Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

A bidirectional Mendelian randomization study of sarcopenia-related traits and inflammatory bowel diseases.

Background: There is increasing evidence pointing to a close relationship between sarcopenia and inflammatory bowel disease. However, it remains unclear whether or in which direction causal relationships exist, because these associations could be confounded. Methods: We conducted a two-sample bidirectional mendelian randomization analysis using data from European genome-wide association studies of the appendicular lean mass(n = 450,243), walking pace(n = 459,915), grip strength (left hand, n = 461,026; right hand, n = 461,089), inflammatory bowel disease (25,042 patients and 34,915 controls), ulcerative colitis (12,366 patients and 33,609 controls), and Crohn's disease (12,194 patients and 28,072 controls) to investigate the causal relationship between sarcopenia-related traits and inflammatory bowel disease and its subtypes on each other. The inverse-variance weighted method was used as the primary analysis method to assess the causality, and a comprehensive sensitivity test was conducted. Results: Genetically predicted appendicular lean mass was significantly associated with inflammatory bowel disease (OR = 0.916, 95%CI: 0.853-0.984, P = 0.017), ulcerative colitis (OR =0.888, 95%CI: 0.813-0.971, P = 0.009), and Crohn's disease (OR = 0.905, 95%CI: 0.820-0.999, P = 0.049). Similar results also revealed that the usual walking pace was causally associated with Crohn's disease (OR = 0.467, 95%CI: 0.239-0.914, P = 0.026). Reverse mendelian randomization analysis results found that genetic susceptibility to inflammatory bowel disease, and Crohn's disease were associated with lower appendicular lean mass. A series of sensitivity analyses ensured the reliability of the present research results. Conclusion: The mendelian randomization study supports a bidirectional causality between inflammatory bowel disease, Crohn's disease and appendicular lean mass, but no such bidirectional causal relationship was found in ulcerative colitis. In addition, genetically predicted usual walking pace may reduce the risk of Crohn's disease. These findings have clinical implications for sarcopenia and inflammatory bowel disease management.

[Effect of aqueous extract of Corni Fructus on Aß_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease].

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

The effect of CALIPER-derived parameters for idiopathic pulmonary fibrosis in predicting prognosis, progression, and mortality: a systematic review.

BACKGROUND: High-resolution computed tomography (HRCT), as the main tool for monitoring idiopathic pulmonary fibrosis (IPF), is characterized by subjective variability among radiologists and insensitivity to subtle changes. Recently, a few studies have aimed to decrease subjective bias by assessing the severity of IPF using computer software, i.e., Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER). However, these studies had diverse research directions. In this review, we systematically assess the effect of CALIPER in the management of IPF. METHODS: A systematic review was conducted through a search of published studies in PubMed, Web of Science, Cochrane, Embase, Scopus, and CNKI databases from database inception through February 28, 2022. The methodological quality would be evaluated by using Methodological Index for Non-Randomized Studies (MINORS). Narrative synthesis summarized findings by participant characteristics, study design, and associations with outcomes. RESULTS: Ten studies were included. They evaluated the relationship between CALIPER-derived parameters and pulmonary function test (PFT) and mortality. CALIPER-derived parameters showed a significant correlation with PFT and mortality. Two studies reported that CALIPER could be used to stratify outcomes. CONCLUSION: CALIPER-derived parameters can be used to evaluate prognosis and mortality. CALIPER-derived parameters combined with composite physiologic index (CPI) or Gender-Age-Physiology (GAP) could help clinicians implement targeted management by refining prognostic stratification. However, research has been constrained by small number of retrospective investigations and sample sizes. Therefore, it is essential to design prospective controlled studies and establish the staging system by CALIPER-derived parameters and combining them with CPI, FVC, or GAP. CLINICAL RELEVANCE STATEMENT: It is beneficial for clinic to provide objective, sensitive, and accurate indicators of disease progression. It also helps the clinic to develop individualized treatment plans based on the stage of disease progression and provides evaluation of efficacy in drug trials. KEY POINTS: • Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) is a quantitative CT analysis software that can be used to evaluate the progression of disease on CT. • The CALIPER-derived vessel-related structure shows great performance in the management of idiopathic pulmonary fibrosis. • CALIPER-derived parameters combined with composite physiologic index or Gender-Age-Physiology can be used to refine prognostic stratification.

