Decreased hospital-acquired respiratory infections among older inpatients during the COVID-19 pandemic: a retrospective observational study in a general hospital in China.

BACKGROUND: To mitigate hospital-acquired transmission of coronavirus disease 2019 (COVID-19), various prevention and control measures have been strictly implemented in medical institutions. These stringent measures can potentially reduce the incidence of hospital-acquired respiratory infections. This study aimed to assess if there were changes in the prevalence of hospital-acquired respiratory infections during a period of national attention focused on COVID-19 prevention. METHODS: A retrospective analysis of the clinical data from adult patients with hospital-acquired respiratory infections admitted between October and December 2019 and during the same period in 2020 was performed. All patients were referred from a general hospital in Beijing China and COVID-19 patients were not treated at the hospital. Hospital-acquired respiratory infections were diagnosed based on the criteria of the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN). A comparison of the incidence and mortality rate of hospital-acquired respiratory infections between the two selected time periods was conducted. Additionally, multivariate logistics regression analysis was used to identify mortality-associated risk factors. RESULTS: This study included 2,211 patients from October to December 2019 (pre-COVID-19 pandemic) and 2,921 patients from October to December 2020 (during the COVID-19 pandemic). The incidence of hospital-acquired respiratory infections in 2019 and 2020 was 4.7% and 2.9%, respectively, with odds ratio (OR): 0.61, 95% confidence interval (CI): 0.46-0.81, and P = 0.001. In-hospital mortality of hospital-acquired respiratory infections in 2019 and 2020 was 30.5% and 38.4%, respectively, with OR: 1.42, 95%CI: 0.78-2.59, and P = 0.25. Multivariate logistics regression analysis revealed that a history of previous malignancy (OR: 2.50, 95%CI: 1.16-5.35, P = 0.02), was associated with in-hospital mortality. CONCLUSIONS: The incidence of hospital-acquired respiratory infections was significantly decreased following the implementation of various prevention and control measures during the COVID-19 pandemic. A history of previous malignancy was associated with higher in-hospital mortality in older inpatients with hospital-acquired respiratory infections.

Risk factors and clinical outcomes of pulmonary hypertension associated with bronchopulmonary dysplasia in extremely premature infants: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the risk factors for bronchopulmonary dysplasia associated pulmonary hypertension (BPD-PH) in extremely premature infants (gestational age < 32 weeks) and its impact on outcomes. A computerized search of eight databases was performed, from the time of library construction to February 2024. The quality of the included studies was assessed with the Newcastle‒Ottawa scale. Statistical analyses were performed using RevMan 5.4.1 and Stata 16.0 software. Meta-analysis of 2137 extremely premature infants revealed that oligohydramnios (OR = 2.21, 95% CI 1.06-4.61), low gestational age (SMD = -0.36, 95% CI -0.47 to -0.24), low birth weight (SMD = -0.54, 95% CI -0.74 to -0.35), small for gestational age (OR = 1.61, 95% CI 1.06-2.44), neonatal respiratory distress syndrome (OR = 2.05, 95% CI 1.45-2.91), grade III bronchopulmonary dysplasia (OR = 4.67, 95% CI 1.34-16.30), and sepsis (OR = 2.25, 95% CI 1.69-4.66) were risk factors for BPD-PH, whereas antenatal steroids (OR = 0.66, 95% CI 0.49-0.88) were protective factors. BPD-PH led to the extension of oxygen therapy (SMD = 0.67, 95% CI 0.42-0.92) and hospital stay (SMD = 0.77, 95% CI 0.14-1.40), and elevated the risk of discharged on oxygen (OR = 2.77, 95% CI 1.35-5.70) and death (OR = 4.38, 95% CI 2.21-8.69). BPD-PH is a multifactorial disease. In this study, a total of seven risk factors, and one protective factor for BPD-PH were identified in extremely premature infants. By managing and mitigating these factors, it is possible to decrease the occurrence of BPD-PH. Furthermore, BPD-PH may increase the risk of a poor prognosis in extremely premature infants.

KMT2D-mediated H3K4me1 recruits YBX1 to facilitate triple-negative breast cancer progression through epigenetic activation of c-Myc.

BACKGROUND: Lysine methyltransferase 2D (KMT2D) mediates mono-methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D-mediated H3K4me1 mark modulates gene expression in triple-negative breast cancer (TNBC) progression is unresolved. METHODS AND RESULTS: We recognized Y-box-binding protein 1 (YBX1) as a "reader" of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP-seq and RNA-seq data indicated that YBX1 was co-localized with KMT2D-mediated H3K4me1 in the promoter regions of c-Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c-Myc and SENP1 in a KMT2D-dependent manner. CONCLUSION: Our results suggest that KMT2D-mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c-Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D-H3K4me1-YBX1 axis for TNBC treatment. HIGHLIGHTS: YBX1 is a KMT2D-mediated H3K4me1-binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c-Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c-Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.

