The study is designed to observe the mechanism of Tongfu Xiefei Guanchang Solution(TFXF) in the treatment of acute lung injury(ALI) in rats by improving intestinal barrier and intestinal flora structure via p38 mitogen-activated protein kinase(p38 MAPK)/myosin light chain kinase(MLCK) signaling pathway. Sixty SPF-grade Wistar rats were randomly divided into the control(CON) group, lipopolysaccharide(LPS) group(7.5 mg·kg~(-1)), LPS + dexamethasone(DEX) group(3.5 mg·kg~(-1)), LPS + high-dose(HD)-TFXF group(14.74 g·kg~(-1)), LPS + middle-dose(MD)-TFXF group(7.37 g·kg~(-1)), and LPS + low-dose(LD)-TFXF group(3.69 g·kg~(-1)). ALI model of the rat was established by intraperitoneal injection of LPS. The lactate dehydrogenase(LDH) activity and total protein concentration in the bronchoalveolar lavage fluid(BALF) were measured; tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) levels in lung and colon tissue of rats were detected by enzyme linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the pathological expression in the lung and colon tissue of rats. The mRNA expression of p38 MAPK, TNF-α, and IL-1β in rat lung tissue was determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). Western blot was used to detect the protein expression related to the p38 MAPK/MLCK signaling pathway in the colon tissue of rats. 16S rRNA sequencing was used to detect changes in the composition and content of intestinal flora in rats, and correlation analyses were performed to explore the regulatory role of intestinal flora in improving ALI in rats. The results showed that compared with those in the LPS group, the histopathological scores of lung and colon tissue, LDH activity, and total protein concentration in BALF were significantly reduced in rats in all groups after drug administration. Except for the LPS + LD-TFXF group, the remaining groups significantly reduced the levels of TNF-α and IL-1β in the lung and colon tissue of rats. The protein expressions of phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)/p38, phosphorylated myosin light chain(p-MLC)/myosin light chain 2(MLC2), and MLCK in colon tissue of rats in each drug administration group were significantly decreased. The mRNA expression levels of p38 MAPK, TNF-α, and IL-1β were significantly reduced in the LPS + HD-TFXF group. 16S rRNA sequencing results showed that the abundance of intestinal flora was significantly higher in the LPS + HD-TFXF group, and intestinal floras including Sobs, Shannon, and Npshannon were significantly higher. The β-diversity distribution of intestinal flora tends toward the CON group, and the abundance of Firmicutes was significantly higher. The abundance of Proteobacteria was significantly reduced; the abundance of Bacteroides was significantly reduced, and the abundance of Ruminococcus was significantly higher. The main species differences were Blautia, Roseburia＿sp＿499, and Butyricicoccus. TNF-α and IL-1β of lung tissue were negatively correlated with Muribaculaceae, unclassified norank＿f＿Eubacterium＿coprostanoligenes, and Ruminococcus and positively correlated with Bacteroides. Meanwhile, TNF-α and IL-1β of colon tissue were negatively correlated with unclassified norank＿f＿Eubacterium＿coprostanoligenes and Ruminococcus and positively correlated with Bacteroides. The predicted biological function of the flora was related to the biosynthesis of secondary metabolites, amino acid biosynthesis, sugar metabolism, and oxidative phosphorylation. The above studies show that TFXF can repair lung and colon tissue structure and regulate inflammatory factor levels by modulating the abundance and diversity of intestinal flora species in ALI rats. Its mechanism of action in ameliorating ALI in rats may be related to the inhibition of inflammation, improvement of intestinal mucosal permeability, and maintenance of intestinal flora homeostasis and barrier through the p38 MAPK/MLCK signaling pathway.
Animals ; Acute Lung Injury/genetics* ; Rats ; p38 Mitogen-Activated Protein Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Myosin-Light-Chain Kinase/genetics* ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Wistar ; Signal Transduction/drug effects* ; Interleukin-1beta/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung/metabolism* ; Intestinal Mucosa/metabolism* ; Humans

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 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.

The functionalized bimetallic organic framework nanozyme (NiFe2-NMOFs) was prepared using solvothermal method for detection of sarcosine content in human urine. The experimental result showed that Fe and Ni were evenly distributed in the material,and Fe existed in the form of Fe2+/Fe3+,Ni existed in the form of Ni2+. Fe2+/Fe3+was the catalytic active center and Ni2+was the adsorption site. The matching of the two elements improved the catalytic activity of the reaction. The successful introduction of amino group induced defects in the structure,formed open accessible sites,and increased water solubility of the material. The NiFe2-NMOFs were proved to have peroxidase-like activity,and the Michaelis-Menten kinetics of NiFe2-NMOFs showd that the material had good kinetic performance and stability. Based on the fact that sarcosine could generate H2O2 under the catalysis of sarcosinase,and the sensing ability of NiFe2-NMOFs to H2O2,a cascade catalytic sensing system of NiFe2-NMOFs-sarcosine oxidase was constructed for detection of sarcosine content in human urine. This sensing system was used to detect sarcosine within the concentration range of 0.2-120μmol/L,with a good linear relationship,and a low detection limit of 0.17μmol/L. This sensing system showed high recoveries (94.1％-99.1％) and lower relative standard deviations (RSDs<5％) when used to detect actual urine samples. As a comparison to the natural peroxidase,this sensing system had better optimum temperature range and other advantages,showing good application prospects in bioanalysis.

