Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

Fingolimod Inhibits Exopolysaccharide Production and Regulates Relevant Genes to Eliminate the Biofilm of K. pneumoniae.

Klebsiella pneumoniae (K. pneumoniae) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) K. pneumoniae in this study. The antibiofilm activity of FLD against K. pneumoniae was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within K. pneumoniae biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (AcrB, kexD, ketM, kdeA, and kpnE), outer membrane (OM) porin proteins (OmpK35, OmpK36), the quorum-sensing (QS) system (luxS), lipopolysaccharide (LPS) production (wzm), and EPS production (pgaA). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of G. mellonella infected with MDR K. pneumoniae. These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating K. pneumoniae infections.

High-power yellow DSR pulses generated from a mode-locked Dy:ZBLAN fiber laser.

Ultrafast yellow lasers are in high demand in recent biomedical and medical applications; however, direct emission of mode-locked pulses in yellow at the high-power level still presents a huge technical challenge to date. By integrating the nonlinear polarization rotation (NPR) scheme into a Dy:ZBLAN fiber laser, dissipative soliton resonance pulses at ∼575 nm are demonstrated for the first time, to the best of our knowledge. The average output power reaches ∼240 mW at maximum, which is an improvement of almost two orders of magnitude over those reported from the latest mode-locked visible fiber lasers. The laser scheme combines a piece of large-core Dy:ZBLAN gain fiber and free-space NPR components designated at the yellow bandwidth. The maximal pulse energy is 2.4 nJ at the repetition rate of ∼100 MHz and the minimal pulse duration is 83 ps. The achieved wavelength of 575 nm is the shortest ever reached from a fiber-based mode-locked laser to date.

Ultrafast true-green Ho:ZBLAN fiber laser inspired by the TD3 AI algorithm.

Ultrafast lasers in the true-green spectrum, which are scarce due to the "green gap" in semiconductor materials, are in high demand for the surging field of biomedical photonics. One ideal candidate for efficient green lasing is Ho:ZBLAN fiber, as ZBLAN-hosted fibers have already reached picosecond dissipative soliton resonance (DSR) in the yellow. When attempting to push the DSR mode locking further into the green, traditional manual cavity tuning is faced with extreme difficulty, as the emission regime for these fiber lasers is so deeply concealed. Breakthroughs in artificial intelligence (AI), however, provide the opportunity to fulfill the task in a fully automated manner. This work, inspired by the emerging twin delayed deep deterministic policy gradient (TD3) algorithm, represents the first application, to the best of our knowledge, of the TD3 AI algorithm to generate picosecond emissions at the unprecedented true-green wavelength of ∼545 nm. The study thus extends the ongoing AI technique further into the ultrafast photonics region.

First-principles calculations of 0D/2D GQDs-MoS2 mixed van der Waals heterojunctions for photocatalysis: a transition from type I to type II.

The fabrication of type II heterojunctions is an efficient strategy to facilitate charge separation in photocatalysis. Here, mixed dimensional 0D/2D van der Waals (vdW) heterostructures (graphene quantum dots (GQDs)-MoS2) for generating hydrogen from water splitting are investigated based on density functional theory (DFT). The electronic and photocatalytic properties of three heterostructures, namely, C6H6-MoS2, C24H12-MoS2 and C32H14-MoS2 are estimated by analyzing the density of states, charge density difference, work function, Bader charge, absorption spectra and band alignment. The results indicated that the built-in electric fields from GQDs to MoS2 boost charge separation. Meanwhile, all the GQDs-MoS2 exhibit strong absorption in the visible light region. Surprisingly, the transition of heterojunctions from type I to type II is realized by tuning the size of GQDs. In particular, C32H14-MoS2 with enhanced visible-light absorption and an appropriate band edge position, as a type II heterostructure, may be a promising photocatalyst for generating hydrogen from water splitting. Thus, in this work a novel type II 0D/2D nanocomposite as a photocatalyst is constructed that provides a strategy to regulate the type of heterostructure from the perspective of theoretical calculation.

