Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

ObjectiveTo evaluate the intervention effect of dihydroartemisinin （DHA） on hippocampal nerve injury in L5 spinal nerve ligation （SNL） model and tumor necrosis factor-α （TNF-α） hippocampal continuous injection model. In primary cultured microglia-hippocampal neurons， the regulatory pattern of DHA on microglia-hippocampal neuronal interactions was confirmed. MethodThe experimental animals were divided into Sham group， SNL group， and DHA group （16 mg·kg^-1）， with 3 mice in each group. The hippocampal CA3 glutamatergic neurons were labeled with adeno-associated virus ［Calmodulin-dependent protein kinase Ⅱ（CaMKⅡ） dTomato AAV］， and their contributions to the hippocampal CA1， prefrontal cortex （Frc）， anterior cortex （ACC）， projections of nucleus accumbens （Nac）， and Basolateral Amygdala （BLA） were traced by immunofluorescence staining. The experimental animals were divided into a Sham group， a TNF-α hippocampus continuous injection model group， DHA-L， DHA-M， and DHA-H groups （4， 8， 16 mg·kg^-1）， and pregabalin group （25 mg·kg^-1）， with 4 mice in each group. The morphology of pyramidal neurons in the hippocampal CA1 and CA3 regions was counted by Golgi staining. The continuous activation of hippocampal primary neurons and microglia was induced， DHA intervention was given by co-culture， and the cell soma area and the expression of postsynaptic density protein 95 （PSD95） inside and outside the primary and secondary dendritic spines of neurons were counted by immunofluorescence. ResultCompared with the Sham group， the projection of CA3 glutamatergic neurons to CA1 region， Frc， and ACC in the SNL group was significantly reduced （P<0.01）， while the projection to Nac and BLA was significantly increased （P<0.01）. As compared with the SNL group， the projection of hippocampal CA3 glutamatergic neurons to CA1 region， Frc， and ACC was significantly increased in the DHA group （P<0.01）， while the projection to Nac and BLA was significantly reduced （P<0.01）. Golgi staining results showed that as compared with the Sham group， the density of dendritic spines and the number of dendritic branches in the CA1 and CA3 pyramidal neurons in the TNF-α hippocampal continuous injection model group were significantly reduced （P<0.01）. As compared with the TNF-α hippocampal continuous injection model， the density of dendritic spines and the number of dendritic branches in hippocampal CA1 and CA3 pyramidal neurons in the DHA-M and DHA-H groups were significantly increased （P<0.05， P<0.01）. Compared with DHA-M group， the total dendrite length of CA1 pyramidal neurons in hippocampus in DHA-H group was significantly increased （P<0.01）， while the total dendrite length of CA1 neurons and the total dendrite base length of CA3 neurons in DHA-L group was significantly decreased （P<0.01）. Compared with the blank control group， the cell soma area of the glycine group and glutamate group increased significantly （P<0.01）. As compared with the glycine group and glutamate group， the cell area of the glycine + glutamate group was significantly increased （P<0.01）， and as compared with the glutamate group， the cell soma area of the glutamate + DHA group was significantly reduced （P<0.01）. As compared with the glycine acid + glutamate group， the cell soma area of the glycine + glutamate + DHA group was significantly reduced （P<0.01）， and as compared with the glutamate + DHA group， the cell soma area of the glycine + glutamate + DHA group was also significantly reduced （P<0.05）. Compared with the blank control group， the cell soma area of the glutamate group was significantly increased （P<0.01）. As compared with the glutamate group， the cell soma area of the glutamate + DHA-L， glutamate + DHA-M， and glutamate + DHA-H groups was significantly reduced （P<0.01）. As compared with the blank control group， the expression of the resting primary microglia + glycine group in primary and secondary dendritic internal and external postsynaptic density protein 95 （PSD95） was significantly increased （P<0.01）. As compared with the resting primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons of the activated primary microglia + glycine group was significantly reduced （P<0.01）. As compared with the activated primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. As compared with the activated primary microglia + DHA group， the expression of PSD95 in the primary and secondary dendritic spines and outside neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. ConclusionDHA has a significant repair effect on vertebral neuronal damage caused by hippocampal microglia and TNF-α overexpression in NP pathology， and this repair is closely related to the dual inhibition of neuronal-microglia by DHA.

