ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E^-∕- （ApoE^-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE^-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg^-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE^-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

OBJECTIVE To investigate the effects of Yiqi tongmai formula on atherosclerosis （AS） in ApoE－/－ mice and its mechanism. METHODS Forty ApoE－/－ mice were randomly divided into model group， positive control group [atorvastatin calcium， 2.6 mg/（kg·d）]， and low-dose， medium-dose and high-dose groups of Yiqi tongmai formula [0.46， 0.91， 1.82 g/（kg·d）， by raw material]， with 8 mice in each group. Eight C57BL/6J mice were selected as the normal group. Except for the normal group， the other groups were given a high-lipid diet and relevant drug or normal saline intragastrically， once a day， for 12 consecutive weeks. After the last medication， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） as well as the contents of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and monocyte chemoattractant protein-1 （MCP-1） were measured in mice. The proportion of aortic plaque area in each group of mice was detected and calculated， and the pathological morphological changes of the aortic sinus were observed； the protein phosphorylation levels of aortic phosphoinositide 3-kinase （PI3K）， protein kinase B （aka Akt） and mammalian target of rapamycin （mTOR） were examined. RESULTS Compared with the model group， the serum levels of TC， TG and LDL-C and the contents of TNF-α， IL-1β and MCP-1 （including low-dose group） were decreased significantly in medium-dose and high-dose groups of Yiqi tongmai formula， while the content of HDL-C in high-dose group was increased significantly （P＜0.05 or P＜0.01）； aortic plaques of the mice were reduced in Yiqi tongmai formula groups to different extents， and pathological changes such as lipid deposition and inflammatory cell infiltration were relieved to different extents； the proportion of aortic plaque area， the protein phosphorylation levels of PI3K， Akt and mTOR in aortic tissue were significantly reduced in medium-dose and high-dose groups of Yiqi tongmai formula （P＜0.05 or P＜0.01）. CONCLUSIONS Yiqi tongmai formula can improve lipid metabolism， reduce inflammatory response， and delay plaque development in AS mice. Its effect may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.

ObjectiveTo decipher the mechanism of modified Sanpiantang in the treatment of nitroglycerin-induced migraine in rats. MethodSeventy-two Wistar rats were randomized into the control， model （nitroglycerin， 10 mg·kg^-1）， positive control （rizatriptan， 0.89 mg·kg^-1）， and high- （12.96 g·kg^-1）， medium- （6.48 g·kg^-1）， and low-dose （3.24 g·kg^-1） modified Sanpiantang groups. The rat model of migraine was established by intraperitoneal injection of 10 mg·kg^-1 nitroglycerin. The behavioral test was carried out to measure the mechanical pain thresholds （MPT） of the periorbital region and hindpaw after successful modeling. The serum levels of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， and interleukin-1β （IL-1β） in rats were determined by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was employed to determine the expression of inducible nitric oxide synthase （iNOS） in the trigeminal nucleus caudalis （TNC）. Western blot was employed to determine the protein levels of iNOS and phospho-p38 mitogen-activated protein kinase （p-p38 MAPK） in the TNC. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of iNOS， p38 MAPK， and IL-1β in the TNC. ResultCompared with the control group， the model group showed decreased MPT （P<0.01）， elevated serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.01）， and up-regulated expression levels of p38 MAPK， iNOS， and IL-1β in the TNC （P<0.05， P<0.01）. Compared with the model group， modified Sanpiantang increased the MPT （P<0.05）， and the medium-dose group showed the most significant effect （P<0.01）. In addition， modified Sanpiantang down-regulated the mRNA levels of iNOS， p38 MAPK， and IL-1β and the protein levels of p-p38 MAPK and iNOS in the TNC of migraine rats （P<0.05， P<0.01） and lowered the serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.05， P<0.01）. ConclusionModified Sanpiantang may treat migraine by down-regulating the expression of pro-inflammatory factors such as NO， TNF-α， IFN-γ， and IL-1β in the p38 MAPK/iNOS signaling pathway to reduce the neurogenic inflammation.

