Posaconazole gastro-resistant tablets for preventing invasive fungal disease after hematopoietic stem cell transplantation: a propensity-matched cohort study.

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in hematopoietic stem cell transplantation (HSCT) patients and analyze POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS) from December 2020 to May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81% [95% CI, 0.09%-5.50%] versus 7.69% [95% CI, 4.60%-10.78%]; P = 0.044). Adverse events were comparable between the groups, with liver changes in 33/144 (22.92%) versus 84/287 (29.27%) (P = 0.162), and renal injuries in 15/144 (10.41%) versus 37/287 (12.89%) (P = 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22post-administration were 930.97 ng/ml, 1143.97 ng/ml, 1569.8 ng/ml, and 1652.57 ng/ml, respectively. CONCLUSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentration in HSCT patients stabilized by day 15 of medication.

Pseudomonas paeninsulae sp. nov. and Pseudomonas svalbardensis sp. nov., isolated from Antarctic intertidal sediment and Arctic soil, respectively.

Two Gram-stain-negative, aerobic, rod-shaped, non-endospore-forming and motile bacterial strains, designated IT1137T and S025T, were isolated from an intertidal sediment sample collected from the Fildes Peninsula (King George Island, Maritime Antarctica) and a soil sample under red snow in the Ny-Ålesund region (Svalbard, High Arctic), respectively. The 16S rRNA gene sequence similarity values grouped them in the genus Pseudomonas. The two strains were characterized phenotypically using API 20E, API 20NE, API ZYM and Biolog GENIII tests and chemotaxonomically by their fatty acid contents, polar lipids and respiratory quinones. Multilocus sequence analysis (concatenated 16S rRNA, gyrB, rpoB and rpoD sequences), together with genome comparisons by average nucleotide identity and digital DNA-DNA hybridization, were performed. The results showed that the similarity values of the two isolates with the type strains of related Pseudomonas species were below the recognized thresholds for species definition. Based on polyphasic taxonomy analysis, it can be concluded that strains IT1137T and S025T represent two novel species of the genus Pseudomonas, for which the names Pseudomonas paeninsulae sp. nov. (type strain IT1137T=PMCC 100533T=CCTCC AB 2023226T=JCM 36637T) and Pseudomonas svalbardensis sp. nov. (type strain S025T=PMCC 200367T= CCTCC AB 2023225T=JCM 36638T) are proposed.

Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.

Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion.

Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.

Development and validation of a vesicle-mediated transport-associated gene signature for predicting prognosis and immune therapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with a poor prognosis. The progression of numerous malignancies has been linked to abnormal vesicle-mediated transport-related gene (VMTRG) expression. The prognostic importance of VMTRGs in HCC is uncertain nonetheless. METHODS: Utilizing HCC data from TCGA and ICGC, we employed univariate cox analysis, unsupervised clustering, and lasso analysis to construct molecular subtypes and prognostic signature of HCC based on the prognostic-associated VMTRGs expression levels. Subsequently, we validated the expression levels of the signature genes. We investigated the probable pathways using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Six methods were utilized to compare immune cell infiltration between two risk groups. Moreover, the "pRRophetic" algorithm was utilized to test the drug sensitivity of both groups. RESULTS: We identified two distinct subtypes with divergent biological behaviors and immune functionality through unsupervised clustering. Subtype C1 demonstrated a poorer prognosis. A prognostic signature incorporating two VMTRGs (KIF2C and RAC1) was formulated. Immunohistochemistry and qRT-PCR analyses unveiled a significant upregulation of these pivotal genes within HCC tissues. The prognosis was worse for the high-risk group, which also had a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), a higher immunological infiltration of CD8 + T cells, a higher expression of immune checkpoints, and enhanced immunotherapy efficacy. These two risk groups also have varied chemotherapy drug sensitivities. CONCLUSIONS: Based on VMTRGs, we have developed a signature that assists in accurate prognosis prediction and formulating personalized treatment strategies for HCC patients.

Development and validation of a ubiquitin-proteasome system gene signature for prognostic prediction and immune microenvironment evaluation in hepatocellular carcinoma.

