1.Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures
Meng LI ; Ke-Jing WANG ; Zhen-Yang GAO ; Yun-Fei XIE ; Tao GUO
China Journal of Orthopaedics and Traumatology 2024;37(5):451-457
Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.
2.Residual neural network-101-feature pyramid network model based on CT for differentiating benign and malignant lung nodules
Gang LIU ; Xiaoting XIE ; Hui HE ; Fei LIU ; Xu MAO ; Jingyao SANG ; Haiyun YANG ; Yueyong XIAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):414-417
Objective To observe the value of residual neural network(ResNet)-101-feature pyramid network(FPN)model based on CT for differentiating benign and malignant lung nodules.Methods Totally 2 040 lung nodules in 2 000 patients were retrospectively enrolled,including 1 150 benign and 890 malignant nodules.The nodules were divided into training set(n=1 632)and test set(n=408)at the ratio of 8∶2,the former including 881 benign and 751 malignant ones,while the latter including 269 benign and 139 malignant ones,respectively.Taken ResNet-101 as the backbone network,combined with FPN,a classification model was established based on chest CT,and the efficiency of this model alone and combined with evaluation of physicians for differentiating benign and malignant lung nodules were evaluated.Results Among 269 benign lung nodules in test set,ResNet-101-FPN model alone correctly diagnosed 214 nodules(214/269,79.55%),while combined with evaluation of physicians correctly diagnosed 230 ones(230/269,85.50%).For 139 malignant nodules in test set,ResNet-101-FPN model alone correctly diagnosed 124 nodules(124/139,89.21%),while combined with evaluation of physicians correctly diagnosed 131 ones(131/139,94.24%).The sensitivity,accuracy and precision of ResNet-101-FPN model combined with evaluation of physicians for distinguishing benign and malignant lung nodules were all higher,while the specificity of the combination was lower than those of ResNet-101-FPN model alone,but the differences were not significant(all P>0.05).Conclusion ResNet-101-FPN model could be used to distinguish benign and malignant lung nodules based on CT.Combining with evaluation of physicians could improve diagnostic efficiency of this model.
3.Multioxidized polyketides from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata
Hongtao LI ; Ruining YANG ; Fei XIE ; Tianpeng XIE ; Linhuan TANG ; Hao ZHOU ; Zhongtao DING
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):1057-1064
Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata.Their chem-ical structures were elucidated using extensive spectroscopic data,electronic circular dichroism calculations,and single X-ray diffrac-tion analysis.All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation.Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core.Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities.Plausible biosynthetic pathways for 1-6 were proposed.Additionally,compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyr-osine phosphatase 1B.
4.Analysis of cerebral venous sinus thrombosis due to inherited protein S deficiency
Lingling HOU ; Fei XU ; Haixiao XIE ; Ke ZHANG ; Yanhui JIN ; Mingshan WANG ; Lihong YANG
Chinese Journal of Neurology 2024;57(11):1247-1253
Objective:To investigate the relationship between inherited protein S deficiency (PSD) and cerebral venous sinus thrombosis (CVST) by phenotype and gene mutation analysis of 2 inherited PSD pedigrees with nonsense mutations.Methods:Retrospective analysis of clinical and imaging data of 2 patients diagnosed with CVST who were treated in the Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University in July and October 2023 was carried out. The peripheral blood samples were collected from proband 1 and her family members (3 subjects, 2 generations in total), and proband 2 and his family members (8 subjects of 3 generations in total). Their protein S (PS) activity (PS:A), the content of total PS antigen (TPS:Ag) and free PS antigen (FPS:Ag) were measured for definite diagnosis. Polymerase chain reaction was done in all 15 exons of the active PROS1 gene and its 5′ and 3′ untranslated regions and the amplification products were analyzed by direct sequencing. The results were compared with human PROS1 reference sequences, using Chromas software to find the mutation sites. Results:The proband 1 is a female, and the proband 2 is a male. Both of them had young onset and the clinical presentation of CVST. The PS:A level was reduced to 29% in the proband 1 and reduced to about 35% in her mother; PS:A was reduced to 21%-27% in the proband 2 and his 6 family members; a decline in the same proportion of TPS:Ag and FPS:Ag was found in the 2 probands and their family members, therefore they were primarily diagnosed as typeⅠPSD. Gene analysis showed that the proband 1 and her mother had a nonsense mutation of c.1680T>A in exon 14 (p.Tyr560 *) of the PROS1 gene; the proband 2 and his 6 family members had a nonsense mutation of c.1687C>T in exon 14 (p.Gln563 *) of the PROS1 gene. Conclusion:The reduced protein S levels in PSD patients and their family members may be associated with the p.Tyr560 * and p.Gln563 * nonsense mutations of the PROS1 gene, and the clinical manifestations of CVST in PSD patients may be related to these 2 nonsense mutations.
