Primary thoracolumbar intraspinal malignant melanoma: A case report.

BACKGROUND: Primary intraspinal malignant melanoma is a very rare tumor that most often occurs in the cervical, thoracic, or thoracolumbar segment. CASE SUMMARY: A rare case of primary thoracolumbar malignant melanoma is described. A 45-year-old female patient complained of low back pain with numbness and fatigue in both lower limbs. MR revealed an intradural space-occupying lesion at the thoracic 12 to lumbar 1 level. The tumor was partially excised, and a malignant melanoma was confirmed by histopathology. CONCLUSION: Primary intraspinal malignant melanoma has rarely been reported, and surgical resection and related characteristics and diagnoses have been discussed.

Fluorescence sensing probe based on functionalized mesoporous MOFs for non-invasive and detection of dopamine in human fluids.

Abnormal amount of dopamine (DA) in human body is closely relate to various diseases, such as Parkinson's disease, pheochromocytoma. Real-time monitoring DA is crucial for disease warning, diagnosis and treatment. Currently, most methods rely on invasive blood testing for detecting DA, which is only completed with the aid of the medical staffs in hospitals. Herein, a non-invasive fluorescence visual strategy is developed for the real-time monitoring DA, based on luminescent nanoparticles and modified mesoporous zeolite imidazole framework (ZIF-8-NH2) dodecahedrons. During the reaction process, DA is enriched through the spatial configuration of ZIF-8-NH2 and hydrogen bonding effect. The luminescence of Cr3+-doped zinc gallate (ZnGa2O4:Cr3+, ZGC) is inhibited by the photo-induced electron transfer (PET) mechanism to realize sensitively detecting DA. The intelligent sensing platform based on the designed fluorescence probe and color recognition system is structured for real-time detection of DA in urine. Furthermore, a skin-fitting hydrogel patch is prepared by combining a fluorescent probe with chitosan, which enables sensitive and accurate detection of DA in sweat without the complex sample pretreatment. The non-invasive fluorescence detection method provides an effective strategy for quantitatively monitoring DA in human fluids.

Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Establishment and Validation of Lactate Metabolism-Related Genes as a Prognostic Model for Gastric Cancer.

BACKGROUND: Gastric Cancer (GC) has become one of the most important causes of cancer-related deaths worldwide due to its intractability. Studying the mechanisms of gastric carcinogenesis, recurrence, and metastasis, and searching for new therapeutic targets have become the main directions of today's gastric cancer research. Lactate is considered a metabolic by-product of tumor aerobic glycolysis, which can regulate tumor development through various mechanisms, including cell cycle regulation, immunosuppression, and energy metabolism. However, the effects of genes related to lactate metabolism on the prognosis and tumor microenvironmental characteristics of GC patients are unknown.

External Validation of the Risk Assessment Model of Venous Thromboembolism in Multicenter Internal Medicine Inpatients.

To external validate the risk assessment model (RAM) of venous thromboembolism (VTE) in multicenter internal medicine inpatients. We prospectively collected 595 internal medical patients (310 with VTE patients, 285 non-VTE patients) were from Beijing Shijitan Hospital, Beijing Chaoyang Hospital, and the respiratory department of Beijing Tsinghua Changgeng Hospital from January 2022 to December 2022 for multicenter external validation. The prediction ability of Caprini RAM, Padua RAM, The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) RAM, and Shijitan (SJT) RAM were compared. This study included a total of 595 internal medicine inpatients, including 242 (40.67%) in the respiratory department, 17 (2.86%) in the respiratory intensive care unit, 49 (8.24%) in the neurology department, 34 (5.71%) in the intensive care unit, 26 (4.37%) in the geriatric department, 22 (3.70%) in the emergency department, 71 (11.93%) in the nephrology department, 63 (10.59%) in the cardiology department, 24 (4.03%) in the hematology department, 6 (1.01%) in the traditional Chinese medicine department, 9 (1.51%) cases in the rheumatology department, 7 (1.18%) in the endocrinology department, 14 (2.35%) in the oncology department, and 11 (1.85%) in the gastroenterology department. Multivariate logistic regression analysis showed that among internal medicine inpatients, age > 60 years old, heart failure, nephrotic syndrome, tumors, history of VTE, and elevated D-dimer were significantly correlated with the occurrence of VTE (P < .05). The incidence of VTE increases with the increase of D-dimer. It was found that the effectiveness of SJT RAM (AUC = 0.80 ± 0.03) was better than Caprini RAM (AUC = 0.74 ± 0.03), Padua RAM (AUC = 0.72 ± 0.03) and IMPROVE RAM (AUC = 0.52 ± 0.03) (P < .05). The sensitivity and Yoden index of SJT RAM were higher than those of Caprini RAM, Pauda RAM, and IMPROVE RAM (P < .05), but specificity was not significantly different between the 4 models (P > .05). The SJT RAM derived from general hospitalized Chinese patients has effective and better predictive ability for internal medicine inpatients at risk of VTE.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

