Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture.

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.

Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: a retrospective observational study based on SEER.

PURPOSE: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. METHODS: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan-Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. RESULTS: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18-45, 46-55, 56-65, and 65-80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18-45 years: OS P = 0.019, BCSS P = 0.016; age group of 46-55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18-45 years: OS P = 0.473, BCSS P = 0.750; age group of 46-55 years: OS P = 0.380, BCSS P = 0.816, age group of 56-65 years: OS P = 0.484, BCSS P = 0.290; age group of 66-80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB. CONCLUSION: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT.

Activatable Dual-Optical Molecular Probe for Bioimaging Superoxide Anion in Epilepsy.

Superoxide anion (O2•-) plays a pivotal role in the generation of other reactive oxygen species within the body and is closely linked to epilepsy. Despite this connection, achieving precise imaging of O2•- during epilepsy pathology remains a formidable challenge. Herein, we develop an activatable molecular probe, CL-SA, to track the fluctuation of the level of O2•- in epilepsy through simultaneous fluorescence imaging and chemiluminescence sensing. The developed probe CL-SA demonstrated its efficacy in imaging of O2•- in neuronal cells, showcasing its dual optical imaging capability for O2•- in vitro. Furthermore, CL-SA was successfully used to observe aberrantly expressed O2•- in a mouse model of epilepsy. Overall, CL-SA provides us with a valuable tool for chemical and biomedical studies of O2•-, promoting the investigation of O2•- fluctuations in epilepsy, as well as providing a reliable means to explore the diagnosis and therapy of epilepsy.

Longitudinal associations between serum IL-34 with severity and prognosis in community-acquired pneumonia patients.

BACKGROUND: Interleukin-34 (IL-34) is a hematopoietic cytokine and a ligand of colony-stimulating factor 1 receptor (CSF-1R). Numerous studies have demonstrated that IL-34 is involved in several inflammatory diseases. Nevertheless, the role of IL-34 is obscure in community-acquired pneumonia (CAP) patients. This research aimed to assess the associations of serum IL-34 with severity and prognosis in CAP patients through a longitudinal study. METHODS: CAP patients and healthy volunteers were recruited. Peripheral blood samples were collected. Serum IL-34 and inflammatory cytokines were tested by enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were acquired through electronic medical records. RESULTS: Serum IL-34 was elevated in CAP patients compared with healthy volunteers. The content of serum IL-34 was gradually upregulated with increased CAP severity scores. Mixed logistic and linear regression models suggested that serum IL-34 elevation was associated with increased PSI and SMART-COP scores. Correlative analysis found that serum IL-34 was positively correlated with inflammatory cytokines among CAP patients. A longitudinal study indicated that higher serum IL-34 at admission elevated the risks of mechanical ventilation and death during hospitalization. Serum IL-34 had a higher predictive capacity for death than CAP severity scores. CONCLUSION: There are prominently positive dose-response associations between serum IL-34 at admission with the severity and poor prognosis, suggesting that IL-34 is implicated in the occurrence and development of CAP. Serum IL-34 may serve as a biomarker to forecast disease progression and poor prognosis in CAP patients.

Effects of stevia extract on production performance, serum biochemistry, antioxidant capacity, and gut health of laying hens.

In the present study, we aimed to elucidate the effects of stevia extract on production performance, serum immune indexes, intestinal structure, and cecum microbial structure. We randomly divided eight hundred 46-wk-old Roman hens into 5 groups, with 8 replicates in each group and 20 chickens in each replicate. The control group was fed a basal diet, whereas the 4 experimental groups were fed 50, 100, 200, and 400 mg/kg stevia extracts. The study period was 24 wk. The addition of different concentrations of the stevia extract to the diet resulted in significant secondary changes in the egg production rate at 1 to 12 wk (P < 0.05). Furthermore, the addition of 50 and 100 mg/kg stevia extract to the diet significantly increased serum IgM and IgG levels in laying hens (P < 0.05) but linearly decreased serum IL-1ß levels (P < 0.05). Serum T-SOD activity linearly increased (P = 0.057); however, serum biochemical indexes showed no significant differences. Stevia extract tended to increase the ratio of the duodenal villi height to the depth of the crypt (P = 0.067), with no obvious lesions in the duodenum, jejunum, and ileum. In addition, stevia extract increased the relative abundance of species at the phylum level, with the abundance of Bacteroides and Firmicutes exhibiting significant secondary changes (P < 0.05). The ACE and Chao1 indexes suggested that stevia extract addition significantly increased the alpha diversity of cecum microorganisms in laying hens. Furthermore, NMDS analysis based on operational taxonomic units revealed that stevia extract addition increased the beta diversity of cecum microorganisms in laying hens. Adding a certain amount of stevia extract to feed can improve the production performance, immune ability, and intestinal health of laying hens to some extent, and we recommend an effective level of 200mg/kg of stevia extract for laying hen diets.