Simultaneously metastatic cholangiocarcinoma and small intestine cancer from breast cancer misdiagnosed as primary cholangiocarcinoma: A case report.

BACKGROUND: Cholangiocarcinoma and small intestine cancer are common clinical malignancies, but metastatic cholangiocarcinoma and small intestine cancer are rare, especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer. Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor, it may lead to misdiagnosis preoperatively. CASE SUMMARY: A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice. Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct, considering a high possibility of primary bile duct tumor. Therefore, we performed a radical bile duct cancer surgery and cholecystectomy, and multiple tumors in the small intestine were found and removed during the surgery process. Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts. The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago. Combining with the immunohistochemical results, the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer. Postoperatively, the patient received four cycles of chemotherapy and targeted therapy with docetaxel, capecitabine and trastuzumab. Unfortunately, the patient eventually died from tumor progression, thoracoabdominal infection, and sepsis 5 mo after surgery. CONCLUSION: Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor. Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment. Treatment should be aimed at relieving biliary obstruction and abdominal pain, and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient's life.

Network pharmacology and bioinformatics analysis identifies potential therapeutic targets of Naringenin against COVID-19/LUSC.

Background: Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that has posed a serious threat to people's daily lives and caused an unprecedented challenge to public health and people's health worldwide. Lung squamous cell carcinoma (LUSC) is a common type of lung malignancy with a highly aggressive nature and poor prognosis. Patients with LUSC could be at risk for COVID-19, We conducted this study to examine the potential for naringenin to develop into an ideal medicine and investigate the underlying action mechanisms of naringenin in COVID-19 and LUSC due to the anti-viral, anti-tumor, and anti-inflammatory activities of naringenin. Methods: LUSC related genes were obtained from TCGA, PharmGKB, TTD,GeneCards and NCBI, and then the transcriptome data for COVID-19 was downloaded from GEO, DisGeNET, CTD, DrugBank, PubChem, TTD, NCBI Gene, OMIM. The drug targets of Naringenin were revealed through CTD, BATMAN, TCMIP, SymMap, Chemical Association Networks, SwissTargetPrediction, PharmMapper, ECTM, and DGIdb. The genes related to susceptibility to COVID-19 in LUSC patients were obtained through differential analysis. The interaction of COVID-19/LUSC related genes was evaluated and demonstrated using STRING to develop a a COX risk regression model to screen and evaluate the association of genes with clinical characteristics. To investigate the related functional and pathway analysis of the common targets of COVID-19/LUSC and Naringenin, KEGG and GO enrichment analysis were employed to perform the functional analysis of the target genes. Finally, The Hub Gene was screened and visualized using Cytoscape, and molecular docking between the drug and the target was performed using Autodock. Results: We discovered numerous COVID-19/LUSC target genes and examined their prognostic value in LUSC patients utilizing a variety of bioinformatics and network pharmacology methods. Furthermore, a risk score model with strong predictive performance was developed based on these target genes to assess the prognosis of LUSC patients with COVID-19. We intersected the therapeutic target genes of naringenin with the LUSC, COVID-19-related targets, and identified 354 common targets, which could be used as potential target genes for naringenin to treat COVID-19/LUSC. The treatment of COVID-19/LUSC with naringenin may involve oxidative stress, anti-inflammatory, antiviral, antiviral, apoptosis, immunological, and multiple pathways containing PI3K-Akt, HIF-1, and VEGF, according to the results of the GO and KEGG enrichment analysis of these 354 common targets. By constructing a PPI network, we ascertained AKT1, TP53, SRC, MAPK1, MAPK3, and HSP90AA1 as possible hub targets of naringenin for the treatment of COVID-19/LUSC. Last but not least, molecular docking investigations showed that naringenin has strong binding activity in COVID-19/LUSC. Conclusion: We revealed for the first time the pharmacological targets and potential molecular processes of naringenin for the treatment of COVID-19/LUSC. However, these results need to be confirmed by additional research and validation in real LUSC patients with COVID-19.

