[Effects of free superficial peroneal artery perforator flap in repairing small and medium-sized thermal crush injury wounds in the hand].

Objective: To investigate the surgical methods and clinical effects of free superficial peroneal artery perforator flap in repairing small and medium-sized thermal crush injury wounds in the hand. Methods: A retrospective observational study was conducted. From August 2018 to December 2021, 12 patients (19 wounds) with small and medium-sized thermal crush injury in the hand who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 7 females, aged from 30 to 54 years. The area of the wound was from 2.5 cm×2.0 cm to 14.0 cm×3.5 cm, and all the wounds were repaired by using free superficial peroneal artery perforator flaps from lower leg on one side (including single flap, multiple flaps, and multiple flaps with one pedicle resected from the same donor site). The area of the flap was from 3.5 cm×3.0 cm to 16.0 cm×4.0 cm. The wound in the donor site was sutured directly. The vascular crisis and survival of the flap were observed after operation. The texture, appearance, color, hyperpigmentation, sensation, and two-point discrimination of the flap repaired area were followed up, as well as the hyperplasia of scar and pain condition in the donor and recipient sites. At the last follow-up, the curative effect of flap repair was evaluated by the comprehensive evaluation scale, and the extension and flexion functions of the reserved digital joint were evaluated by the total active movement systematic evaluation method recommended by American Academy for Surgery of Hand. Results: One flap developed arterial crisis on the first day after operation but survived after timely exploration. The other 18 flaps survived successfully after operation. Follow-up of 4 to 24 months after operation showed good texture and appearance in the flap repaired area; the color of the flap repaired area was similar to that of the normal skin around the recipient site, without pigmentation; the protective sensation was restored in all cases, but there was no two-point discrimination; there was no obvious hypertrophic scarring or pain in the donor or recipient site. At the last follow-up, the curative effect of flap repair was evaluated with 3 flaps being excellent and 16 flaps being good; the extension and flexion functions of the reserved digital joint were also assessed, being excellent in 8 fingers, good in 9 fingers, and fair in 2 fingers. Conclusions: The blood supply of superficial peroneal artery perforator flap is sufficient and reliable, and multiple flaps of this type or multiple flaps with one pedicle can be resected from one donor site. The use of this flap to repair small and medium-sized thermal crush injury wounds in the hand results in minimal damage to the donor area, and good postoperative appearance and texture of the flap.

[Effects of tensile force on the vascular lumen formation in three-dimensional printed tissue].

Objective: To explore the effects of tensile force on vascular lumen formation in three-dimensional printed tissue. Methods: The experimental research method was used. Human umbilical vein endothelial cells (HUVECs) were extracted from discarded umbilical cord tissue of 3 healthy women (aged 22 to 35 years) who gave birth in the Department of Gynaecology and Obstetrics of Suzhou Ruihua Orthopaedic Hospital from September 2020 to May 2021. Human skin fibroblasts (HSFs) were extracted from discarded normal skin tissue of 10 male patients (aged 20 to 45 years) who underwent wound repair in the Department of Hand Surgery of Suzhou Ruihua Orthopaedic Hospital from September 2020 to September 2022. After identification of the two kinds of cells, the 4th to 6th passage of cells were taken for the follow-up experiments. HUVECs and HSFs were used as seed cells, and polycaprolactone, gelatin, hyaluronic acid, and fibrin were used as scaffold materials, and the three-dimensional printed vascularized tissue was created by three-dimensional bioprinting technology. The printed tissue with polycaprolactone scaffold of 6 and 10 mm spacing, and without polycaprolactone scaffold were set as 6 mm spacing polycaprolactone group, 10 mm spacing polycaprolactone group, and non-polycaprolactone group, respectively. After 4 days of culture, the printed tissue in 10 mm spacing polycaprolactone group was selected to detect the cell survival by cell viability detection kit, and the cell survival rate was calculated. After 14 days of culture, the printed tissue in three groups were taken, and the shape change of tissue was observed by naked eyes; immunofluorescence staining was performed to observe the arrangement of filamentous actin, and lumen diameter, total length, and number of branches of vessel in the tissue. The tissue with micro-spring structure in the above-mentioned three groups was designed, printed, and cultured for 9 days, and the tensile force applied in the printed tissue was measured according to the force-displacement curve. The number of samples was all 3 in the above experiments. Data were statistically analyzed with one-way analysis of variance and Tukey test. Results: After 4 days of culture, the cell survival rate in printed tissue in 10 mm spacing polycaprolactone group was (91.3±2.2)%. After 14 days of culture, the shape change of printed tissue in non-polycaprolactone group was not obvious, while the shape changes of printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were obvious. After 14 days of culture, the arrangement of filamentous actin in the printed tissue in non-polycaprolactone group had no specific direction, while the arrangement of filamentous actin in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group had a specific direction. After 14 days of culture, The vascular lumen diameters of the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were (6.0±1.3) and (10.8±1.3) µm, respectively, which were significantly larger than 0 µm in non-polycaprolactone group (P<0.05), and the vascular lumen diameter of printed tissue in 10 mm spacing polycaprolactone group was significantly larger than that in 6 mm spacing polycaprolactone group (P<0.05); the total length and number of branches of blood vessel in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were significantly shorter or less than those in non-polycaprolactone group (P<0.05), and the total length and number of branches of blood vessel in the printed tissue in 10 mm spacing polycaprolactone group were significantly shorter or less than those in 6 mm spacing polycaprolactone group. After 9 days of culture, the tensile forces applied in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were (2 340±59) and (4 284±538) µN, respectively, which were significantly higher than 0 µN in non-polycaprolactone group (P<0.05), and the tensile force applied in the printed tissue in 10 mm spacing polycaprolactone group was significantly higher than that in 6 mm spacing polycaprolactone group (P<0.05). Conclusions: The three-dimensional printed scaffold structure can exert different tensile force in the printed tissue, and the vascular lumen diameter of the printed tissue can be regulated by adjusting the tensile force.

