[Retracted] Protective effect of microRNA­381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the certain of the cell proliferation assay data shown in Fig. 4C on p. 1444 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes, which had already been submitted for publication [Shi N, Shan B, Song Y, Chu H and Qian L: Circular RNA circ­PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR­3680­3p in esophageal squamous cell carcinoma. J Cell Biochem 120: 10021­10030, 2019]. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 21: 1439­1448, 2020; DOI: 10.3892/mmr.2020.10957].

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Comparative chloroplast genomes: insights into the identification and phylogeny of rapid radiation genus Rhodiola.

Rhodiola L. is a genus exhibiting rapid radiation and represents a typical case for studying plastid gene adaptation in species that spread from high altitudes to low altitudes. In this study, 23 samples of 18 Rhodiola species were collected from the Qinghai-Tibetan Plateau and five scattered alpine areas, and the plastid genomes (plastomes) of these species were sequenced, annotated, and compared between high-altitude and widely distributed groups. The plastomes of Rhodiola were found to be highly conserved in terms of gene size, content, and order but highly variable in several lineage-specific features, such as codon usage bias, IR boundary shifting, and distinct repeat sequence structures binding to SSRs. Codon usage in the genes of photosystem II exhibited an obvious preference, reflecting significant environmental adaptation pressures. In this study, three repeat regions compounded with trinucleotide and mononucleotide repeats were found for the first time in R. forrestii, R. himalensis, and R. yunnanensis. High-variability regions such as ndhF, ycf1, trnH-psbA, and rpoC1-rpoB were screened, laying the foundation for the precise identification of these species. The phylogenetic analysis revealed the occurrence of cyto-nuclear discordance, likely originating from the frequent interspecific hybridization events observed within Rhodiola species during rapid radiation. Dioecious and hermaphrodite species can be broadly categorized into two subclades, probably they have different environmental adaptation strategies in response to climate change. In addition, the phylogenetic tree supported the monophyly of R. forrestii and R. yunnanensis, which compose R. Sect. Pseudorhodiola. In conclusion, plastome data enrich the genetic information available for the Rhodiola genus and may provide insight into species migration events during climate change.

Efficacy of the COVID-19 vaccination in patients with asymptomatic or mild illness during the Omicron epidemic in Guangzhou: a multi-centre retrospective cohort study.

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.

High-risk histopathologic features in local advanced conjunctival melanoma.

PURPOSE: To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). METHODS: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. RESULTS: Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E, NRASQ61R, CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). CONCLUSIONS: Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer.

Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.

Genetic landscape and prognosis of conjunctival melanoma in Chinese patients.

AIMS: Conjunctival melanoma (CoM) is a rare but highly lethal ocular melanoma and there is limited understanding of its genetic background. To update the genetic landscape of CoM, whole-exome sequencing (WES) and targeted next-generation sequencing (NGS) were performed. METHODS: Among 30 patients who were diagnosed and treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2018 to January 2023, WES was performed on 16 patients, while targeted NGS was conducted on 14 patients. Samples were analysed to identify the mutated genes, and the potential predictive factors for progression-free survival were evaluated. Furthermore, the expression of the mutated gene was detected and validated in a 30-patient cohort by immunofluorescence. RESULTS: Mutations were verified in classic genes, such as BRAF (n=9), NRAS (n=5) and NF1 (n=6). Mutated FAT4 and BRAF were associated with an increased risk for the progression of CoM. Moreover, decreased expression of FAT4 was detected in CoM patients with a worse prognosis. CONCLUSIONS: The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.

Advance of microfluidic flow cytometry enabling high-throughput characterization of single-cell electrical and structural properties.

This paper reported a micro flow cytometer capable of high-throughput characterization of single-cell electrical and structural features based on constrictional microchannels and deep neural networks. When single cells traveled through microchannels with constricted cross-sectional areas, they effectively blocked concentrated electric field lines, producing large impedance variations. Meanwhile, the traveling cells were confined within the cross-sectional areas of the constrictional microchannels, enabling the capture of high-quality images without losing focuses. Then single-cell features from impedance profiles and optical images were extracted from customized recurrent and convolution networks (RNN and CNN), which were further fused for cell-type classification based on support vector machines (SVM). As a demonstration, two leukemia cell lines (e.g., HL60 vs. Jurkat) were analyzed, producing high-classification accuracies of 99.3% based on electrical features extracted from Long Short-Term Memory (LSTM) of RNN, 96.7% based on structural features extracted from Resnet18 of CNN and 100.0% based on combined features enabled by SVM. The microfluidic flow cytometry developed in this study may provide a new perspective for the field of single-cell analysis.