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs.

BACKGROUND: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

Systematic review and metanalysis of neutrophil to lymphocyte ratio and prognosis in patients with nasopharyngeal carcinoma.

Background: Hematological parameters have been associated with prognosis in patients with nasopharyngeal carcinoma (NPC). The present meta-analysis investigated the utility of neutrophil-lymphocyte ratio (NLR) in the prognosis of patients with NPC. Methods: Multiple electronic databases, including PubMed, Embase, the Cochrane Library, and the Web of Science, were systematically searched for studies assessing the association between NLR and NPC from 2011 to 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to estimate effect size. Use of a fixed effect or random effect model was based on heterogeneity stability was tested by sensitivity analysis, and the risk of bias was assessed by funnel plots. Random effects models were used based on the actual results. Because the NLR grouping criteria for the included studies differed, subgroup analyses were performed. Results: A search of the electronic databases identified 14 studies, encompassing 6693 patients, that met the selection criteria. NLR higher than the cutoff value was significantly associated with poorer OS [HR 1.760, 95% CI 1.470-2.120, p <0.00001] and PFS [HR 1.850, 95% CI 1.430-2.390, p = .006]. Sensitivity analysis showed that the results of the meta-analysis were relatively stable, and funnel plots were used to exclude the risk of bias. Conclusions: Elevated pretreatment NLR in peripheral blood is predictive of poorer OS and PFS in patients with NPC. NLR is an easily measured and important prognostic factor in patients with NPC.

Ultrasensitive Bio-H2S Gas Sensor Based on Cu2O-MWCNT Heterostructures.

Developing a respiratory analysis disease diagnosis platform for the H2S biomarker has great significance for the real-time detection of various diseases. However, achieving highly sensitive and rapid detection of H2S gas at the parts per billion level at low temperatures is one of the most critical challenges for developing portable exhaled gas sensors. Herein, Cu2O-multiwalled carbon nanotube (MWCNT) heterostructures with excellent gas sensitivity to H2S at room temperature and a lower temperature were successfully synthesized by a facile two-dimensional (2D) electrodeposition in situ assembly method. The combination of Cu2O and MWCNTs via the principle of optimal conductance growth not only reduced the initial resistance of the material but also provided an ideal interfacial barrier structure. Compared to the response of the pure Cu2O sensor, that of the Cu2O-MWCNT sensor to 1 ppm of H2S increased nearly 800 times at room temperature, and the response time decreased by more than 500 s. In addition to the excellent sensitivity with detection limits as low as 1 ppb, the Cu2O-MWCNT sensor was extremely selective with low-temperature adaptability. The sensor had a response value of 80.6 to 0.1 ppm of H2S at -10 °C, which is difficult to achieve with sensors based on oxygen adsorption/desorption mechanisms. The sensor was used for the detection of real oral exhaled breath, confirming its feasibility as a real-time disease monitoring sensor. The Cu2O-MWCNT heterostructures maximized the advantages of the individual components and laid the experimental foundation for future applications of highly sensitive portable breath analysis platforms for monitoring H2S.

Integrated analysis of microRNA expression in tears of Kazakh patients with climatic droplet keratopathy in Xinjiang, China.

Climatic droplet keratopathy (CDK) is a corneal diseases, which is characterized by increased oil-like deposits on the anterior elastic lamina and anterior stromal layer. Severe CDK can even cause blindness, with no specific available treatment. Besides. CDK is poorly understood in terms of its pathogenic mechanisms. Thus, to determine potential biomarkers for CDK, we analyzed the microRNA expression profile in tear samples from CDK patients and investigated their putative roles in the pathogenesis of CDK. Herein, miRNA sequencing and following bioinformatics analysis was performed to explore the roles of their target genes in CDK. A total of 67 differentially expressed miRNAs were identified, of which 25 were upregulated and 42 were downregulated. qPCR verification showed that among the up- and down-regulated miRNAs, expression of five and six, respectively, was most significantly different.The target genes of the differentially expressed miRNAs are involved in the FoxO signaling pathway, tumor necrosis factor (TNF) signaling pathway, and steroid hormone biosynthesis. Protein-protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. In conclusion, the panel of differentially expressed miRNAs identified may have potential utility as early diagnostic biomarkers for CDK. Moreover, the TNF signaling pathway is a new potential target in CDK for the development of treatments.

