1.Characterization and correlation analysis of lung flora in rats with silica-induced acute lung injury
Chang LIU ; Jun LU ; Rong XIAO ; Yingqiu LI ; Jue HU ; Yue TIAN ; Jiaxiang ZHANG ; Fangguo LU
Chinese Journal of Pathophysiology 2024;40(1):81-88
AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.
2.Exploring mechanism and experimental validation of Gubiao Fanggan Modified Formula in preventing influenza virus in immunosuppressive mice based on network pharmacology
Xinyue MA ; Jiawang HUANG ; Mengchen ZHU ; Zhuolin LIU ; Ziye XU ; Fangguo LU ; Ling LI
Chinese Journal of Immunology 2024;40(7):1447-1453,中插2-中插5
Objective:To invastigate the targets and signaling pathways of Gubiao Fanggan Modified Formula in regulating the defense against influenza A virus in immunosuppressed mice by network pharmacology,and the key targets were verified by immuno-suppressive mice model.Methods:TCMSP database was used to search the active ingredients of Gubiao Fanggan Modified Formula,and GeneCard,OMIM,PharmGkb databases were used to obtain the potential targets of the active ingredients to prevent influenza,and take their intersection targets were taken;STRING11.5 database was used to make protein-protein interaction network analyzed and finded the core targets;Cytoscape3.8.1 was used to build a traditional Chinese medicine-ingredient-disease target network,and GO enrichment analysis and KEGG enrichment analysis were performed.Intraperitoneal injection of cyclophosphamide was used to construct a mouse model of immune function suppression,normal group,model control group,Gubiao Fanggan Modified Formula group and oseltamivir group were set up,followed by prophylactic administration,and influenza virus intervention was performed on the fourth day.After 7 days of intragastric administration,the key targets were verified by mouse spleen index,HE staining,RT-qPCR and immunohistochemistry.Results:There were 82 active ingredients in five traditional Chinese medicines in Gubiao Fanggan Modi-fied Formula,and 72 common targets of drugs and diseases such as IL-6,TNF-α,IL-2,etc,mainly involving IL-17,TNF and AGE-RAGE signaling pathway.Gubiao Fanggan Modified Formula could increase spleen index and significantly reduce mRNA and protein expressions of IL-6 and TNF-α in spleen tissue of mice(P<0.05 or P<0.01).Conclusion:Gubiao Fanggan Modified Formula may regulate body's immune function through targets such as IL-6 and TNF-α,thereby preventing influenza virus infection.
3.Network pharmacology and experimental validation of Maxing Shigan decoction in the treatment of influenza virus-induced ferroptosis.
Jiawang HUANG ; Xinyue MA ; Zexuan LIAO ; Zhuolin LIU ; Kangyu WANG ; Zhiying FENG ; Yi NING ; Fangguo LU ; Ling LI
Chinese Journal of Natural Medicines (English Ed.) 2023;21(10):775-788
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals
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Mice
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Ferroptosis
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Network Pharmacology
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Reactive Oxygen Species
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Vascular Endothelial Growth Factor A
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Influenza A virus
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Iron
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Hypoxia
4.Correlation analysis for the lateral condylar tibial plateau fracture and complete medial collateral ligament rupture
Xuelei WEI ; Jie SUN ; Hui ZHAO ; Jie LU ; Yandong LU ; Sipin LUO ; Meng CUI ; Yunjiao LIU ; Xi ZHANG ; Fangguo LI
Chinese Journal of Orthopaedics 2023;43(3):179-184