The prognostic role of albumin-bilirubin grade in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

OBJECTIVE: Our aim was to explore the prognostic role of baseline albumin-bilirubin levels (ALBI) on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This retrospective study enrolled 58 cases of advanced NSCLC patients who received immune checkpoint inhibitor therapy from January 2019 to February 2022 in People's Hospital of Macheng. Patients were grouped according to the levels of baseline ALBI. The corresponding cut-off values ​​were determined by receiver operating characteristic (ROC) curves. We also assessed potential predictive models for predicting efficacy of immunotherapy in advanced NSCLC. RESULTS: The median overall survival (OS) was not reached. The median OS of patients with PS ≤ 1 after immunotherapy was significantly longer than that of PS ≥ 2, which was NR vs. 6.67 months (HR=0.14, 95% CI: 0.05-0.46; p<0.01). The risk of death for patients with low ALBI (<-2.52) was significantly lower than that of patients with high ALBI (HR=0.28, 95% CI: 0.08-0.94; p=0.03). Univariate analysis showed that baseline ALBI and PS were factors significantly affecting OS in patients with advanced NSCLC after immunotherapy (p<0.05 for all). The combination of ALBI and PS showed a good predictive value in prognosis of these patients after immunotherapy (p<0.01). CONCLUSIONS: The baseline ALBI and PS may serve as prognostic factors for advanced NSCLC patients treated with immunotherapy.

Features and clinical significance of tertiary lymphoid structure in cutaneous squamous cell carcinoma.

BACKGROUND: Tertiary lymphoid structure (TLS) plays an important role in antitumour immunity, largely reflecting the prognosis. However, its clinical implication in cutaneous squamous cell carcinoma (cSCC) remains unknown. OBJECTIVES: To explore the features of TLS in cSCC and its association with clinicopathological characteristics. METHODS: Two independent RNA-seq data of cSCC were used to investigate the tumour immune microenvironment, as well as TLS-related chemokines and cytokines. The density and location of TLSs were assessed in a total of 82 cSCC patients, and the clinicopathologic association was examined. RESULTS: Bioinformatics analysis showed that a large amount of immune cell infiltration and significant up-regulation of TLS-related chemokines were observed in cSCC. Histologically, TLSs appeared as highly organized structures in 72 (87.8%) cases with different levels of density and maturation, among which 14 cases were in low-density group and 58 cases were in high-density group. Clinically, the presence of TLS was prominently associated with better degree of histopathological grades and higher level of sun exposure. Furthermore, the presence of intratumoral TLS was associated with lower lymphovascular invasion. CONCLUSIONS: TLS is highly organized in cSCC, and the presence of TLS is a positive prognostic factor for cSCC, which will provide a theoretical basis for the future diagnostic and therapeutic value in cSCC.