BACKGROUND: The ubiquitin proteasome has a major role in the development of many tumors. However, the prognostic importance of ubiquitin proteasome-system genes (UPSGs) in hepatocellular carcinoma (HCC) is not fully defined. METHODS: The TCGA and ICGC datasets were utilized to obtain transcriptional profiling data as well as clinicopathological information about HCC. The 3-UPSGs signature for the TCGA cohort was developed via univariate and LASSO Cox regression analyses. Differential expression of genes was demonstrated by qRT-PCR and immunohistochemistry (IHC). Biological pathways were studied using GSVA and GSEA. Six algorithms were used to compare immune infiltration between the two risk groups. Furthermore, drug sensitivity was measured using the "pRRophetic" R package. The predictive capacity of the 3-UPSGs signature for sensitivity to immunotherapy was also explored. Moreover, we performed a pan-cancer analysis of the 3-UPSGs signature. RESULTS: A risk model containing 3 UPSGs (DCAF13, CDC20 and PSMB5) was developed. IHC and qRT-PCR results showed that signature genes were significantly overexpressed in HCC tissues. The high-risk group had a worse prognosis, with a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), elevated levels of immune checkpoint (IC) expression, as well as increased sensitivity to immunotherapy. The two risk groups also differ in their sensitivity to chemotherapeutic drugs. Furthermore, the three UPSGs may play crucial roles in the progression of multiple types of cancers. CONCLUSION: We created a 3-UPSGs signature to estimate the prognosis of HCC and to assist in individualized treatment.

The use of mammography-based radiomics nomograms for the preoperative prediction of the histological grade of invasive ductal carcinoma.

BACKGROUND: Accurate prediction of the grade of invasive ductal carcinoma (IDC) before treatment is vital for individualized therapy and improving patient outcomes. This study aimed to develop and validate a mammography-based radiomics nomogram that would incorporate the radiomics signature and clinical risk factors in the preoperative prediction of the histological grade of IDC. METHODS: The data of 534 patients from our hospital with pathologically confirmed IDC (374 in the training cohort and 160 in the validation cohort) were retrospectively analyzed. A total of 792 radiomics features were extracted from the patients' craniocaudal and mediolateral oblique view images. A radiomics signature was generated using the least absolute shrinkage and selection operator method. Multivariate logistic regression was adopted to establish a radiomics nomogram, the utility of which was evaluated using a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: The radiomics signature was found to have a significant correlation with histological grade (P < 0.01), but the efficacy of the model is limited. The radiomics nomogram, which incorporated the radiomics signature and spicule sign into mammography, showed good consistency and discrimination in both the training cohort [area under the curve (AUC) = 0.75] and the validation cohort (AUC = 0.75). The calibration curves and DCA demonstrated the clinical usefulness of the proposed radiomics nomogram model. CONCLUSIONS: A radiomics nomogram based on the radiomics signature and spicule sign can be used to predict the histological grade of IDC and assist in clinical decision-making for patients with IDC.

Sappanone A: A natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the heartwood of Caesalpinia sappan L.