The application of artificial intelligence for Rapid On-Site Evaluation during flexible bronchoscopy.

Background: Rapid On-Site Evaluation (ROSE) during flexible bronchoscopy (FB) can improve the adequacy of biopsy specimens and diagnostic yield of lung cancer. However, the lack of cytopathologists has restricted the wide use of ROSE. Objective: To develop a ROSE artificial intelligence (AI) system using deep learning techniques to differentiate malignant from benign lesions based on ROSE cytological images, and evaluate the clinical performance of the ROSE AI system. Method: 6357 ROSE cytological images from 721 patients who underwent transbronchial biopsy were collected from January to July 2023 at the Tangdu Hospital, Air Force Medical University. A ROSE AI system, composed of a deep convolutional neural network (DCNN), was developed to identify whether there were malignant cells in the ROSE cytological images. Internal testing, external testing, and human-machine competition were used to evaluate the performance of the system. Results: The ROSE AI system identified images containing lung malignant cells with the accuracy of 92.97% and 90.26% on the internal testing dataset and external testing dataset respectively, and its performance was comparable to that of the experienced cytopathologist. The ROSE AI system also showed promising performance in diagnosing lung cancer based on ROSE cytological images, with accuracy of 89.61% and 87.59%, and sensitivity of 90.57% and 94.90% on the internal testing dataset and external testing dataset respectively. More specifically, the agreement between the ROSE AI system and the experienced cytopathologist in diagnosing common types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, demonstrated almost perfect consistency in both the internal testing dataset (κ = 0.930) and the external testing dataset (κ = 0.932). Conclusions: The ROSE AI system demonstrated feasibility and robustness in identifying specimen adequacy, showing potential enhancement in the diagnostic yield of FB. Nevertheless, additional enhancements, incorporating a more diverse range of training data and leveraging advanced AI models with increased capabilities, along with rigorous validation through extensive multi-center randomized control assays, are crucial to guarantee the seamless and effective integration of this technology into clinical practice.

First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial.

BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

Comprehensive pan-carcinoma analysis of ITGB1 distortion and its potential clinical significance for cancer immunity.

The human protein-coding gene ITGB1 (Integrin 1), also known as CD29, has a length of 58048 base pairs. The Integrin family's most prevalent subunit, it participates in the transmission of numerous intracellular signaling pathways. A thorough examination of ITGB1's functions in human malignancies, however, is inadequate and many of their relationships to the onset and development of human cancers remain unknown. In this work, we examined ITGB1's role in 33 human cancers. Finally, a multi-platform analysis revealed that three of the 33 malignancies had significantly altered ITGB1 expression in tumor tissues in comparison to normal tissues. In addition, it was discovered through survival analysis that ITGB1 was a stand-alone prognostic factor in a number of cancers. ITGB1 expression was linked to immune cell infiltration in colon cancer, according to an investigation of immune infiltration in pan-cancer. In the gene co-expression research, ITGB1 showed a positive connection with the majority of the cell proliferation and EMT indicators, indicating that ITGB1 may have an essential function in controlling cancer metastasis and proliferation. Our pan-cancer analysis of ITGB1 gives evidence in favor of a further investigation into its oncogenic function in various cancer types.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Application of rapid on-site evaluation combined with flexible bronchoscopy in the diagnosis of lung lesions.