Objective:To investigate the relationship between the CT images of a lateral condylar tibial plateau fractures and complete medial collateral ligament (MCL) injury.Methods:Data of 59 patients with lateral condylar fracture of tibial plateau complicated with MCL injury admitted to Tianjin Hospital from January 2020 to November 2021 were collected, including 32 males and 27 females, aged 42.4±12.3 years (range, 19-65 years), there were 26 cases of extension injury and 33 cases of flexion injury. The patients were separated into two groups: those with partial MCL injury and those with total rupture based on preoperative MR examination and intraoperative valgus stress test following fracture fixation. According to the ABC fracture classification of lateral condyle tibial plateau proposed by Sun et al., the fracture locations were determined on CT images, and the lateral plateau collapse depth (LPD) was measured. The relationship between LPD and MCL complete rupture was analyzed by receiver operating characteristic (ROC) curve.Results:Among 59 patients with lateral condylar tibial plateau fracture and MCL injury, 42 had partial injuries and 17 had complete ruptures. According to the ABC fracture classification, there were 26 cases of extension injury (involving area A), 21 cases of AB type, and 5 cases of ABC type; and 33 cases of flexion type injury, 19 cases of B type, 12 cases of BC type, and 2 cases of C type. All the 17 cases of MCL complete fracture occurred in extension injury, including type AB (14 cases) and type ABC (3 cases). The difference between the mean LPDs of the MCL full rupture group and the partial injury group was not statistically significant ( t=0.11, P=0.567), and the mean LPDs of both groups were 11.7±5.3 mm (range, 4.3-28.1 mm) and 11.5±4.8 mm (range, 3.8-23.6 mm), respectively. The area under the curve (AUC) of the ROC curve analysis was 0.504, and there was no statistical correlation between lateral platform collapse depth and MCL injury. Among the 26 patients with extensional injury area, MCL was completely ruptures in 17 cases and partially injury in 9 cases, LPD was 11.7±5.3 mm (range, 4.3-28.1 mm) and 6.6±1.8 mm (range, 3.8-9.4 mm), respectively, and the difference was statistically significant ( t=3.57, P=0.009). The best predictive cut-off value of LPD was 7.25 mm, the sensitivity was 88.2%, the specificity was 77.8%, and the AUC was 0.868. Conclusion:When the lateral condyle fracture of the tibial plateau is located in the extensional injury area (involving the A area in the ABC fracture classification) and the LPD measured on the CT image is greater than 7.25 mm, the complete rupture of the MCL should be considered. Clinical MCL repair is required after the fracture fixation surgery for improved surgical outcomes.
5.Tendency analysis of incidence and mortality of mechanical injuries among Chinese residents from 1990 to 2019
Tao LIU ; Zhao YANG ; Fangguo LI ; Yue LI ; Xin LIU ; Zhenlong WU ; Chunxia CAO
Chinese Critical Care Medicine 2022;34(10):1082-1087
Objective:To analyze the tendency of incidence and mortality of mechanical injuries among Chinese residents from 1990 through 2019 and to estimate the age-period-cohort effect.Methods:Based on the Global Burden of Disease (GBD) 2019 database, the incidence and mortality data of mechanical injuries among Chinese residents from 1990 to 2019 were extracted. The trends of age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of mechanical injuries among Chinese residents by gender was analyzed using the joinpoint regression model, and the annual percent change (APC) and average annual percent change (AAPC) were calculated. The age-period-cohort model was used to quantitatively assess the effects of age, period, and cohort on ASIR and ASDR for mechanical injuries.Results:① Overall tendency: from 1990 to 2019, the ASIR of mechanical injuries showed an increasing trend (540.95/100 000 in 1990 vs. 815.34/100 000 in 2019), and the ASDR first increased slightly and then decreased (2.62/100 000 in 1990 vs. 2.87/100 000 in 2005 vs. 1.77/100 000 in 2019) among Chinese residents. During the observation period, ASIR and ASDR for mechanical injuries of male were higher than female. ② Joinpoint regression model analysis showed that the ASIR of mechanical injuries had a fluctuating trend of increasing first and then decreasing and then rising rapidly among Chinese residents from 1990 to 2019 (AAPC = 1.42%, t = 9.59, P < 0.001). The ASIR of the Chinese male showed a slight decrease and then continued to increase (AAPC = 1.47%, t = 8.72, P < 0.001), while the ASIR of the Chinese female showed a rapid rising at first, then rapidly declining and then rising again (AAPC = 1.31%, t = 12.11, P < 0.001). From 1990 to 2019, the ASDR of mechanical injuries showed a