Objective To study the stability of plate-assisted intramedullary nailing for fixing proximal third tibiafractures, compare and observe biomechanical characteristics of anterolateral or posteromedial plate-assisted intramedullary nailing after fixation of proximal third tibia fractures. Methods Eight artificial tibia of 4th-generation sawbones were divided into two groups based on location of the assisted plate, namely, anterolateral plate group and posteromedial plate group, with 4 specimens in each group. Each two locking bolts were fixed to theintramedullary nail proximally and distally, and each three bicortical screws were fixed to the plate proximally and distally. The specimens were osteotomized with a 10-mm defect which located 0. 5 cm to the proximal locking bolt of intramedullary nail or 5-6 cm distally to the knee joint line, in order to simulate an AO/ OTA 41-A2 type proximal third tibia fracture after fixation of intramedullary nail. After osteotomy was finished, axial compression test, three point bending test, cyclic loading and overstress test were conducted by mechanical testing machine. The results of axial stiffness and three-point stiffness between two groups were compared and analyzed. Results Axial compression test showed that the average axial stiffness in posteromedial plate group was lower than that in anterolateral plate group, but no significantly statistical differences were found between the two groups. Three point bending test showed that the average bending stiffness in posteromedial plate group was significantly higher than that in anterolateral plate group when stimulating either varus stress (plate located at pressure side of the fracture, t = 3. 679, P<0. 05) or valgus stress (plate located at tension side of the fracture, t = 8. 975, P<0. 05). Conclusions Plate-assisted intramedullary nailing for fixation of proximal third tibia fractures can minimize the angulation malalignment, improve the stability of nailed proximal tibial fragment and allow the early weight bearing. Both anterolateral and posteromedial plate-assisted intramedullary nail can provide satisfactory axial stability for proximal third tibia fractures, while posteromedial plate-assisted intramedullary nail shows better bending stability than anterolateral plate in countering varus or valgus stress deformity. This study provides an essential basis for clinical decision making about plate-assisted intramedullary nailing for fixing proximal third tibia fractures.

Objective:To compare the clinical effects of acute shortening-lengthening technique with antibiotic calcium sulfate-loaded bone transport technique for the treatment of segmental tibial defects after trauma.Methods:The clinical data of 58 patients with large tibial defects treated by Ilizarov technique in Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from May 2014 to December 2019 were retrospectively analyzed. Thirty patients were treated by acute shortening-lengthening (group A), and they were divided into those who were successful in one-time shortening during operation (group A1) and those who needed gradual shortening after operation (group A2) according to different shortening conditions. And 28 patients by antibiotic calcium sulfate-loaded bone transport (group B). The external fixation time (EFT) and external fixation index (EFI) of the two groups were compared. Bone defect healing and limb functions were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Complications were compared by Paley classification. The measurement data of normal distribution were expressed as ± s, and t-test was used for comparison between groups; the count data were expressed as n(%), and the chi-square test, Fisher exact probability method or Mann-Whitney U test were used for comparison between groups. Results:Patients were followed for(27.5±5.1)months. There was no significant difference in EFT, EFI, bone defect healing and limb functions between the two groups( P>0.05). The incidence of Grade-Ⅱ[41.2% (7/17)], Grade-Ⅲ [47.1% (8/17)] pin-tract infection in group A1 and Grade-Ⅱ[46.2% (6/13)], Grade-Ⅲ pin-tract [53.8% (7/13)] in group A2 was significantly higher than those in group B[14.3% (4/28)], [17.9% (5/28)] ( P<0.05). The number of complications per capita in group A1 [(1.4±0.3) times/case] and in group A2 [(1.5±0.3) times/case]was significantly higher than that in group B [(1.1±0.5) times/case]. Conclusions:Patients can be cured successfully by both acute shortening-lengthening and bone transport techniques. Compared with acute shortening-lengthening group, the complication incidence in antibiotic calcium sulfate-loaded bone transport group was lower, especially, the infection-related complications. Therefore, antibiotic calcium sulfate-loaded bone transport technique has a greater application prospect in patients with large segmental bone defects caused by infection or osteomyelitis.

Objective:To analyze the therapeutic effect of sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft of chronic calcaneal osteomyelitis.Methods:A retrospective analysis was peformed in 29 patients with chronic calcaneal osteomyelitis treated with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from April 2013 to January 2020. There were 19 males and 10 females, with the age of (45.38±12.85) years, ranged from 22 to 67 years. The course of disease was (16.00±6.96) months, ranged from 6 to 36 months. The skin defect area was (41.9±15.9) cm 2, ranged from 11.8 to 86.8 cm 2. The causes of injury: 18 cases of high fall, 6 cases of traffic accidents, 3 cases of heavy rolling, the remaining 2 cases were machine strangulation and sharp stab wounds. The inflammatory markers [white blood cell (WBC), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C reactive protein (CRP)] and bone healing time were recorded before operation, 2, 4, 8 weeks and 6 months after operation. During the follow-up period, the flap texture, survival were observed, and the ankle-posterior foot function recovery was evaluated by the American Association of Foot and Ankle Surgery (AOFAS) score were observed before and after the operation, and the incidence of complications were recorded. The measurement data were expressed as mean±standard deviation ( ± s), and the t-test was used for inter-group comparison; the levels of WBC, ESR, PCT and CRP at different time points before and after operation were compared by repeated measurement ANOVA, and the LSD t-test was used for pairwise comparison. Results:All the 29 patients were followed up for (14.51±6.10) months, ranged from 6 to 30 months. All the flaps survived without abrasion, ulceration, or skin protrusion, and all patients could walk normally with shoes. There were 28 cases of stage I bone healing, with an average of (5.87±2.07) months, ranged from 3 to 12 months. The inflammatory indexes was significantly decreased at different time points after operation ( P<0.05). There was no significant difference between 6 months and 8 weeks after operation ( P>0.05), while there was significant difference at other time points ( P<0.05). The ankle-posterior foot score of AOFAS at 6 months after treatment was significantly higher than that before treatment (83.44±7.93 vs 55.37±8.07), the differences was statistically significant ( P<0.05). The clinical efficacy of foot function recovery was excellent in 12 cases, good in 15 cases and fair in 2 cases among 29 patients .The excellent and good rate was 93.1% (27/29). One patient recurred 1 month after operation and was re-implanted with antibiotic-loaded calcium sulfate mixed autogenous iliac bone after debridement, no recurrence was found. The total complication rate was 31.0%, but there was no significant impact on the patient's life in the later period. All patients returned to daily life and work. Conclusion:The treatment of chronic calcaneal osteomyelitis with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft can effectively control infection, reconstruct calcaneal and soft tissue structure, promote functional recovery of affected limb, and ultimately improve the patient′s quality of life.

