Preoperative sequential chemotherapy and hypofractionated radiotherapy combined with comprehensive surgical resection for high-risk soft tissue sarcomas: a retrospective study.

Introduction: The management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas. Materials and methods: We performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25-35 Gy across 5-7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors. Results: All patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%. Conclusion: Neoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.

Study on dynamic response characteristics of the scanning angle in a liquid crystal cladding waveguide beam scanner.

This paper studies the dynamic response characteristics of the scanning angle in a liquid crystal cladding waveguide beam scanner. Based on liquid crystal dynamic theory, finite element analysis and vectorial refraction law, a dynamic response calculation model of scanning angle is constructed. The simulation results show that the dynamic responses of the scanning angle during the electric field-on and field-off processes are asymmetric, and exhibit "S"-shape and "L"-shape changing trends, respectively. In addition, by comparing with the bulk phase modulation response process of traditional liquid crystal devices, the intrinsic physical reason for the rapid light regulation of the liquid crystal cladding waveguide beam scanner is clarified to be that the liquid crystal close to the core layer has a faster rotation speed during the electric field-off process. Moreover, the liquid crystal cladding waveguide beam scanner is experimentally tested, and the experiment results are in good agreement with theoretical simulations.

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

A novel 193-plex MPS panel integrating STRs and SNPs highlights the application value of forensic genetics in individual identification and paternity testing.

Massively parallel sequencing (MPS) has emerged as a promising technology for targeting multiple genetic loci simultaneously in forensic genetics. Here, a novel 193-plex panel was designed to target 28 A-STRs, 41 Y-STRs, 21 X-STRs, 3 sex-identified loci, and 100 A-SNPs by employing a single-end 400 bp sequencing strategy on the MGISEQ-2000™ platform. In the present study, a series of validations and sequencing of 1642 population samples were performed to evaluate the overall performance of the MPS-based panel and its practicality in forensic application according to the SWGDAM guidelines. In general, the 193-plex markers in our panel showed good performance in terms of species specificity, stability, and repeatability. Compared to commercial kits, this panel achieved 100% concordance for standard gDNA and 99.87% concordance for 14,560 population genotypes. Moreover, this panel detected 100% of the loci from 0.5 ng of DNA template and all unique alleles at a 1:4 DNA mixture ratio (0.2 ng minor contributor), and the applicability of the proposed approach for tracing and degrading DNA was further supported by case samples. In addition, several forensic parameters of STRs and SNPs were calculated in a population study. High CPE and CPD values greater than 0.9999999 were clearly demonstrated and these results could be useful references for the application of this panel in individual identification and paternity testing. Overall, this 193-plex MPS panel has been shown to be a reliable, repeatable, robust, inexpensive, and powerful tool sufficient for forensic practice.

Peripheral B-cell levels predict efficacy and overall survival in advanced melanoma patients under PD-1 immunotherapy.

Aims: Programmed death-1 (PD-1) blockade is a vital therapy for solid tumors, but not all patients benefit. Identifying which patients will benefit from immunotherapy is a key focus in oncology research. Patients & Methods: This study analyzed the correlation between the number of peripheral lymphocytes and the efficacy and prognosis of immunotherapy in advanced malignant melanoma. Results: Patients with a partial response had significantly lower peripheral B cell levels, and patients with a lower number of B lymphocytes had a longer survival time. Conclusion: These results suggest that peripheral B cells are correlated with the efficacy of PD-1 antibody and prognosis and are thus potential biomarkers for the efficacy and prognosis of PD-1 antibody immunotherapy in malignant melanoma.

Immunotherapy is an important treatment for cancer patients with solid tumors. Because immunotherapy does not work equally well for everybody, an important area of research is to determine for which patients the treatment will work. Our study focused on skin cancer patients. We examined the relationship between the number of B cells (a type of immune cell) in patients' blood, and how well they responded to immunotherapy. We observed that patients who partially responded to treatment had lower levels of B cells. Additionally, patients who had a lower number of B cells also had a longer survival time. This could mean that looking at patients' B cell levels might be useful in working out how well they well respond to immunotherapy.

Ultrawide-view achromatic circular polarization dynamic converter using an easy-to-integrate multi-layer structure.

What we believe to be a novel integrated circular polarization dynamic converter (CPDC) is proposed based on the four-layer mirror symmetry structure. By designing the twisted structure and rearranging the orientation direction of liquid crystal molecules for each layer, the application wavelength range could be broadened. For the viewing angle expansion, negative birefringent films are selected to compensate for the retardation deviation under oblique incidence. Finally, the particle swarm algorithm is used to optimize the whole configuration, and the polarization conversion efficiency calculated by the finite element method (FEM) can achieve 90% in the wavelength range from 320 nm to 800 nm at an ultrawide view of 160°. Compared with traditionally active liquid crystal waveplates, the design has potential advantages in both wavelength and field of view (FOV) and provides the possibility for the integrated and flimsy fabrication of devices.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death.

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS: GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/ß-catenin and activating TGF-ß/Smad signaling.