Successful treatment of breast metastasis from primary transverse colon cancer: A case report.

BACKGROUND: The incidence of colon cancer is increasing worldwide. Treatments for colon cancer include surgery and surgery combined with chemotherapy and radiotherapy, but the median survival rate is still poor. Colon cancer most commonly metastasizes to the lymph nodes, lungs, liver, peritoneum, and brain, but breast metastasis is rare. There is no agreement on its treatment. CASE SUMMARY: A 23-year-old woman was admitted to our hospital for further treatment with a history of acute abdominal pain, nausea, and vomiting. Her physical examination and computed tomography scan revealed an abdominal tumor. Transverse colectomy was successfully performed. Histopathological examination revealed that the tumor was a mucosecretory adenocarcinoma with signet ring cells. The patient inadvertently found a mass in the outer upper quadrant of the right breast after four cycles of XELOX chemotherapy [oxaliplatin 130 mg/m2, d1, intravenous (iv) drip for 2 h; capecitabine 1000 mg/m2, po, bid, d1-d14]. After discussion with the patient, we performed a lumpectomy and frozen biopsy. The latter revealed that the breast tumor was intestinal metastasis. Genetic testing showed wild-type RAS and BRAF. So we replaced the original chemotherapy with FOLFIRI [irinotecan 180 mg/m2, d1, iv drip for 3-90 min; leucovorin 400 mg/m2, d1, iv drip for 2 h; 5-fluorouracil (5-FU) 400 mg/m2, d1 and 5-FU 1200 mg/(m2 d) × 2 d, continuous iv drip for 46-48 h] + cetuximab (500 mg/m2, d1, iv drip for 2 h). Serum levels of tumor markers returned to normal after several treatment cycles, and there was no evidence of tumor recurrence or metastasis. CONCLUSION: Breast metastasis from colon cancer is rare. Radical breast surgery should be avoided unless needed for palliation. Chemotherapy combined with targeted therapy should be the first choice.

A Retrospective Comparative Study of Endoscopic Treatment of Gastrocnemius Contracture using the Modified Soft Tissue Release Kit.

Background and Objectives: This study aimed to evaluate the effectiveness and safety of endoscopic gastrocnemius recession using the self-developed Modified Soft Tissue Release Kit. Materials and Methods: This retrospective review followed up 22 patients (34 feet) who underwent endoscopic surgery and 20 patients (30 feet) who received open surgery between January 2020 and January 2022. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the maximum ankle dorsiflexion angle were evaluated preoperatively and at the last follow-up. Postoperative complications were recorded. Patient satisfaction was surveyed at the last follow-up. The comparison between quantitative data was analyzed with the Wilcoxon signed-rank test. The comparison between qualitative data was analyzed with the chi-square test. Results: There was no significant difference in the baseline characteristics between the two groups. The AOFAS score in the endoscopic group increased from 50 (18) points preoperatively to 90 (13) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.7 (2.8) degrees to 10.6 (3.6) degrees. The AOFAS score in the open group improved from 47 (15) points preoperatively to 90 (18) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.6 (4.0) degrees to 10.7 (3.3) degrees. The change values of the AOFAS scores in the endoscopic and open groups were 39 (15) and 40.5 (11) points, respectively, and there was no significant difference between them. The change values of the maximum ankle dorsiflexion angles in the endoscopic and open groups were 19.5 (4.3) and 19.1 (4.9) degrees, respectively, and there was no significant difference between them. There were no complications, such as sural nerve injury, in both groups. There was no significant difference between the two groups in satisfaction with the surgical outcome. Conclusions: Endoscopic gastrocnemius recession using the Modified Soft Tissue Release Kit can significantly improve the foot function with significant mid-term efficacy and high safety.

[Development of a flow cytometry method for detection of bovine multi-cytokines].