MicroRNA-543 inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of triple-negative breast cancer cells via down-regulation of ACTL6A gene.

PURPOSE: To investigate the effect of microRNA-543 (miR-543) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells, and the associated mechanism. METHODS: Human breast cancer cells (MDA-MB-231, HCC1937, and MCF-7, ZR-75-1) and normal human breast epithelial cell line (MCF10A) were transfected with miR-543 mimics or inhibitor using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the mRNA and protein expression levels of miR-543, actin-like protein 6A (ACTL6A), vimentin, Snail, and E-cadherin in breast cancer cells/tissue. Cell counting kit-8 (CCK-8), wound-healing, and Transwell assays were used to measure the effect of miR-543 on TNBC cell proliferation, invasion, and migration. Overall survival was determined using data from Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis and luciferase reporter gene assay were used to determine the regulatory effect of miR-543 on ACTL6A. RESULTS: The level of expression of miR-543 was significantly lower in breast cancer cells/tissue than in normal human breast epithelial cell/tissue (p < 0.05). MicroRNA-543 expression level was significantly reduced in TNBC cells/tissue, relative to the other breast cancer cells/normal breast tissue (p < 0.05). MicroRNA-543 significantly suppressed tumor growth and the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, in mouse xenograft model (p < 0.05). CONCLUSIONS: miR-543 influences the biological behavior of TNBC cells by directly targeting ACTL6A gene. miR-543 could serve as a novel diagnostic and therapeutic target for TNBC.

[Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases].

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

[Reconstruction of orbital floor defect with preserved orbital contents after advanced maxillary sinus cancer resection].

Objective: To analyze the method and effect of reconstruction of the orbital floor defect with preserved orbital contents after advanced maxillary sinus cancer resection. Methods: Thirty-three patients of T3/T4 stage maxillary sinus cancer with orbital invasion who were treated in Shandong Provincial Hospital from January 2010 to October 2016 were retrospectively analyzed, including 20 males and 13 females, aged from 12 to 80 years old. Patients were treated with appropriate surgical methods according to their clinical manifestation, imaging finding, invasion range, preoperative and intraoperative pathology. Surgical approaches such as maxillectomy, expanded maxillectomy and superstructure maxillectomy were used for patients with Medpor orbit floor repairment. Patients were followed up regularly after surgery, and the surgical efficacy was discussed by descriptive statistical method. Results: Of those 33 cases, 19 were squamous cell carcinoma, 8 were adenoid cystic carcinoma, 5 were inverted papilloma malignant transformation, and 1 was myoepithelial carcinoma in our study. After tumor resection and orbital floor repair, the orbital contents and eyeball function of all patients remained intact. During follow-up time ranged from 3 to 8 years, a total of 6 patients relapsed at 3 years and died of ineffective treatment. The survival rate was 81.8% (27/33). Conclusion: Tumor resection and Medpor orbital floor repair in maxillary sinus cancer patients with orbital invasion can preserve the function of the eyeball well, greatly improve the quality of patient's life.

[Progressive necrosis of lipid: A case report].