Effect of loading history on material properties of human heel pad: an in-vivo pilot investigation during gait.

BACKGROUND: This study was aimed to develop a novel dynamic measurement technique for testing the material properties and investigating the effect of continuous compression load on the structural and mechanical properties of human heel pad during actual gait. METHODS: The dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, elastic modulus, viscous modulus and energy dissipation rate (EDR), both at time zero and following continuous loading. Ten healthy pilot subjects, aged from 23 to 72 (average: 46.5 ± 17.6), were enrolled. A "three-step gait cycle" is performed for all subjects, with the second step striking at a marked position on the force plate with the heel to maintain the location of the tested foot to be in the view of fluoroscopes. The subjects were measured at both relaxed (time-zero group) and fatigue (continuous-loading group) statuses, and the left and right heels were measured using the identical procedures. RESULTS: The peak strain, peak stress, elastic modulus, and EDR are similar before and after continuous load, while the viscous modulus was significantly decreased (median: 43.9 vs. 20.37 kPa•s; p < 0.001) as well as primary thicknesses (median: 15.99 vs. 15.72 mm; p < 0.001). Age is demonstrated to be moderately correlated with the primary thicknesses both at time zero (R = -0.507) and following continuous load (R = -0.607). The peak stress was significantly correlated with the elastic modulus before (R = 0.741) and after continuous load (R = 0.802). The peak strain was correlated with the elastic modulus before (R = -0.765) and after continuous load (R = -0.801). The correlations between the viscous modulus and peak stress/ peak strain are similar to above(R = 0.643, 0.577, - 0.586 and - 0.717 respectively). The viscous modulus is positively correlated with the elastic modulus before (R = 0.821) and after continuous load (R = 0.784). CONCLUSIONS: By using dynamic fluoroscopy combined with the plantar pressure plate, the in vivo viscoelastic properties and other data of the heel pad in the actual gait can be obtained. Age was negatively correlated with the primary thickness of heel pad and peak strain, and was positively correlated with viscous modulus. Repetitive loading could decrease the primary thickness of heel pad and viscous modulus.

FBLN1 promotes chondrocyte proliferation by increasing phosphorylation of Smad2.

BACKGROUND: The role of fibulin-1 or FBLN1 in chondrocyte proliferation has not been reported so far. In this study, we aimed to verify whether FBLN1 promotes chondrocyte proliferation in elderly patients with knee osteoarthritis by phosphorylating Smad2. METHODS: Chondrocytes were isolated from cartilage samples collected from elderly patients with osteoarthritis (n = 6) and young patients (n = 6). The isolated chondrocytes were divided into the following three groups: control (medium only); cells transfected with adenovirus expressing green fluorescent protein (Ad-GFP); and those transfected with adenovirus expressing green fluorescent protein and FBLN1 (Ad-GFP-FBLN1). Furthermore, chondrocytes were divided into the following three groups in the mechanistic analysis: group 1, medium only; group 2, Ad-FBLN1; and group 3, Ad-FBLN1+pSmad2 inhibitor. The cells were analyzed for the relevant indicators after culturing for 48 h. RESULTS: There were more EdU-positive cells in the Ad-GFP-FBLN1 group than in the other two groups (both P < 0.05). Compared with the other two groups, the level of pSmad2 and Col2 in the Ad-GFP-FBLN1 group was significantly increased (P < 0.05). The gene expression level of each indicator was consistent with the protein expression level. There was no significant difference in the indicators between groups 1 and 3. The percentage of EdU-positive cells in group 2 was higher than that in the other two groups (P < 0.05). The expression of pSmad2 and Col2 in group 2 was higher than that in the other two groups (both P < 0.05). CONCLUSION: FBLN1 can promote chondrocyte proliferation in the knee cartilage in elderly patients by phosphorylating Smad2.

GDF15 enhances proliferation of aged chondrocytes by phosphorylating SMAD2.

