Clinical Guidelines on Compression Therapy in Venous Diseases.

BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (Grade I), moderate (Grade IIa and IIb), and weak (Grade III) recommendations based on high quality (Class A), moderate quality (Class B), and low quality (Class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on seven fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome, chronic venous insufficiency, varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (Grade I) and 17 were based on high quality (Class A) evidence, highlighting the need for further research of the use of compression therapy for .

Bamboo polysaccharides elicit hypocrellin A biosynthesis of a bambusicolous fungus Shiraia sp. S9.

Hypocrellin A (HA), a fungal perylenequinone from bambusicolous Shiraia species, is a newly developed photosensitizer for photodynamic therapy in cancer and other infectious diseases. The lower yield of HA is an important bottleneck for its biomedical application. This study is the first report of the enhancement of HA production in mycelium culture of Shiraia sp. S9 by the polysaccharides from its host bamboo which serve as a strong elicitor. A purified bamboo polysaccharide (BPSE) with an average molecular weight of 34.2 kDa was found to be the most effective elicitor to enhance fungal HA production and characterized as a polysaccharide fraction mainly composed of arabinose and galactose (53.7: 36.9). When BPSE was added to the culture at 10 mg/L on day 3, the highest HA production of 422.8 mg/L was achieved on day 8, which was about 4.0-fold of the control. BPSE changed the gene expressions mainly responsible for central carbon metabolism and the cellular oxidative stress. The induced generation of H2O2 and nitric oxide was found to be involved in both the permeabilization of cell membrane and HA biosynthesis, leading to enhancements in both intra- and extracellular HA production. Our results indicated the roles of plant polysaccharides in host-fungal interactions and provided a new elicitation technique to improve fungal perylenequinone production in mycelium cultures.

SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

Effects of branched-chain amino acids on Shiraia perylenequinone production in mycelium cultures.

BACKGROUND: Perylenequinones from Shiraia fruiting bodies are excellent photosensitizers and widely used for anti-cancer photodynamic therapy (PDT). The lower yield of Shiraia perylenequinones becomes a significant bottleneck for their medical application. Branched-chain amino acids (BCAAs) not only serve as important precursors for protein synthesis, but also are involved in signaling pathway in cell growth and development. However, there are few reports concerning their regulation of fungal secondary metabolism. In present study, the eliciting effects of BCAAs including L-isoleucine (L-Ile), L-leucine (L-Leu) and L-valine (L-Val) on Shiraia perylenequinone production were investigated. RESULTS: Based on the analysis of the transcriptome and amino acid contents of Shiraia in the production medium, we revealed the involvement of BCAAs in perylenequinone biosynthesis. The fungal conidiation was promoted by L-Val treatment at 1.5 g/L, but inhibited by L-Leu. The spore germination was promoted by both. The production of fungal perylenequinones including hypocrellins A (HA), HC and elsinochromes A-C (EA-EC) was stimulated significantly by L-Val at 1.5 g/L, but sharply suppressed by L-Leu. After L-Val treatment (1.5 g/L) in Shiraia mycelium cultures, HA, one of the main bioactive perylenequinones reached highest production 237.92 mg/L, about 2.12-fold than that of the control. Simultaneously, we found that the expression levels of key genes involved in the central carbon metabolism and in the late steps for perylenequinone biosynthesis were up-regulated significantly by L-Val, but most of them were down-regulated by L-Leu. CONCLUSIONS: Our transcriptome analysis demonstrated that BCAA metabolism was involved in Shiraia perylenequinone biosynthesis. Exogenous BCAAs exhibit contrasting effects on Shiraia growth and perylenequinones production. L-Val could promote perylenequinone biosynthesis via not only enhancing the central carbon metabolism for more precursors, but also eliciting perylenequinone biosynthetic gene expressions. This is the first report on the regulation of BCAAs on fungal perylenequinone production. These findings provided a basis for understanding physiological roles of BCAAs and a new avenue for increasing perylenequinone production in Shiraia mycelium cultures.

Case report: A rare case of massive peripheral nerve melanotic schwannoma and review of the literature.

Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations. Just about 200 cases have been reported worldwide, in which occurred in peripheral nerves has even less reported. Due to the lack of cognition of melanotic schwannoma, it is easy to be misdiagnosed and mistreatment in primary hospitals. Herein, we presented a case of massive melanotic schwannoma growing in the brachial plexus of an elderly male patient. First, the patient underwent a left forearm tumor resection in the local primary hospital because a painless lump was found there in 2017, of which details remain unclear. After this operation, the patient developed the symptoms of left median nerve injury. Thus, he came to our hospital and underwent a second operation. During this operation, we found that a part of the median nerve was absent at the left forearm, and the remanent median nerve, from the broken end to the elbow, was totally turned black, which was accompanied by petroleum-like exudate. Losing the opportunity for nerve repair, the black nerve was removed extensively and thoroughly. Postoperative pathological diagnosis revealed that the tumor was melanotic schwannoma. Then 4 years later, the tumor recurrence again, which led to the paralysis of the whole left arm and severe nerve pain, and the pulmonary metastasis of the tumor was detected at the same time. The black nerve was resected again in our hospital, and the nerve pain was partially relieved after the operation. To the best of our knowledge, it is the first time to report a melanotic schwannoma case that happened in the peripheral nerve trunk and then spread to the whole brachial plexus. There were many questions that worthy of discussion could be invited from this case, and we analyzed and discussed them based on the relevant literature. In conclusion, we reported a rare case of melanotic schwannoma that happened in the brachial plexus and illustrated the problems of the diagnosis and treatment of it based on the analysis of the relevant literature, which is helpful for the cognition of this rare nerve tumor.

Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation.

OBJECTIVE: To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects. METHODS: From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed. RESULTS: A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05). CONCLUSIONS: The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.

STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis.

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

Effects of preoperative serum vitamin D levels on early clinical function outcomes and the moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty.

OBJECTIVE: To investigate the impact of vitamin D levels on early clinical function outcomes and the potential risk factors of moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty (TKA). METHODS: From April 2017 to December 2019, 226 women were retrospectively recruited. The women were divided into two groups based on their preoperative serum 25-hydroxyvitamin D levels: (1) vitamin D-sufficient group (≥30 ng/mL); (2) vitamin D-deficient group (<30 ng/mL). The visual analog scale, Western Ontario and McMaster Arthritis Index score, and Knee Society Score were used to evaluate clinical outcomes. Risk factors for developing postoperative moderate-to-severe knee pain were studied using multivariate binary logistic regression analyses. RESULTS: There was no significant difference in preoperative clinical function assessment between the two groups. The difference in postoperative Western Ontario and McMaster Arthritis Index score between the two groups was statistically significant (15.3 ±â€Š0.7 vs 15.6 ±â€Š0.7: P = 0.02). However, the differences in postoperative visual analog scale and Knee Society Score scores between the two groups were not significant (P > 0.05). The incidence of postoperative moderate-to-severe pain was 16.4% (95% CI 11.8%-21.9%). Multivariate logistic regression analysis revealed that vitamin D deficiency, smoking, and high body mass index were potential risk factors for moderate-to-severe knee pain in postmenopausal women early after TKA (P < 0.05). CONCLUSION: Preoperative vitamin D deficiency may adversely affect early functional outcomes in postmenopausal women after TKA. In addition, vitamin D deficiency, smoking, and high body mass index were independent risk factors for moderate-to-severe knee pain after surgery.

FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

Drug-Coated Balloon versus Bare Nitinol Stent in Femoropopliteal Artery: 12 Months Outcome from a Single Center in China.

OBJECT: The study sought to compare the safety and effectiveness of drug-coated balloon (DCB) with bare nitinol stent in patients with complex femoropopliteal(FP) lesions in real-world practice. METHODS: Patients with symptomatic (Rutherford stage 2 to 5) femoropopliteal lesions who underwent DCB or bare nitinol stent implantation at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital from June 2016 to September 2017 were included. Demographics, angiographic and procedural variables were included. Freedom from target lesion revascularization (TLR), primary patency and major adverse events were obtained from follow-up results at 3,6 and12 months. Descriptive analysis was performed on all variables. RESULTS: A total of 90 eligible patients were enrolled, which included 51 DCB subjects (mean age, 63.1 ± 13.2 years; 76.5% male) with 55 lesions and 39 nitinol stent subjects (mean age, 66.5 ± 10.5 years; 61.5% male) with 42 lesions. Significant higher primary patency was observed in the DCB group compared with the stent group (74.5% vs. 52.4%; log-rank test P = 0.018; HR 0.335, 95%CI 0.124-0.903, P = 0.031). The rates of freedom from TLR (f-TLR) were 78.2% and 59.5% (log-rank test P = 0.032) for the DCB group and the stent group, respectively, at 12 months. CD-TLR rates were 18.2% vs. 38.1% with a P-value of 0.023. Female sex (HR 6.122, 95%CI 1.880-19.934, P = 0.003), lesion length over 20 cm (HR 5.514, 95%CI 2.312-13.148, P < 0.001) and renal insufficiency (HR 2.609, 95%CI 1.087-6.260, P = 0.032) were suggested as independent risk factors of reducing primary patency. There were no significant differences in major adverse events between the 2 groups. CONCLUSION: The result above demonstrates that DCB treatment has higher primary patency and lower TLR at 12 months than nitinol stent. These data confirm the safety and effectiveness of the DCB for patients with complex femoropopliteal lesions.