Serum sCD25 is an indicator for rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: CD25 (IL-2Rα) is one of IL-2 receptor's polypeptide subunits, and its soluble form is increased in patients with various inflammatory or autoimmune diseases. This study aimed to evaluate the clinical correlation of serum soluble CD25 (sCD25) with interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: 294 RA patients, including 72 in the discovery cohort (15 patients with ILD, 57 patients without ILD), 222 in the validation cohort (41 patients with ILD and 181 patients without ILD), and 58 healthy controls (HCs) were recruited. High-resolution computed tomography (HRCT) scan provided evidence and patterns of RA-ILD. Serum sCD25 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory data were recorded and the association with sCD25 was also analysed. RESULTS: In the discovery cohort, 16 RA-related molecules including cytokines, chemokines and functional soluble cell surface proteins were investigated. The results showed that sCD25 was significantly higher in RA-ILD than in RA-no-ILD group (p=0.004). ROC analysis also showed RA-ILD was discriminated with RA-no-ILD by sCD25 (AUC=0.695, 95% CI=0.541-0.849). Logistics regression demonstrated that sCD25 was one of the risk factors of RA-ILD. This result was further confirmed in validation cohort (p<0.001). According to the cut-off value in the discovery cohort, the sensitivity and specificity of sCD25 in RA-ILD were 51.2%, 77.3%, respectively. Compared with RA-no-ILD, serum level of sCD25 was also higher in different HRCT patterns including UIP, NSIP and RA-ILA. The ROC curves revealed sCD25 as diagnostic marker in UIP, NSIP and RA-ILA (with AUCs of 0.730, 0.761, and 0. 694, respectively, p<0.05). The result indicated that sCD25 was a biomarker for RA-ILD subtypes. Although sCD25 was not correlated with HRCT scores, it was significantly higher in consolidation pattern by HRCT. CONCLUSIONS: sCD25 was significantly elevated in RA-ILD (including UIP, NSIP and RA-ILA) compared to RA-no-ILD and HCs, which supports their value as a potential biomarker in RA-ILD screening and assessment.

Intraoperative pain prediction of percutaneous kyphoplasty under local anesthesia by preoperative experimental pain assessment.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the preferred treatment for osteoporotic vertebral compression fractures (OVCF) Currently, the preoperative anesthesia methods for PKP are mainly local anesthesia and tracheal intubation general anesthesia. OBJECTIVE: To assess whether patient sensitivity to pain measured preoperatively could predict the patients' pain response during PKP treatment under local anesthesia, to facilitate the development of an optimal preoperative anesthesia plan for patients. METHODS: Fifty-five female patients diagnosed with osteoporotic single vertebral fracture who were treated with PKP under local anesthesia were selected. The patients' pain sensitivities, including pain threshold and pain tolerance threshold, were evaluated with a pain test device on the day before the operation in the ward. Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were recorded before anesthesia, post-anesthesia, after needle puncture, and after balloon dilatation. At the same time, blood was drawn at the above time points to determine the level of norepinephrine (NA) as an indicator of intraoperative pain stress response. The numerical rating scale (NRS) during surgery was recorded at the end of the surgery. RESULTS: The preoperative pain tolerance threshold of 55 surgical patients was correlated with the intraoperative NRS score (r=-0.768, P< 0.001), as well as with the preoperative and intraoperative changes in HR (r=-0.791, P< 0.001), MAP (r=-0.819, P< 0.001), and NA (r=-0.553, P< 0.001). Thus, the lower the preoperative pain tolerance threshold, the more severe the patient's response to pain during PKP treatment under local anesthesia, and the greater the hemodynamic changes. Consequently, the intraoperative experience becomes worse. However, there was no correlation between preoperative pain threshold and NRS scores (r=-0.069, P= 0.616) nor between the preoperative and intraoperative changes in HR (r= 0.103, P= 0.453), MAP (r= 0.086, P= 0.535), and NA (r=-0.058, P= 0.674). CONCLUSION: The results indicated that preoperative pain assessment could predict the level of pain response in OVCF patients during PKP surgery under local anesthesia.