BACKGROUND: Aging is one of the primary factors influencing development of osteoarthritis, and the TGF-ß pathway plays an important role in age-related osteoarthritis. Specifically, GDF15 phosphorylates SMAD2/3 in the TGF-ß pathway to inhibit cardiomyocyte hypertrophy, and promote proliferation of chondrocytes. However, age-dependent changes in the level of GDF15 are unclear, as is whether GDF15 phosphorylates SMAD2/3 in the TGF-ß pathway to promote proliferation of old chondrocytes. This study, therefore, sought to examine the effect of various GDF15 concentrations on old chondrocyte proliferation. METHODS: Serum and cartilage specimens of young adults and older adults were collected, and GDF15 expression was quantified. Human chondrocytes were then cultured following routine protocols, and different concentrations of recombinant human GDF15 or pSMAD2 inhibitor were added into the culture medium. After 48 h of culturing, the proliferation of chondrocytes was detected by EdU, and the expression MMP13, SMAD2, and pSMAD2 was detected in chondrocytes via western blot and qRT-PCR analysis. RESULTS: The GDF15 content in serum and cartilage of young adults was higher than that of older adults (p < 0.05). The number of EdU-positive cells in the experimental group (containing recombinant human GDF15) was higher than that in the control group (medium only) (p < 0.05). Compared with the control group, chondrocytes in the experimental group showed increased pSMAD2 and type II collagen content (p < 0.05) and decreased MMP13 (p < 0.05), with no significant difference in SMAD2 content (p > 0.05). Moreover, no significant differences were observed between the control group and the TGF-ß signaling inhibitor group. The gene expression level of each index was consistent with the protein expression level. CONCLUSIONS: The GDF15 content of serum and cartilage in young adults is higher than in older adults, and GDF15 functions to promote the proliferation of chondrocytes by phosphorylating SMAD2 in older individuals.

Study of asymmetric biconical fiber tapers for in-fiber Mach-Zehnder interferometers and applications in single-frequency fiber lasers.

In this paper, asymmetric biconical fiber tapers (ABFTs) for in-fiber Mach-Zehnder interferometers (IFMZIs) are proposed and analyzed to enhance the interference effect. The proposed ABFT-IFMZIs are fabricated, tested, and demonstrated in applications of single-frequency (SF) emissions when incorporated into an all-fiber laser cavity as the frequency selecting component. In comparison with the traditional IFMZIs composed of all symmetric biconical fiber tapers (SBFTs), higher average transmittance and fringe contrast have been demonstrated with the ABFT-based IFMZIs. When applied to the SF fiber laser emission, lower pump threshold and higher slope efficiency have also been confirmed with the ABFT-IFMZI device. The theoretical and experimental results have indicated that the interference effect of IFMZIs can indeed be improved by the designated asymmetry of conical taper angles in ABFTs that can offer an extra flexibility in fiber taper design, fabrication, and applications.

Bone marrow-derived mesenchymal stem cells alleviate severe acute pancreatitis-induced multiple-organ injury in rats via suppression of autophagy.

Patients with severe acute pancreatitis (SAP) represent a substantial challenge to medical practitioners due to the high associated rates of morbidity and mortality and a lack of satisfactory therapeutic outcomes. In a previous study, our group demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate SAP; however, the mechanisms of action remain to be fully understood. BMSCs were intravenously injected into SAP rats 12 h after experimental induction of SAP using sodium taurocholate (NaT). Histopathological changes and the levels of pro-inflammatory mediators were assessed by hematoxylin and eosin (H&E) staining and ELISA, respectively. Autophagy levels were assessed using qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, and transmission electron microscopy. AR42J cells and human umbilical vein endothelial cells (HUVECs) were administered BMSC-conditioned media (BMSC-CM) after NaT treatment, and cell viability was measured using a Cell Counting Kit-8 (CCK-8) and flow cytometry. In vivo, BMSCs effectively reduced multiple systematic inflammatory responses, suppressed the activation of autophagy, and improved intestinal dysfunction. In vitro, BMSC-CM significantly improved the viability of injured cells, promoted angiogenesis, and decreased autophagy. We therefore propose that the administration of BMSCs alleviates SAP-induced multiple organ injury by inhibiting autophagy.