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

Objective:To explore the feasibility and technical tips of donor-site reconstruction of the latissimus dorsi myocutaneous flap using the perforator propeller flap technique.Methods:Between July 2012 and January 2019, a total of 24 patients, including 9 males and 15 females, underwent reconstructions of defects in various locations using the latissimus dorsi myocutaneous flap. The average patient age was 43.6 years (range, 4-81 years). Before surgery, perforators adjacent to the latissimus dorsi muscle were explored using an ultrasound Doppler probe and marked on the skin. A latissimus dorsi myocutaneous flap was elevated according to the resultant defect following the removal of the lesion and transferred to reconstruct the defect. The donor-site defects were reconstructed using one, dual, or even triple perforator propeller flap.Results:All the 24 myocutaneous flaps survived completely. The dimension and width of the myocutaneous flaps ranged from 16 cm × 11 cm to 33 cm × 17 cm and 9 cm to 20 cm, respectively. The donor-site defects of the myocutaneous flap were all closed by perforator propeller flaps including 22 pedicled flaps and 2 free flaps. The defect was reconstructed by one perforator propeller flap in 12 patients, two flaps in 11, and three flaps in the remaining one patient. There were 36 posterior intercostal artery perforator propeller flaps and one freestyle perforator propeller flap. The size, pedicle length, and rotation angle of the propeller flaps were 13 cm × 5 cm to 23 cm × 14 cm, 3 cm to 6 cm, and 90 to 180 degrees, respectively. All the donor sites of the perforator propeller flaps were closed primarily. Total necrosis of the propeller flap occurred in one patient and small-sized distal flap necrosis in another one. The remaining propeller flaps survived completely. All patients were followed up for one to 38 months and the mean follow-up time was 7 months. Tumor recurrence was noticed in four patients. All patients were satisfied with the final functional and aesthetic outcomes.Conclusions:Using the perforator propeller flaps could guarantee not only harvesting a wide latissimus dorsi myocutaneous flap, but also primary donor-site closure of the myocutaneous flap, and therefore greatly improve the versatility and capability of the latissimus dorsi myocutaneous in defect reconstruction.

Objective:To explore the indications and technical tips of defect reconstruction in the elbow and upper arm using the radial collateral artery perforator (RCAP) propeller flap.Methods:From October 2016 to December 2019, 6 patients underwent defect reconstruction using the RCAP propeller flaps. All patients were female, aged from 5 to 66 years, with an average of 31 years. All of the defects were repaired with radial collateral artery perforator propeller flap. Before the surgery, the RCAP was thoroughly explored using the hand-held ultrasound Doppler and marked on the skin. According to the size, shape and location of the defect, a RCAP propeller flap was elevated based on the chosen RCAP, rotated in a certain degree with the perforating point as the rotation point. The large paddle was used to repair the defect of the upper extremity, and the small paddle was used to assist in closing the donor site. The donor sites were sutured directly or repaired with free skin graft. Capillary filling test or indocyanine green SPY fluorescence imaging system was used to evaluate the blood supply of the flap immediately. The effect was observed.Results:The defect size ranged from 6.0 cm × 3.0 cm to 10.0 cm × 7.0 cm. The flap size ranged from 6.0 cm × 3.5 cm to 20.0 cm × 8.0 cm. All perforators were septocutaneous perforators. The pedicle of the pedicle ranged from 2.5 cm to 5.0 cm and the mean length was 3.6 cm. The flaps were rotated 180° in 5 patients, and 150° in one patient. The donor sites were sutured directly in 5 patients and repaired with free skin graft in one patient. Five flaps survived completely without any major complications. Wound infection occurred in one flap, which healed after debridement. All donor sites were closed primarily, except one which was covered by free skin grafting. All patients were followed up for 3 months to 3 years and the average follow-up time was 2.4 years. The appearance and texture of the flap were good, and the motion of elbow joint was normal. All patients were satisfied with the functional and aesthetic outcomes of the upper extremities. Tumor recurrence was not noticed in the oncologic patients.Conclusions:For selected patients, the RCAP propeller flap could be an alternative option for soft-tissue defect reconstruction in the upper extremity.

