[Clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns].

Objective: To explore the clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 12 male patients with thumb destructive defects caused by electrical burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 27 to 58 years, including 10 cases with degree Ⅲ thumb defect and 2 cases with degree Ⅳ thumb defect after thorough debridement. The thumb was reconstructed with free hallux-nail flap combined with composite tissue flap of the second phalangeal bone, joint, and tendon with skin island. The donor site of hallux-nail flap was covered with artificial dermis in the first stage and performed with continuous vacuum sealing drainage, and covered with medium-thickness skin graft from the groin site in the second stage. The donor site in the second toe was filled and fixed with iliac bone strips. The survival of reconstructed thumb was observed 1 week after the reconstruction surgery, the survival of skin graft in the donor site of hallux-nail flap was observed 2 weeks after skin grafting, and the callus formation of the reconstructed thumb phalanx and the second toe of the donor foot was observed by X-ray 6 weeks after the reconstruction surgery. During the follow-up, the shape of reconstructed thumb was observed and the sensory function was evaluated; the function of reconstructed thumb was evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association; whether the interphalangeal joints of the hallux and the second toe were stiff, the scar hyperplasia of the foot donor site, and whether the walking and standing functions of the donor feet were limited were observed. Results: One week after the reconstruction surgery, all the reconstructed thumbs of the patients survived. Two weeks after skin grafting, the skin grafts in the donor site of hallux-nail flap of 11 patients survived, while the skin graft in the donor site of hallux-nail flap of 1 patient was partially necrotic, which was healed completely after 10 days' dressing change. Six weeks after the reconstruction surgery, callus formation was observed in the reconstructed thumb and the second toe of the donor foot of 10 patients, the Kirschner wires were removed; while callus formation of the reconstructed thumb was poor in 2 patients, and the Kirschner wires were removed after 2 weeks of delay. During the follow-up of 6 to 24 months, the shape of reconstructed thumb was similar to that of the healthy thumb, the discrimination distance between the two points of the reconstructed thumb was 7 to 11 mm, and the functional evaluation results were excellent in 4 cases, good in 6 cases, and fair in 2 cases. The interphalangeal joints of the hallux and the second toe of the donor foot were stiff, mild scar hyperplasia was left in the donor site of foot, and the standing and walking functions of the donor foot were not significantly limited. Conclusions: The application of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns adopts the concept of reconstruction instead of repair to close the wound. It can restore the shape and function of the damaged thumb without causing great damage to the donor foot.

[A prospective randomized controlled study of the effectiveness of artificial dermis combined with split-thickness skin for repairing wounds with bone and tendon exposure in hands and feet].

Objective: To explore the clinical effects of artificial dermis combined with split-thickness skin for repairing wounds with bone and tendon exposure in hands and feet. Methods: A prospective randomized controlled study was conducted. From October 2018 to February 2020, 82 patients with bone and tendon exposed wounds in hands and feet admitted to the Department of Burns of Zhengzhou First People's Hospital who met the inclusion criteria were selected. All the patients were divided into flap group (41 cases, including 27 males and 14 females) and artificial dermis+split-thickness skin group (41 cases, including 29 males and 12 females) according to the random number table, with age of (37±7) years. After complete debridement of wounds of patients in the two groups, the wounds of patients in flap group were transplanted with anterolateral femoral free flaps; the wounds of patients in artificial dermis+split-thickness skin group were grafted with artificial dermis with continuous negative pressure suction applied, and then grafted with split-thickness skin from autologous lateral thigh once the vascularization of artificial dermis was completed. One week after autologous skin graft/flap grafting, the survival of wound graft was observed and the graft survival rate was calculated. The complete wound healing time, number of operation, length of hospital stay, hospitalization cost, and the occurrence of surgery-related complications during hospitalization after autologous skin graft/flap grafting were recorded, and the incidence of complications was calculated. Six months after autologous skin graft/flap grafting, the scar hyperplasia of recipient area was evaluated by Vancouver Scar Scale (VSS), while the recovery of hand and foot function was evaluated by Total Action Mobility (TAM) System Rating method and American Orthopaedic Foot and Ankle Society Ankle and Hindfoot Function Scale (AOFAS-AHS), respectively. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and independent sample t test. Results: One week after autologous skin graft/flap grafting, the survival rates of wound grafts were similar in the two groups (P>0.05). The complete wound healing time and length of hospital stay were (29±5) and (35±5) d for patients in artificial dermis+split-thickness skin group, respectively, which were significantly longer than (22±4) and (28±5) d in flap group (t=6.96, 6.22, P<0.01). Compared with those in flap group, the number of operations was fewer (t=7.39, P<0.01), the incidence of surgery-related complications during hospitalization after autologous skin graft/flap grafting was lower (P<0.01), but there was no significant change in hospitalization cost of patients in artificial dermis+split-thickness skin group (P>0.05). Six months after autologous skin graft/flap grafting, the VSS scores of recipient area of patients in the two groups were similar (t=0.32, P>0.05); the TAM score of hand function and AOFAS-AHS score of foot function of patients in artificial dermis+split-thickness skin group were 40±6 and 62±12, respectively, which were significantly higher than 34±6 and 53±11 of flap group (t=4.66, 3.41, P<0.01). Conclusions: The combined application of artificial dermis and split-thickness skin results in fewer number of operation compared with using flaps in the repair of wounds with bone and tendon exposure in hands and feet, reducing the incidence of surgery-related complications and improving the postoperative hand and foot joint function of patients, without significant scar hyperplasia, although it may also prolong the wound healing time and length of hospital stay accordingly.