ETHNOPHARMACOLOGICAL RELEVANCE: Sumu (Lignum sappan), the dry heartwood of Caesalpinia sappan L., is a traditional Chinese medicine used as an analgesic and anti-inflammatory agent. AIM OF THE STUDY: The study aspired to discover natural phosphodiesterase 4 (PDE4) inhibitors with dual anti-inflammatory and antioxidant activities from Sumu for the treatment of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: To accurately and efficiently identify natural PDE4 inhibitors from Sumu, molecular docking and molecular dynamics (MD) analysis methods were used for structure-based virtual screening of a self-built database of primary polyphenols in Sumu. According to the previous studies of Sumu and the free radical scavenging mechanism of polyphenols, the reported antioxidant components from Sumu and the potential antioxidants with the antioxidant pharmacophore of catechol and π-conjugated moieties were selected from the potential PDE4 inhibitors predicted by docking. Sappanone A, a potential PDE4 inhibitor with antioxidant activity from Sumu, was selected, calculated and synthesized to evaluate its dual anti-inflammatory and antioxidant functions in vitro and in vivo studies. Herein sappanone A was assayed for its inhibitory effects against PDE4 enzyme activity, tumor necrosis factor-alpha (TNF-α) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and malondialdehyde (MDA) production induced by Fe2+ in mouse lung homogenate; sappanone A was also assayed for its abilities of radical (DPPH) scavenging, reducing Fe3+ and complexing Fe2+ in vitro. Additionally, LPS-induced acute lung injury (ALI) in mice was used to evaluate its anti-inflammatory activity as a PDE4 inhibitor in vivo, and the levels of TNF-α and total protein in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung were assayed. RESULTS: The present study predicted and validated that sappanone A was a promising PDE4 inhibitor from Sumu with dual anti-inflammation and antioxidant activities from Sumu. In vitro, sappanone A remarkably inhibited PDE4 enzyme activity and reduced TNF-α production induced by LPS in RAW264.7 macrophages and MDA production induced by Fe2+ in mouse lung homogenate. Meanwhile, it showed outstanding abilities of scavenging DPPH radicals, reducing Fe3+ and complexing Fe2+. In vivo, sappanone A (25 mg/kg and 50 mg/kg, i.p., twice daily for 7 days) distinctly prevented LPS-induced ALI in mice by reducing the levels of TNF-α and total protein in BALF and MPO activity in the lung. CONCLUSION: Sappanone A is a natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the traditional Chinese medicine Sumu, which may be a promising therapeutic agent to prevent the vicious cycle of COPD inflammation and oxidative stress.

Chlorogenic acid regulates the proliferation and migration of high-grade serous ovarian cancer cells through modulating the miR199a5p/DDR1 axis.

This study aimed to demonstrate that chlorogenic acid (CGA) has anticancer effects against ovarian cancer. The MTT assay was used to assess the optimum concentrations of CGA on the ovarian cancer cell lines OVCA433 and SKOV3, followed by the rate of apoptosis using Annexin V-FITC/PI. The mitochondrial membrane potential of ovarian tumour cells treated with CGA was evaluated using mitochondrial staining kits followed by Western blot analysis, immunofluorescence, and RT-PCR assays. The Trans-well migration assay conducted the percentage of cell migration, followed by wound healing and colony formation assays. CGA induces activation of mitochondria-mediated intrinsic apoptotic pathways in ovarian cancer cells. The discovery that miR-199a-5p is inversely correlated to DDR1, a receptor tyrosine kinase involved in collagen synthesis, was the major consequence of examining the various mechanisms involved in the development of ovarian cancer. After treatment with CGA, cells derived from ovarian cancer cells were deregulated partially via the miR199a5p/DDR1 axis, significantly affecting tumour suppression. DDR1 has been identified as a direct target of miR199a5p in these ovarian cancer cells. We found that CGA-induced loss of DDR1 caused the inactivation of NF-κB signalling downstream in the MMP, migration, and EMT pathways. The study results showed that CGA is a promising drug candidate for treating ovarian cancer, particularly because it exhibits anti-invasive and migrastatic properties.

Electroacupuncture Promotes Motor Function Recovery in MCAO/R Rats by Activating Astrocyte-Related PI3K/AKT Pathway.

Background: Electroacupuncture (EA) is a widely used traditional Chinese medicine method to manage various diseases, including cerebral ischemia-reperfusion injury (CIRI). Objectives: We assessed the neuroprotective effects of EA and examined its mechanism in a rat model of the middle cerebral artery occlusion-reperfusion (MCAO/R). The gait analysis was performed to evaluate the neuroprotective effects. Western blot and immunohistochemistry assays were carried out to determine the molecular mechanisms of EA. Methods: Male SD rats were randomly divided into the sham operation group, right MCAO/R group, and EA group. EA was administered every day (4/20 Hz, 10 min/1 d) at the following acupoints: Baihui (DU20), Yintang (EX-HN3), and Zusanli (ST36). Gait and motor function were analyzed from day 8 onward. Results: The plantar support and balance coordination of MCAO/R rats decreased, and the cellular structure of the ischemic penumbra was unclear. EA improved the gait dynamics of the rats, adjusted the cell structure, further activated astrocytes, and increased the expression and phosphorylation of phosphoinositide 3-kinase/protein kinase B (PI3K/PKB or AKT). Conclusion: EA promoted astrocyte-related effects in the rat model. Our findings suggest that the neuroprotective mechanism of EA may be related to the activation of the PI3K/AKT signaling pathway. The intervention enhanced brain protection and improved motor functions.