ITPKA1 Promotes Growth, Migration and Invasion of Renal Cell Carcinoma via Activation of mTOR Signaling Pathway.

BACKGROUND: Renal cell cancer (RCC) is one of the most lethal malignancies of the kidney in adults. mTOR (mammalian target of rapamycin) signaling pathway plays a pivotal role in RCC tumorigenesis and progression and inhibitors targeting the mTOR pathway have been widely used in advanced RCC treatment. Therefore, it is of great significance to explore the potential regulators of the mTOR pathway as RCC therapeutic targets. MATERIALS AND METHODS: Bioinformatics analysis was used to screen out the most significant differentially expressed genes in the RCC dataset of The Cancer Genome Atlas (TCGA). Real-time PCR and Western-blot analysis were utilized to examine the expression of inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) in four RCC cell lines and one human embryonic kidney cell line. Cell counting Kit-8 and colony formation assay were performed to estimate the effect of ITPKA on the proliferation ability of RCC cells. Wound healing and Transwell assays were used to test the effect of ITPKA on RCC cell migration and invasion. Xenograft formation assay was performed in nude mice to investigate the effect of ITPKA in vivo. mTORC1 pathway inhibitor was added to explore the mechanisms by which ITPKA regulates RCC cell growth and progression. RESULTS: Based on bioinformatics analysis, ITPKA is screened out as one of the most significant differentially expressed genes in RCC. ITPKA is upregulated and positively correlated with RCC malignancy and poorer prognosis. ITPKA promotes RCC growth, migration and invasion in cultured cells, and accelerates tumor growth in nude mice. Mechanistically, ITPKA stimulates the mTORC1 signaling pathway which is a requirement for ITPKA modulation of RCC cell proliferation, migration and invasion. CONCLUSION: Our data demonstrate a critical regulatory role of the ITPKA in RCC and suggest that ITPKA/mTORC1 axis may be a promising target for diagnosis and treatment of RCC.

Enhancement of Low-Temperature Gas-Sensing Performance Using Substoichiometric WO3-x Modified with CuO.

To verify the effect of oxygen vacancy on gas sensitivity, we have systematically investigated the gas-sensing performance of copper oxide/substoichiometric tungsten oxide (CuO/WO3-x) nanocomposite sensors. Oxygen deficiency in WO3-x facilitates the reaction of hydrogen sulfide (H2S) gas with chemisorbed oxygen species (i.e., O2-, O-, and O2-) at low temperature. The oxygen/sulphur exchange reaction between CuO and H2S in the sensing process can achieve room temperature operation of gas sensors. After the WO3-x nanorods were modified by a low content of CuO nanoparticles (Cu:W = 1:20), the sensors present an n-type sensing behavior. Their best working temperatures drop from 289 °C (or 386 °C) to 99 °C (or 70 °C) at which the responses are improved by 14 to 163 times for different x values. Among them, CuO(L)/W5O14 shows the highest sensitivity of 1575.7 to 10 ppm H2S at 99 °C and 171.5 to 10 ppm H2S at room temperature. Once WO3-x were loaded with a high concentration of CuO nanoparticles (Cu:W = 1:2), they exhibit a p-type behavior, and the optimal working temperatures reduce suddenly to room temperature at which CuO(H)/W18O49 displays the most sensitive response of 7.2 even toward trace amounts of H2S as low as 100 ppb. In addition, p-type CuO weakens the metal-like characteristics of W18O49 and such weakening effect enhances with an increase in the CuO content. Therefore, the sensing performance of the CuO/W18O49 composite is the best among the four CuO/WO3-x sensors. The two designs for low and high Cu/W molar ratios all achieve enhanced room-temperature H2S gas response, with a fast recovery time of ∼60 s under heating pulse, as well as an excellent selectivity, which makes the sensors a promising candidate for practical applications. Moreover, the micro-Raman spectra confirmed CuS formation and the thermal effect on the decomposition of CuS in the sensing process was studied.

Gas Sensing Performance and Mechanism of CuO(p)-WO3(n) Composites to H2S Gas.