Role of miR-155-5p expression and its involvement in apoptosis-related factors in thyroid follicular carcinoma.

WHAT IS KNOWN AND OBJECTIVE: Thyroid follicular carcinoma is a malignant tumor from thyroid follicular epithelium, which is prone to involve capsular and vascular invasion. The present study was conducted in order to detect the expression of microRNA-155-5p (miR-155-5p) in thyroid follicular carcinoma with an attempt to analyze its involvement in apoptosis-related factors. METHODS: Forty-five patients with thyroid follicular carcinoma made up the observation group and 45 patients with thyroid follicular adenoma were included into the control group. Tissues of thyroid follicular carcinoma and thyroid follicular adenoma were obtained from the patients, and analysed for expression of miR-155-5p by real-time fluorescence quantitative PCR (qPCR). The expression of cysteine-containing aspartic acid protein hydrolase-3 (Caspase-3) in thyroid follicular carcinoma was detected with the use of Western Blot analyses. Immunohistochemical method was used to detect the expression of B-cell lymphoma protein-2 (Bcl-2) in thyroid follicular carcinoma. RESULTS: There was significant difference in the expression of miR-155-5p between the two groups (Observation vs Control: 1.46 ± 0.42 vs 0.98 ± 0.33 P < .05). The expression of miR-155-5p was significantly different in the maximum diameter of tumor, vascular invasion and neural invasion (maximum diameter of tumor <4 cm vs ≥4 cm: 1.36 ± 0.40 vs 1.68 ± 0.32, vascular invasion N vs Y: 1.35 ± 0.42 vs 1.69 ± 0.39, Neural invasion N vs Y: 1.35 ± 0.38 vs 1.70 ± 0.31 P < .05). However, there was no significant difference in the expression of miR-155-5p in terms of different gender, age and group with or without lymph node metastasis (P > .05). Based on survival analysis, patients with high expression of miR-155-5p experienced short survival time (median survival time was 45 months, P < .05). There was a negative correlation between miR-155-5p and Caspase-3 (r = -.50, P < .05). In addition, positive correlation was observed between miR-155-5p and Bcl-2 (r = .55, P < .05). WHAT IS NEW AND CONCLUSION: There was increased expression of miR-155-5p in thyroid follicular carcinoma. The abnormal expression of miR-155-5p may be an independent prognostic factor for thyroid follicular carcinoma associated with cell apoptosis.

Impact of first metatarsal shortening on forefoot loading pattern: a finite element model study.

BACKGROUNDS: There has long been a consensus that shortening of the first metatarsal during hallux valgus reconstruction could lead to postoperative transfer metatarsalgia. However, appropriate shortening is sometimes beneficial for correcting severe deformities or relieving stiff joints. This study is to investigate, from the biomechanical perspective, whether and how much shortening of the first metatarsal could be allowed. METHODS: A finite element model of the human foot simulating the push-off phase of the gait was established. Progressive shortening of the first metatarsal from 2 to 8 mm at an increment of 2 mm were sequentially applied to the model, and the corresponding changes in forefoot loading pattern during push-off phase, especially the loading ratio at the central rays, was calculated. The effect of depressing the first metatarsal head was also investigated. RESULTS: With increasing shortening level of the first metatarsal, the plantar pressure of the first ray decreased, while that of the lateral rays continued to rise. When the shortening reaches 6 mm, the load ratio of the central rays exceeds a critical threshold of 55%, which was considered risky; but it could still be manipulated to normal if the distal end of the first metatarsal displaced to the plantar side by 3 mm. CONCLUSIONS: During the first metatarsal osteotomy, a maximum of 6 mm shortening length is considered to be within the safe range. Whenever a higher level of shortening is necessary, pushing down the distal metatarsal segment could be a compensatory procedure to maintain normal plantar force distributions.

Outcome Comparison Between Functional Ankle Instability Cases With and Without Anterior Ankle Impingement: A Retrospective Cohort Study.