[Effect of gMDSCs on natural killer cell functionality in chronic hepatitis C patients treated with direct-acting antiviral agents].

Objective: To investigate the changes of natural killer(NK) cell function, and clarify the effect of granulocytic myeloid derived suppressor cells (G-MDSCs) on NK cell functionality in patients with treatment-naive chronic hepatitis C (CHC) who were cured by direct-acting antiviral agents (DAAs). Methods: Thirteen treatment-naive CHC patients and 13 healthy controls were prospectively included in this study from March 2016 to January 2017. They were divided into case group and control group, respectively. The patients of case group,6 males and 7 females aged 21-65 years old with an average of (37±14),were treated with daclatasvir and asunaprevir combination (DCV/ASV) at the Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital. While 13 healthy individuals, 6 males and 7 females aged 21-57 (36±11) years old, were enrolled as healthy controls(control group). Flow cytometry was used to determine the immunological characteristics of peripheral blood NK cells subset, and detect the frequencies of gMDSCs in peripheral blood of people in two groups. It was specifically notes that CHC patients of case group would be detected before, during and after treatment. The correlations between gMDSCs and each NK cell subset function were also examined. The impact of gMDSCs on NK cell functionalities and the relevant regulatory mechanisms were explored using co-culture experiments of sorted NK cells and gMDSCs in vitro. Results: Compared with healthy controls, the decreased IFN-γ production[M(Q1,Q3)] [3.182 (2.757, 4.237) vs 6.675 (4.476, 8.280),1.434 (1.127, 2.434) vs 3.045 (1.680, 4.856), 2.611 (1.749, 3.498) vs 5.160 (4.232, 7.683)] and increased CD107a degranulation [9.314 (7.838, 13.543) vs 3.480 (2.938, 6.824), 2.544 (1.366, 4.768) vs 0.552 (0.408, 1.560), 10.339 (9.145, 12.534) vs 3.488 (3.117, 5.651)] (all P<0.05) were found on NK cell and its subsets. The frequencies of gMDSCs and plasma concentration of arginase-1 in CHC patients was significantly higher than that in healthy controls [7.050 (4.180, 12.538) vs 1.440 (0.444, 2.261), 114.278 (68.492, 163.724) vs 64.753 (50.809, 93.278)](all P<0.05). The production of IFN-γ was increased and the secretion of CD107a was decreased in NK cell and its subsets after DAAs treatment (P<0.05). The frequencies of gMDSCs and plasma arignase I levels were also decreased in CHC patients treated with DAAs (P<0.05).The results of the study indicated that the frequencies of G-MDSCs were inversely associated with the levels of IFN-γproduction of NK cells and CD56dim NK cells in CHC patients (r=0.668, -0.750, respectively, both P<0.05). In addition, the frequencies of gMDSCs were positively associated with the expression of CD107a in the CD56bright NK cell subset (r=0.711, P=0.021). In vitro, the inhibition of gMDSCs on the IFN-γ production of NK cells was demonstrated in the co-culture experiments of sorted NK cells and gMDSCs, and blocking arginase I can significantly increase the ability of NK cells to produce IFN-γ, restore NK cell IFN-γ production. Conclusions: gMDSCs in peripheral blood of CHC patients has been shown to suppress NK cell IFN-γ production in an arginase I-dependent manner. Direct-acting antiviral-mediated clearance of HCV is associated with the normalization of NK cell function and gMDSCs frequency.