A 61-year-old woman was referred to our department with a 11-year-erythra. In the anterior tibia of both lower extremities, we could see large dark red infiltrating erythema, waxy luster, clear boundary, slight central atrophy, depression and capillary dilatation. He was diagnosed with "dermatitis contusiformis" in local hospitals, but the treatment of traditional Chinese medicine and external drugs was not effective. She had normal laboratory findings for blood routine test, biochemical indexes, C reactive protein(CRP) and erythrocyte sedimentation rate(ESR)．Furthermore, autoimmune antibodies were all negative. The skin pathology showed degeneration and necrosis of collagen fibers, chronic granulomatous inflammation in the dermis, and there were more acute and chronic inflammatory cell infiltration around the small vessels and in the wall of the tube. We eventually diagnosed it as necrobiosis lipoidica (NL) according to the history, erythra morphology and skin pathology. After treatment of low dose hormone and thalidomide for 1 year, the color and range of skin lesions gradually alleviated. NL was a rare chronic granulomatous inflammatory disease. There appeared to be a predominance in females. The incidence of NL was higher in patients with diabetes mellitus, although this asscoiation was currently questioned. NL might also be connected with autoimmune diseases, such as rheumatoid arthritis, sarcoidosis, ulcerative colitis and Crohn's disease. The pathological changes of the tissue were mainly in the dermis, including necrotic type, granulomatous type or mixed type. NL typically presented on the pretibial surface of lower extremities. Less typical locations included the face, scalp, vulva and upper limbs. Leisions usually began with small papules and nodules that gradually infiltrated into brownyellow patches and developed central wax-like atrophy. The diagnosis is often based on clinical examination and skin biopsy. NL is rare and easy to be misdiagnosed. For rheumatologists, we should carefully compare with the nodular erythema, the microscopic polyangitis and allergic purpura. It is significant for differential diagnosis to perform skin biopsy. Lacking of randomized controlled trials, no specific treatment has proven to be the gold standard. First-line therapy mainly consists of intralesional and systemic corticosteriods. Additionally, other reported treatment options include immunomodulator, biological agent, antiplatelet aggregation drug and plateletrich plasma. These patients need long term follow up continuously for progression of the disease, ulcerations, and possibility of malignant tranformation.

[Multiple free homologous superficial peroneal artery perforator flaps of crus for repair of multiple hand wounds].

Objective: To explore the effects of multiple free homologous superficial peroneal artery perforator flaps of crus for repair of multiple hand wounds. Methods: From November 2017 to December 2018, eight cases with eighteen hand wounds were hospitalized in our unit. Among them, wounds were distributed in the forefinger and middle finger in four cases, wounds were distributed in the middle finger and ring finger in two cases, wounds were distributed in the forefinger, middle finger, and ring finger in one case, and wounds were distributed in the middle finger, ring finger, and little finger in one case. The area of skin defect ranged from 1.5 cm×0.8 cm to 4.0 cm×3.0 cm. There were 4 males and 4 females, aged 34-62 years. Wounds of six cases were repaired by two free superficial peroneal artery perforator flaps from homolateral crus, and those of two cases were repaired by three free superficial peroneal artery perforator flaps from homolateral crus. Superficial peroneal artery and its accompanying vein of flap were anastomosed by end to end with digital artery and palmar or dorsal subcutaneous vein of recipient site during the operation. The area of flap ranged from 2.5 cm×1.2 cm to 5.0 cm×4.0 cm. No nerve was harvested during the operation, and donor site was sutured directly. The survival of the flaps and the healing of donor sites were recorded. During follow-up, the recovery of donor and recipient sites was observed. Results: All flaps survived well, donor site healed well. No vascular crisis occurred. Follow-up for 4 to 12 months showed that the appearance of flap was satisfactory with good color, texture, elasticity, and function. Protective sensation of recipient site was recovered. Five months after operation, flap of finger pulp in one case was swollen slightly with two-points discrimination of 10 mm, which received the thinning surgery. Obvious scar formation was not observed in donor site of crus. The appearance of the donor site was good without functional damage. Conclusions: The application of multiple free homologous superficial peroneal artery perforator flaps of crus to repair the multiple hand wounds has advantages of easy acquisition, easy operation, little effect on donor sites, and satisfactory clinical effects.

[Clinical characteristics of human adenovirus type 7 pneumonia and genetic characteristics of human adenovirus type 7].

