of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia
Ling ZHOU ; Qiuyuan PENG ; Pan ZHAO ; Jin WEI ; Xiaojing LIN ; Xingli ZOU ; Wenfeng LUO ; Jing WANG ; Kunying XIE ; Xianglong LI ; Yang LIU ; Xun NI
China Pharmacy 2024;35(14):1743-1747
OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia (AML). METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan, with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection, and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine, with 28 days as one cycle. The short-term efficacy, negative rate of minimal residual disease (MRD), duration of granulocyte deficiency, duration of platelet (PLT) <20×109 L-1, transfusion volume of suspended red blood cells and platelet, and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in the observation group was significantly higher than control group (P<0.05), and the negative rate of MRD in the observation group was also significantly higher than control group (P<0.05). However, in low-, medium- and high-risk patients, there was no statistical significance in CR/CRi rates between the two groups (P>0.05). There were no significant differences in the duration of agranulocytosis, the duration of PLT <20×109 L-1, the amount of suspended red blood cell transfusion, the amount of platelet transfusion, the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups (P>0.05). CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.
4.The incidence and metabolic profiles of adrenal incidentalomas in patients with diabetes
Yingning LIU ; Xiantong ZOU ; Wei ZHAO ; Xun YAO ; Lexuan WANG ; Lingli ZHOU ; Rui ZHANG ; Yingying LUO ; Meng LI ; Xiuying ZHANG ; Yu ZHU ; Xiaoling CAI ; Xianghai ZHOU ; Xueyao HAN ; Linong JI
Chinese Journal of Endocrinology and Metabolism 2024;40(3):192-197
Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.
5.HIC Value of Mild Traumatic Rats under Anterior-Posterior and Lateral-Medial Craniocerebral Impact:An Equivalent Study
Guoxiang WANG ; Linna ZHU ; Xun WANG ; Qiuju CHEN ; Tao XIONG ; Qinghang LUO ; Jia YU ; Jingyu XU ; Zhiyong YIN ; Shengxiong LIU
Journal of Medical Biomechanics 2024;39(4):730-735
Objective To investigate the equivalent conversion of head injury criterion(HIC)under anterior-posterior(AP)and lateral-medial(LM)craniocerebral impact for mild craniocerebral injury in rats using motor evoked potential(MEP)and β-amyloid precursor protein(β-APP)immunohistochemistry(IHC).Methods Sixty healthy adult male SD rats were randomly divided into 0 m control group,0.5 m-AP and 0.5 m-LM injury groups,and 1 m-AP and 1 m-LM injury groups(12 rats in each group).The control group did not undergo any impact injury experiment.After the impact injury experiment,the injury and control groups were subjected to excessive anesthesia to produce β-APP immunohistochemical stained slices,and the percentage of positive area and integral optical density(IOD)in the brainstem pyramidal tract area of the slices were determined.The MEP groups were divided in the same manner as the IHC groups and the MEP amplitudes of the MEP and control groups were measured after the impact injury experiment.Results With an increase in the degree of injury,the decrease in MEP amplitude,percentage of positive areas,and IOD in the injury groups significantly increased.When the degree of injury was low,the sensitivity of IHC was higher than that of MEP.When the degree of injury was the same,the HIC in the LM direction was lower than that in the AP direction.When the HIC was the same,the degree of injury in the LM direction was greater than that in the AP direction.Conclusions The joint evaluation of MEP and β-APP can provide experimental references for the study of HIC equivalent conversion in AP-LM craniocerebral impact injury.
6.Schisandrin A ameliorates DSS-induced acute ulcerative colitis in mice via regulating the FXR signaling pathway
Jia-rui JIANG ; Kua DONG ; Yu-chun JIN ; Xin-ru YANG ; Yi-xuan LUO ; Shu-yang XU ; Xun-jiang WANG ; Li-hua GU ; Yan-hong SHI ; Li YANG ; Zheng-tao WANG ; Xu WANG ; Li-li DING
Acta Pharmaceutica Sinica 2024;59(5):1261-1270
Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects
7.Effects of Needle Retention Time for Scalp Acupuncture on Motor Dysfunction and Serum C-Reactive Protein,Blood Glucose and Blood Lipid of Post-Stroke Patients
Qi ZHONG ; Hai-Yan CAI ; Bing-Xu JIN ; Zhan-Xin HUO ; Hui-Yi LUO ; Qiu-Xia ZHONG ; Hao-Xun GUO ; Jia-Wen CHEN ; Shu-Hui ZOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1510-1516
Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P<0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P<0.05 or P<0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P<0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P<0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P<0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P>0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P<0.05 or P<0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P<0.05 or P<0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P<0.05 or P<0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P>0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.
8.Morphological classification and molecular identification of Hyalomma asiaticum in parts of Xindi Township,Xinjiang
Xiao-Qing ZAN ; Qiao-Yun REN ; Jin LUO ; Yan-Long WANG ; Pei-Wen DIAO ; Li-Yan CHE ; Jian-Xun LUO ; Hong YIN ; Gui-Quan GUAN ; Guang-Yuan LIU ; Hong-Xi ZHAO
Chinese Journal of Zoonoses 2024;40(4):289-294
The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.
9.Development of a GeXP assay for simultaneous differentiation of the H7 subtype and five NA subtypes of avian influenza viruses
Si-Si LUO ; Zhi-Xun XIE ; Meng LI ; Dan LI ; Li-Ji XIE ; Sheng WANG ; Min-Xiu ZHANG ; Jiao-Ling HUANG ; Zhi-Qin XIE ; Ting-Ting ZENG ; Yan-Fang ZHANG
Chinese Journal of Zoonoses 2024;40(7):670-677
Cases of human infection with H7 subtype avian influenza virus(AIV)combined with five NA subtypes(N2,N3,N4,N7,and N9)have been reported.This study was aimed at establishing a method for simultaneous detection and dif-ferential diagnosis of H7 and five NA subtypes of AIV.Seven pairs of specific primers were designed according to the conserved sequences of the HA gene of H7 subtype AIV,the NA gene of five NA AIV subtypes,and the M gene of all AIV subtypes.A high-throughput GeXP typing method was established for simultaneous detection of the H7 subtype and the five NA subtypes of AIV by using GeXP multiple gene expression and capillary electrophoresis analysis technology.The specificity and sensitivity of the method were determined,and clinical samples were tested.The specificity results indicated that this method was able to simultaneously detect seven target genes in a single tube;each pair of specific primers was able to detect the corresponding AIV subtype,and the universal detection primers were able to detect all subtypes of AIV,with no cross-reaction with other common avian disease pathogens.Sensitivity results demonstrated that this method was able to simultaneously detect seven target genes with a threshold detection limit was 100 copies/μL.The detection results for 150 clinical samples were consistent with those of viral isolation and identification.The high-throughput GeXP method for simultaneous differential diagnosis of the H7 subtype and five subtypes of AIV established in this study has advantages of high specificity,high sensitivity,rapidity,and simplicity,thus providing a new detection method for the effective prevention and control of AIV.
10.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

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