Objective:To evaluate the bone hook pulling technique in reduction of valgus-impacted femoral neck fractures.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients who had been treated from September 2021 to September 2022 for valgus-impacted femoral neck fractures at Department of Orthopaedics and Traumatology, Honghui Hospital. There were 6 males and 6 females with an age of (43.8±10.1) years. By the Garden classification, the 12 cases were all type Ⅰ; by the Pauwels classification, 10 cases were type Ⅰ and 2 cases type Ⅱ. All patients were definitively diagnosed preoperatively by radiographs and CT images. The bone hook pulling technique was used to extend the bone hook from the lateral side to the medial side of the lesser trochanter, pull the bone hook to the lateral side, and reset the fracture with the help of pulling force and the action of the surrounding soft tissue hinge. The fractures were then fixed with the Femoral Neck System (FNS). Length of surgical incision, number of fluoroscopy for bone hook-related operations, operation time, quality of fracture reduction, fracture healing time, functional recovery of the hip and shortening of the femoral neck at the last follow-up were recorded.Results:The 12 valgus-impacted femoral neck fractures were successfully reset by the hook pulling technique. In this cohort, the length of surgical incision was (4.6±0.7) cm, the number of fluoroscopy for bone hook-related operations (4.3±0.7) times, and the operation time (54.3±4.2) min. The 12 patients were followed up for (11.5±4.2) months postoperatively and the fracture healing time (4.2±0.7) months. According to the Garden score, the quality of postoperative fracture reduction was assessed as grade Ⅰ in 10 cases and as grade Ⅱ in 2 cases. According to the Harris hip score, the hip function was assessed as excellent in 10 cases and as good in 2 cases at the last follow-up. The length of femoral neck shortening was (1.17±0.68) mm at the last follow-up in the 12 patients; no complications related to fracture reduction were observed.Conclusion:In the reduction of valgus-impacted femoral neck fractures, bone hook pulling technique shows advantages of operational simplicity, a high rate of successful reduction, and satisfactory clinical effects.

Objective:To evaluate the bone hook pulling technique in reduction of valgus-impacted femoral neck fractures.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients who had been treated from September 2021 to September 2022 for valgus-impacted femoral neck fractures at Department of Orthopaedics and Traumatology, Honghui Hospital. There were 6 males and 6 females with an age of (43.8±10.1) years. By the Garden classification, the 12 cases were all type Ⅰ; by the Pauwels classification, 10 cases were type Ⅰ and 2 cases type Ⅱ. All patients were definitively diagnosed preoperatively by radiographs and CT images. The bone hook pulling technique was used to extend the bone hook from the lateral side to the medial side of the lesser trochanter, pull the bone hook to the lateral side, and reset the fracture with the help of pulling force and the action of the surrounding soft tissue hinge. The fractures were then fixed with the Femoral Neck System (FNS). Length of surgical incision, number of fluoroscopy for bone hook-related operations, operation time, quality of fracture reduction, fracture healing time, functional recovery of the hip and shortening of the femoral neck at the last follow-up were recorded.Results:The 12 valgus-impacted femoral neck fractures were successfully reset by the hook pulling technique. In this cohort, the length of surgical incision was (4.6±0.7) cm, the number of fluoroscopy for bone hook-related operations (4.3±0.7) times, and the operation time (54.3±4.2) min. The 12 patients were followed up for (11.5±4.2) months postoperatively and the fracture healing time (4.2±0.7) months. According to the Garden score, the quality of postoperative fracture reduction was assessed as grade Ⅰ in 10 cases and as grade Ⅱ in 2 cases. According to the Harris hip score, the hip function was assessed as excellent in 10 cases and as good in 2 cases at the last follow-up. The length of femoral neck shortening was (1.17±0.68) mm at the last follow-up in the 12 patients; no complications related to fracture reduction were observed.Conclusion:In the reduction of valgus-impacted femoral neck fractures, bone hook pulling technique shows advantages of operational simplicity, a high rate of successful reduction, and satisfactory clinical effects.

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.