Objective: To better understand the clinical features of human adenovirus type 7 (hAdV7) pneumonia and to identify whether there is a variation in the genome of the strain (CHN/BeiJing/2018) isolated during the small-scale epidemic. Method: Forty-two patients were diagnosed with hAdV7 pneumonia between October 27th, 2017 and February 28th, 2018. They were all males with an average age of (21±2) years. Demographic and clinical data were reviewed and analyzed in detail. The nucleic acid of the epidemic strain was extracted from a bronchoalveolar lavage fluid sample. Whole genome sequencing (WGS) was then performed and sequences were compared with other hAdV7 strains distributed globally. Phylogenetic tree analysis was conducted based on whole genome sequences of the epidemic strain. Results: Thirty-eight cases with hAdV7 pneumonia presented with influenza-like symptoms (90.5%) at the onset and 36 cases developed fever (85.7%), followed by cough (97.6%), expectoration (90.5%) and chest pain (28.6%). Five cases presented with tonsillitis(11.9%) and 4 had transient hemoptysis (9.5%), while 3 patients reported dyspnea (7.1%). Moist rales were only heard in 3 patients (7.1%). Notably elevated creatine kinase (CK) concentrations were observed in 8 patients (19.1%), but all returned to normal after treatment. Four cases developed hypoxemia (9.5%), but none of them progressed to respiratory failure or acute respiratory distress syndrome (ARDS). Chest CT imaging showed bilateral patchy parenchymal opacities with a random distribution with or without consolidation. Ten patients were co-infected with influenza virus (23.8%), while 32 patients developed atypical pneumonia (76.2%). Genomic analysis revealed that the strain isolated during this epidemic was 99% similar to the known hAdV7 strains (19BOVLB/Volgograd/Rus/2014 and 0901HZ/ShX/CHN/2009). Phylogenetic tree analysis suggested that the strain was closely related to the hAdV7 strain isolated in Jingmen China in 2012. Conclusions: Cases with hAdV7 pneumonia were generally mild. Symptomatic treatment was sufficient for a favorable prognosis. A good genome stability of the hAdV7 strain was observed, indicating that hAdV7 could remain stable for a long period and cause continuing sporadic cases and clusters.

[Effect of downregulation of phosphatase and tensin homolog gene expression on p130crk- related substrate protein and paxillin signal transduction in activated hepatic stellate cells in vitro].

Objective: To investigate the role of adenovirus-mediated short hairpin RNA (shRNA) in down-regulating the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN) on p130Crk-related substrates(p130Cas) and paxillin signal transduction to activate hepatic stellate cell (HSC) in vitro. Methods: The rat hepatic stellate cell line, HSC-T6 was cultured and activated in vitro. The adenovirus was used as a vector to transiently transfect shRNA targeting PTEN to activate HSC in vitro, and then PTEN low expression model of activated HSC in vitro was established. Western blot and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expression of PTEN, p130cas and paxillin in activated HSC. The experiment was divided into control group (HSC were transfected with DMEM medium instead of adenovirus), Ad-GFP group (HSC were infected with empty the adenovirus expressing green fluorescent protein (GFP) alone), and Ad-shRNA/PTEN group (HSC were infected with the recombinant adenovirus containing both shRNA targeting PTEN and GFP gene). One-way analysis of variance was used for comparison of multiple groups, and LSD test was used for inter-group comparison. Results: shRNA targeting PTEN was successfully transfected and significantly down-regulated the PTEN protein and mRNA expression of HSC in vitro (P < 0.05), and the PTEN low expression model of HSC in vitro was successfully constructed. Compared with the expression of p130cas mRNA in the three groups of HSC, the expression fold of p130cas mRNA in the Ad-GFP group and the Ad-shRNA / PTEN group was 1.01 times and 1.52 times, respectively. The expression of p130cas mRNA in HSC of the Ad-shRNA / PTEN group was significantly higher than control group and Ad-GFP group (P < 0.05), but there was no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). The expression of p130cas protein in the three groups was higher than that in the control group (0.74 ± 0.07) and the Ad-GFP group (0.72 ± 0.02); P < 0.05, but there was no statistically significant difference between the Ad-GFP group and the control group (P > 0.05). The expression of paxillin mRNA in the three groups of HSCs was compared with the expression of paxillin mRNA in the control group of HSC being 1, the expression folds of paxillin mRNA in the Ad-GFP group and Ad-shRNA / PTEN group were 0.97 times and 1.58 times, respectively. The expression of paxillin mRNA in the Ad-shRNA / PTEN group was higher than that in the control group and the Ad-GFP group (P < 0.05), and there was no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). The expression of paxillin protein in the three groups of HSCs was higher in the Ad-shRNA / PTEN group (0.91 ± 0.05) than control group (0.46 ± 0.03) and Ad-GFP group (0.50 ± 0.04), P < 0.05, and there was no statistically significant difference between the Ad-GFP group and the control group (P > 0.05). Conclusion: Down-regulation of PTEN expression can significantly boost p130cas and signal transduction activity of paxillin protein in activated HSC in vitro.

UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response.

Despite the pivotal role of MYC in tumorigenesis, the mechanisms by which it promotes cancer aggressiveness remain incompletely understood. Here, we show that MYC transcriptionally upregulates the ubiquitin fusion degradation 1 (UFD1) gene in T-cell acute lymphoblastic leukemia (T-ALL). Allelic loss of ufd1 in zebrafish induces tumor cell apoptosis and impairs MYC-driven T-ALL progression but does not affect general health. As the E2 component of an endoplasmic reticulum (ER)-associated degradation (ERAD) complex, UFD1 facilitates the elimination of misfolded/unfolded proteins from the ER. We found that UFD1 inactivation in human T-ALL cells impairs ERAD, exacerbates ER stress, and induces apoptosis. Moreover, we show that UFD1 inactivation promotes the proapoptotic unfolded protein response (UPR) mediated by protein kinase RNA-like ER kinase (PERK). This effect is demonstrated by an upregulation of PERK and its downstream effector C/EBP homologous protein (CHOP), as well as a downregulation of BCL2 and BCLxL. Indeed, CHOP inactivation or BCL2 overexpression is sufficient to rescue tumor cell apoptosis induced by UFD1 knockdown. Together, our studies identify UFD1 as a critical regulator of the ER stress response and a novel contributor to MYC-mediated leukemia aggressiveness, with implications for targeted therapy in T-ALL and likely other MYC-driven cancers.

CXCR4 antagonist AMD3100 enhances the response of MDA-MB-231 triple-negative breast cancer cells to ionizing radiation.

Radiation therapy (RT) is one of the primary modalities for triple-negative breast cancer (TNBC) treatment. However, due to the pro-metastatic potential of radiation and the intrinsic radiation resistance of some tumors, many patients experience RT failure, which leads to cancer relapse and distant metastasis. This preclinical study evaluated the efficacy of the antagonist of the SDF-1 receptor CXCR4, AMD3100, as a radiosensitizer in TNBC models. The combined effect of ionizing radiation and AMD3100 was determined in vitro by surviving fraction, cell cycle distribution, Bax and Bcl-2 expression, and apoptosis assays in a TNBC cell line (MDA-MB-231). For in vivo studies, human xenograft athymic nude mice were used. Treatment of TNBC cells with AMD3100 significantly augmented cellular radiosensitivity. Radiosensitivity was enhanced specifically through increased Bax expression, reduced Bcl-2 expression, prolonged G2-M arrest, and increased apoptosis. Combined treatment with AMD3100 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.5 to 1.8. These findings support the evaluation of antagonists of the SDF-1 receptor CXCR4, such as AMD3100, as potent radiosensitizers in TNBC.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma.

X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and anti-tumor activities, evidenced by perforin upregulation, CD107a degranulation (cytotoxicity) and Th1-type cytokines (IFN-γ/IL-2/TNF-α) production in response to HLA-A24+ MM cells. The multipeptide-specific CTL included antigen-specific memory CD8+ T cells expressing both T-cell activation (CD38, CD69) and immune checkpoints antigens (CTLA, PD-1, LAG-3, TIM-3). These results provide the framework for a multipeptide vaccination therapy to induce tumor-specific CTL in HLA-A24-positive patients with myeloma and other cancers expressing these antigens.

[Refractory kaposiform hemangioendothelioma with Kasabach-Merritt syndrome: clinical analysis of 10 cases].