MicroRNA-155 and FOXP3 jointly inhibit the migration and invasion of colorectal cancer cells by regulating ZEB2 expression.

OBJECTIVE: The study aimed to explore whether microRNA-155 and FOXP3 could regulate invasive and migratory capacities of colorectal cancer (CRC) cells by mediating Zinc finger E-box binding homeobox 2 (ZEB2) expression. MATERIALS AND METHODS: Dual-luciferase reporter gene assay was performed to detect the binding condition between microRNA-155, FOXP3, and ZEB2. Protein and mRNA levels of ZEB2 in CRC cells were detected after overexpression of microRNA-155 and FOXP3 by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. In vitro experiments were conducted using HCT116 and SW620 cell lines. We first detected expression levels of microRNA-155, FOXP3, and ZEB2 in the normal colorectal epithelial cell line (NCM460) and CRC cell lines (HCT116 and SW620) by qRT-PCR. Protein expressions of ZEB2, E-cadherin, and vimentin in WT, LV-GFP, and LV-FOXP3 groups were detected. Wound healing assay and transwell assay were conducted to determine the regulatory effects of microRNA-155 and FOXP3 on invasive and migratory capacities of CRC cells, respectively. RESULTS: Dual-luciferase reporter gene assay found that FOXP3 binds to the promoter and intron regions of ZEB2, and microRNA-155 binds to the 3'UTR region of wild-type ZEB2. Overexpression of FOXP3 downregulated mRNA and protein levels of ZEB2. ZEB2 was highly expressed, whereas microRNA-155 and FOXP3 were lowly expressed in HCT116 and SW620 cells than NCM460 cells. MicroRNA-155 overexpression upregulated E-cadherin and downregulated vimentin in CRC cells. Overexpression of FOXP3 and microRNA-155 inhibited invasive and migratory capacities of CRC cells. CONCLUSIONS: MicroRNA-155 and FOXP3 can jointly regulate ZEB2 expression, thereby inhibiting the migration and invasion of colorectal cancer cells.

[Soft-tissue angiosarcoma with pulmonary metastases: case report and literature review].

Objective: To investigate the differential diagnosis between pulmonary metastases from soft-tissue angiosarcoma and primary pulmonary angiosarcoma. Methods: A case of soft-tissue angiosarcoma with pulmonary metastases was reported and related literatures were reviewed. Results: A 39 year-old man complaining of hemoptysis, cough, and sputum for 10 months was admitted to our hospital in September 2013. He was initially diagnosed as having primary pulmonary angiosarcoma after wedge-resection biopsy of the lung. After 22 months since onset, he felt discomfort in his leg, which led to the confirmative diagnosis of soft-tissue angiosarcoma of the leg with multiple pulmonary metastases by a full-body PET/CT scan and core needle biopsy of the leg. Twenty-three articles concerning primary pulmonary angiosarcoma with complete records of history, treatment and follow-up of patients were included in the literature review. A total of 26 patients were reported in these articles, including 18 males, 8 females, age 19-85 years, average (52±18) years. Primary pulmonary angiosarcoma was mainly manifested as single or multiple pulmonary nodules or masses, with or without ground glass opacity. In our case, chest CT showed multiple thin-wall cysts and ground glass opacities, and recurrent spontaneous pneumothorax, which had never been reported in literatures on primary pulmonary angiosarcoma. Conclusions: Pulmonary metastases from soft-tissue angiosarcoma differed from primary pulmonary lesions in terms of chest imaging, with the former usually showing thin-wall cysts and pneumothorax. A full-body PET-CT was essential for differential diagnosis between primary and metastatic pulmonary angiosarcoma.