5.Strategies and clinical effects of free tissue flaps in repairing massive destructive burn wounds
Wei ZHANG ; Weidong ZHANG ; Lan CHEN ; Weiguo XIE ; Fei YANG ; Junhui XU ; Feng LIU
Chinese Journal of Burns 2024;40(9):818-827
Objective:To investigate the strategies and clinical effects of free tissue flaps in repairing massive destructive burn wounds.Methods:This study was a retrospective observational study. From June 2014 to October 2023, 51 burn patients with 53 massive destructive burn wounds which met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 47 males and 4 females, aged 21 to 77 years. After debridement, the wound area needed to be repaired by tissue flaps ranged from 20.0 cm×12.5 cm to 50.0 cm×15.0 cm. Emergency, early, or delayed transplantation of tissue flaps was performed to repair the wounds. Six head, face, and neck wounds, 5 upper limb wounds, and 1 lower limb wound were repaired with latissimus dorsi myocutaneous flaps. Eleven upper limb wounds and 6 lower limb wounds were repaired with anterolateral thigh flaps. Seven upper limb wounds, 5 lower limb wounds, and 2 face and neck wounds were repaired with paraumbilical perforator flaps. One lower limb wound was repaired with lower abdominal flap. Two face and neck wounds, 2 upper limb wounds, and 1 lower limb wound were repaired with inguinal flaps. One upper limb wound was repaired with scapular flap. One trunk wound was repaired with the "fillet flap" from the abandoned upper limb after amputation. Three head, face, and neck wounds, 3 lower limb wounds, and 1 upper limb wound were repaired with omental flaps. Four wounds were repaired by combined transplantation of the above-mentioned tissue flaps. Three wounds were repaired by fractional transplantation of the above-mentioned tissue flaps. The size of a single harvested tissue flap ranged from 15.0 cm×5.0 cm to 45.0 cm×25.0 cm. The arterial and venous anastomoses were added as the circumstances might require to improve tissue flap circulation. The wounds in the flap donor sites were sutured directly or repaired by split-thickness skin grafts from head. The general condition of patients during treatment was recorded. After surgery, the survival of tissue flaps, the healing of wounds in the recipient sites, limb salvage, the healing of wounds in the flap donor sites, and the survival of skin grafts were observed. The healing of wounds in the recipient sites was observed during follow-up. At the last follow-up, the upper limb function after successful limb salvage was evaluated by the Arm, Shoulder, and Hand Disability Scoring Scale, the weight-bearing walking ability of patients with successful lower limb salvage was evaluated by the Holden walking ability classification, and the patient's satisfaction with the efficacy was assessed by 5-grade Likert scale.Results:During treatment, one case with electrical burn of the head suffered from aggravated cerebral edema, cerebral hernia and coma recurred. After dehydration, hormone therapy, and so on, the patient recovered and incomplete hemiplegia on the right limb was left. The shock symptoms of 4 patients got worse, which were gradually controlled after anti-shock with fluid supplement and colloid injection. One patient developed hemorrhagic shock after tissue flap transplantation, which was corrected by fluid infusion and red blood cell suspension transfusion. Vascular crisis occurred in 3 tissue flaps after surgery, of which 2 survived and 1 eventually became necrotic after exploration. Partial necrosis occurred in 2 tissue flaps and slight necrosis occurred at the edge of 5 tissue flaps, which all healed after tissue flap trimming, vacuum sealing drainage (VSD), and skin grafting treatment. All the other tissue flaps survived. There were 12 recipient wounds with residual necrotic tissue after surgery, which healed after debridement, VSD, and skin grafting treatment. The remaining 41 wounds healed well. Among the 40 limb wounds of 39 patients, 5 patients had 3 upper limb and 2 lower limb amputations. The remaining 35 limbs of 34 patients were successfully salvaged. The donor site wounds healed well, and the skin grafts survived well. During the follow-up of 6 to 52 months, all the head, face, neck, and trunk wounds were well repaired. The fester recurred in 7 limb wounds 3 to 9 months after surgery and healed after debridement, drainage, and tissue flap repair. At the last follow-up, the functional scores of 22 upper limbs after successful limb salvage ranged from 0 to 100 (with an average of 50), and the Holden walking ability classification of 12 patients with 13 lower limbs after successful limb salvage was level Ⅴ in 8 cases, level Ⅳ in 2 cases, and level Ⅲ in 2 cases. The patients were very satisfied with the efficacy in 33 cases, relatively satisfied in 12 cases, and not quite satisfied in 6 cases.Conclusions:Systematic evaluation and treatment of the whole body condition, choosing the appropriate repair time, and using appropriate tissue flaps to repair massive destructive burn wounds will help ensure the safety of treatment, improve the repair effect, and reduce the injury of donor sites, thus optimizing the repair effect.