ECM1 and ANXA1 in urinary extracellular vesicles serve as biomarkers for breast cancer.

Objective: Although urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer. Methods: This study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC). The dysregulation of ECM1 and ANXA1 in the uEVs was validated in a larger cohort of 128 BC patients, 25 HC and 25 benign breast nodules (BBN) by chemiluminescence assay (CLIA). The expression levels of ECM1 and ANXA1 were also confirmed in the uEVs of MMTV-PyMT transgenic breast cancer mouse models. Results: LC-MS/MS analysis identified 571 dysregulated proteins in the uEVs of BC patients. ECM1 and ANXA1 were selected for validation in 128 BC patients, 25 HC and 25 BBN using CLIA, as their fold change showed a significant difference of more than 10 with p-value<0.05. Protein levels of ECM1 and ANXA1 in uEVs were significantly increased in BC patients. In addition, the protein levels of ECM1 and ANXA1 in the uEVs of MMTV-PyMT transgenic mice were observed to increase progressively with the progression of breast cancer. Conclusion: We developed a simple and purification-free assay platform to isolate uEVs and quantitatively detect ECM1 and ANXA1 in uEVs by WGA-coupled magnetic beads and CLIA. Our results suggest that ECM1 and ANXA1 in uEVs could potentially serve as diagnostic biomarkers for breast cancer.

Efficacy of Lenvatinib Combined with Anti-PD-1 Antibodies plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Blockade of pan-viral propagation by inhibition of host cell PNPT1.

For successful viral propagation within infected cells, the virus needs to overcome the cellular integrated stress response (ISR), triggered during viral infection, which, in turn, inhibits general protein translation. This paper reports a tactic employed by viruses to suppress the ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus and hepatovirus within their respective host cells induces PNPT1 expression. Notably, when PNPT1 is knocked down, the propagation of all three viruses is prevented. Mechanistically, the inhibition of PNPT1 facilitates the relocation of mitochondrial double-stranded RNAs (mt-dsRNAs) to the cytoplasm, where they activate RNA-activated protein kinase (PKR). This activation leads to eukaryotic initiation factor 2α (eIF2α) phosphorylation, resulting in the suppression of translation. Furthermore, by scrutinizing the PNPT1 recognition element and screening 17,728 drugs and bioactive compounds approved by the US Food and Drug Administration, lanatoside C was identified as a potent PNPT1 inhibitor. This compound impedes the propagation of adenovirus, murine cytomegalovirus and hepatovirus, and suppresses production of the severe acute respiratory syndrome coronavirus-2 spike protein. These discoveries shed light on a novel strategy to impede pan-viral propagation by activating the host cell mt-dsRNA-PKR-eIF2α signalling axis.

EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.

Mono-methylation of histone H3 on Lys 4 (H3K4me1), which is catalyzed by histone-lysine N-methyltransferase 2D (KMT2D), serves as an important epigenetic regulator in transcriptional control. In this study, the authors identify early B-cell factor 2 (EBF2) as a binding protein of H3K4me1. Combining analyses of RNA-seq and ChIP-seq data, the authors further identify killin (KLLN) as a transcriptional target of KMT2D and EBF2 in pancreatic ductal adenocarcinoma (PDAC) cells. KMT2D-dependent H3K4me1 and EBF2 are predominantly over-lapped proximal to the transcription start site (TSS) of KLLN gene. Comprehensive functional assays show that KMT2D and EBF2 cooperatively inhibit PDAC cells proliferation, migration, and invasion through upregulating KLLN. Such inhibition on PDAC progression is also achieved through increasing H3K4me1 level by GSK-LSD1, a selective inhibitor of lysine-specific demethylase 1 (LSD1). Taken together, these findings reveal a new mechanism underlying PDAC progression and provide potential therapeutic targets for PDAC treatment.

[Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma].

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION: For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.

Effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway: a randomized clinical trial.

