1.Photodynamic performance and anti-lung cancer effect of novel chlorin compounds
Yan QIU ; Hao WU ; Yafen DONG ; Ye CHEN ; Jian WANG ; Hui JIN
Journal of Pharmaceutical Practice and Service 2026;44(1):39-45
Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) acetic acid(D1)and 4-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) butanoic acid (D2). Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro (P<0.01). However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.
2.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
3.Deep learning-based automatic morphological assessment of the aortic root in bicuspid aortic valve patients before transcatheter aortic valve replacement
Guozhong CHEN ; Yu MAO ; Aiqing JI ; Yingsong HUO ; Qian CHEN ; Wei WANG ; Jian YANG ; Jian LIU ; Haibo ZHANG ; Chenming MA ; Yifei QU ; Hui XU ; Zhengcan WU
Chinese Journal of Radiology 2025;59(9):1029-1036
Objective:To explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955
4.Construction and evaluation of a predictive model for pancreatic fistula after pancreaticoduodenectomy
Jian WANG ; Chengguo WANG ; Dongfeng DUAN ; Liliang HUI ; Jianguo LU
Chinese Journal of Hepatobiliary Surgery 2025;31(7):534-539
Objective:To analyze the influencing factors of pancreatic fistula after pancreaticoduodenectomy (PD), and to construct and evaluate the prediction model of postoperative pancreatic fistula (POPF).Methods:Clinical data of 255 PD patients undergoing PD at the General Surgery Department of the Second Affiliated Hospital of Air Force Military Medical University from January 2016 to January 2023 were retrospectively analyzed as the training set, including 148 males and 107 females, aged 58.0 (52.0, 64.5) years. According to the occurrence of POPF, patiennts were divided into the pancreatic fistula group ( n=65, including grade B and C POPF) and the non-pancreatic fistula group ( n=190). The age, gender, body mass index (BMI), white blood cell (WBC) count and neutrophil/lymphocyte ratio (NLR) before surgery and on the postoperative day (POD) 3, albumin, diameter of pancreatic duct, texture of the pancreas, operation time, and amylase concentration in the drainage fluid on POD3 were compared between the groups. Multivariate logistic regression analyses were conducted to identify the influencing factors of POPF. The nomogram of the pancreatic fistula prediction model was constructed using the rms package. One thousand cases were selected as the test set through the Bootstrap resampling method. And in the test set the receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate the model. Results:Logistic univariate analysis showed that there were significant differences between the two groups in terms of age, BMI, WBC count and NLR (preoperative and on POD3), the concentration of amylase in drainage fluid on POD3, pancreatic duct diameter, and operation time (all P<0.05). The results of logistic multivariate regression analysis showed age ( OR=1.050, 95% CI: 1.011-1.091), BMI ( OR=1.127, 95% CI: 1.005-1.264) and the amylase concentration of the drainage fluid >367.5 U/L on POD3 ( OR=3.688, 95% CI: 1.849-7.354) were the influencing factors of POPF ( P<0.05). Based on the three influencing factors screened out by multivariate analysis, a histogram for the prediction of pancreatic fistula was constructed using the rms package. The area under the ROC curve of the nomogram for predicting the occurrence of pancreatic fistula after PD was 0.744 (95%CI: 0.679-0.809), with a sensitivity of 69.2% and a specificity of 70.5%. The calibration curve shows that the model's prediction is consistent with the actual situation in the overall trend, indicating a relatively high degree of calibration. Conclusion:Age, BMI and amylase concentration of drainage fluid >367.5 U/L on POD3 are the influencing factors for pancreatic fistula after PD. The nomogram model for predicting pancreatic fistula constructed based on this has good predictive and application value.
5.Study on synergistic promotion of ferroptosis in human hypertrophic scar fibroblasts by erastin combined with shikonin
Jian-jun WANG ; Yan-hua WANG ; Yu-ting TANG ; Jing-yi ZHANG ; Fang MA ; Xi HE ; Hui-xia YANG ; Qi-peng ZHAO ; Zhi-gang BAI ; Yin-ju HAO ; Gui-zhong LI ; Yi-deng JIANG ; Jiang-yong SHEN
Chinese Pharmacological Bulletin 2025;41(2):268-276
Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50%).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P<0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P<0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P<0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P<0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.
6.Deep learning-based fusion of color and spectral features from hyperspectral imaging for the origin identification of Salvia miltiorrhiza
Ruibin BAI ; Feng XIONG ; Hui WANG ; Meiqi LUAN ; Junhui ZHOU ; Xiufu WAN ; Zihan ZHAO ; Xiaobo ZHANG ; Chu ZHANG ; Jian YANG
Science of Traditional Chinese Medicine 2025;3(3):250-258
Background: Salvia miltiorrhiza Bunge, commonly known as “Danshen” in China due to the distinctive red color of its roots, is one of the most widely used traditional Chinese medicines. It is cultivated in various regions across China, and environmental differences among these regions can affect the secondary metabolites of plants, thereby influencing the quality of S. miltiorrhiza. In recent years, increasing demand for S. miltiorrhiza has exacerbated the problem of origin fraud. Therefore, ensuring the authenticity of its geographical origin is crucial for the sustainable development of the industry. Objective: The red coloration of S. miltiorrhiza is closely associated with the content of its primary active compounds, particularly tanshinones. Therefore, both its internal chemical composition and external color characteristics serve as key indicators for quality assessment. This study utilized hyperspectral imaging technology to evaluate its potential in classifying the geographical origin of S. miltiorrhiza. Methods: Spectral data reflecting the internal chemical properties of S. miltiorrhiza were integrated with color information representing its external features through 3 levels of data fusion. These fused datasets were then combined with deep learning algorithms to achieve accurate origin classification. Results: The results demonstrated that the Transformer model combined with soft-voting decision-level fusion achieved the highest classification accuracy of 98.72% by integrating image color and short-wave infrared spectral data. Conclusion: This study demonstrates that integrating hyperspectral imaging spectral data with color information provides a reliable and innovative approach for verifying the authenticity and traceability of S. miltiorrhiza.