This study aims to develop a method to detect bovine multi-cytokines based on flow cytometry. Previously we have prepared and screened monoclonal antibodies against bovine cytokines IFN-γ, IL-2, TNF-α, IP-10 and MCP-1. These bovine cytokine monoclonal antibodies were fluorescently labeled, and the combination of antibody and cell surface molecules were used to develop the method for detecting bovine multi-cytokines. Subsequently, the developed method was used to determine the cytokine expression profile of Mycobacterium bovis BCG infected bovine peripheral blood mononuclear cells in vitro, and evaluate the cytokine expression level of peripheral blood CD4+ T cells of tuberculosis-positive cattle. The bovine multi-cytokine flow cytometry detection method can effectively determine the cytokine expression of BCG-infected bovine peripheral blood T lymphocytes. Among them, the expression levels of IFN-γ, IL-2, and TNF-α continue to increase after 40 hours of infection, while the expression levels of IP-10 and MCP-1 decreased. The combined detection of IFN-γ, IL-2, and TNF-α on CD4+ T lymphocytes in peripheral blood of cattle can effectively distinguish tuberculosis-positive and tuberculosis-negative samples. This method may facilitate evaluating the level of cellular immune response after bovine pathogen infection and vaccine injection.

Polydopamine-coated 3D-printed ß-tricalcium phosphate scaffolds to promote the adhesion and osteogenesis of BMSCs for bone-defect repair: mRNA transcriptomic sequencing analysis.

Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed ß-tricalcium phosphate (ß-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed ß-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed ß-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in ß-TCP scaffolds. In summary, 3D-printed ß-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.

A Retrospective Clinical Study of Endoscopic Treatment of Carpal Tunnel Syndrome using the Modified Soft Tissue Release kit.

OBJECTIVE: Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy, and endoscopic carpal tunnel release (ECTR) is one of the minimally invasive procedures for the treatment of CTS. Based on the shortcomings of ECTR, we designed the "Modified Soft Tissue Release Kit" to assist the endoscopic operation. This study aimed to evaluate the effectiveness and safety of endoscopic treatment of CTS using this kit. METHODS: This retrospective review included 57 patients (86 wrists) who underwent ECTR using the "Modified Soft Tissue Release Kit" at our department between January 2017 and August 2019. Three scale scores (i.e., Quick-Disabilities of the Arm, Shoulder, and Hand [QDASH]; Boston Carpal Tunnel Syndrome Questionnaire [BCTSQ]: symptom severity [BCTSQ-SS] and functional status [BCTSQ-FS]) were recorded to assess hand function and symptoms preoperatively, 1 month postoperatively, 3 months postoperatively, and at the last follow-up. We also asked patients to answer a satisfaction question during follow-up. Pre- and post-operation scores were compared using paired Wilcoxon signed-rank test. Spearman's rank-order correlation was used to evaluate the relationship between scale scores and patient satisfaction. RESULTS: A total of 55 patients (83 wrists) were followed up, with an average follow-up of 27.2 ± 9.3 months. The median preoperative QDASH score was 45.5; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 4.5, 0, and 0, respectively, with a significant decrease noted compared with the preoperative scores (P < 0.001). The median preoperative BCTSQ-SS and BCTSQ-FS scores were 3.3 and 2.8, respectively; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 1.2, 1.0, and 1.0, and 1.1, 1.0, and 1.0, respectively, all of which decreased significantly compared with the preoperative scores (P < 0.001). The incidence of nerve injury was 0. The incidence of pillar pain was 0 at the last follow-up. One patient showed no improvement in hand symptoms and function postoperatively, and two patients showed long-term recurrence despite postoperative symptom remission. Approximately 94.5% (52/55) of the patients were satisfied or very satisfied with the outcome. CONCLUSIONS: ECTR with the "Modified Soft Tissue Release Kit" can significantly relieve symptoms and improve function in patients with CTS, with significant short- and mid-term efficacy and high safety.

Hemoptysis caused by Parvimonas micra: case report and literature review.

Background: Parvimonas micra (P. micra), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for P. micra-related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to P. micra exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to P. micra, drawing insights from an extensive literature review of pertinent case reports. Case presentation: A 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient's symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to P. micra. Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where P. micra was identified as the causative agent. Conclusion: The literature analysis underscores the predilection of P. micra for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with P. micra infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, ß-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of P. micra-associated infections.

Simple and affordable soft brace application in dystrophic epidermolysis bullosa patients.