In this work, the compositional optimization in copper oxide/tungsten trioxide (CuO/WO3) composites was systematically studied for hydrogen sulfide (H2S) sensing. The response of CuO/WO3 composites changes from p-type to n-type as the CuO content decreases. Furthermore, the p-type response weakens while the n-type response strengthens as the Cu/W molar ratio decreases from 1:0 to 1:10. The optimal Cu/W molar ratio is 1:10, at which the sensor presents the ultrahigh n-type response of 1.19 × 105 to 20 ppm H2S gas at 40 °C. Once the temperature rises from 40 °C to 250 °C, the CuO/WO3 (1:1) sensor presents the p-n response transformation, and the CuO/WO3 (1:1.5) sensor changes from no response to n-type response, because the increased temperature facilitates the Cu-S bonds break and weakens the p-type CuO contribution to the total response, such that the CuS bond decomposition by a thermal effect was verified by a Raman analysis. In addition, with a decrease in CuO content, the CuO is transformed from partly to completely converting to CuS, causing the resistance of CuO to decrease from increasing and, hence, a weakening mode of p-CuO and n-WO3 to the total response turns to a synergistic mode to it.

Studies on Sensing Properties and Mechanism of CuO Nanoparticles to H2S Gas.

In this work, the high crystalline copper oxide (CuO) nanoparticles were fabricated by a hydrothermal method, and their structural properties were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The sensing results show that CuO nanoparticles exhibit enhanced sensitivity and good selectivity for hydrogen sulfide (H2S) gas at a low temperature. There are two working mechanisms involved in the H2S sensing based on CuO nanoparticle sensors. They are the H2S oxidation mechanism and the copper sulphide (CuS) formation mechanism, respectively. The two sensing mechanisms collectively enhance the sensor's response in the H2S sensing process. The Cu-S bonding is stable and cannot break spontaneously at a low temperature. Therefore, the CuS formation inhibits the sensor's recovery process. Such inhibition gradually enhances as the gas concentration increases from 0.2 ppm to 5 ppm, and it becomes weaker as the operating temperature rises from 40 °C to 250 °C. The XPS results confirmed the CuS formation phenomenon, and the micro Raman spectra demonstrated that the formation of CuS bonding and its decomposition can be effectively triggered by a thermal effect. Gas-sensing mechanism analysis supplied abundant cognition for the H2S sensing phenomena based on CuO materials.

Advanced oxidation protein products increase TNF-α and IL-1ß expression in chondrocytes via NADPH oxidase 4 and accelerate cartilage degeneration in osteoarthritis progression.

Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1ß expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1ß in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1ß in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1ß and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1ß in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.

CCL2-CCR2 Axis Potentiates NMDA Receptor Signaling to Aggravate Neuropathic Pain Induced by Brachial Plexus Avulsion.

Brachial plexus avulsion (BPA) represents the most devastating nerve injury in the upper extremity and is always considered as a sophisticated problem due to its resistance to most standard pain relief medications or neurosurgical interventions. There is also a lack of understanding on the underlying mechanisms. Our study aimed to investigate whether spinal CCL2-CCR2 signaling contributed to the development of neuropathic pain following BPA via modulating glutamate N-methyl-d-aspartate receptor (NMDAR). A rat model of BPA on lower trunk (C8-T1) was established, and the sham- and BPA-operated animals were intrathecally injected with saline, C-C chemokine receptor type 2 (CCR2) inhibitor INCB3344 and NMDAR antagonist DL-AP5 one week postoperatively, the behavioral performance of the treated animals and expressions of C-C motif ligand 2 (CCL2), CCR2, and N-methyl-D-aspartic acid receptor 2B (NR2B) in spinal cord sections of each group were examined. It was shown that BPA injury significantly reduced mechanic withdrawal thresholds the next day after surgery until the end of the observation. Both CCL2 and CCR2 expressions increased in BPA rats compared to those in sham rats. CCL2 was mainly localized in astrocytes, and CCR2 was preferably expressed on astrocytes and neurons. Besides, NMDAR subunit NR2B increased in BPA-operated rats, which was reversed in response to CCR2 and NR2B inhibition. However, these inhibitors didn't change the spinal NMDAR level in sham rats. CCR2 and NMDAR inhibition efficiently alleviated mechanical allodynia caused by BPA either at early or late phase of neuropathic pain. Collectively, CCL2-CCR2 axis is associated with mechanical pain after BPA by elevating NMDAR signaling.

Hydroxytyrosol promotes autophagy by regulating SIRT1 against advanced oxidation protein product­induced NADPH oxidase and inflammatory response.