Intercellular adhesion molecule 2 as a novel prospective tumor suppressor induced by ERG promotes ubiquitination-mediated radixin degradation to inhibit gastric cancer tumorigenicity and metastasis.

BACKGROUND: Gastric cancer (GC) is a fatal cancer with unclear pathogenesis. In this study, we explored the function and potential mechanisms of intercellular adhesion molecule 2 (ICAM2) in the development and advancement of GC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to quantify ICAM2 expression in harvested GC tissues and cultured cell lines. Immunohistochemical analyses were conducted on a GC tissue microarray to quantify ICAM2 expression and explore its implication on the prognosis of GC patients. In vitro experiments were carried out to reveal the biological functions of ICAM2 in GC cell lines. Further, in vivo experiments were conducted using xenograft models to assess the impact of ICAM2 on GC development and metastasis. Western blot, immunofluorescence, immunoprecipitation, luciferase assay, chromatin immunoprecipitation, and ubiquitination analysis were employed to investigate the underlying mechanisms. RESULTS: ICAM2 expression was downregulated in GC, positively correlating with advanced T stage, distant metastasis, advanced clinical stage, vessel invasion, and shorter patient survival time. ICAM2 overexpression suppressed the proliferation, migration, invasion, metastasis of GC cells as well as their ability to form tumors, whereas ICAM2 knockdown yielded opposite results. Erythroblast transformation-specific-related gene (ERG) as a transcription factor promoted the transcription of ICAM2 by binding to the crucial response element localized within its promoter region. Further analysis revealed that ICAM2 reduced radixin (RDX) protein stability and expression. In these cells, ICAM2 bound to the RDX protein to promote the ubiquitination and degradation of RDX via NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L), and this post-translational modification resulted in the inhibition of GC. CONCLUSIONS: In summary, this study demonstrates that ICAM2, which is induced by ERG, suppresses GC progression by enhancing the ubiquitination and degradation of RDX in a NEDD4L-dependent manner. Therefore, these results suggest that ICAM2 is a potential prognostic marker and a therapeutic target for GC.

Advances in the relationship between temporal muscle thickness and prognosis of patients with glioblastoma: a narrative review.

The most dangerous variety of glioma, glioblastoma, has a high incidence and fatality rate. The prognosis for patients is still bleak despite numerous improvements in treatment approaches. We urgently need to develop clinical parameters that can evaluate patients' conditions and predict their prognosis. Various parameters are available to assess the patient's preoperative performance status and degree of frailty, but most of these parameters are subjective and therefore subject to interobserver variability. Sarcopenia can be used as an objective metric to measure a patient's physical status because studies have shown that it is linked to a bad prognosis in those with cancers. For the purpose of identifying sarcopenia, temporal muscle thickness has demonstrated to be a reliable alternative for a marker of skeletal muscle content. As a result, patients with glioblastoma may use temporal muscle thickness as a potential marker to correlate with the course and fate of their disease. This narrative review highlights and defines the viability of using temporal muscle thickness as an independent predictor of survival in glioblastoma patients, and it evaluates recent research findings on the association between temporal muscle thickness and prognosis of glioblastoma patients.

The improving effect of soybean isoflavones on ovarian function in older laying hens.