Functional ankle instability (FAI) and anterior ankle impingement (AAI) are likely to occur simultaneously. Nevertheless, how AAI affects ankle instability remains largely unknown. This study aimed to assess patients with FAI + AAI and those having FAI without AAI after arthroscopic synovectomy combined with the modified Broström procedure. Patients with chronic ankle instability who underwent surgery at the Huashan Hospital of Fudan University (China) from January 2010 to December 2015 were reviewed. Propensity score matching was performed (FAI + AAI: n = 86; FAI without AAI: n = 43). Ankle function was assessed by the American Orthopedic Foot and Ankle Society (AOFAS) and the Meislin criteria at 3 months, 1 year, and final follow-up. In the FAI + AAI group, AOFAS scores increased from 52.6 ± 7.2 to 78.6 ± 8.2, 84.2 ± 6.4, and 83.6 ± 11.3 at 3 months, 1 year, and last follow-up, respectively (p < .001). In the FAI without AAI group, AOFAS scores increased from 64.3 ± 10.5 to 85.2 ± 8.6, 91.4 ± 7.9, and 90.2 ± 9.8 at 3 months, 1 year, and last follow-up, respectively (p < .001; all p < .05 for differences between the 2 groups at each time point). The 2 groups showed similar scores based on the Meislin criteria (p = .38). Hypertrophic distal fascicle of the anteroinferior tibiofibular ligament showed lower AOFAS scores (all p < .05). Patients with FAI with or without AAI had improved outcomes with arthroscopic synovectomy combined with the modified Broström procedure; however, patients with combined FAI and AAI showed a relatively poorer outcome in comparison with those suffering from FAI alone, probably because of hypertrophic distal fascicle of the anteroinferior tibiofibular ligament.

Proline-Rich Protein 11 Regulates Self-Renewal and Tumorigenicity of Gastric Cancer Stem Cells.

BACKGROUND/AIMS: Gastric cancer is a highly aggressive tumor containing cancer stem cells (CSCs), which participate in tumor initiation, therapeutic resistance, and tumor relapse. Proline-rich protein 11 (PRR11) has been shown to be up-regulated in human cancers; however, its role in gastric CSCs is unknown. We hypothesize that PRR11 may affect tumorigenicity of gastric CSCs. In this study, we explored the biological function and regulation of PRR11 in gastric CSCs. METHODS: Expression of PRR11 was evaluated in gastric CSC cell line by real-time quantitative PCR and western blot. The effect of PRR11 on tumorigenicity was examined by interference with gene expression using lentiviral vector-loaded shRNA. A xenograft tumor model using NOD/SCID mice was established to examine the role of PRR11 in tumor development. RESULTS: Data showed that PRR11 was highly expressed in gastric CSCs. PRR11 was responsible for the maintenance of self-renewal and tumorigenicity of gastric CSCs, and overexpression of exogenous PRR11 could restore the self-renewal of gastric non-CSCs. Furthermore, interference with PRR11 altered the expression of stemness transcription factors. Interestingly, MAPK signaling controlled PRR11 expression by increasing PRR11 protein stability, and maintained gastric CSCs self-renewal in a PRR11 dependent manner. CONCLUSIONS: PRR11 regulated self-renewal and tumorigenicity of gastric CSCs through MAPK signaling, and could be used as a therapeutic target for gastric cancer.

Genome mining of Streptomyces xinghaiensis NRRL B-24674T for the discovery of the gene cluster involved in anticomplement activities and detection of novel xiamycin analogs.