Background: Dystrophic epidermolysis bullosa (DEB) is a hereditary disease characterized by increased fragility of the epidermis and mucosa and is accompanied by blister formation following minor trauma. Repeated injuries cause contracture and scar formation, which can further result in hand deformity, leading to a decline in hand ability and a lower quality of life. In this study, after the scar release of patients' hands, we developed a new and practical portable soft support, and evaluated its efficacy in delaying the scar contracture of hands after operation. Methods: According to the hand function scores, the patients were divided into two groups. Those with excellent and good grades were assigned to the open hand function group, and those with poor grades were allocated to the restricted hand function group. The primary conditions, the use of a postoperative soft brace, and some common factors in the two groups were compared to determine whether these parameters influence postoperative hand function. Results: There were no significant differences in age, gender, body mass index, ADL assessment index, albumin concentration, hemoglobin concentration, fasting blood glucose level, prothrombin time, and activated partial thromboplastin time between the two groups (p > 0.05). In contrast, there was a significant difference between the two groups in the use of soft braces following the operation (p < 0.05). The odds ratio of patients fixed with a brace compared with patients not fixed with soft braces was 11.01. Conclusions: Soft brace is a critical factor impacting the hand function of patients with dystrophic epidermolysis bullosa after scar contracture release in both hands. Indeed, a hand brace worn after the operation can delay the recurrence of scar contracture in both hands and offer patients a longer time to use their hands effectively. In addition, by restoring the appearance of patients' hands and some hand functions, patients' mental state and quality of life have been greatly improved.

Outcomes of V-cut Osteotomy on the First Metatarsal Head Combined with Fixation in Mortise-shaped Bone Groove-Plasty and Akin Osteotomy on the First Toe for Hallux Valgus Correction.

OBJECTIVE: Hallux valgus (HV) is a common foot deformity, and recurrence is one of the most serious complications after HV correction. As a result, the surgical technique with a lower recurrence rate is a dream. The purpose of the article should be to observe the correction effect of hallux valgus using a novel "V-cut" osteotomy on the first metatarsal head combined with fixation in mortise-shaped bone groove-plasty technique. METHODS: Twenty-three consecutive patients (40 feet) with HV were included from March 2019 to May 2020, who were all treated using single screw fixation with V-cut osteotomy on the first metatarsal head combined with mortise-shaped metatarsal bone groove-plasty and Akin osteotomy on the first toe for hallux valgus correction. With a mean follow-up time of 21.7 months, the visual analogue scale (VAS) score and American Orthopedic Foot and Ankle Society (AOFAS) forefoot score and the changes of the hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA) were evaluated during the clinical follow-up. The paired t test was used for analytical statistics. RESULTS: The VAS score improved from 6.78 ± 1.74 to 1.87 ± 1.45 and the AOFAS score improved from 53.9 ± 12.3 preoperatively to 94.7 ± 6.8 in the latest follow-up postoperatively (P < 0.01). Besides, the HVA improved from 30.0 ± 6.1° to 5.7 ± 2.8° (P < 0.01); the IMA changed from 13.1 ± 2.8° into 3.3 ± 1.6° (P < 0.01); and the DMAA ameliorated from 27.0 ± 8.4° to 5.9 ± 3.5° (P < 0.01). Only five toes had slight numbness and stiffness in early postoperative period, and these symptoms disappeared completely at 6 months after the surgery. Only one foot was corrected to excess. One screw stern protruding beneath the skin happened, which needed secondary screw removal under local anesthesia. CONCLUSIONS: Single screw fixation with V-cut osteotomy on the first metatarsal head combined with fixation in mortise-shaped metatarsal bone groove-plasty and Akin osteotomy on the first toe is an effective way with low recurrence rate for HV correction.

3D-Printed ß-Tricalcium Phosphate Scaffolds Promote Osteogenic Differentiation of Bone Marrow-Deprived Mesenchymal Stem Cells in an N6-methyladenosine-Dependent Manner.