BACKGROUND: Pathology is considered the gold standard for the diagnosis of lung lesions, but the pathological result is relatively lagging and cannot provide real-time guidance for the biopsy procedure. OBJECTIVE: To investigate the potential application of rapid on-site evaluation (ROSE) during flexible bronchoscopy (FB) in the evaluation and diagnosis of lung lesions. PATIENTS AND METHODS: Consecutive patients who underwent FB for the diagnosis of lung lesions between August 2022 and February 2023 were included in this retrospective study. 294 patients underwent FB with ROSE, while 304 patients underwent FB without ROSE. The final pathological results and the number of patients undergoing repeat biopsies were recorded in both groups. Specifically, we conducted separate statistical analysis for patients undergoing different biopsy methods, including the endobronchial biopsy (EBB), radial probe endobronchial ultrasound transbronchial lung biopsy with guide sheath (r-EBUS-GS-TBLB), and the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to study the detailed roles that ROSE plays under different biopsy methods. RESULTS: The adequacy rate of biopsy specimens from the non-ROSE group was significantly lower than that of the ROSE group (259/281 = 92.17 % vs. 263/268 = 98.13 %, p = 0.001). Meanwhile, fewer patients underwent repeat biopsies in the ROSE group compared to the non-ROSE group (2/294 = 0.68 % vs. 10/304 = 3.29 %, p = 0.023). For the ROSE group, the consistency between ROSE diagnoses and final pathological diagnoses was 94.40 % (κ = 0.886), with 95.58 % for benign diseases and 93.55 % for malignant diseases. CONCLUSION: The utility of ROSE during FB increases the adequacy rate of biopsy specimens and thus decreases the need for repeat biopsies in patients with lung lesions to get a definite diagnosis. Moreover, the high consistency between ROSE diagnoses and final pathological diagnoses suggests that ROSE is a reliable tool for optimizing the diagnosis of lung lesions.

Thyroid dysfunction and risk of cutaneous malignant melanoma: a bidirectional two-sample Mendelian randomization study.

Background: Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work. Methods: A genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction. Hypothyroidism was linked to 22,687 cases and 440,246 controls. For hyperthyroidism, there were 3545 cases and 459,388 controls. A total of 3751 cases and 372016 controls were included in the genetic data for CMM from UK Biobank (http://www.nealelab.is/uk-biobank) (the Dataset: ieu - b - 4969). Among them, inverse variance weighting (IVW) is the main MR Analysis method for causality assessment. MR-Egger method, MR Pleiotropic residual and outlier test (MR-PRESSO), and simple and weighted median (VM) were used to supplement the IVW method. Sensitivity analyses, mainly Cochran's Q test, leave-one-out analysis, and MR Egger intercept test were performed to assess the robustness of the outcomes. Results: The two-sample MR Analysis results revealed a negative correlation between genetically predicted hypothyroidism and the probability of CMM (OR=0.987, 95%CI =0.075-0.999, p=0.041). The supplemental MR Analysis did not reveal any statistically significant differences, although the direction of the effect sizes for the other approaches was consistent with the IVW effect sizes. The results of the causal analysis were relatively robust, according to a sensitivity analysis. The risk of CMM was unaffected by hyperthyroidism (p>0.05). No correlation between CMM and thyroid dysfunction was seen in the reverse MR analysis. Conclusion: Although the magnitude of the causal association is weak and further investigation of the mechanism of this putative causal relationship is required, our findings imply that hypothyroidism may be a protective factor for CMM.

A roadmap for safety during facial filler injections: A fresh frozen cadaver study.

BACKGROUND: Filler injections are commonly applied to reshape facial contouring. However, cadaveric injections of filler for facial contouring on the whole face, followed by anatomic analysis and measurement, have rarely been reported. This study aimed to provide comprehensive anatomical information, including topographies and roadmap of injection point entry, penetration depth, filler location, the hierarchy of facial structure, and vital vascular course. METHODS: Thirty faces on fresh frozen cadaver heads were used for this anatomic study. The whole face was divided into seven facial zones and 14 injection points for penetration depth measurement and cadaveric injection. Static periosteum injections with a sharp-needle technique were performed. Specimens were then dissected to observe the precise locations of fillers and their relationships with surrounding anatomic structures. RESULTS: The topography of penetration depth gradually increased from the upper face to the middle face, lower face, and temporal region. Most of the injected hyaluronic acid filler flowed backward to the loose areolar tissue layer between the superficial musculoaponeurotic system and periosteum or deep fascia. Multilevel layer distributions and anastomosis of the vessels were found in the face, especially in the glabella, dorsum nasi, and temporal regions. CONCLUSIONS: This study can provide clinicians with a comprehensive reference for facial contouring injections: topographies of the injection point and penetration depth and the vascular anatomical structure in high-risk facial zones. The static periosteum injection with effective aspiration is recommended as a relatively safe technique. Clinicians are supposed to grasp the anatomy and injection technique to achieve maximum safety during filler injections.

miR-26b-5p promotes osteogenesis of bone mesenchymal stem cells via suppressing FGF21.