Marine actinobacterium Streptomyces xinghaiensis NRRL B-24674T has been characterized as a novel species, but thus far, its biosynthetic potential remains unexplored. In this study, the high-quality genome sequence of S. xinghaiensis NRRL B-24674T was obtained, and the production of anticomplement agents, xiamycin analogs, and siderophores was investigated by genome mining. Anticomplement compounds are valuable for combating numerous diseases caused by the abnormal activation of the human complement system. The biosynthetic gene cluster (BGC) nrps1 resembles that of complestatins, which are potent microbial-derived anticomplement agents. The identification of the nrps1 BGC revealed a core peptide that differed from that in complestatin; thus, we studied the anticomplement activity of this strain. The culture broth of S. xinghaiensis NRRL B-24674T displayed good anticomplement activity. Subsequently, the disruption of the genes in the nrps1 BGC resulted in the loss of anticomplement activity, confirming the involvement of this BGC in the biosynthesis of anticomplement agents. In addition, the mining of the BGC tep5, which resembles that of the antiviral pentacyclic indolosesquiterpene xiamycin, resulted in the discovery of nine xiamycin analogs, including three novel compounds. In addition to the BGCs responsible for desferrioxamine B, neomycin, ectoine, and carotenoid, 18 BGCs present in the genome are predicted to be novel. The results of this study unveil the potential of S. xinghaiensis as a producer of novel anticomplement agents and provide a basis for further exploration of the biosynthetic potential of S. xinghaiensis NRRL B-24674T for the discovery of novel bioactive compounds by genome mining.

Arthrodesis for Treatment of Intra-Articular Synovial Cysts of the Hallux Interphalangeal Joint.

Synovial cysts are benign tissue masses that develop near joints and tendons as a result of fluid leakage. They can be difficult to eradicate, and adjacent tendon and joint surfaces can complicate their treatment. We retrospectively analyzed the data from 4 consecutive patients who had undergone hallux interphalangeal fusion from January 2009 to December 2010. Of the 4 patients, 3 were male and 1 was female, with a mean age of 55 ± 22 (range 26 to 79) years. These 4 patients had developed painful interphalangeal arthritis with radiographic cystic changes of 1 to 4 years' duration. All patients were treated at a single facility, with surgical fixation of the joint performed by insertion of a single 4.3-mm headless lag screw across the interphalangeal joint. A final postoperative follow-up examination was performed at 22 ± 7 (range 14 to 30) months postoperatively. The mean American Orthopaedic Foot and Ankle Society hallux functional scores increased significantly from 70.8 ± 6.1 preoperatively to 90.5 ± 5.2 postoperatively (p < .01). No complications were observed, and complete interphalangeal joint fusion was observed at a mean of 9.2 ± 1.2 weeks. In conclusion, these preliminary data suggest that arthrodesis is an alternative effective treatment of symptomatic synovial cyst formation localized to the hallux interphalangeal joint.

Arsenic trioxide intravenous infusion combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with pulmonary metastasis: Long-term outcome analysis.

OBJECTIVE: To evaluate the safety, clinical efficacy, and long-term outcome of arsenic trioxide (As2 O3 ) intravenous infusion for pulmonary metastases in patients with HCC. MATERIALS AND METHODS: Sixty consecutive patients who were diagnosed with advanced hepatocellular carcinoma (HCC) with pulmonary metastasis were randomized 1:1 into the treatment and control groups. Treatment group underwent transcatheter arterial chemoembolization (TACE) for the primary liver tumor and then underwent As2 O3 treatment, whereas control group underwent TACE alone. The treatment group underwent a continuous 5-h intravenous infusion of 10 mg/day As2 O3 . The course of As2 O3 treatment was initiated 3-5 days after TACE (to allow liver and gastrointestinal function to recover) and continued for 14 consecutive days. All patients in the treatment group underwent at least four treatment courses. Response to treatment was evaluated after four treatment courses. RESULT: In treatment group, two patients had a complete response (CR), six had a partial response (PR), 10 had stable disease (SD), and 12 had progressive disease. A clinically effective rate (CR + PR) was achieved in 26.7%, and the clinical benefit rate (CR + PR + SD) was 60%. In the control group, no patients had a CR or PR, five had SD, and 25 had progressive disease. The clinically effective rate was 0%, and the clinical benefit rate was 16.7%. The overall 1-year survival was 56.7% in treatment group and 36.7% in control group. The overall 2-year survival was 16.7% in treatment group and 3.3% in control group. CONCLUSION: Transcatheter arterial chemoembolization plus an intravenous infusion of As2 O3 effectively controlled pulmonary metastasis and prolonged overall survival in patients with HCC compared with TACE alone.