Emerging evidence suggests an association between estrogen levels and reduced egg-laying performance as the layer became old. Since soy isoflavones (SF) have estrogen-mimic effects, whether it can enhance production performance and ovarian function of older layers is still not known. A total of 160 Lohmann pink layers (66-wk-old) were used in a 2 × 2 factorial design, which included 2 egg-laying levels [low (76.89 ± 1.65%; LOW) and normal (84.96 ± 1.01%; NOR)] and 2 different dietary groups [0 mg/kg SF, 20 mg/kg SF] were used. The results showed the NOR group had higher egg-laying rate, egg mass, and feed efficiency during the all phases (P(laying) < 0.05). The unqualified egg rate was lower in NOR group (9-12 wk, 1-12 wk) (P(laying) < 0.05). Dietary supplementation with SF increased the egg-laying rate and feed efficiency (5-8 wk, 9-12 wk, 1-12 wk), increased egg mass (9-12 wk, 1-12 wk) (P(SF) < 0.05). The NOR layers presented higher eggshell quality (redness, yellowness, brightness, eggshell ratio) at 12 wk (P(laying) < 0.05). Eggshell quality was found to be improved by SF (eggshell strength and eggshell thickness), egg albumen quality (higher albumen height and Haugh unit) at 12 wk (P(SF) < 0.05). Supplementing with SF led to an increase in eggshell strength in LOW group (P(laying*SF) < 0.05). The higher serum lever of glucose (GLU) and lower serum lever of follicle stimulating hormone (FSH) were in NOR group (P(laying) < 0.05). Supplementing SF in diets increased serum of estradiol (E2) and insulin-like growth factors-1 (IGF-1), decreased serum of FSH (P(SF) < 0.05). The NOR layers presented lower estrogen receptor α (ERα), estrogen receptor ß (ERß), B lymphoma 2 associated X protein (Bax), cytochrome c (Cytc), interleukin 6 (IL-6), caspase3, caspase9, IKKα, P50, and P65 expression in the ovary (P(laying) < 0.05). Dietary SF supplementation decreased the anti-Müllerian hormone receptor (AMHR), Bax, caspase3, caspase9, Cytc, IL-6, IKKα, P50, P65 expression in the ovary (P(SF) < 0.05). These findings indicated that layers with NOR group had higher production performance, egg quality, and ovarian function, while dietary supplementation with SF improved production performance and ovarian function by reducing inflammation and apoptosis-related genes expression in ovary.

Lever positioning manipulation alters real-time brain activity in patients with lumbar disc herniation: An amplitude of low-frequency fluctuation and regional homogeneity study.

INTRODUCTION: Lumbar disk herniation (LDH) is the preeminent disease of lever positioning manipulation (LPM), a complex disorder involving alterations in brain function. Resting-state functional magnetic resonance imaging (rs-fMRI) has the advantages of non-trauma, zero radiation, and high spatial resolution, which has become an effective means to study brain science in contemporary physical therapy. Furthermore, it can better elucidate the response characteristics of the brain region of LPM intervention in LDH. We utilized two data analysis methods, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of rs-fMRI, to assess the effects of LPM on real-time brain activity in patients with LDH. METHODS: Patients with LDH (Group 1, n = 21) and age-, gender- and education-matched healthy controls without LDH (Group 2, n = 21) were prospectively enrolled. Brain fMRI was performed for Group 1 at two-time points (TPs): before LPM (TP1) and after one LPM session (TP2). The healthy controls (Group 2) did not receive LPM and underwent only one fMRI scan. Participants in Group 1 completed clinical questionnaires assessing pain and functional disorders using a Visual Analog Scale and the Japanese Orthopaedic Association (JOA), respectively. Furthermore, we employed MNL90 (Montreal Neurological Institute) as a brain-specific template. RESULTS: Compared to the healthy controls (Group 2), the patients with LDH (Group 1) had significant variation in ALFF and ReHo values in brain activity. After the LPM session (TP2), Group 1 at TP1 also showed significant variation in ALFF and ReHo values in brain activity. In addition, the latter (TP2 vs TP1) showed more significant changes in brain regions than the former (Group 1 vs Group 2). The ALFF values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The Reho values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The ALFF values were increased in the Precuneus_R and decreased in the Frontal_Mid_Orb_L in Group 1 compared with Group 2. Only three brain areas with significant activity in Group 1 compared with Group 2: Frontal_Mid_Orb_L, Frontal_Sup_Orb_L, and Frontal_Mid_R. ALFF value in the Frontal_Mid_R at TP2 correlated positively with the change rates of JOA scores between TP1 and TP2 (P = 0.04, r = 0.319, R2 = 0.102). DISCUSSION: Patients with LDH showed abnormal brain ALFF and ReHo values, which were altered after LPM. The default mode network, prefrontal cortex, and primary somatosensory cortex regions could predict real-time brain activity for sensory and emotional pain management in patients with LDH after LPM.