7.Deep learning-based automatic morphological assessment of the aortic root in bicuspid aortic valve patients before transcatheter aortic valve replacement
Guozhong CHEN ; Yu MAO ; Aiqing JI ; Yingsong HUO ; Qian CHEN ; Wei WANG ; Jian YANG ; Jian LIU ; Haibo ZHANG ; Chenming MA ; Yifei QU ; Hui XU ; Zhengcan WU
Chinese Journal of Radiology 2025;59(9):1029-1036
Objective:To explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955
8.Construction and evaluation of a predictive model for pancreatic fistula after pancreaticoduodenectomy
Jian WANG ; Chengguo WANG ; Dongfeng DUAN ; Liliang HUI ; Jianguo LU
Chinese Journal of Hepatobiliary Surgery 2025;31(7):534-539
Objective:To analyze the influencing factors of pancreatic fistula after pancreaticoduodenectomy (PD), and to construct and evaluate the prediction model of postoperative pancreatic fistula (POPF).Methods:Clinical data of 255 PD patients undergoing PD at the General Surgery Department of the Second Affiliated Hospital of Air Force Military Medical University from January 2016 to January 2023 were retrospectively analyzed as the training set, including 148 males and 107 females, aged 58.0 (52.0, 64.5) years. According to the occurrence of POPF, patiennts were divided into the pancreatic fistula group ( n=65, including grade B and C POPF) and the non-pancreatic fistula group ( n=190). The age, gender, body mass index (BMI), white blood cell (WBC) count and neutrophil/lymphocyte ratio (NLR) before surgery and on the postoperative day (POD) 3, albumin, diameter of pancreatic duct, texture of the pancreas, operation time, and amylase concentration in the drainage fluid on POD3 were compared between the groups. Multivariate logistic regression analyses were conducted to identify the influencing factors of POPF. The nomogram of the pancreatic fistula prediction model was constructed using the rms package. One thousand cases were selected as the test set through the Bootstrap resampling method. And in the test set the receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate the model. Results:Logistic univariate analysis showed that there were significant differences between the two groups in terms of age, BMI, WBC count and NLR (preoperative and on POD3), the concentration of amylase in drainage fluid on POD3, pancreatic duct diameter, and operation time (all P<0.05). The results of logistic multivariate regression analysis showed age ( OR=1.050, 95% CI: 1.011-1.091), BMI ( OR=1.127, 95% CI: 1.005-1.264) and the amylase concentration of the drainage fluid >367.5 U/L on POD3 ( OR=3.688, 95% CI: 1.849-7.354) were the influencing factors of POPF ( P<0.05). Based on the three influencing factors screened out by multivariate analysis, a histogram for the prediction of pancreatic fistula was constructed using the rms package. The area under the ROC curve of the nomogram for predicting the occurrence of pancreatic fistula after PD was 0.744 (95%CI: 0.679-0.809), with a sensitivity of 69.2% and a specificity of 70.5%. The calibration curve shows that the model's prediction is consistent with the actual situation in the overall trend, indicating a relatively high degree of calibration. Conclusion:Age, BMI and amylase concentration of drainage fluid >367.5 U/L on POD3 are the influencing factors for pancreatic fistula after PD. The nomogram model for predicting pancreatic fistula constructed based on this has good predictive and application value.
9.Esophageal carcinoma with ductal differentiation of esophageal gland:clinicopath-ological characteristics and whole exome sequencing analyses
Zhu ZHU ; Xiao HU ; Zhengyang WANG ; Jiajing LI ; Feng WANG ; Hui QIN ; Xiangyu JIAN ; Wencai LI ; Yihui MA
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):291-297
Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophage-al carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driv-ing mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopatho-logical features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the e-sophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epitheli-um,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation character-istics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett's esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 ca-ses surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,character-ized by unique morphological,immunohistochemical,and molecular changes.
10.Protective effects of Shuangyi Qushi Tongluo Capsules on dexamethasone-induced osteoporosis in mice
Yi LI ; Jian-bin HE ; Jia-xiu XIE ; Quan-mou LUO ; Dong-mei LI ; Jun-hui HE ; Dong-mei WEI ; Chao WEI ; Hong-cong QIU ; Gui-ning WEI ; Bo WANG
Chinese Traditional Patent Medicine 2025;47(6):1834-1842
AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P<0.05,P<0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P<0.05,P<0.01);and decreased RANKL protein expression(P<0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P<0.05,P<0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P<0.05,P<0.01);decreased RANKL protein expression(P<0.05,P<0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

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