Bone defect is a serious orthopedic disease which has been studied for a long time. Alternative degradable biomaterials are required for bone repairing and regeneration to address the limitation of autogenous bone. ß-tricalcium phosphate (ß-TCP) is an alternative material with good cytocompatibility and has been used in bone defect treatment. However, whether ß-TCP contributes to osteogenesis of bone marrow stem cells (BMSCs) through N6-methyladenosine (m6A) modification remains unknown. To address this issue, we verified the effects of ß-TCP on osteogenesis of BMSCs. We also studied the expression of m6A-related enzymes in BMSCs after ß-TCP treatment. Furthermore, the m6A level and stability of Runt-related transcription factor 2 (RUNX2) mRNA were investigated after ß-TCP treatment. Finally, rat calvarial defect models were performed to detect expression level of osteogenic factors and m6A-related enzymes after the stimulation of three-dimension (3D)-printed ß-TCP scaffolds. We found that ß-TCP showed good biocompatibility and was osteoinductive. Meanwhile, methyltransferase-like 3 (METTL3) increased, causing the elevation of m6A level of RUNX2, results in stabler RUNX2 mRNA level. At last, based on the animal experiments, we demonstrated that the increase of RUNX2 and METTL3 levels was induced by ß-TCP. These findings suggest that METTL3 increases the m6A level of RUNX2 mRNA after ß-TCP induction, contributing to its stability, and the results in vivo also confirmed the osteogenic and bone-repair properties of ß-TCP.

Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood via the Akt/p27 Signaling Pathway.

Objective: Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established. Methods: SD rats were exposed to propofol on postnatal day 7 (PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus (DG). The expression of p-Akt and p27 were measured by western blotting. The Morris water maze, novel object recognition test, and object location test were used to evaluate neurocognitive function 2-month-old rats. Results: Phosphorylation of Akt was inhibited, while p27 expression was enhanced after neonatal exposure to propofol. Propofol also inhibited proliferation of neural stem cells (NSCs) and decreased differentiation to neurons and astroglia. Moreover, the neurocognitive function in 2-month-old rats was weakened. Of significance, intra-hippocampal injection of the Akt activator, SC79, attenuated the inhibition of p-AKT and increase of p27 expression. SC79 also rescued the propofol-induced inhibition of NSC proliferation and differentiation. The propofol-induced neurocognition deficit was also partially reversed by SC79. Conclusion: Taken together, these results suggest that neurogenesis is hindered by neonatal propofol exposure. Specifically, neonatal propofol exposure was shown to suppress the proliferation and differentiation of NSCs by inhibiting Akt/p27 signaling pathway.

Enhanced therapeutic efficacy of Listeria-based cancer vaccine with codon-optimized HPV16 E7.

Cervical cancer is a leading cause of high mortality in women in developing countries and has a serious impact on women's health. Human papilloma virus (HPV) prophylactic vaccines have been produced and may hold promise for reducing the incidence of cervical cancer. However, the limitations of current HPV vaccine strategies make the development of HPV therapeutic vaccines particularly important for the treatment of HPV related lesions. Our previous work has demonstrated that LM4Δhly::E7 was safe and effective in inducing antitumor effect by antigen-specific cellular immune responses and direct killing of tumor cell on a cervical cancer model. In this study, the codon usage effect of a novel Listeria-based cervical cancer vaccine LM4Δhly::E7-1, was evaluated for effects of codon-optimized E7 expression, cellular immune response and therapeutic efficacy in a tumor-bearing murine model. Our data demonstrated that up-regulated expression of E7 was strikingly elevated by codon usage optimization, and thus induced significantly higher Th1-biased immunity, lymphocyte proliferation, and strong specific CTL activity ex-vivo compared with LM4Δhly::E7-treated mice. Furthermore, LM4Δhly::E7-1 enhanced a remarkable therapeutic effect in establishing tumors. Taken together, our results suggest that codon usage optimization is an important consideration in constructing live bacterial-vectored vaccines and is required for promoting effective T cell responses.

WbaP is required for swarm motility and intramacrophage multiplication of Salmonella Enteritidis spiC mutant by glucose use ability.