Results after open lunate excision alone or in combination with palmaris longus tendon ball arthroplasty for the treatment of Kienböck's disease.

PURPOSE: This study aims to compare results after open lunate excision alone and in combination with palmaris longus tendon ball arthroplasty for the treatment of late-staged Kienböck's disease (KD). METHODS: This is a retrospective study using the prospectively collected data, and patients who had a discharge diagnosis of KD (stage IIIB based on Lichtman staging criteria) and underwent surgical treatment by lunate excision alone or in combination with palmaris longus tendon ball arthroplasty between January 2011 and December 2020 were included in this study. Variables of interest involved demographics, disease condition, operative procedure, and the outcomes evaluated at the last follow-up. Within and between comparisons were performed. RESULTS: Thirty-five patients underwent lunate excision alone, and 40 patients underwent the combination procedure. At the final follow-up, patients in both groups exhibited significant improvements compared to pre-operation, such as wrist flexion, wrist extension, carpal height ratio, PRWE score, Cooney score, and grip strength (all P < 0.05). Compared to the excision group, combination procedure group had significantly longer surgical time (P < 0.001), more blood loss (P < 0.001) and exhibited better wrist flexion (P = 0.001), PRWE score (P = 0.001), Cooney score (P = 0.0034), and grip strength (P = 0.017). The excellent or good rate based on Cooney wrist score was not significantly different (87.5% vs 71.4%, P = 0.083). CONCLUSION: Lunate excision in combination with palmaris longus tendon ball arthroplasty is a better option than lunate excision alone for the treatment of stage III KD and can be considered as an operative option.

A simplified non-coplanar volumetric modulated arc therapy for the whole brain radiotherapy with hippocampus avoidance.

Purpose: To evaluate the feasibility of using a simplified non-coplanar volumetric modulated arc therapy (NC-VMAT) and investigate its dosimetric advantages compared with intensity modulated radiation therapy (IMRT) and coplanar volumetric modulated arc therapy (C-VMAT) for hippocampal-avoidance whole brain radiation therapy (HA-WBRT). Methods: Ten patients with brain metastase (BM) were included for HA-WBRT. Three treatment plans were generated for each case using IMRT, C-VMAT, and NC-VMAT, respectively. Results: The dosimetric results of the three techniques complied roughly with the RTOG 0933 criteria. After dose normalization, the V30Gy of whole brain planned target volume (WB-PTV) in all the plans was controlled at 95%. Homogeneity index (HI) of WB-PTV was significantly reduced in NC-VMAT (0.249 ± 0.017) over IMRT (0.265 ± 0.020, p=0.005) and C-VMAT (0.261 ± 0.014, p=0.020). In terms of conformity index (CI), NC-VMAT could provide a value of 0.821 ± 0.010, which was significantly superior to IMRT (0.788 ± 0.019, p<0.001). According to D2% of WB-PTV, NC-VMAT could provide a value of 35.62 ± 0.37Gy, significantly superior to IMRT (36.43 ± 0.65Gy, p<0.001). According to D50% of WB-PTV, NC-VMAT can achieve the lowest value of 33.18 ± 0.29Gy, significantly different from IMRT (33.47 ± 0.43, p=0.034) and C-VMAT (33.58 ± 0.37, p=0.006). Regarding D2%, D98%, and Dmean of hippocampus, NC-VMAT could control them at 15.57 ± 0.18Gy, 8.37 ± 0.26Gy and 11.71 ± 0.48Gy, respectively. D2% and Dmean of hippocampus for NC-VMAT was significantly lower than IMRT (D2%: 16.07 ± 0.29Gy, p=0.001 Dmean: 12.18 ± 0.33Gy, p<0.001) and C-VMAT (D2%: 15.92 ± 0.37Gy, p=0.009 Dmean: 12.21 ± 0.54Gy, p<0.001). For other organs-at-risk (OARs), according to D2% of the right optic nerves and the right lenses, NC-VMAT had the lowest values of 31.86 ± 1.11Gy and 7.15 ± 0.31Gy, respectively, which were statistically different from the other two techniques. For other organs including eyes and optic chiasm, NC-VMAT could achieve the lowest doses, different from IMRT statistically. Conclusion: The dosimetry of the three techniques for HA-WBRT could roughly comply with the proposals from RTOG 0933. After dose normalization (D95%=30Gy), NC-VMAT could significantly improve dose homogeneity and reduce the D50% in the brain. Besides, it can reduce the D2% of the hippocampus, optic nerves, and lens. With this approach, an efficient and straightforward plan was accomplished.