Advanced oxidation protein products (AOPPs) can trigger NADPH oxidase (NOX) and lead to the production of reactive oxygen species (ROS) in the pathophysiology of rheumatoid arthritis (RA). Hydroxytyrosol (HT) is a phenolic composite in olive oil that has antioxidant and anti­inflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy and alleviate the cartilage inflammatory response caused by H2O2. However, whether HT can attenuate AOPP­induced NOX and inflammatory responses remains to be elucidated. The present study aimed to investigate how HT can alleviate the damage caused by AOPPs. In cell experiments, chondrocytes were pre­stimulated with HT and then exposed to AOPPs. First, it was found that HT promoted autophagy through the SIRT1 pathway, increased the expression of autophagy­related proteins including microtubule­associated protein 1 light chain 3, autophagy related (ATG)5 and ATG7, and decreased the expression of P62. Furthermore, HT reduced the expression of NOX, which was affected by AOPPs in chondrocytes through the SIRT1 pathway. Finally, the expression of inflammatory cytokines caused by AOPPs was downregulated following HT treatment. In conclusion, it was found that HT reduced the expression of NOX and inhibited the inflammatory response caused by AOPPs in chondrocytes through the SIRT1 pathway.

Comparing Performance of Combinations of Shear Wave Elastography and B-Mode Ultrasound in Diagnosing Breast Masses: Is It Influenced by Mass Size?

We determined the diagnostic performance of combinations of shear wave elastography (SWE) and B-mode ultrasound (US) in differentiating malignant from benign breast masses, and we investigated whether performance is affected by mass size. In this prospective study of 315 consecutive patients with 326 breast masses, US and SWE were performed before biopsy. Masses were categorized into two subgroups on the basis of mass size (≤15 mm and >15 mm), and the optimal thresholds for the SWE parameters were determined for each subgroup using receiver operating characteristic curves. The combination proposed here achieved an area under the receiver operating characteristic curve of 0.943, 95.00% sensitivity and 81.18% specificity, which approximated the diagnostic performance of US alone. The performance of the combinations using the subgroups' thresholds did not differ significantly from those based on the entire study group's thresholds, but the optimal thresholds were higher in the subgroup of larger masses. Further research is needed to determine whether mass size affects the performance of combinations of SWE and US.

3D Printing Technology in Planning Thumb Reconstructions with Second Toe Transplant.

OBJECTIVE: To report preoperative planning using 3D printing to plan thumb reconstructions with second toe transplant. METHODS: Between December 2013 and October 2015, the thumbs of five patients with grade 3 thumb defects were reconstructed using a wrap-around flap and second toe transplant aided by 3D printing technology. CT scans of hands and feet were analyzed using Boholo surgical simulator software (www.boholo.com). This allowed for the creation of a mirror image of the healthy thumb using the uninjured thumb. Using 3D images of the reconstructed thumb, a model of the big toe and the second toe was created to understand the dimensions of the donor site. This model was also used to repair the donor site defect by designing appropriate iliac bone and superficial circumflex iliac artery flaps. The polylactic acid model of the donor toes and reconstructed thumb was produced using 3D printing. Surgically, the wrap-around flap of the first dorsal metatarsal artery and vein combined with the joint and bone of the second toe was based upon the model donor site. Sensation was reconstructed by anastomosing the dorsal nerve of the foot and the plantar digital nerve of the great toe. Patients commenced exercises 2 weeks after surgery. RESULTS: All reconstructed thumbs survived, although partial flap necrosis occurred in one case. This was managed with regular dressing changes. Patients were followed up for 3-15 months. The lengths of the reconstructed thumbs are 34-49 mm. The widths of the thumb nail beds are 16-19 mm, and the thickness of the digital pulp is 16-20 mm. The thumb opposition function was 0-1.5 cm; the extension angle was 5°-20° (mean, 16°), and the angle of flexion was 38°-55° (mean, 47°). Two-point discrimination was 9-11 mm (mean, 9.6 mm). The reconstructed thumbs had good appearance, function and sensation. Based on the criteria set forth by the Standard on Approval of Reconstructed Thumb and Finger Functional Assessment of the Chinese Medical Association, the results were considered excellent for four cases and good for one case. The success rate was 100%. CONCLUSIONS: When planning a wrap-around flap and second toe transplant to reconstruct a thumb, both the donor and recipient sites can be modeled using 3D printing. This can shorten the operative time by supplying digital and accurate schematics for the operation. It can also optimize the function and appearance of the reconstructed thumb while minimizing damage to the donor site.