6.Research progress on mucus related complications after ileal ureteral replacement surgery
Fei SHI ; Denghao YANG ; Wen TANG ; Zhifei XIE ; Mingwen LIU ; Zeju ZHAO
Journal of Chinese Physician 2024;26(4):633-636
The repair and reconstruction of long ureteral defects is a technical challenge faced by urologists. The ileal ureter replacement is currently the main surgical method for treating long segment ureteral defects. After the ileal ureter replacement surgery, mucin 2 (MUC2) and mucin 3 (MUC3), which are the main functional components of ileal mucus, continue to be strongly expressed. In addition, the expression of MUC2 gene after surgery is not limited to goblet cells, but can even be expressed in absorption cells of the ileum, ultimately leading to a large amount of mucin synthesis and mucus secretion. Mucus can cause many complications such as obstruction and infection, seriously affecting the treatment effect. At present, the industry has tried various methods to reduce the secretion of mucus and related complications after ileal ureteral replacement surgery, such as cutting the ileum to reduce mucosal area and mucosal exfoliation to reduce mucus production, and has achieved certain results. This article provides a review of research progress on the types, molecular mechanisms, and solutions of mucus related complications after ileal ureteral replacement surgery.
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Expert consensus on the construction, evaluation and application of bone organoids (version 2024)
Jian WANG ; Long BAI ; Xiao CHEN ; Yuanyuan LIU ; Guohui LIU ; Zhongmin SHI ; Kaili LIN ; Chuanglong HE ; Jing WANG ; Zhen GENG ; Weiyang SHI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Lili YANG ; Zhiwei WANG ; Haodong LIN ; Yunfei ZHANG ; Fuxin WEI ; Wei CHEN ; Wenguo CUI ; Fei LUO ; Jun FEI ; Hui XIE ; Jian LUO ; Chengtie WU ; Xuanyong LIU ; Yufeng ZHENG ; Changsheng LIU ; Jiacan SU
Chinese Journal of Trauma 2024;40(11):974-986
Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.
9. Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism
Yun-Fei DENG ; Hui-Hong LI ; Yang-Jie ZHOU ; Wei WEI ; Xie-Hua XUE ; Xie-Hua XUE ; Xie-Hua XUE
Chinese Pharmacological Bulletin 2024;40(1):83-90
Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol
10.Qidi Tangshen Prescription (QDTS) Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy
Fei GAO ; Huidi XIE ; Borui YU ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):90-97
ObjectiveTo explore the mechanism of Qidi Tangshen prescription (QDTS) in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy (DN). MethodUsing network pharmacology methods, we collected the chemical components and targets of QDTS, as well as the targets related to DN. Subsequently, we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model, QDTS (3.34 g·kg-1), and losartan capsules (10.29 mg·kg-1) groups, and db/m mice served as the normal group. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and the urinary albumin excretion rate (UAER) and renal pathological changes were measured and observed. The expression levels of protein kinase B1 (Akt1), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated B-cell lymphoma-extra-large (p-Bcl-xl), as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein p62 (p62), and autophagy-related gene 6 homolog (Beclin1), were determined. Furthermore, mouse podocytes were divided into the normal glucose (5.5 mmol·L-1), high glucose (35 mmol·L-1), DMSO (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder) groups. After 48 h of intervention, the protein levels of Akt1, HIF-1α, p-Bcl-xl, LC3, p62, and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN, and 55 targets were related to autophagy, in which Akt1, HIF-1α, and Bcl-xl were the key targets. Compared with the normal group, mice in the model group exhibited significantly increased UAER, glomerular hypertrophy, deposition of blue collagen fibers, thickening of the glomerular basement membrane, and noticeable fusion of podocyte foot processes in some segments. Furthermore, the modeling up-regulated the protein levels of p-Akt1, HIF-1α, and p62 and down-regulating the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). Compared with the model group, QDTS and losartan decreased UAER (P<0.05) and alleviated the pathological damage in the renal tissue. Moreover, QDTS and losartan down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). In comparison to the normal glucose group, the high glucose group displayed up-regulated protein levels of p-Akt1, HIF-1α, and p62 and down-regulated protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). Compared with the high glucose group, QDTS down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway, thereby enhancing podocyte autophagy.

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