Objective:To investigate the clinical effects of antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap in the one-stage treatment of chronic calcaneus osteomyelitis plus skin and soft tissue defects.Methods:From January 2013 to September 2019, 48 patients were admitted to Department of Orthopedic Trauma, Xi'an Honghui Hospital Affiliated to Xi'an Jiaotong University for chronic calcaneal osteomyelitis complicated with skin and soft tissue defects. They were divided into 2 groups according to different bone grafts. In group A of 26 patients treated at one stage by antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap, there were 16 males and 10 females with an age of (45.0±11.7) years and an area of skin defect of (56.0±16.7) cm 2. In group B of 22 patients treated at one stage by simple autologous iliac bone combined with sural neurocutaneous flap, there were 13 males and 9 females with an age of (43.6±9.6) years and an area of skin defect of (53.8±16.2) cm 2. The volume of the ilium harvested, fracture healing time, infection control, donor site complications, pain score of visual analogue scale (VAS) and function recovery of the ankle were compared between the 2 groups. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for (15.3±6.0) months. Group A had a significantly smaller volume of the ilium harvested [(67.3±14.1) cm 3] than group B [(90.7±23.5) cm 3], a significantly lower rate of donor site complications [3.8% (1/26)] than group B [31.8% (7/22)], significantly lower VAS pain scores at 6, 12, 24, 48 and 72 hours than group B, and significantly lower WBC count, erythrocyte sedimentation rate and C-reactive protein at 2, 4, 8 weeks after operation than group B (all P<0.05). There was no statistically significant difference between the 2 groups in the infection control rate [96.2% (25/26) versus 77.3% (17/22)], the fracture healing time [(6.2±1.9) months versus (6.4±2.1) months], or the ankle-hindfoot score of AOFAS (The American Orthopaedic Foot and Ankle Society) (83.9±7.2 versus 82.5±8.7) at 6 months after operation (all P>0.05). Conclusion:In one-stage treatment of chronic calcaneal osteomyelitis complicated with skin and soft tissue defects, compared with simple autologous iliac bone combined with sural neurocutaneous flap, antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap can reduce the volume of the ilium harvested, pain score of VAS, and incidence of donor site complications, and improve the recovery of inflammatory indicators, leading to fine clinical effects.

Objective:To compare the clinical efficacy between bone transport technique combined with bone grafting plus internal fixation and simple bone transport technique in the treatment of large segmental bone defects at lower limbs after trauma.Methods:A retrospective study was conducted to analyze the clinical data of 42 patients with large segmental bone defects at lower limbs after trauma who had been treated at Department of Trauma Orthopaedics, Honghui Hospital Affiliated to Medicine College, Xi'an Jiaotong University from September 2015 to September 2019. The patients were divided into 2 groups according to the different methods of repairing bone defects. In group A of 18 patients subjected to bone transport combined with bone grafting plus internal fixation, there were 11 males and 7 females with an age of (35.2±10.3) years, and 12 tibial defects and 6 femoral defects; in group B of 24 patients subjected to simple bone transport, there were 15 males and 9 females with an age of (37.3±9.4) years, and 17 tibial defects and 7 femoral defects. The external fixation time (EFT), external fixation index (EFI), total cure time and complications were recorded and compared between the 2 groups. At the last follow-up, the Ennecking score for limb functional recovery (score/total score 30) and Self-rating Anxiety Scale (SAS) were used to evaluate respectively the functional recovery of the limbs and postoperative anxiety.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). There was no statistically significant difference in the number of surgeries between the 2 groups ( P>0.05). The EFT [(5.9±1.5) months], EFI [(0.45±0.09) months/cm], total treatment time [(16.2±2.4) months], Ennecking score for limb functional recovery (87.0%±8.6%), SAS score [(43.2±9.0) points], and complications per capita [(0.4±0.2) times/case] in group A were significantly better than those in group B [(15.3±4.2) months, (1.19±0.28) months/cm, (19.7±3.5) months, (77.3%±9.2%), (58.2±9.3) points, and (1.2±0.5) times/case] (all P<0.05). Conclusion:In the treatment of large segmental bone defects at lower limbs, compared with simple bone transport technique, bone transport technique combined with bone grafting plus internal fixation has advantages of shorter external fixation time and overall cure time, a lower rate of complications, and better functional recovery of the limbs.