Background: Few studies have examined the effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway (SGA). This study investigated the surgical condition scores for such procedures in cases where neuromuscular block, epidural block, or neither was used. Methods: A total of 150 patients aged 3-12 years undergoing laparoscopic orchiopexy with a ProSeal SGA device were randomly allocated to one of three groups: the control group (did not receive neuromuscular block and epidural block), the NMB group [received a neuromuscular block (train-of-four 1-2 twitches) using rocuronium], or the EDB group (received an epidural block using ropivacaine). The primary outcome was the quality of surgical conditions evaluated with the Leiden-Surgical Rating Scale by the blinded surgeon. The secondary outcome measures included intraoperative hemodynamic data (including mean arterial pressure and heart rate), the SGA device removal time, the PACU discharge time, the pain score in the PACU and intraoperative adverse events (including bradycardia, hypotension, peak airway pressure > 20 cmH2O, and poor or extremely poor surgical conditions occurred during the operation). Statistical analysis was performed with one-way analysis of variance, the Kruskal-Wallis test, the chi-square test or Fisher's exact test. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Results: Surgical condition scores were significantly higher in the NMB and EDB groups than in the control group (median difference: 0.8; 95% confidence interval [CI], 0.5-1.0; p < 0.0001; and median difference: 0.7; 95% CI, 0.5-0.8; p < 0.0001, respectively). Blood pressure and heart rate were significantly lower in the EDB group than in the other two groups (p < 0.0001 and p = 0.004). Patients in the EDB group had significantly lower pain scores during PACU than those in the other two groups (p < 0.0001). The sufentanil dose was lower in the EDB group than in the other two groups (p = 0.001). Conclusion: Epidural block can improve surgical conditions during pediatric subumbilical laparoscopic surgery involving a SGA to a degree comparable to that with moderate neuromuscular block.

Controllable Star Cationic Poly(Disulfide)s Achieve Genetically Cascade Catalytic Therapy by Delivering Bifunctional Fusion Plasmids.

The absence of effective delivery vectors and suitable multifunctional plasmids limits cancer gene therapy development. The star cationic poly(disulfide)s with ß-cyclodextrin cores (termed ß-CD-g-PSSn ) for caveolae-mediated endocytosis are designed and prepared via mild and controllable disulfide exchange polymerization for high-efficacy cancer therapy. Then, ß-CD-g-PSSn /pDNA complexes are transported to the Golgi apparatus and endoplasmic reticulum. Disulfides in ß-CD-g-PSSn vectors are degraded by glutathione in tumor cells, which not only promotes intracellular pDNA release but also reduces in vitro and in vivo toxicity. One bifunctional fusion plasmid pCATKR, which expresses catalase (CAT) fused to KillerRed (KR) (CATKR) in the same target cell, is also proposed for genetically cascade catalytic therapy. When compared with pCAT-KR (plasmid expressing CAT and KR separately in the same cell), delivered pCATKR decomposes hydrogen peroxide, alleviates tumor hypoxia more effectively, generates stronger reactive oxygen species (ROS) capabilities under moderate irradiation, and leads to robust antitumor cascade photodynamic effects. These impressive results are attributed to fusion protein design, which shortens the distance between CAT and KR catalytic centers and leads to improved ROS production efficiency. This work provides a promising strategy by delivering a catalytic cascade functional plasmid via a high-performance vector with biodegradable and caveolae-mediated endocytosis characteristics.

HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1.

Solid tumors have developed robust ferroptosis resistance. The mechanism underlying ferroptosis resistance regulation in solid tumors, however, remains elusive. Here, we report that the hypoxic tumor microenvironment potently promotes ferroptosis resistance in solid tumors in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner. In combination with HIF-2α, which promotes tumor ferroptosis under hypoxia, HIF-1α is the main driver of hypoxia-induced ferroptosis resistance. Mechanistically, HIF-1α-induced lactate contributes to ferroptosis resistance in a pH-dependent manner that is parallel to the classical SLC7A11 and FSP1 systems. In addition, HIF-1α also enhances transcription of SLC1A1, an important glutamate transporter, and promotes cystine uptake to promote ferroptosis resistance. In support of the role of hypoxia in ferroptosis resistance, silencing HIF-1α sensitizes mouse solid tumors to ferroptosis inducers. In conclusion, our results reveal a mechanism by which hypoxia drives ferroptosis resistance and identify the combination of hypoxia alleviation and ferroptosis induction as a promising therapeutic strategy for solid tumors.

Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Chemotherapy in Acute Myeloid Leukemia.