Objective:To explore the feasibility and technical tips of donor-site reconstruction of the latissimus dorsi myocutaneous flap using the perforator propeller flap technique.Methods:Between July 2012 and January 2019, a total of 24 patients, including 9 males and 15 females, underwent reconstructions of defects in various locations using the latissimus dorsi myocutaneous flap. The average patient age was 43.6 years (range, 4-81 years). Before surgery, perforators adjacent to the latissimus dorsi muscle were explored using an ultrasound Doppler probe and marked on the skin. A latissimus dorsi myocutaneous flap was elevated according to the resultant defect following the removal of the lesion and transferred to reconstruct the defect. The donor-site defects were reconstructed using one, dual, or even triple perforator propeller flap.Results:All the 24 myocutaneous flaps survived completely. The dimension and width of the myocutaneous flaps ranged from 16 cm × 11 cm to 33 cm × 17 cm and 9 cm to 20 cm, respectively. The donor-site defects of the myocutaneous flap were all closed by perforator propeller flaps including 22 pedicled flaps and 2 free flaps. The defect was reconstructed by one perforator propeller flap in 12 patients, two flaps in 11, and three flaps in the remaining one patient. There were 36 posterior intercostal artery perforator propeller flaps and one freestyle perforator propeller flap. The size, pedicle length, and rotation angle of the propeller flaps were 13 cm × 5 cm to 23 cm × 14 cm, 3 cm to 6 cm, and 90 to 180 degrees, respectively. All the donor sites of the perforator propeller flaps were closed primarily. Total necrosis of the propeller flap occurred in one patient and small-sized distal flap necrosis in another one. The remaining propeller flaps survived completely. All patients were followed up for one to 38 months and the mean follow-up time was 7 months. Tumor recurrence was noticed in four patients. All patients were satisfied with the final functional and aesthetic outcomes.Conclusions:Using the perforator propeller flaps could guarantee not only harvesting a wide latissimus dorsi myocutaneous flap, but also primary donor-site closure of the myocutaneous flap, and therefore greatly improve the versatility and capability of the latissimus dorsi myocutaneous in defect reconstruction.

Objective:To explore the indications and technical tips of defect reconstruction in the elbow and upper arm using the radial collateral artery perforator (RCAP) propeller flap.Methods:From October 2016 to December 2019, 6 patients underwent defect reconstruction using the RCAP propeller flaps. All patients were female, aged from 5 to 66 years, with an average of 31 years. All of the defects were repaired with radial collateral artery perforator propeller flap. Before the surgery, the RCAP was thoroughly explored using the hand-held ultrasound Doppler and marked on the skin. According to the size, shape and location of the defect, a RCAP propeller flap was elevated based on the chosen RCAP, rotated in a certain degree with the perforating point as the rotation point. The large paddle was used to repair the defect of the upper extremity, and the small paddle was used to assist in closing the donor site. The donor sites were sutured directly or repaired with free skin graft. Capillary filling test or indocyanine green SPY fluorescence imaging system was used to evaluate the blood supply of the flap immediately. The effect was observed.Results:The defect size ranged from 6.0 cm × 3.0 cm to 10.0 cm × 7.0 cm. The flap size ranged from 6.0 cm × 3.5 cm to 20.0 cm × 8.0 cm. All perforators were septocutaneous perforators. The pedicle of the pedicle ranged from 2.5 cm to 5.0 cm and the mean length was 3.6 cm. The flaps were rotated 180° in 5 patients, and 150° in one patient. The donor sites were sutured directly in 5 patients and repaired with free skin graft in one patient. Five flaps survived completely without any major complications. Wound infection occurred in one flap, which healed after debridement. All donor sites were closed primarily, except one which was covered by free skin grafting. All patients were followed up for 3 months to 3 years and the average follow-up time was 2.4 years. The appearance and texture of the flap were good, and the motion of elbow joint was normal. All patients were satisfied with the functional and aesthetic outcomes of the upper extremities. Tumor recurrence was not noticed in the oncologic patients.Conclusions:For selected patients, the RCAP propeller flap could be an alternative option for soft-tissue defect reconstruction in the upper extremity.