OBJECTIVE: We aimed to explore the effect and mechanism of the Src inhibitor PP2 on osteoarthritis (OA) progression. METHODS: The protein expressions of Src, p-Src (y418) and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence (IF) analysis. Chondrocytes from the femur and tibial plateau of 3-day-old mice were extracted and inoculated into 6-well plates. The chondrocytes were co-cultured with IL-1ß and different doses of PP2, and then the degeneration of extracellular matrix was analyzed. A mouse OA model was induced by destabilizing medial meniscectomy of the right knee. Two weeks after the operation, different doses of PP2 were injected intraperitoneally. The drug was given three times a week for 6 weeks, and then the mice were sacrificed. Histopathological, IF and immunoblotting analyses were used to detect key OA catabolic markers and protein expression and related signaling. RESULTS: The levels of Src, p-Src (y418) and p-FAK in the knee cartilage tissue of patients with OA were abnormally increased. After chondrocytes were co-treated with IL-1ß and different doses of PP2, the results showed that PP2 reduced the abnormal increase of ß-catenin, p-ß-catenin and other proteins induced by IL-1ß, and reversed the decrease of p-Smad3, aggrecan and collagen Ⅱ protein levels. Meanwhile, intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage in the OA mouse model. CONCLUSION: Our data indicate that targeting Src with PP2 protected against cartilage destruction in an OA mouse model by inhibiting Wnt/ß-catenin and activating TGF-ß/Smad signaling, suggesting that Src may be a potential therapeutic target for OA treatment.

Development and validation of a custom panel including 114 InDels using massively parallel sequencing for forensic application.

Insertion/deletion polymorphisms (InDels) have particular characteristics, such as a relatively low mutation rate, small amplicon size, and no stutter artifacts when genotyped via the capillary electrophoresis platform. It would be an important complementary tool for individual identification and certain kinship analyses. At present, massively parallel sequencing (MPS) has shown excellent application value in forensic studies. Therefore, in this study, we developed a custom MPS InDel panel that contains 114 InDels [77 autosomal InDels (A-InDels), 32 X-chromosomal InDels (X-InDels), and 5 Y-chromosomal InDels) based on previous studies. To assess this panel's performance, several validation experiments were performed, including sensitivity, inhibitor, degraded DNA testing, species specificity, concordance, repeatability, case-type samples, and population studies. The results showed that the lowest DNA input was 0.25 ng. All genotypes were obtained in the presence of 80 ng/µL humic acid, 2000 µmol/L calcium, 3000 µmol/L EDTA and indigo. In degraded DNA testing, 90% of loci could be detected for 16-day-old formalin-fixed hearts. In addition, this panel has good species specificity. The values of combined power of discrimination and the combined power of exclusion for 77 A-InDels were 1-3.9951 × 10-32 and 1-4.2956 × 10-7 , respectively. The combined mean exclusion chance for 32 X-InDels was 0.99999 in trios and 0.99904 in duos. The validation results indicate that this newly developed MPS multiplex system is a robust tool for forensic applications.

Design of prism coupling structure for liquid crystal cladding waveguide beam steerer.

This paper proposes an extended prism coupling analysis method to accurately analyze the coupling structure of liquid crystal (LC) cladding waveguide beam steerer. We analyze the effects of LC anisotropy on the coupling of transverse electric (TE) and transverse magnetic (TM) modes and derive the expression of the optical field distribution that perfectly matches the given coupling structure. Based on this method, we present the optimal coupling structure for Gaussian beam. Taking into account the practical manufacturing process, we propose a simplified coupling structure and perform a detailed analysis of its performance based on numerical simulations. Experimental results show a coupling efficiency of 91% and a coupling angle full width at half maximum (FWHM) of about ±0.02°, demonstrating the effectiveness of the proposed method in predicting the coupling performance of anisotropic cladding waveguides.

Inference of drowning sites using bacterial composition and random forest algorithm.

Diagnosing the drowning site is a major challenge in forensic practice, particularly when corpses are recovered from flowing rivers. Recently, forensic experts have focused on aquatic microorganisms, including bacteria, which can enter the bloodstream during drowning and may proliferate in corpses. The emergence of 16S ribosomal RNA gene (16S rDNA) amplicon sequencing has provided a new method for analyzing bacterial composition and has facilitated the development of forensic microbiology. We propose that 16S rDNA amplicon sequencing could be a useful tool for inferring drowning sites. Our study found significant differences in bacterial composition in different regions of the Guangzhou section of the Pearl River, which led to differences in bacteria of drowned rabbit lungs at different drowning sites. Using the genus level of bacteria in the lung tissue of drowned rabbits, we constructed a random forest model that accurately predicted the drowning site in a test set with 100% accuracy. Furthermore, we discovered that bacterial species endemic to the water were not always present in the corresponding drowned lung tissue. Our findings demonstrate the potential of a random forest model based on bacterial genus and composition in drowned lung tissues for inferring drowning sites.

Three-dimensional printing of microfiber- reinforced hydrogel loaded with oxymatrine for treating spinal cord injury.

Spinal cord injury (SCI) causes severe neural tissue damage and motor/sensory dysfunction. Since the injured spinal cord tissue has limited self-regeneration ability, several strategies, including cell therapy, drug delivery, and tissue engineering scaffold implantation, have been employed to treat SCI. However, each of these strategies fails to obtain desirable outcomes due to their respective limitations. In comparison, advanced tissue engineering scaffolds with appropriate topographical features, favorable composition, and sustained drug delivery capability can be employed to recruit endogenous neural stem cells (NSCs), induce neuronal differentiation, and facilitate neuron maturation. This can lead to the regeneration of injured spinal cord tissue and the recovery of motor function. In this study, fiber bundle-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with oxymatrine (OMT) were produced through nearfield direct write electrospinning. The spinal cord extracellular matrix-based hydrogel was then coated with OMT. The physical/chemical properties and in vitro degradation behavior of the composite scaffolds were investigated. The in vitro cell culture results showed that composite scaffolds loaded with OMT promoted the differentiation of NSCs into neurons and inhibited differentiation into astrocytes. The in vivo results showed that the composite scaffolds loaded with OMT recruited NSCs from the host tissue, promoted neuronal differentiation and axon extension at the lesion site, inhibited glial scar formation at/around the lesion site, and improved the recovery of motor function in rats with SCI. To sum up, 3D-printed microfiber-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with OMT are promising biomaterials for the treatment of SCI.