Background: Acute myeloid leukemia (AML) is a highly heterogenous disease with varying clinical outcomes among patients. Epithelial-mesenchymal transition (EMT) is an important mechanism underlying cancer metastasis and chemotherapy resistance. However, few EMT-based signatures have been established to predict AML prognosis and treatment efficacy. Methods: By conducting comparative RNA-seq analysis, we discovered the differential expression of EMT genes between AML patients with relapse and those without relapse. Based on the prognostic analysis of the differentially expressed EMT genes, a metastasis-related EMT signature (MEMTs) was constructed. An analysis was conducted on both TARGET and TCGA cohorts to explore the possible association between MEMTs and prognosis in AML. Three separate chemotherapy treatment cohorts were utilized to assess the predictive efficacy of MEMTs for chemotherapy response. In addition, the potential correlation between MEMTs and the tumor microenvironment was also investigated. Finally, random forest analysis and functional experiments were conducted to verify the key MEMTs gene associated with AML metastasis. Results: Based on expression and prognostic analysis, we constructed MEMTs that include three EMT genes (CDH2, LOX, and COL3A1). Our findings suggested that the MEMTs could act as a prognostic factor for AML patients, and furthermore, it proved to be a predictor of their response to chemotherapy. Specifically, high MEMTs was associated with worse prognosis and poor response to chemotherapy, while low MEMTs was linked to better prognosis and higher response rates. Random forest and functional experiments demonstrate that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes. Conclusion: The identification of MEMTs could potentially act as a predictor for the prognosis and the response to chemotherapy in AML patients. Individual tumor evaluation based on MEMTs could provide personalized treatment options for AML patients in the future.

A Novel Pathway of Functional microRNA Uptake and Mitochondria Delivery.

Extracellular microRNAs (miRNAs) play a critical role in horizontal gene regulation. Uptake of extracellular miRNAs by recipient cells and their intracellular transport, however, remains elusive. Here RNA phase separation is shown as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ≈110 nm discrete nanoparticles, which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which majority of miRNAs are accumulated in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1(PNPT1)-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of cytochrome b (CYB), leading to increase in adenosine triphosphate (ATP) and reactive oxygen species (ROS) reduction in HEK293T cells. The findings thus reveal a previously unrecognized mechanism for uptake and delivery functional extracellular miRNAs into mitochondria.

Advances in nanotechnology for the treatment of GBM.

Glioblastoma (GBM), a highly malignant glioma of the central nervous system, is the most dread and common brain tumor with a high rate of therapeutic resistance and recurrence. Currently, the clinical treatment methods are surgery, radiotherapy, and chemotherapy. However, owning to the highly invasive nature of GBM, it is difficult to completely resect them due to the unclear boundary between the edges of GBM and normal brain tissue. Traditional radiotherapy and the combination of alkylating agents and radiotherapy have significant side effects, therapeutic drugs are difficult to penetrate the blood brain barrier. Patients receiving treatment have a high postoperative recurrence rate and a median survival of less than 2 years, Less than 5% of patients live longer than 5 years. Therefore, it is urgent to achieve precise treatment through the blood brain barrier and reduce toxic and side effects. Nanotechnology exhibit great potential in this area. This article summarizes the current treatment methods and shortcomings of GBM, and summarizes the research progress in the diagnosis and treatment of GBM using nanotechnology.

Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment.

Gut microbiota disorders damage the intestinal barrier, which causes intestinal disease. Thus, we screened the microbiota with significant changes using an in situ malignant colorectal cancer (CRC) model. Among the colonies with increased abundance, Akkermansia muciniphila (A. muciniphila) is known for its characteristic of breaking down mucin, which is an essential component of the intestinal barrier. The role of A. muciniphila remains controversial. To investigate the effect of excess A. muciniphila on the intestinal barrier, we established an over-colonized A. muciniphila mouse model by administering a live bacterial suspension after disrupting the original gut microbiome with antibiotics. The results showed that over-colonization of A. muciniphila decreased intestinal mucin content. The mRNA and protein expression levels of tight junction proteins also decreased significantly in the over-colonized A. muciniphila mouse model. Our findings reveal that excess colonization by A. muciniphila breaks the dynamic balance between mucin secretion and degradation, reduces the thickness of the intestinal mucus layer, and damages the intestinal barrier, which would eventually aggravate the development of colitis and CRC. These results will raise awareness about the safety of A. muciniphila serving as a probiotic.