Salmonella spp. can survive and replicate in macrophage cells to cause persistent infection, SpiC is a necessary T3SS effector, but its pathogenic mechanism is still not known completely. In our study, Salmonella Enteritidis spiC mutant (SEΔspiC) was found to have stronger swarming motility and intramacrophage hyperproliferation which was closely related to glucose metabolism. SEΔspiC wbaP::Tn5 mutant was screened out by transposon mutagenesis, which had weaker swarming motility and intramacrophage replication ability than SEΔspiC in the presence of glucose. Bioinformatics displayed that undecaprenyl-phosphate galactose phosphotransferase (Wbap), encoded by wbaP gene, was a key enzyme for glucose metabolism and Lipopolysaccharide(LPS) synthesis, which confirmed our outcome that Wbap was involved in intramacrophage replication ability by glucose use in addition to swarming motility based on SEΔspiC. This discovery will further promote the understanding of the interaction between wbaP gene and spiC gene and the intracellular Salmonella replication mechanism.

inlF Enhances Listeria monocytogenes Early-Stage Infection by Inhibiting the Inflammatory Response.

The internalin family proteins, which carry the leucine repeat region structural motif, play diverse roles in Listeria monocytogenes (Lm) infection and pathogenesis. Although Internalin F, encoded by inlF, was identified more than 20 years ago, its role in the Lm anti-inflammatory response remains unknown. Lm serotype 4b isolates are associated with the majority of listeriosis outbreaks, but the function of InlF in these strains is not fully understood. In this study, we aimed to elucidate the role of inlF in modulating the inflammatory response and pathogenesis of the 4b strain Lm NTSN. Strikingly, although inlF was highly expressed at the transcriptional level during infection of five non-phagocytic cell types, it was not involved in adherence or invasion. Conversely, inlF did contributed to Lm adhesion and invasion of macrophages, and dramatically suppressed the expression of pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF-α). Consistent with the in vitro results, during Lm infection mice, inlF significantly inhibited the expression of IL-1ß and IL-6 in the spleen, as well as IL-1ß, IL-6, and TNF-α in the liver. More importantly, inlF contributed to Lm colonization in the spleen, liver, and ileum during the early stage of mouse infection via intragastric administration, inducing severe inflammatory injury and histopathologic changes in the late stage. To our knowledge, this is the first report to demonstrate that inlF mediates the inhibition of the pro-inflammatory response and contributes to the colonization and survival of Lm during the early stage of infection in mice. Our research partly explains the high pathogenicity of serovar 4b strains and will lead to new insights into the pathogenesis and immune evasion of Lm.

Contrasting activities of estrogen receptor beta isoforms in triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC), an aggressive subtype of breast cancer, lacks the three major receptors for predicting outcome or targeting therapy. Hence, our aim was to evaluate the potential of estrogen receptor beta (ERß) as a possible endocrine therapy target in TNBC. METHODS: The expression and prognostic effect of ERß isoforms were analyzed using TCGA breast tumor data, and the expression of ERß isoform mRNA and protein in TNBC cell lines was assayed. Endogenous ERß2 and ERß5 were knocked down with siRNA, and ERß2, ERß5, and ERß1 were upregulated using a doxycycline-inducible lentiviral system. Cell proliferation, migration and invasion, and specific gene expressions were evaluated. RESULTS: ERß2 and ERß5 were the predominant endogenous forms of ERß in TNBC tumors and cell lines. High ERß2 predicted worse clinical outcome. Knockdown of endogenous ERß2/ERß5 in cell lines suppressed proliferation, migration and invasion, and downregulated proto-oncogene survivin expression. ERß2/ERß5 upregulation did the reverse, increasing survivin and these cell activities. ERß1 was barely detectable in TNBC cell lines, but its upregulation reduced survivin, increased tumor suppressor expression (E-cadherin and cystatins), and suppressed proliferation, migration and invasion in both ligand-independent and dependent manners, suggesting the possible translational benefit of ERß ligands. CONCLUSIONS: ERß2/ERß5 and ERß1 exhibit sharply contrasting activities in TNBC cells. Our findings imply that delineating the absolute amounts and relative ratios of the different ERß isoforms might have prognostic and therapeutic relevance, and could enable better selection of optimal approaches for treatment of this often aggressive form of breast cancer.