BACKGROUND: miR-26b-5p actively participates in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The database showed that fibroblast growth factor (FGF)-21 is a potential binding site of miR-26b-5p. This study aimed to investigate the molecular osteogenic mechanisms of miR-26b-5p targeting FGF21. METHODS: Bone marrow was aspirated from the anterior superior iliac spine during bone marrow puncture. BMSCs were used to establish an in vitro cell model, and BMSCs markers were analyzed by flow cytometry. miR-26b-5p were overexpressed for 48 hours, and then placed in an osteogenic induction medium for osteogenic induction culture, the expression of RNA was detected using RT-qPCR. On day 7 of induction, RT-qPCR was used to measure Runx2, Osterix (Osx), and target gene FGF21 expression levels in each group. RT-qPCR, the dual-luciferase reporter gene system and western blot were used to verify that FGF21 was a direct target of miR-26b-5p. RESULTS: BMSCs were identified according to the antigenic characteristics. miR-26b-5p expression was significantly upregulated after the expression of miR-26b-5p mimics, and FGF21 expression was downregulated; in miR-26b-5p inhibitor, the opposite results were revealed. After overexpression of miR-26b-5p, the alkaline phosphatase activity and nodules of Alizarin red S in the culture medium was increased; the opposite results were revealed in miR-26b-5p inhibitor. The expressions of Runx2 and Osx in the miR-26b-5p group were also significantly higher; in the miR-26b-5p inhibitor group, the opposite results were revealed. Luciferase reporter assays demonstrated that FGF21 was a direct target of miR-26b-5p. The western blotting analysis showed that FGF21 expression was significantly downregulated in the miR-26b-5p overexpressed group. Finally, the expressions of the characteristic osteogenic factors in the miR-26b-5p control + FGF21 group was significantly lower, but then increased significantly in the miR-26b-5p mimics + FGF21 group; the expressions of the characteristic osteogenic factors in the miR-26b-5p control + si-FGF21 group was significantly higher. CONCLUSIONS: miR-26b-5p can regulate the osteogenic differentiation of BMSCs and participate in PMOP pathogenesis via suppressing FGF21.

Analysis of the anatomical and biomechanical characteristics of the pelvic floor in cystocele.

INTRODUCTION: Stress urinary incontinence (SUI) occurs due to disruption of the pelvic floor anatomy; however, the complexity of the pelvic floor support structures and individual patient differences make it difficult to identify the weak points in the pelvic floor support that cause SUI to occur, develop, and recur. This study aimed to analyze the pelvic floor anatomy, structural features, and biomechanics of cystoceles to develop more effective treatment plans with individualized and precise healthcare. MATERIAL AND METHODS: In this observational case-controlled study (clinical trial identifier BOJI201855L), 102 women with normal pelvic floor function and 273 patients diagnosed with cystocele degrees I-III were identified at Shanghai General Hospital from October 2016 to December 2019. We combined ultrasound and vaginal tactile imaging (VTI) to assess the anatomy and biomechanical functions of the anterior and posterior vaginal walls. Both examinations included relaxation and muscle tension tests. RESULTS: Of the 42 VTI parameters, 13 were associated with the degree of cystocele, six with an increase in the urethral rotation angle (pointing to the mobility of the urethra), and six with a decrease in the retrovesical angle (pointing to hypsokinesis and decrease in bladder position). According to these data, the strength of tissues, especially the muscles in both the anterior and posterior compartments, contributes to the stability of the pelvic floor structure. The strength of the levator ani muscle (LAM) is important for the degree of cystocele, mobility of the urethra, hypsokinesis, and decrease in bladder position. CONCLUSIONS: In general, the biomechanical status of the pelvic floor in patients with cystocele is complex and involves various muscles, ligaments, tendons, and fascia. Of these, repair and exercise of the LAM have not received much attention in the treatment of patients with cystoceles, which may be an important risk factor for the high recurrence rate.