Objective: To explore the clinical effects of scapular region flaps pedicled with circumflex scapular artery in the reconstruction of axillary burn scar contractures. Methods: From December 2008 to December 2018, 21 patients with axillary burn scar contractures were admitted to our department. There were 12 male patients and 9 female patients, aged 2-48 years, with an average of 17.4 years. According to the characteristics of axillary scar contractures, the patients were divided into type Ⅰ of 5 patients, type Ⅱ of 2 patients, type Ⅲ of 5 patients, and type Ⅳ of 9 patients. The preoperative abduction ranges of shoulder joint were 20-150°, with an average of 68.33°. The wound areas after resection and release of scar contractures ranged from 12 cm×4 cm to 33 cm×11 cm, with an average of 18.13 cm×5.41 cm, and the wounds were repaired with scapular region flaps pedicled with circumflex scapular artery in the areas of 14 cm×5 cm-35 cm×14 cm, with an average of 20.19 cm×7.71 cm. The donor sites of 5 patients were expanded prior to flap repair operation, and the other 16 patients were repaired by direct transfer of flaps. The donor sites were closed directly. The type, number, and transfer way of scapular region flaps were calculated, and the improvement of abduction angle of shoulder joint and condition of the flaps were observed during follow-up after operation. Results: There were 5 ascending scapular flaps, 13 scapular flaps, and 3 parascapular flaps. The flaps were transferred through open wounds in 18 cases, subcutaneous tunnel in 1 case, and trilateral foramia in the remaining 2 cases. All the flaps survived after operation. During follow-up of 3 months to 5 years, with an average of 19.4 months, the abduction angles of shoulder joints were 90-180°, with an average of 137.62°, which showed that the abduction function of shoulder joint improved obviously. The texture of flap was soft, and the color of the flap was close to the surrounding skin. The patients and/or their family members were satisfied with the operation results. Conclusions The scapular region flap pedicled with circumflex scapular artery has a lot of advantages, including a long vascular pedicle, simple technique for flap harvest, a hidden donor site, and flexible and diverse transfer mode of flap. It is an effective option for clinical reconstruction of severe axillary burn scar contracture.

Objective: To screen and verify the differential expression profiles of long non-coding RNAs(LncRNAs) in peripheral blood of patients with type 2 diabetes mellitus(T2DM), to identify the potential molecular specific markers of early T2DM. Methods: The blood samples of 4 type 2 diabetic patients and 4 normal control subjects were collected for microarray analysis. Then six candidate markers of LncRNAs screened from the differential expression profile were tested by qRT-PCR among the subjects (80 cases in the T2DM group and 50 cases in the control group). The possibility of these LncRNAs as molecular diagnostic markers was analyzed, and finally two of them were carried out by receiver operating characteristic (ROC) analysis. Results: Compared with control subjects, there were differentially expressed 133 LncRNAs in type 2 diabetic patients, among which 5 were up-regulated with the maximum up-regulated fold 3.29 and 128 were down-regulated with the maximum down-regulated fold 8.99. Six down-regulated LncRNAs were selected for validation and revealed a similar result to that of microarray.The expressions of two LncRNAs(NONHSAT160746 and NONHSAT140069) in peripheral blood of diabetic patients were significantly lower than those of control subjects (P<0.01). The areas under the ROC curve of the two LncRNAs were 0.734 and 0.703, respectively(P<0.01). Conclusion LncRNAs NONHSAT160746 and LncRNAs NONHSAT140069 are the potential molecular specific markers for the diagnosis of diabetes mellitus.

Objective: To explore the feasibility and technical points of soft tissue defect reconstruction using the pedicled anterolateral thigh flap based on perforating vessels from the lateral circumflex femoral artery oblique branch. Methods: Between November 2009 and April 2019, 27 pedicled anterolateral thigh flaps were performed to repair the wound of trunk and lower extremity, based on perforating vessels from the lateral circumflex femoral artery oblique branch. 16 flaps were proximally based and 11 were distally based. Results: The proximally based flap ranged from 15 cm×8 cm to 32 cm×12 cm. The mean length of the pedicle was 8.2 cm. The distally based flap ranged from 9 cm×7 cm to 24 cm×8 cm. The mean length of the pedicle was 18.6 cm. All flaps survived after surgery. Venous congestion occurred in one flap and relieved in five days. Conclusions With oblique branch as the pedicle, the vascular dissection was easy and donor site morbidity was minimized while harvesting the proximally based anterolateral thigh flaps; long pedicle could be obtained, and the reconstructive sphere was extended when using the distally based anterolateral thigh flaps.