Transcriptomics-proteomics Integration reveals alternative polyadenylation driving inflammation-related protein translation in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a complex disease involving the upregulation of many inflammation-related proteins. Alternative polyadenylation (APA), a crucial post-transcriptional regulatory mechanism, has been proven to play vital roles in many inflammatory diseases. However, it is largely unknown whether and how APA exerts function in DN. METHODS: We performed transcriptomics and proteomics analysis of glomeruli samples isolated from 50 biopsy-proven DN patients and 25 control subjects. DaPars and QAPA algorithms were adopted to identify APA events from RNA-seq data. The qRT-PCR analysis was conducted to verify 3'UTR length alteration. Short and long 3'UTRs isoforms were also overexpressed in podocytes under hyperglycemia condition for examining protein expression. RESULTS: We detected transcriptome-wide 3'UTR APA events in DN, and found that APA-mediated 3'UTR lengthening of genes (APA genes) increased their expression at protein but not mRNA level. Increased protein level of 3'UTR lengthening gene was validated in podocytes under hyperglycemia condition. Pathway enrichment analysis showed that APA genes were enriched in inflammation-related biological processes including endoplasmic reticulum stress pathways, NF-κB signaling and autophagy. Further bioinformatics analysis demonstrated that 3'UTR APA of genes probably altered the binding sites for RNA-binding proteins, thus enhancing protein translation. CONCLUSION: This study revealed for the first time that 3'UTR lengthening of APA genes contributed to the progression of DN by elevating the translation of corresponding proteins, providing new insight and a rich resource for investigating DN mechanisms.

Extranodal natural killer/T-cell lymphoma invading a patient's heart: A rare case report and literature review.

Extranodal NK/T-cell lymphoma (ENKTL) is a rare but aggressive subtype of non-Hodgkin lymphoma, which is derived from NK cells or T cells. There are very few cases of ENKTL invading the heart. Only 12 cases of ENKTL invading the heart have been reported in the English literature. Due to the rarity of this lymphoma, an effective therapeutic strategy has not been defined. Here, we present a case of a 51-year-old Chinese male with extranodal NK/T-cell lymphoma invading the heart and review the literature. The patient received a chemotherapy regimen of PD1 monoclonal antibody (Sintilimab) in combination with first-line P-Gemox. The patient survived for 2 months after diagnosis.

Trastuzumab treatment of invasive breast ductal carcinoma induces severe edema: a case report.

Background: Trastuzumab, a monoclonal antibody which binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), is the first biological drug approved for the treatment of HER2-positive breast cancer. However, trastuzumab exhibits a series of clinical adverse effects, including cardiac toxicity, nerve damage, abnormal liver function, thrombocytopenia, etc. Case Description: We report a case of a 46-year-old female patient with invasive breast ductal carcinoma (classified as Stage 2B) who developed a rare severe edema in neck, face, chest, abdomen and both upper limbs after a single dose trastuzumab treatment. The patient (~60 kg weight) was administered with trastuzumab (420 mg) with an infusion time of 2 hours. The most severe edema symptom was observed in patient's hands, in which the epidermis was markedly transparent and tight. One month after trastuzumab administration, the patient was administered with methylprednisone (80 mg per day) for 5 days. The edema in patient's neck, face and both upper limbs was mildly reduced though the CT image showed no significant reduction of edema. Conclusions: Trastuzumab treatment for breast cancer patients, particularly those who have an allergic constitution, may have an adverse effect to develop severe edema, and treatment with methylprednisone at early stage can reduce such adverse reaction.

A Nomogram for Predicting Cardiovascular Diseases in Chronic Obstructive Pulmonary Disease Patients.

Cardiovascular diseases (CVDs) are the most common comorbidities in the chronic obstructive pulmonary disease (COPD), which increase the risk of hospitalization, length of stay, and death in COPD patients. This study aimed to identify the predictors for CVDs in COPD patients and construct a prediction model based on these predictors. In total, 1022 COPD patients in National Health and Nutrition Examination Surveys (NHANES) were involved in the cross-sectional study. All subjects were randomly divided into the training set (n = 709) and testing set (n = 313). The differences before and after the manipulation of the missing data were compared via sensitivity analysis. Univariate and multivariable analyses were employed to screen the predictors of CVDs in COPD patients. The performance of the prediction model was evaluated via the area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and calibration. Subgroup analysis was performed in patients using different COPD diagnosis methods and patients smoking or not smoking in the testing set. We found that male, older age, a smoking history, overweight, a history of blood transfusion, a history of heart disease in close relatives, higher levels of white blood cell (WBC), and monocyte (MONO) were associated with the increased risk of CVDs in COPD patients. Higher levels of platelets (PLT) and lymphocyte (LYM) were associated with reduced risk of CVDs in COPD patients. A prediction model for the risk of CVDs in COPD patients was established based on predictors including gender, age, a smoking history, BMI, a history of blood transfusion, a history of heart disease in close relatives, WBC, MONO, PLT, and LYM. The AUC value of the prediction model was 0.75 (95% CI: 0.71-0.79) in the training set and 0.79 (95%CI: 0.73-0.85) in the testing set. The prediction model established showed good predictive performance in predicting CVDs in COPD patients.