Computed tomography (CT) characteristics and pathologic basis of ciliated muconodular papillary tumors of the lung.

Background: Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor with papillary architecture. Most studies have focused on the clinicopathological features of CMPT, while computed tomography (CT) characteristics have rarely been systematically described. Methods: A cohort of 27 patients with surgically resected CMPT were identified. Clinical and demographic features were recorded. Preoperative CT images of the CMPTs and the corresponding histopathological basis were also retrospectively analyzed. Results: All of the tumors appeared as solitary nodules. Pure ground glass, part-solid nodules and solid nodules were detected in 2/27 (7.4%), 17/27 (63.0%), and 8/27 (29.6%) patients, respectively. Twenty-one tumors (77.8%) were located in the lower lobe. The average tumor size was 1.21±0.74 (range, 0.44-3.46) cm. Eighteen (66.7%) of the 27 patients had tumors with well-defined margins and lobulated contours. Fifteen patients (55.6%) had air bronchograms in the tumor, and 19 patients (70.4%) had air-containing space. There were two patients whose tumor size was enlarged and accompanied by an increase in solid components, and one patient simply had an increase in tumor size at the preoperative follow-up duration. Notably, one patient with solid tumor components was finally diagnosed with CMPT accompanied by adenocarcinoma. Conclusions: CMPTs of the lung mostly manifest as solitary, lobulated, well-defined tumors with air-containing spaces on CT and often occur in the periphery of the pulmonary lower lobe. When CT findings meet these criteria, the possibility of CMPT should be considered. Additionally, CMPT can coexist with adenocarcinoma. Further investigation will contribute significantly to the biological properties of CMPT and its relationship to the potential for malignant transformation.

Probiotic potential of Lactobacillus sakei L-7 in regulating gut microbiota and metabolism.

A growing body of research suggests that gut microbiota is inextricably linked to host health and disease，so we are committed to finding more probiotic resources that are beneficial to human health. This study evaluated the probiotic properties of Lactobacillus sakei L-7 isolated from home-made sausages. The basic probiotic properties of L. sakei L-7 were evaluated through in vitro tests. The strain showed 89% viability after 7 h of digestion in simulating gastric and intestinal fluid. The hydrophobicity, self-aggregation and co-aggregation of L. sakei L-7 showed it had a strong adhesion ability. C57BL/6 J mice were fed L. sakei L-7 for 4 weeks. 16 S rRNA gene analysis indicated that intake of L. sakei L-7 increased the richness of gut microbiota and abundance of beneficial bacteria Akkermansia, Allobaculum and Parabacteroides. Metabonomics analysis revealed that beneficial metabolite gamma-aminobutyric acid and docosahexaenoic acid increased significantly. While the level of metabolite sphingosine and arachidonic acid significantly decreased. In addition, serum levels of inflammatory cytokines interleukin (IL)- 6 and tumor necrosis factor (TNF)-α were significantly decreased. The results suggested that L. sakei L-7 may promote gut health and reduce the occurrence of inflammatory response, it has the potential to become a probiotic.

Extreme γ-Ray Radiation Tolerance of Spectrometer-Grade CsPbBr3 Perovskite Detectors.

The perovskite compound CsPbBr3 has recently been discovered as a promising room-temperature semiconductor radiation detector, offering an inexpensive and easy-to-manufacture alternative to the current benchmark material Cd1-x Znx Te (CZT). The performance of CsPbBr3 sensors is evaluated under harsh conditions, such as high radiation doses often found in industrial settings and extreme radiation in space. Results show minimal degradation in detector performance after exposure to 1 Mrad of Co-60 gamma radiation, with no significant change to energy resolution or hole mobility and lifetime. Additionally, many of the devices are still functional after being exposed to a 10 Mrad dose over 3 days, and those that do not survive can still be refabricated into working detectors. These results suggest that the failure mode in these devices is likely related to the interface between the electrode and material and their reaction, or the electrode itself and not the material itself. Overall, the study suggests that CsPbBr3 has high potential as a reliable and efficient radiation detector in various applications, including those involving extreme fluxes and energies of gamma-ray radiation.

Homeostatic control of an iron repressor in a GI tract resident.

The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.