Effects of dietary theabrownins on production performance, egg quality, and ovarian function of laying hens with different ages.

This experiment was conducted to investigate the effect of theabrownins (TB) on production performance, egg quality, and ovarian function of laying hens at different ages. A total of 240 Lohmann laying hens were assigned in a 2 × 2 factorial design, which encompassed 2 layers ages (47-wk-old and 67-wk-old) and 2 dietary levels of TB (0 and 100 mg/kg) for 12 wk. Results showed that older layers had lower laying rate, egg mass, and higher feed-to-egg ratio (F/E), egg weight and unqualified egg rate than the younger layers (P(AGE) < 0.01) during all the experimental period. The effect of TB was found to increase egg laying rate and feed efficiency during 5 to 8 wk, 9 to 12 wk and the overall phases and decreased unqualified egg rate during 1 to 4 wk and the overall phases (P(TB) ≤ 0.05). The eggshell quality (strength, thickness), albumen quality (albumen height and Haugh unit) of eggs from older layers were decreased during overall phases (P(AGE) ≤ 0.05). TB increased eggshell strength during all phases and enhanced eggshell thickness at the end of wk 4 and 8 and increased albumen height and Haugh unit at the end of wk 8 and 12 of older layers (P(Interaction) ≤ 0.05). In addition, TB also increased egg quality of older layers after 14 d storage. A decrease in the serum concentration of progesterone, melatonin, follicle stimulating hormone, estradiol was observed in the older compared to the younger ones (P(AGE) < 0.05), while the increase in serum concentration of progesterone, melatonin, anti-Müllerian hormone (AMH) were more emphasized when older hens received TB supplemented diet (P(Interaction) < 0.05). The older layer demonstrated lower the concentration of glutathione (GSH) (P(AGE) < 0.05). And the activity of glutathione-s-transferase (GST) was significantly decreased in layers under 67-wk-old (P(AGE) <0.05). The increase in concentration of GSH and the decrease in concentration of malondialdehyde (MDA) were more pronounced when TB were supplemented in 67-wk-old layers (P(Interaction) ≤ 0.05). Layers at 67-wk-old had lower mRNA expression of Heme oxygenase 1 (HO-1) (P(AGE) < 0.01) in ovary. Dietary TB supplementation upregulated mRNA gene expression of HO-1, Nuclear factor E2 related factor 2 (Nrf2), Quinone oxidoreductase 1 (NQO1) (P(TB) < 0.01). Dietary TB upregulated mRNA expression of ovarian reproductive hormone receptor (estrogen receptor 1 [ESR1] and steroidogenic acute regulatory protein 1 [StAR1]]; P(TB) < 0.01). The results suggest feeding TB (100 mg/kg) could improve the egg production rate, egg quality, and antioxidant capacity of the ovary. Moreover, the effect of TB was more pronounced in older layers (64-wk-old vs. 47-wk-old).

Repolarization of macrophages to improve sorafenib sensitivity for combination cancer therapy.

Sorafenib is the first line drug for hepatocellular carcinoma (HCC) therapy. However, HCC patients usually acquire resistance to sorafenib treatment within 6 months. Recent evidences have shown that anticancer drugs with antiangiogenesis effect (e.g., sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues. Therefore, repolarization of TAMs phenotype could be expected to not only eliminate the influence of TAMs on sorafenib lethality to HCC cells, but also provide an additional anticancer effect to achieve combination therapy. However, immune side effects remain a great challenge due to the non-specific macrophage repolarization in normal tissues. We herein employed a tumor microenvironment (TME) pH-responsive nanoplatform to concurrently transport sorafenib and modified resiquimod (R848-C16). This nanoparticle (NP) platform is made with a TME pH-responsive methoxyl-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymer. After intravenous administration, the co-delivery NPs could highly accumulate in the tumor tissues and then respond to the TME pH to detach their surface PEG chains. With this PEG detachment to enhance uptake by TAMs and HCC cells, the co-delivery NPs could combinatorially inhibit HCC tumor growth via sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs into tumoricidal M1-like macrophages. STATEMENT OF SIGNIFICANCE: Anticancer drugs with antiangiogenesis effect (e.g., sorafenib) can aggravate the hypoxia microenvironment and promote the infiltration of more tumor-associated macrophages (TAMs) into the tumor tissues to restrict the anticancer effect. In this work, we designed and developed a tumor microenvironment (TME) pH-responsive nanoplatform for systemic co-delivery of sorafenib and resiquimod in hepatocellular carcinoma (HCC) therapy. These co-delivery NPs show high tumor accumulation and could respond to the TME pH to enhance uptake by TAMs and HCC cells. With the sorafenib-mediated lethality to HCC cells and R848-mediated repolarization of TAMs, the co-delivery NPs show a combinational inhibition of HCC tumor growth in both xenograft and orthotopic tumor models.