fluctuating downward trend of first decreasing, then increasing, and then rapidly decreasing among Chinese residents (AAPC = -1.39%, t = -6.72, P < 0.001). The decrease rate of ASDR among male was as same as that among all population (AAPC = -1.44%, t = -7.29, P < 0.001), but the decrease rate of ASDR in female was relatively slow (AAPC = -1.08%, t = -4.54, P < 0.001). ③ Age-period-cohort model analysis showed that, with the increase of age, the risk of mechanical injuries among the overall population, male and female in China increased, then decreased, and then increased rapidly. The first small peak was at the age of 45-49 years old in male and 65-69 years old in female. The overall death risk showed an increasing trend with age, with a slowly increasing trend before 75 years old, and a sudden increase after 75 years old. The peak age of death risk was between 90 and 94 years. In terms of period effect, the risk of mechanical injuries showed a gradually increasing trend with time among the overall population, male, and female in China, and the risk of death showed a trend of decreasing first and then rapidly increasing and then decreasing. In terms of cohort effect, the risk of mechanical injuries among the overall population, male, and female in China showed a gradual upward trend with the increase in the birth year, and the risk of death showed an M-shaped trend. Conclusions:From 1990 to 2019, the incidence of mechanical injuries showed an increasing trend, and the mortality increased first and then decreased. Although the disease burden has improved, it is still high. More attention needs to be paid to the prevention and control of mechanical injuries, especially in the young population.
6.Risk factors for preoperative venous thromboembolism in lower extremity in patients with tibial plateau fracture
Shucai BAI ; Xiaoying CHEN ; Chunxia ZHU ; Xi ZHANG ; Yandong LU ; Jie LU ; Xuelei WEI ; Meng CUI ; Yunjiao LIU ; Fangguo LI ; Jie SUN
Chinese Journal of Orthopaedics 2021;41(15):1052-1058
Objective:To analyze the risk factors of deep venous thrombosis (DVT) in patients with tibial plateau fracture during preoperative period.Methods:From July 2017 to October 2019, a total of 264 patients undergoing surgeries of tibial plateau fractures were enrolled. Duplex ultrasonography (DUS) during hospitalization was used to screen for DVT of the bilateral lower extremities. Patients were divided into DVT group and non-DVT group according to results of DUS. Data on demographics, comorbidities, injury-related data, fracture type, laboratory biomarkers were collected and compared between groups with and without DVT.Results:The incidence of preoperative DVT was 39.0% (103/264) among 264 patients with traumatic tibial plateau fractures, and distal thrombosis predominated in DVT group. There were 103 cases in DVT group. 55 were males and 48 were females. The average age was 54.00±11.12. According to the Schatzker classification of tibial plateau fractures, 7 cases belonged to type I, 37 to type II, 2 to type III, 11 to type IV, 29 to type V, and 17 to type VI. There were 161 cases in non-DVT group. 89 were males and 72 were females. The average age was 48.57±13.25. According to the Schatzker classification of tibial plateau fractures, 23 cases belonged to type I, 76 to type II, 2 to type III, 10 to type IV, 33 to type V, and 17 to type VI. Univariate analysis showed that age ( t=3.451, P=0.001), the type of tibial plateau fracture ( χ2=8.314, P=0.004), D-dimer ( χ2=18.552, P<0.001), APTT ( t=2.869, P=0.004), ALB ( t=2.292, P=0.023) and Hb ( t=1.983, P=0.048) were statistically different than those in non-DVT group. Multivariate analysis showed age ( OR=1.033, 95% CI: 1.009, 1.058; P=0.007), the type of tibial plateau fracture ( OR=1.829, 95% CI: 1.014, 3.299; P=0.045) and D-dimer ( OR=1.914, 95% CI: 1.057, 3.464; P=0.032) were independent risk factors. Conclusion:The incidence of DVT in patients with tibial plateau fractures during preoperative period is high, and distal thrombosis is the main part of venous thrombosis of lower extremity. The type of tibial plateau fracture, age and the level of D-dimer are independent risk factors of preoperative DVT in patients with tibial plateau fractures.