[Risk factors of lung cancer complicated with symptomatic venous thromboembolism].

OBJECTIVE: To seek risk factors of VTE in patients with lung cancer through analysis of clinical features of patients with lung cancer complicated with venous thromboembolism (VTE). METHODS: Retrospective investigation was performed on patients diagnosed with lung cancer and with complete clinical data who were hospitalized in Peking University People's Hospital from January 1, 2010 to December 31, 2014. According to the presence of symptomatic VTE, patients were distributed into two groups, VTE group and control group. Patients' clinical data and laboratory parameters were collected. Single factor analysis was applied to compare the differences between the two groups. t test or nonparametric test was applied for intragroup comparison of measurement data, and chi-square test was applied for the comparison of counting information. Logistic regression analysis was applied to explore risk factors of venous thromboembolism. For VTE patients with this diagnosis when they were hospitalized, D-dimer and PT were obtained after the occurrence of VTE, so D-dimer and PT were eliminated in the multiple factors analysis. SPSS 13.0 statistical software was applied for statistical management and analysis. RESULTS: 548 patients with lung cancer were include in the investigation, with male 357, female 191, average age of (63.8±10.9) years old, 46 patients in VTE group and 502 patinets in control group. According to the results of single factor analysis in gender, age, tumor pathologic type, tumor stage, WBC, Hb, PLT, CEA, ALT, FIB, D-dimer, PT, APTT, PT-INR, the tumor stage (χ(2)=14.177), CEA (t=2.129) and Hb (t=-2.424) were risk factors for lung cancer patients complicated with venous thromboembolism. Logistic regression analysis showed that tumor stage was the independent risk factor of lung cancer complicated with venous thromboembolism (OR 2.058, 95%CI 1.307-3.238, P=0.002) , and CEA (r=0.395, P<0.001) and Hb (r=-0.144, P=0.001) were associated with lung cancer stage. The area under the curve formed by D-dimer predicting VTE was 0.825 (95%CI 0.751-0.900, P<0.001). CONCLUSION: Tumor stage is the only risk factor for lung cancer patients complicated with venous thromboembolism in the study. However, because this study is a retrospective study, other potential high risk factors causing VTE cannot be excluded.

Effect of the ARG1 gene on arsenic resistance of 293T cells.

To study the relationship between arsenic resistance of 293T cells and overexpression of ARG1, the ARG1 gene in a recombinant plasmid was transfected into 293T cells via liposomes, and then ARG1 overexpression was examined by real-time PCR and immunocytochemistry. The survival rate, arsenic accumulation and arsenic efflux, GSH level, and GST activity of 293T cells overexpressing ARG1 were assayed by MTT, atomic absorption spectrophotometry, and DTNB, and expression of MRP-2 was detected by Western blot analysis. Compared to that in the control cells, the survival rate of ARG1 gene-overexpressing cells was much higher following exposure to lower sodium arsenite (≤ 8 µM). When cells were exposed to lower sodium arsenite for 24 h, the arsenite content of ARG1 gene-overexpressing cells decreased and arsenic efflux increased. After 48 h, the GSH level, GST activity, and expression of MRP2 increased in a concentration-dependent manner. We conclude that the ARG1 gene increases arsenic resistance of 293T cells.

The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of gefitinib and the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a series of Chinese patients with pretreated advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 98 patients who had failed at least one platinum-based regimen received gefitinib 250 mg once daily. The mutation analysis of the EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor tissue. RESULTS: The response rate was 31.6% and the disease control rate was 67.3%. Objective response was correlated with adenocarcinoma, female gender and non-smokers. Median progress free survival (PFS) was 7.0 months, median overall survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and OS were improved among patients with adenocarcinoma, gefitinib responders and non-smokers. Active gene mutation was detected in 12 patients. Mutation rates were higher among gefitinib responders, non-smokers, patients with adenocarcinoma and female patients. OS was longer for patients with gene mutation than for patients without mutation. CONCLUSION: Gefitinib demonstrated significant antitumor activity with a favorable toxicity profile for pretreated Chinese patients with advanced NSCLC. The active mutation of the EGFR kinase domain was strongly associated with response to gefitinib and prolonged overall survival.