Focusing on OB-OC-MΦ Axis and miR-23a to Explore the Pathogenesis and Treatment Strategy of Osteoporosis.

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.

Effects of smoking on the prognosis of anterior circulation acute ischemic stroke with intravenous thrombolysis.

OBJECTIVE: This is a single-center retrospective analysis of the clinical data of 516 patients with acute ischemic stroke who underwent intravenous thrombolysis. This study was conducted to compare the therapeutic efficacy of smokers and non-smokers. METHODS: Univariate analysis was used to analyze and compare the clinical data of smokers and non-smokers. Multivariate analysis was used to assess risk factors affecting the 90-day modified Rankin Scale (mRS) score. RESULTS: Among the 516 patients, 235 (45.5 %) were smokers. Univariate analysis showed that smokers have a better 90-day prognosis and a lower 90-day mRS score than non-smokers. Multivariate logistic regression analysis showed that smoking is not a protective factor affecting prognosis, while baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent risk factor affecting the 90-day functional outcome. Subgroup analysis did not determine a relationship between the 90-day mRS score and the smoking intensity and duration. CONCLUSION: Smoking was not associated with a good 90-day prognosis after intravenous thrombolysis (IVT) treatment. The good clinical outcome of smokers in univariate analysis was bound up with their baseline characteristics. Baseline NIHSS score was the independent risk factor that affected the 90-day outcome of AIS patients undergoing IVT.

SIX3 function in cancer: progression and comprehensive analysis.

The homeobox gene family encodes transcription factors that are essential for cell growth, proliferation, and differentiation, and its dysfunction is linked to tumor initiation and progression. Sine oculis homeobox (SIX) belongs to the homeobox gene family, with SIX3 being a core member. Recent studies indicate that SXI3 functions as a cancer suppressor or promoter, which is mainly dependent on SIX3's influence on the signal pathways that promote or inhibit cancer in cells. The low expression of SIX3 in most malignant tumors was confirmed by detailed studies, which could promote the cell cycle, proliferation, migration, and angiogenesis. The recovery or upregulation of SIX3 expression to suppress cancer is closely related to the direct or indirect inhibition of the Wnt pathway. However, in some malignancies, such as esophageal cancer and gastric cancer, SIX3 is a tumor-promoting factor, and repressing SIX3 improves patients' prognosis. This review introduces the research progress of SIX3 in tumors and gives a comprehensive analysis, intending to explain why SIX3 plays different roles in different cancers and provide new cancer therapy strategies.

Anticancer effects of Pimaric acid is mediated via endoplasmic reticulum stress, caspase-dependent apoptosis, cell cycle arrest, and inhibition of cell migration in human ovarian cancer cells.

Pimaric acid is a naturally occurring resin and has been found to perform many pharmacological activities including, anticancer activity. However, the role of Pimaric acid in ovarian cancer is still not known. This investigation aimed to evaluate the anticancer effects of Pimaric acid and its molecular mechanism in human ovarian cancer cells. MTT assay was used to examine cell viability. Cell morphology was determined through phase contrast microscopy. DAPI staining and TUNEL assay were performed for apoptotic study. Examination of cell cycle phase distribution was carried out through flow cytometry. In vitro wound healing assay was used for cell migration determination. Pimaric acid induced cytotoxicity in human ovarian cancer cells (PA-1) in a dose-dependent manner without causing too much cytotoxicity in human ovarian epithelial cells (T1074). Cell morphology in treated cancer cells showed significant changes compared to untreated controls. Furthermore, it was observed that the cytotoxic effects of Pimaric acid were apoptosis-mediated and caspase-dependent cascade. Western blotting analysis showed that the expression of apoptosis-associated proteins like BAX, p-53 and caspase-3 was enhanced and BCL-2 expression was diminished. The induction of cytotoxicity was mediated via endoplasmic reticulum stress through expressions of related proteins which showed a tremendous increase in p-PERK, PERK, AT-4, CHOP and IRE-1 levels after treatment. Cell cycle analysis through cytometry showed significant results as it revealed G2/M phase cell cycle arrest. Furthermore, the in vitro wound healing assay showed specific anti-migratory effects of Pimaric acid on PA-1 cells. In conclusion it can be assumed that Pimaric acid may act as a potential anticancer agent against ovarian carcinoma, however further investigations are required to validate this initial claim.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report.