Integrative evaluation and experimental validation of the immune-modulating potential of dysregulated extracellular matrix genes in high-grade serous ovarian cancer prognosis.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a challenging malignancy characterized by complex interactions between tumor cells and the surrounding microenvironment. Understanding the immune landscape of HGSOC, particularly the role of the extracellular matrix (ECM), is crucial for improving prognosis and guiding therapeutic interventions. METHODS AND RESULTS: Using univariate Cox regression analysis, we identified 71 ECM genes associated with prognosis in seven HGSOC populations. The ECMscore signature, consisting of 14 genes, was validated using Cox proportional hazards regression with a lasso penalty. Cox regression analyses demonstrated that ECMscore is an excellent indicator for prognostic classification in prevalent malignancies, including HGSOC. Moreover, patients with higher ECMscores exhibited more active stromal and carcinogenic activation pathways, including apical surface signaling, Notch signaling, apical junctions, Wnt signaling, epithelial-mesenchymal transition, TGF-beta signaling, and angiogenesis. In contrast, patients with relatively low ECMscores showed more active immune-related pathways, such as interferon alpha response, interferon-gamma response, and inflammatory response. The relationship between the ECMscore and genomic anomalies was further examined. Additionally, the correlation between ECMscore and immune microenvironment components and signals in HGSOC was examined in greater detail. Moreover, the expression of MGP, COL8A2, and PAPPA and its correlation with FAP were validated using qRT-PCR on samples from HGSOC. The utility of ECMscore in predicting the prospective clinical success of immunotherapy and its potential in guiding the selection of chemotherapeutic agents were also explored. Similar results were obtained from pan-cancer research. CONCLUSION: The comprehensive evaluation of the ECM may help identify immune activation and assist patients in HGSOC and even pan-cancer in receiving proper therapy.

Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern.

Despite similar infection rates, COVID-19 has resulted in more deaths in men than women. To understand the underlying mechanisms behind this sex-biased difference in disease severity, we infected K18-human angiotensin converting enzyme 2 (ACE2) mice of both sexes with SARS-CoV-2. Our study revealed a unique protein expression profile in the lung microenvironment of female mice. As a result, they were less vulnerable to severe infection, with higher ACE2 expression and a higher estrogen receptor α (ERα)/androgen receptor (AR) ratio that led to increased antiviral factor levels. In male mice, inhaling recombinant ACE2 neutralized the virus and maintained the ERα/AR ratio, thereby protecting the lungs. Our findings suggest that inhaling recombinant ACE2 could serve as a decoy receptor against SARS-CoV-2 and protect male mice by offsetting ERα-associated protective mechanisms. Additionally, our study supports the potential effectiveness of recombinant ACE2 therapy in human lung organoids infected with the Delta variant.

Tartary buckwheat root polysaccharides ameliorate non-alcoholic fatty liver disease via the IL6-SOCS3-SREBP1c pathway.

Our previous study demonstrated that Tartary buckwheat root polysaccharides (TBRP) could reduce insulin resistance in diabetes mellitus by inhibiting SOCS3-stimulated IRS1 protein degradation. However, whether TBRP has the efficiency to treat non-alcoholic fatty liver disease (NAFLD) is still undetermined. This investigation aimed to examine the effects of TBRP on a high-fat diet (HFD)-triggered NAFLD, and elucidate the underlying molecular mechanisms. Briefly, TBRP toxicity in hepatoma (BEL7404) and pancreatic cancer (BxPC3) cells and zebrafish embryos developmental models, were evaluated in-vitro and in-vivo, respectively. TBRP inhibited cellular lipid accumulation by suppressing fat synthesis, furthermore, it improved body weight gain, liver weight, liver-to-body weight ratio, serum lipids triglyceride, total cholesterol, ALT, LDL-C, HDL-C, and AST levels in the NAFLD mice model. Additionally, TBRP treatment also lowered the nitric oxide content. The qPCR assay revealed that mRNA expression of TNF, IL1ß, and IL6 was also markedly reduced in TBRP-treated NAFLD mice. The expression of SOCS3, SREBP1c, and STAT3 was elucidated by western blot analysis, which indicated that TBRP markedly decreased the gene expression for de novo fat synthesis by the SOCS3-SREBP1c pathway. These findings reveal that TBRP ameliorates NAFLD via the IL6-SOCS3-SREBP1c signaling pathway and therefore, may represent a promising approach for NAFLD treatment.

Tumor and Nodal Disease Growth Rates in Patients with Oropharyngeal Squamous Cell Carcinoma.

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012-2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

Lycium barbarum glycopetide prolong lifespan and alleviate Parkinson's disease in Caenorhabditis elegans.

Introduction: Lycium barbarum glycopeptide (LbGp) is the main bioactive compound extracted from the traditional Chinese medicine. L. barbarum berries and has been proven to have numerous health benefits, including antioxidative, anti-inflammatory, anticancer, and cytoprotective activities. However, the antiaging effect of LbGp remains unknown. Methods: The lifespan and body movement of C. elegans were used to evaluate the effect of LbGp on lifespan and health span. The thrashing assay was used to determine the role of LbGp in Parkinson's disease. To investigate the mechanisms of LbGp-induced antiaging effects, we analyzed changes in lifespan, movement, and the expression of longevity-related genes in a series of worm mutants after LbGp treatment. Results: We found that LbGp treatment prolonged the lifespan and health span of C. elegans. Mechanistically, we found that LbGp could activate the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, as well as the nuclear receptor DAF-12, thereby upregulating longevity-related genes to achieve lifespan extension. In addition, we found that the lifespan extension induced by LbGp partially depends on mitochondrial function. Intriguingly, LbGp also ameliorated neurodegenerative diseases such as Parkinson's disease in a DAF-16-, SKN-1-, and HSF-1-dependent manner. Conclusion: Our work suggests that LbGp might be a viable candidate for the treatment and prevention of aging and age-related diseases.

Anlotinib as Monotherapy or Combination Therapy for Recurrent High-Grade Glioma: A Retrospective Study.

Background: Anlotinib is a multi-target anti-angiogenic agent. The retrospective study was conducted to evaluate the safety and effectiveness of anlotinib as monotherapy or combination therapy for the treatment of recurrent high-grade gliomas. Methods: In this retrospective study, patients with recurrent high-grade glioma (according to the 2021 World Health Organization classification as levels III-IV) at Sichuan Cancer Hospital from June 2019 to June 2022 were included. The patients were divided into an anlotinib-monotherapy group and an anlotinib-combination group, and received oral anlotinib 8 to 12 mg once a day, with 2 weeks on/1 week off. The primary endpoint was progression-free survival (PFS). The Secondary endpoints included overall survival (OS), 6-month PFS rate, objective response rate (ORR), and disease control rate (DCR). Also, adverse events were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Results: A total of 29 patients (including 20 glioblastomas, 1 diffuse midline glioma, 5 anaplastic astrocytoma, and 3 anaplastic oligodendroglioma) were included in this study. Of these, 34.48% of the patients were treated with anlotinib alone and 65.52% with anlotinib combination therapy. The median follow-up time was 11.6 months (95% confidence interval [CI]: 9.4-15.7). The median PFS was 9.4 months (95% CI: 6.5-12.3), and the 6-month PFS rate was 62.1%. The median OS was 12.7 months (95% CI: 9.7-15.7), and the 12-month OS rate was 48.3%. Evaluation of treatment response was performed according to RANO (response assessment in neuro-oncology, RANO) criteria, including 21 partial response, 6 stable disease, and 2 PFS events. The ORR and DCR were 72.4%, and 93.1%, respectively. Grade III AEs occurred in 2 patients, and the others were less than grade III. The most common AE was thrombocytopenia, with an incidence rate of 31.0%. All AEs were alleviated and controlled by symptomatic treatment. No treatment-related deaths occurred. Conclusion: Anlotinib had a low incidence of AEs and good safety in the treatment of recurrent high-grade glioma. Moreover, it showed good short-term effectiveness and significantly prolonged the PFS of patients, which may become a promising therapeutic option for recurrent high-grade glioma and lay a foundation for further clinical studies.

Integrated Network Analysis to Determine CNN1, MYL9, TAGLN, and SORBS1 as Potential Key Genes Associated with Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is challenging to treat. It is necessary to screen for related biological markers to accurately predict the prognosis and recurrence of prostate cancer. METHODS: Three data sets, GSE28204, GSE30521, and GSE69223, from the Gene Expression Omnibus (GEO) database were integrated into this study. After the identification of differentially expressed genes (DEGs) between PCa and normal prostate tissues, network analyses including protein-protein interaction (PPI) network, and weighted gene co-expression network analysis (WGCNA) were used to select hub genes. Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to annotate the functions of DEGs and hub modules of the networks. Survival analysis was performed to validate the correlation between the key genes and PCa relapse. RESULTS: In total, 867 DEGs were identified, including 201 upregulated and 666 downregulated genes. Three hub modules of the PPI network and one hub module of the weighted gene co-expression network were determined. Moreover, four key genes (CNN1, MYL9, TAGLN, and SORBS1) were significantly associated with PCa relapse (p < 0.05). CONCLUSIONS: CNN1, MYL9, TAGLN, and SORBS1 may be potential biomarkers for PCa development.

Comparison of unipedicular and bipedicular kyphoplasty for treating acute osteoporotic vertebral compression fractures in the lower lumbar spine: a retrospective study.

BACKGROUND: Unipedicular and bipedicular approaches for percutaneous kyphoplasty are reportedly both effective in treating osteoporotic vertebral compression fractures (OVCFs). However, most studies have reported thoracolumbar fractures, with few reports describing the treatment of the lower lumbar spine. Here, we compared the clinical and radiological results of unipedicular and bipedicular approaches for percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures. METHODS: We retrospectively reviewed the records of 160 patients who underwent percutaneous kyphoplasty for lower lumbar (L3-L5) osteoporotic vertebral compression fractures between January 2016 and January 2020. Patient characteristics, surgical outcomes, operation time, blood loss, clinical and radiological features, and complications were compared between two groups. Cement leakage, height restoration, and cement distribution were calculated from the radiographs. Visual pain analog scale (VAS) and Oswestry Disability Index (ODI) were calculated before surgery, immediately post-surgery, and 2 years after surgery. RESULTS: The mean age, sex, body mass index, injury time, segmental distribution, and morphological classification of fractures before surgery did not differ significantly between the groups. The results showed significant improvements in the VAS score, ODI score, and vertebral height restoration in each group (p < 0.05), with no significant differences between the two groups (p > 0.05). The mean operation time and extent of blood loss were lower in the unipedicular group than those in the bipedicular group (p < 0.05). Different types of bone cement leakage were observed in both groups. Leakage rate was higher in the bipedicular group than in the unipedicular group. Patients in the bipedicular group showed greater improvement in bone cement distribution than those in the unipedicular group (p < 0.05). CONCLUSIONS: The clinical and radiological results of unipedicular percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures in the lower lumbar region were similar to those of bipedicular percutaneous kyphoplasty. However, the unipedicular approach resulted in shorter surgical time, less blood loss, and less bone cement leakage. Thus, the unipedicular approach may be preferable owing to its several advantages.

Machine learning-based integration develops an immune-related risk model for predicting prognosis of high-grade serous ovarian cancer and providing therapeutic strategies.

Background: High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecological cancer that requires accurate prognostic models and personalized treatment strategies. The tumor microenvironment (TME) is crucial for disease progression and treatment. Machine learning-based integration is a powerful tool for identifying predictive biomarkers and developing prognostic models. Hence, an immune-related risk model developed using machine learning-based integration could improve prognostic prediction and guide personalized treatment for HGSOC. Methods: During the bioinformatic study in HGSOC, we performed (i) consensus clustering to identify immune subtypes based on signatures of immune and stromal cells, (ii) differentially expressed genes and univariate Cox regression analysis to derive TME- and prognosis-related genes, (iii) machine learning-based procedures constructed by ten independent machine learning algorithms to screen and construct a TME-related risk score (TMErisk), and (iv) evaluation of the effect of TMErisk on the deconstruction of TME, indication of genomic instability, and guidance of immunotherapy and chemotherapy. Results: We identified two different immune microenvironment phenotypes and a robust and clinically practicable prognostic scoring system. TMErisk demonstrated superior performance over most clinical features and other published signatures in predicting HGSOC prognosis across cohorts. The low TMErisk group with a notably favorable prognosis was characterized by BRCA1 mutation, activation of immunity, and a better immune response. Conversely, the high TMErisk group was significantly associated with C-X-C motif chemokine ligands deletion and carcinogenic activation pathways. Additionally, low TMErisk group patients were more responsive to eleven candidate agents. Conclusion: Our study developed a novel immune-related risk model that predicts the prognosis of ovarian cancer patients using machine learning-based integration. Additionally, the study not only depicts the diversity of cell components in the TME of HGSOC but also guides the development of potential therapeutic techniques for addressing tumor immunosuppression and enhancing the response to cancer therapy.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.