7.The value of cross raft screws technique to prevent postoperative collapse of tibial plateau fracture
Xi ZHANG ; Jie SUN ; Fangguo LI ; Yongcheng HU ; Baotong MA ; Yandong LU ; Jie LU ; Lin GUO ; Meng CUI ; Xuelei WEI ; Yunjiao LIU
Chinese Journal of Orthopaedics 2018;38(15):897-904
Objective To assess the clinical value of cross raft screws technique in preventing postoperative collapse of tibial plateau fracture.Methods From September 2014 to November 2017,data of 14 patients with tibial plateau fracture who were treated by cross raft screws technique were retrospectively analyzed.There were 9 males and 5 females aged from 30-65 years old (average,44.4± 1.7 years).There were 8 patients that the thickness of subchondral cancellous bone measured preoperatively by CT data was less than 4 mm,and 6 patients that the thickness of subchondral cancellous bone measured intraoperatively was less than 4 mm.1/4 tubular plate was placed along the anterior rim of lateral tibial plateau,and the 3.5 mm cortical bone screws were fixed as bamboo raft from anterior to posterior through the plate.The collapse of tibial plateau after surgery were measured by CT scan after union of the fracture.The function of knee was evaluated by Rasmussen Anatomical and Functional Grading.Results The time of tubular plate procedure was 18 to 35 min (average,24.1±5.4 min).All 14 patients were successfully followed-up for 13.8±5.1 months.The height of collapse preoperatively by CT scan was 5-21 mm (average,8.00± 1.40 mm).3 days after the operation,the height between articular line and lateral articular surface was 0-2 mm (average,0.80±0.06 mm).Compared with CT data preoperatively,the collapse was corrected postoperatively that was proved by CT scan (P< 0.05).After the fracture was healed,according to CT data,the height between articular line and lateral articular surface was 0-2 mm (average,0.70±0.08 mm).Compared with CT data postoperatively,there was no postoperative collapse happened (P=0.466).The position and length of nails were placed appropriately.The average healing time of fracture was 3.6 months.There were no infection,nonunion and pain of tendon happened.The plate could be touched subcutaneously in 2 patients,who had no discomfort feelings.The patient's postoperative Rasmussen Anatomical Grading were 13-18 (average,16.7),including 8 cases excellent and 6 cases good.The postoperative Rasmussen Functional Grading was 18-28 (average,25.7),including 11 cases excellent and 3 cases good.Conclusion The cross raft screws technique is a good way to prevent the postoperative collapse of the lateral articular surface of tibial plateau.