BACKGROUND: Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY: A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION: CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

Carbon ion radiotherapy for bladder cancer: A case report.

BACKGROUND: Radical cystectomy is considered the first choice for the treatment of muscle-invasive bladder cancer. However, for some patients who have lost the indications for surgery, external beam radiotherapy is a non-invasive and effective treatment. CASE SUMMARY: A 76-year-old patient with bladder cancer who had serious comorbidities and could not tolerate surgery or chemotherapy came to the Wuwei Heavy Ion Center. He received carbon ion radiotherapy (CIRT) with a whole-bladder dose of 44 GyE and tumor boost of 20 GyE. When he finished CIRT, his bladder cancer-related hematuria completely disappeared, and computed tomography examination showed that the tumor had obviously decreased in size. At the 3-mo follow-up, the tumor disappeared, and there were no acute or late adverse events. CIRT was well tolerated in this patient. CONCLUSION: CIRT may allow for avoiding resection and was well tolerated with curative outcomes.

Bystander effect and abscopal effect in recurrent thymic carcinoma treated with carbon-ion radiation therapy: A case report.

BACKGROUND: Although the bystander effect and abscopal effect are familiar in medicine, they are relatively rare in clinical practice. Herein, we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma. CASE SUMMARY: A 44-year-old female presented with shortness of breath. Eleven years prior, she was diagnosed with athymic tumor located in the anterosuperior mediastinum. She underwent extensive tumor resection, and the postoperative pathologic diagnosis was thymic carcinoma. She was administered 50 Gy/25 Fx of postoperative radiation. In 2019, she was diagnosed with a recurrence of thymic carcinoma, with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity, the largest of which was in the diaphragm pleura proximal to the pericardium, with a size of 6.7 cm × 5.3 cm × 4.8 cm. She received carbon-ion radiotherapy. After carbon-ion radiotherapy treatment, the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging. We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case. CONCLUSION: This report is the first of obvious abscopal and bystander effects following carbon-ion irradiation in a human patient, and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.

Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: adjusting macrophage polarization through the activin receptor-follistatin system.

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

Histamine H3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation.

NLRP3 inflammasome has been implicated in impaired post-injury muscle healing and in muscle atrophy. Histamine receptors play an important role in inflammation, but the role of histamine H3 receptor (H3R) in myocyte regeneration and in the regulation of NLRP3 inflammasome is not known. We studied the effects of H3R signaling on C2C12 myocyte viability, apoptosis, and tumor necrosis factor alpha (TNFα)-induced NLRP3 inflammasome activation during striated myogenic differentiation at three time points (days 0, 3, and 6). Expression of Nlrp3, interleukin-1ß (IL-1ß), and myogenesis markers were determined. TNFα reduced overall viability of C2C12 cells, and exposure to TNFα induced apoptosis of cells at D6. Activation of H3R had no effect on viability or apoptosis, whereas inhibition of H3R increased TNFα-induced apoptosis. Stimulation of C2C12 cells with TNFα increased Nlrp3 mRNA expression at D3 and D6. Moreover, TNFα reduced the expression of myogenesis markers MyoD1, Myogenin, and Myosin-2 at D3 and D6. H3R attenuated TNFα-induced expression of Nlrp3 and further inhibited the myogenesis marker expression; while H3R -blockage enhanced the proinflammatory effects of TNFα and increased the myogenesis marker expression. TNFα-induced secretion of mature IL-1ß was dependent on the activation of the NLRP3 inflammasome, as shown by the reduced secretion of mature IL-1ß upon treatment of the cells with the small molecule inhibitor of the NLRP3 inflammasome (MCC950). The activation of H3R reduced TNFα-induced IL-1ß secretion, while the H3R blockage had an opposite effect. In conclusion, the modulation of H3R activity regulates the effects of TNFα on C2C12 myocyte differentiation and TNFα-induced activation of NLRP3 inflammasome. Thus, H3R signaling may represent a novel target for limiting postinjury muscle inflammation and muscle atrophy.