Integrated analysis of multiple microarray studies to establish differential diagnostic models of Crohn's disease and ulcerative colitis based on a metalloproteinase-associated module.

Background: The ulcerative colitis (UC) and Crohn's disease (CD) subtypes of inflammatory bowel disease (IBD) are autoimmune diseases influenced by multiple complex factors. The clinical treatment strategies for UC and CD often differ, indicating the importance of improving their discrimination. Methods: Two methods, robust rank aggregation (RRA) analysis and merging and intersection, were applied to integrate data from multiple IBD cohorts, and the identified differentially expressed genes (DEGs) were used to establish a protein-protein interaction (PPI) network. Molecular complex detection (MCODE) was used to identify important gene sets. Two differential diagnostic models to distinguish CD and UC were established via a least absolute shrinkage and selection operator (LASSO) logistic regression, and model evaluation was performed in both the training and testing groups, including receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA). The potential value of MMP-associated genes was further verified using different IBD cohorts and clinical samples. Results: Four datasets (GSE75214, GSE10616, GSE36807, and GSE9686) were included in the analysis. Both data integration methods indicated that the activation of the MMP-associated module was significantly elevated in UC. Two LASSO models based on continuous variable (Model_1) and binary variable (Model_2) MMP-associated genes were established to discriminate CD and UC. The results showed that Model_1 exhibited good discrimination in the training and testing groups. The calibration analysis and DCA showed that Model_1 exhibited good performance in the training group but failed in the testing group. Model_2 exhibited good discrimination, calibration and DCA results in the training and testing groups and exhibited greater diagnostic value. The effects of Model_1 and Model_2 were further verified in a new IBD cohort of GSE179285. The MMP genes exhibited high value as biomarkers for the discrimination of IBD patients using published cohort and immunohistochemistry (IHC) staining data. The MMP-associated gene levels were statistically significantly positively correlated with the levels of the differentially expressed cell types, indicating their potential value in differential diagnosis. The single-cell analysis confirmed that the expression of ANXA1 in UC was higher than that in CD. Conclusion: MMP-associated modules are the main differential gene sets between CD and UC. The established Model_2 overcomes batch differences and has good clinical applicability. Subsequent in-depth research investigating how MMPs are involved in the development of different IBD subtypes is necessary.

Rosmarinic Acid Prevents Cisplatin-Induced Liver and Kidney Injury by Inhibiting Inflammatory Responses and Enhancing Total Antioxidant Capacity, Thereby Activating the Nrf2 Signaling Pathway.

Drug-induced liver and kidney damage is an emergent clinical issue that should be addressed. Rosmarinic acid (RA) has obvious anti-inflammatory and antioxidant effects, so we evaluated the anti-inflammatory and antioxidant effects of RA pretreatment on serum and liver and kidney tissues of cisplatin (CP)-treated mice and explored the possible mechanisms. The results showed that RA pretreatment effectively downregulated the serum, liver, and kidney levels of ALT, AST, BUN, and CRE and the inflammatory factors IL-1ß, IL-6, and TNF-α, and simultaneously enhanced the total antioxidant capacity of the liver and kidney. RA pretreatment significantly reduced the levels of MPO, MDA, and NO in liver and kidney tissue, inhibited the mRNA expression of IL-1ß, IL-6, and TNF-α in liver and kidney tissue, activated the Nrf2 signaling pathway, and upregulated the mRNA expression of downstream target genes. Our findings show that RA could effectively prevent and alleviate acute liver and kidney injury caused by CP.