8.Observation of curative effect of avulsion fracture of anterolateral ligament of knee joint
Xuelei WEI ; Jie SUN ; Zengliang WANG ; Jie LU ; Yandong LU ; Meng CUI ; Fangguo LI ; Xi ZHANG
Chinese Journal of Orthopaedics 2017;37(14):841-847
Objective To explore the clinical effect of periarticular knee fractures combined with anterolateral ligament (ALL) avulsion fracture.Methods From June 2014 to November 2015,13 patients with ALL avulsion fracture in periarticular knee fractures were fixed by the star plate,cannulated or screws suture anchor,including 9 male and 3 female with the mean age of 39.5 years (range from 28 to 51 years).6 patients were diagnosed distal femoral fracture,4 tibial plateau fracture,and 3 tibial intercondylar eminence avulsion fracture which all combined with ALL avulsion fracture.Postoperatively,all patients were treated with the adjustable knee brace for 3 months.Results All patients were followed up for 4-20 months,the mean follow-up time was 13.5 months.The average surgical time was 130 min (range from 90 to 210 min).In all 13 patients,ALL was found and identified.Bone union was obtained in all patients,and the bone union time was 11.4 weeks (10-12 weeks).7 cases were fixed with star plate,5 cases were fixed with hollow screw,and 1 case was fixed with anchor.All follow-up patients underwent anteroposterior and lateral X-rays.Pain,swelling and functional recovery of the knee joint were observed.Patients were assessed postoperatively with International Knee Documentation Committee (IKDC) score,Lysholm score,and Tegner activity scale to evaluate the clinical effect.At the last follow-up,all patients had full range of motion of the knee joint which from 0° to approximate 120°.The Lysholm,objective IKDC were 86.5 and 84.6 respectively.Among the 13 patients evaluated,9 patients were graded A,and 4 patients were graded B by subjective IKDC.The Tegner activity scale at the last follow-up was 6.7.Incision of poor healing in 1 case,and got healed after 32 d cleaning dressing.Conclusion This study confirmed the presence of the ALL.The fixation of ALL avulsion fracture in periarticular knee fractures can be an effective procedure at a minimum follow-up of 13.5 months.
9.Selection of implants and repair in posterolateral fractures of the tibial plateau
Yandong LU ; Fangguo LI ; Jun MIAO ; Jie SUN
Chinese Journal of Tissue Engineering Research 2017;21(23):3741-3746
BACKGROUND:Tibial plateau fractures involving the posterolateral articular surface present a great challenge due to its complex anatomy.The posterolateral corner complex and the proximity of the common peroneal nerve restrict both the exposure of the joint surface and the ability to distract across the joint using a varus force.OBJECTIVE:To analyze the anatomy,morphology and classifications of the posterolateral fractures of the tibial plateau,and compare different surgical approaches and fixation materials.METHODS:A computer-based research of PubMed and CNKI databases was performed for the relative literatures published from 1990 to 2016 using the keywords of tibial plateau,posterolateral fragment,fixation in English and Chinese,respectively.The anatomy,morphology and typing of posterolateral fractures of the tibial plateau were analyzed and different surgical approaches and fixation materials were compared.RESULTS AND CONCLUSION:Posterolateral fractures of the tibial plateau should be treated in accordance with the intra-articular fracture principle,such as repairing joint surface to normal morphology,restoring the lower limb alignment,and maintaining joint mobility painlessly.Fractures are clarified according to Schatzker,AO,and three-column classification systems,but still need to be improved.To choose a proper surgical approach mainly depends on the fracture pattern.Biomechanics tests suggest that posterolateral locked plate exhibits excellent biomechanics characters,and can avoid the reduction loss caused by the shear force of fracture fragments.
10.Acupoints heat-sensitive moxibustion in the application of traditional Chinese surgery.
Shiying ZHANG ; Wanchun WANG ; Li ZOU ; Zhangren YAN ; Yanrong CAI ; Fangguo LU
Chinese Acupuncture & Moxibustion 2016;36(1):109-112
Under the guidance of meridian theory, the acupoints heat-sensitive moxibustion is a treatment method which applies moxa stick to perform mild moxibustion at heat-sensitive acupoints, which can arouse the meridian sensation transmission and promote the movement of meridian qi; consequently, the qi can be extended to the diseases. For its many advantages, such as no direct contact on skin, no injuries, no pains, fewer side effects, easy operating and moderate cost, the acupoints heat-sensitive moxibustion is widely accepted in dermatology, male urology disease, rectum and anus diseases and breast diseases. The application and research status of the acupoints heat-sensitive moxibustion in traditional Chinese surgery in recent years is reviewed, and several problems and suggestions in its clinical application and research are proposed, aiming to provide clinical basis for its further development and clinical application in traditional Chinese surgery.
Acupuncture Points
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Clinical Trials as Topic
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General Surgery
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Humans
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Moxibustion
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Sensation

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