Objective:To analyze the therapeutic effect of 3D printing technology combined with locking plate fixation on femoral shaft fracture in patients with femoral deformity.Methods:The clinical data of 33 patients with femoral shaft fracture with femoral deformity who met the inclusion criteria and underwent locking plate fixation in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to December 2020 were retrospectively analyzed. The patients were divided into 3D printing group ( n=18) and control group ( n=15) according to whether 3D printing was performed before operation. The 3D printing group including 11 males and 7 females with an age of (46.78±13.76) years.The control group including 9 males and 6 females with an age of (48.20±14.27) years.The operation time, intraoperative blood loss, fracture healing time and complications of the two groups were recorded. Visual analogue scale (VAS) scores of pain were evaluated before and 6, 12, 24, 48 and 72 h after operation. According to the Harris hip score, the Hospital for Special Surgery (HSS) knee score and The MOS 36-item short-from Health Survey (SF-36), the hip and knee function and quality of life of the patients before and 12 months after injury were evaluated. The measurement data were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data between groups was conducted by Chi-square test or Fisher exact probability. Results:The operation time, intraoperative blood loss, and incidence of complications in the 3D printing group were (91.50±9.07) min, (191.11±16.01) mL, and 0(0/18), respectively, and those in the control group were (118.07±14.19) min, (270.27±17.59) mL, and 26.7% (4/15), the differences between the two groups were statistically significant ( P <0.05). The pain VAS scores of the 3D printing group were significantly better than those of the control group at 6, 12, 24, 48, and 72 h after operation ( P<0.05). There were no differences in fracture healing time and preoperative pain VAS between the two groups( P>0.05). There were no significant differences in hip function, knee function and quality of life scores between the two groups before injury and 12 months after injury( P>0.05). Conclusion:In the treatment of femoral shaft fractures in patients with femoral deformity with locking plate fixation, the application of 3D printing technology can be used for preoperative design and plate preshaping, which can shorten the operation time, reduce the amount of intraoperative blood loss, reduce the VAS of pain and the incidence of complications, improve the satisfaction of surgery, and provide a new option for the treatment of femoral shaft fractures in patients with femoral deformity.

Objective To investigate the neuroprotective effect and mechanism of cerebrotein hydrolysate- (CH-) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson's disease (PD) mice. Methods Totally 36 healthy male C57BL/6 mice were randomly divided into control group(Ctrl), model group(MPTP) and CH- group. MPTP was used to induce PD model in mice, and CH- was injected intraperitoneally for intervention. The behavioral function of mice was detected by pole test, the expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry, and the composition and diversity of intestinal microflora were detected by gene sequencing and bioinformatics analysis. Results Compared with the control group, MPTP induced behavioral deficits in PD mice after modeling (P<0.05), after CH- treatment, the behavioral defects of PD mice were improved compared with MPTP group (P<0.05). Immunohistochemical result showed that MPTP decreased the expression of the rate-limiting enzyme TH in dopamine synthesis, and increased the expression of TH after CH- treatment. The result of microbial diversity showed that the intestinal microflora diversity of mice decreased after MPTP treatment (P<0.05). At the “phylum” level, the number of Epsilonbacteraeota and Deferribacteres decreased sharply, while the number of Verrucomicrobia increased significantly. At the level of “family”, the number of Desulfovibrionaceae, Lachnospiraceae, Helicobacteraceae and Rikenellaceae decreased, while the number of Akkermansiaceae and Erysipelotrichaceae increased, suggesting that the original homeostasis of intestinal microflora was destroyed. After CH- treatment, the number of intestinal microflora tended to be normal, which reduced the abundance of pathogenic microbiota and increased the relative abundance of beneficial bacteria. Conclusion CH- can improve the composition of intestinal microflora and the behavioral function of PD mice by decreasing the abundance of pathogenic microbiota and increasing the relative abundance of beneficial bacteria.