Objective: To analyze the clinical value of sirolimus plus prednisone for the treatment of the refractory kaposiform hemangioendothelioma(RKHE) and Kasabach-Merritt syndrome(KMS). Method: Clinical retrospective analysis was carried out for 10 patients recruited in Children's Hospital Affiliated to Capital Institute of Paediatrics from January 2014 to January 2017 who were non responders to or relapsers after the treatment of propranolol, prednisone, pingyangmycin and lauromacrogol(5 cases RKHE, 5 cases RKHE plus KMS, age ranged from 6 days to 9 years); patients were treated with sirolimus at the dosage of 0.035 ml/(kg·d), once a day, for 6-410 days; the diagnosis of 10 patients were confirmed by pathological biopsy and immunohistochemical examination(IHC); the difference of the coagulation parameters and the platelet counts, the size of tumor and ecchymosis at different stages of treatment were recorded and measured by scale and ultrasonography; the side effects of sirolimus were recorded as well. Result: Clinical characteristics of 10 cases (6 male and 4 female) RKHE with KMS were refractory dark red hard hemangioma or ecchymosis, the platelet counts were lower than 30.0×10(9)/L, (15±7)×10(9)/L, coagulation tests were obviously abnormal, fibrinogens were significantly decreased(0.8±0.5)g/L, the fibrin lysates and D-dimer were significantly increased(100±23)mg/L, (10 000±2 200)ng/L, the prothrombin time and activated partial thromboplastin time were prolonged(25.0±2.1)s, (58.0±3.4)s. The pathologic characteristics of the tumors were similar: spindle tumor cells, mass distribution and deeply stained nuclei tumor cells. IHC revealed positive staining for D2-40, CD31 and CD34. Stainings for factor Ⅷ and GLUT-1 were negative. In five cases RKHE plus KMS were treated with sirolimus and prednisone, after (6.5±0.7) days treatment, the platelet counts were obviously increased(72.0±0.6)×10(9)/L, coagulation parameters were obviously improved, fibrinogen significantly increased(1.5±0.2)g/L, the fibrinlysates and D-dimer significantly decreased(7±3)mg/L, (2 300±200)ng/L, the prothrombin time and activated partial thromboplastin time were prolonged(15±2.3)s, (42±3.4) s, and the sizes of tumor and ecchymosis were slightly shrunken 18%±3%, 38%±5%; after (30±5.7) days treatment, the platelet counts and coagulation parameters returned to normal(146±36)×10(9)/L, and the size of tumor and ecchymosis were obviously shrunken 73%±3%, 97%±3%; after (3±0.4) months treatment, the tumor was obviously shrunken by 93%±2% and no longer palpable. In five cases with RKHE without KMS manifested stubborn dark red hard hemangiomatous plaques, coagulation tests and platelet were obviously normal, these patients were treated with sirolimus, after (2.0±0.6) months treatment, the tumor became shrunken 8%±3%, with continuous treatment the tumor shrunk gradually, after (4.0±3.2)months(2-18 mouths) the tumor was not eliminated 51%±7%. Conclusion: RKHE and KMS have typical clinical, laboratory and pathological characteristics, sirolimus plus prednisone have remarkable efficacy and minor side effects, it should be recommended for the treatment of KHE with KMS.

[Diagnostic value of combination of US and MRI in preoperative prediction for the extrathyroidal extension of papillary thyroid carcinoma].

Objective: The purpose of the present study was to evaluate the diagnostic performance of preoperative ultrasonography(US), magnetic resonance imaging(MRI) and US combined with MRI in the prediction of extrathyroidal extension(ETE) in patients with papillary thyroid carcinoma(PTC). Methods: Between January 2013 and December 2016, a total of 83 consecutive patients underwent surgery for pathologically confirmed PTCs with ETE. We analyzed all patients with PTC with ETE who received preoperative combination of US and MRI scan to evaluate ETE. Results: For minimal ETE, the accuracy was 92.2%(47/51) of US, 74.5%(38/51) of MRI, and their combination was 98.0%(50/51). The differences of the three methods for minimal ETE were statistically significantly different(P=0.000). For extensive ETE, the accuracy was 62.5%(20/32) of US, 87.5%(28/32) of MRI, and their combination was 93.8%(30/32). The different of the three methods for extensive ETE was statistically significantly different(P=0.000). For the total accuracy of ETE, US was 80.7%(67/83), MRI was 79.5% (66/83), and their combination was 96.4%(80/83). The difference of the three methods for ETE was statistically significantly different(P=0.001). Conclusion: The combination of US and MRI can improve the preoperative diagnostic accuracy of ETE for PTC.

Protective Effect of Edaravone Against Aß25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.

Amyloid-ß (Aß)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aß accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aß25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 µM edaravone before treatment with 25 µM Aß25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aß25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aß in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis.

OBJECTIVES: The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a meta-analysis to estimate the prognostic value of the PLR in ovarian cancer. METHODS: We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. RESULTS: Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference = 63.57, 95% CI 39.47-87.66, p < 0.00001). CONCLUSION: An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer.