Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

Construction of a Novel Damage-Associated Molecular-Pattern-Related Signature to Assess Lung Adenocarcinoma's Prognosis and Immune Landscape.

Immunogenic death (ICD) stimulates adaptive immunity and affects immunotherapeutic efficacy, an important part of which is damage-associated molecular patterns (DAMPs). However, the function of these DAMPs for lung adenocarcinoma (LUAD) remains obscure. We initially found differentially expressed genes (DEGs) with prognostic significance related to DAMPs with the TCGA database and then used the least absolute shrinkage and selection operator (LASSO) regression to create a risk signature strongly correlated with overall survival (OS) with eight DEGs. Validation was performed externally using the external data set GSE68465. Lower-risk LUAD patients were found to be more chemotherapy-resistant and enriched for more immune-related pathways than those with higher risk scores, and patients with different risks showed different levels of immune cell infiltration. PANX1, a crucial gene closely associated with lung adenocarcinoma, was identified using the weighted correlation network analysis (WGCNA), and experiments revealed that PANX1 promotes the proliferation as well as invasion of LUAD cells. Furthermore, PANX1 was found to be positively correlated with CD274, CD276, and M2 macrophage markers. We developed and validated an entirely new gene signature related to DAMPs that may be useful for LUAD patient prognosis, immune microenvironment, and chemotherapeutic drug sensitivity prediction. The results may also guide clinical immunotherapy and chemotherapy approaches for LUAD patients.

Study on detection method of microplastics in farmland soil based on hyperspectral imaging technology.

Microplastics (MPs) in farming soils can have a substantial impact on soil ecology and agricultural productivity, as well as affecting human health and the food chain cycle. As a result, it is vital to study MPs detection technologies that are rapid, efficient, and accurate in agriculture soils. This study investigated the classification and detection of MPs using hyperspectral imaging (HSI) technology and a machine learning methodology. To begin, the hyperspectral data was preprocessed using SG convolution smoothing and Z-score normalization. Second, the feature variables were extracted from the preprocessed spectral data using bootstrapping soft shrinkage, model adaptive space shrinkage, principal component analysis, isometric mapping (Isomap), genetic algorithm, successive projections algorithm (SPA), and uninformative variable elimination. Finally, three support vector machine (SVM), back propagation neural network (BPNN), and one-dimensional convolutional neural network (1D-CNN) models were developed to classify and detect three microplastic polymers: polyethylene, polypropylene, and polyvinyl chloride, as well as their combinations. According to the experimental results, the best approaches based on three models were Isomap-SVM, Isomap-BPNN, and SPA-1D-CNN. Among them, the accuracy, precision, recall and F1_score of Isomap-SVM were 0.9385, 0.9433, 0.9385 and 0.9388, respectively. The accuracy, precision, recall and F1_score of Isomap-BPNN were 0.9414, 0.9427, 0.9414 and 0.9414, respectively, while the accuracy, precision, recall and F1_score of SPA-1D-CNN were 0.9500, 0.9515, 0.9500 and 0.9500, respectively. When their classification accuracy was compared, SPA-1D-CNN had the best classification performance, with a classification accuracy of 0.9500. The findings of this study shown that the SPA-1D-CNN based on HSI technology can efficiently and accurately identify MPs in farmland soils, providing theoretical backing as well as technical means for real-time detection of MPs in farmland soils.

SOX2 Promotes Radioresistance in Non-small Cell Lung Cancer by Regulating Tumor Cells Dedifferentiation.

Background: Radiation therapy plays an important role in the treatment of patients with non-small cell lung cancer (NSCLC). However, the radiocurability is greatly limited because of radioresistance which leads to treatment failure, tumor recurrence, and metastasis. Cancer stem cell (CSC) has been identified as the main factor that contributes to radiation resistance. SOX2, one of the transcription factors specifically expressed in CSC, is involved in tumorigenesis, progression, and maintenance of cell stemness. But the association between SOX2 and NSCLC radioresistance is not clear now. Methods: We constructed the radiotherapy-resistant cell line of NSCLC by multiple radiotherapy treatments. Colony formation assay, western blot, and immunofluorescence were performed to detect the radiosensitivity of cells. Western blot, qRT-PCR, and sphere formation assay were used to detect CSC characteristics of cells. Wound healing assay and Transwell assay were used to determine cell migration motility. The SOX2-upregulated model and SOX2-downregulated model was constructed by lentivirus transduction. Finally, the expression and clinical relevance of SOX2 in NSCLC were investigated by bioinformatics analysis based on TCGA and GEO datasets. Results: The expression of SOX2 was increased in radioresistant cells and a trend of dedifferentiation were observed. The results of wound healing assay and Transwell assay showed that SOX2 overexpression significantly promote the migration and invasion of NSCLC cells. Mechanistically, overexpression of SOX2 enhanced radioresistance and DNA damage repair capability of parental cells, while down-regulation of SOX2 led to decreased radioresistance and DNA repair ability in radioresistant cells, all of which were related to cells dedifferentiation regulated by SOX2. In addition, bioinformatics analysis show that high expression of SOX2 was strongly associated with the progression and poor prognosis of patients with NSCLC. Conclusions: Our study revealed that SOX2 regulates radiotherapy resistance in NSCLC via promoting cell dedifferentiation. Therefore, SOX2 may be a promising therapeutic target for overcoming radioresistance in NSCLC, providing a new perspective to improve the curative effect.

Multifunctional effects of hollow flower-like CoTiO3 microspheres wrapped by reduced graphene as sulfur host in Li-S battery.

The poor conductivity of sulfur, the shuttle effect and sluggish redox reaction kinetics of lithium polysulfides (LiPSs) are considered the main obstacles to the practical application of Lithium-sulfur (Li-S) batteries. Thus, it is urgent to design multifunctional host materials to eliminate these obstacles. Herein, we designed a hollow flower-like CoTiO3 wrapped by reduced graphene oxide (h-CoTiO3@rGO) as sulfur host materials. The hollow structure of h-CoTiO3@rGO not only endows sufficient space for high sulfur loading, but also physically and chemically confines the shuttle effect of LiPSs through the formation of Co-S chemical bonding. The large specific surface area and excellent electrocatalytic ability of h-CoTiO3@rGO provide amounts of active sites to accelerate the redox reaction of LiPSs. Meanwhile, the conductive reduced graphene oxide (rGO) covered on the surface of CoTiO3 microspheres offers an interconnected conductive network to support the fast electron/ion transfer. Profit from these merits, the battery employing the multifunctional h-CoTiO3@rGO as sulfur host exhibited excellent cycling stability with an ultralow capacity fading of 0.0127 % per cycle after 500 cycles at 1C. Even the battery with high sulfur loading of 5.2 mg/cm2 still delivered a high area capacity of 5.02 mAh/cm2, which was competitive with the commercial Li-ion batteries. Therefore, the competitive capacity and superior cycling stability suggest that the h-CoTiO3@rGO/S cathode is a potential candidate for high-performance Li-S batteries.

CD1B is a Potential Prognostic Biomarker Associated with Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Adenocarcinoma.

Purpose: Tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) have been well recognized as molecular determinants of immunotherapy responsiveness. In this study, we aimed to construct a TMB prognostic model and explore biomarkers that have predictive potential for prognosis and therapeutic effect in lung adenocarcinoma (LUAD). Patients and Methods: The TCGA, GEO and Immport databases were used to analyze the mutation profiles and immune infiltration of LUAD. TMB scores were calculated and differential analysis was conducted to identify TMB-related genes. Then, Cox regression model and survival analysis were applied to identify the prognostic genes and construct a TMB prognostic model. The expression and prognostic value of CD1B were further verified by immunohistochemistry (IHC) in 92 patient tissue samples. GSEA was performed to analyze the signaling pathways associated with CD1B expression. Results: High-TMB samples exhibited higher infiltration of CD8+ T cells, CD4+ memory T cells, and M1 macrophages. A total of 397 TMB-related differentially expressed genes were identified, of which 47 were immune-related genes. Cox regression analyses determined 3 hub TMB-related immune genes (CD1B, SCGB3A1, and VEGFD) with prognostic effects, and a TMB prognostic model was constructed. The model demonstrated robust predictive ability in both the training (TCGA) and testing (GEO) datasets. Notably, CD1B was identified as an independent prognostic factor. IHC of clinical samples showed that low expression of CD1B was related to poor overall survival and advanced pathological stages. In addition, there was a strong positive correlation between CD1B and most immune checkpoint molecules, including PD-L1. CD1B expression was associated with immune cell infiltration and immune activation in LUAD. Conclusion: Our study constructed a TMB prognostic model that effectively predicted the prognosis of LUAD patients. CD1B expression is correlated with better prognosis and promotes antitumor immunity in LUAD, which may serve as a potential prognostic biomarker and immune-related therapeutic target for LUAD.

The clinical efficacy of Shengyu decoction in the treatment of anemia after PFNA for elderly intertrochanteric fracture: A protocol of prospective, randomized, controlled trial.

BACKGROUND: Femoral intertrochanteric fractures (ITF) occur frequently in the elderly, accounting for 45% of all hip fractures. Postoperative anemia after fracture tends to cause ischemia, hypoxia in cells, tissues and organs, increasing the rate of blood transfusion, risk of infection, disability and mortality. Meanwhile, traditional Chinese medicine is widely used in the treatment of anemia for activating blood circulation and removing blood stasis. METHODS: This study is a prospective, outcome assessor-, and data analyst-blinded randomized controlled clinical trial. The objective of this proposed study was to investigate whether Shengyu Decoction could improve the symptoms of anemia after proximal femoral nail antirotation in elderly ITF patients. After qualifying for screening, patients will be randomized into 2 groups with an allocation ratio of 1:1. Hemoglobin concentration, HBL, and HHS score are outcome measurements. The other outcomes also included time to get out of bed, discharge to home, 30-day readmission rates, and mortality. DISCUSSION: ITF is commonly occurring in senior citizens, and those who are senior in age generally suffer 1 or more basic diseases, whose nutritional status is already poor. Trauma and surgical stimulation not only aggravate the existing disease or induce corresponding cardiovascular complications, but also worsen the nutritional status, which can easily cause postoperative anemia in patients. Because of the limited clinical modalities available for the treatment of postoperative anemia after fracture surgery, and most of them have various side effects that are not easily tolerated by the elderly. Therefore, from a traditional Chinese medicine perspective, we proposed a protocol using mild Chinese herbal decoction to treat postoperative anemia in ITF.Registration number: OSF Registration number: DOI 10.17605/OSF.IO/JQ6ZF.

Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway.

BACKGROUND: Bladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear. METHODS: The clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments. RESULTS: Bioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated that ANXA1 silencing inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss of ANXA1 decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown of ANXA1 accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling. CONCLUSIONS: These findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.

Bizarre parosteal osteochondromatous proliferation co-occurring with a metatarsal fatigue fracture: a case report.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a relatively rare benign extraperiosteal osteochondroma-like proliferative lesion that shares similarities with malignant tumours in terms of morphology. The aetiology of BPOP has yet to be determined and there are no previous reports of BPOP associated with fracture. CASE PRESENTATION: A 57-year-old woman presented with a one-month history of pain and swelling in her right foot, which were worsened by activity and improved with rest. Physical examination revealed a hard, non-mobile mass measuring 1.5 cm × 1.5 cm on the dorsal aspect of the third metatarsal of the right foot. There was overlying erythema and tenderness on palpation. Computed tomography (CT) of the right foot demonstrated a fracture of the neck of the third metatarsal, osteolysis at the fracture site and soft tissue swelling. Bone scintigraphy revealed increased tracer uptake suggesting abnormal bone metabolism at the neck of the third metatarsal. Surgical excision of the lesion was performed. Histopathology and immunohistochemistry confirmed the diagnosis of BPOP. CONCLUSION: BPOP is a rare benign lesion that is commonly misdiagnosed. Differential diagnosis is mainly achieved through imaging and histopathological assessment.

One-dimensional architecture with reduced graphene oxide supporting ultrathin MoO2 nanosheets as high performance anodes for lithium-ion batteries.

Two-dimensional (2D) materials have been widely studied and used as anode materials for lithium ion batteries (LIBs) because of their high specific surface area and intrinsic mechanical flexibility which could offer numerous active sites and protect effect for LIBs. However, 2D nanosheets are easy to stack and partially lose surface area for Li-ion storage thus greatly affecting their electrochemical performance. Here, we develop a simple strategy to obtain a nanosheets-based one-dimensional structure hybrid by in situ reduction from MoO3 nanorods to MoO2 nanosheets and nanoparticles which are anchored on a 1D reduced graphene oxide skeleton (MoO2-rGO). It was demonstrated that the primary MoO2 nanosheets and nanoparticles are uniformly dispersed on the reduced graphene oxide nanosheets, which are further assembled into a 1D loosened nanostructure. The loosened nanosheets offer more accessible surface area and facilitate transport of electrons and Li-ions. Moreover, MoO2 nanoparticles effectively avoid agglomeration from nanosheets. Results show that MoO2-rGO hybrid demonstrates an enhanced cyclic life, high stability and prominent rate performance when evaluated as anode material for LIBs. The first discharge capacity can reach 1256.4 mAh g-1 and provide a highly reversible capacity of 1003.7 mA h g-1 after 100 cycles at 0.1 A g-1, which makes MoO2-rGO a promising candidate for LIBs. The excellent performance can be attributed to the unique 1D loosened structure consists of MoO2 and conducting rGO nanosheets, which facilitates fast transfer of Li-ion and electron, and the reduced graphene oxide nanosheets acting as a skeleton provide a continuous conductive network and simultaneously strengthen the structural stability.

Evaluating the Reliability and Reproducibility of the AO and Lauge-Hansen Classification Systems for Ankle Injuries.

Ankle injuries are responsible for more than 5 million emergency department visits each year. The AO and Lauge-Hansen classification systems are widely used in the clinical diagnosis of ankle injuries. This study aimed to analyze the intraobserver reliability and interobserver reproducibility of the AO and Lauge-Hansen classification systems. In addition, the authors explored the differences among physicians' classification responses and evaluated the clinical value for diagnosis. Fifty-six patients with an ankle injury with complete clinical and radiologic data were enrolled. The definition of injury type, the index score typing methods, and the specific study criteria were explained in detail. Five observers, who were orthopedic surgeons, determined the classifications according to both the AO and Lauge-Hansen systems. The classification was repeated 1 month later. Cronbach's alpha and Cohen's kappa test were used to determine interobserver reliability and intraobserver reproducibility. The physicians conducted 560 classifications (56 cases × 5 physicians × 2 times per patient). Average inter- and intraobserver kappa values for the AO system were 0.708 and 0.608, respectively. Average inter- and intraobserver kappa values for the Lauge-Hansen system were 0.402 and 0.398, respectively. Cronbach's alpha coefficient was 96.7% for the AO system and 76.0% for the Lauge-Hansen system. The Lauge-Hansen classification system is a comprehensive yet cumbersome system. Comparatively, the AO classification system is easier to understand. This study shows that the AO classification system has more reliability and reproducibility, and thus has more value in clinical practice, than the Lauge-Hansen classification system.