Ovarian Torsion: A Review of the Evidence.

Importance: Ovarian torsion is a gynecological emergency caused by the twisting of the ovary and/or fallopian tube, further resulting in ischemic changes of the adnexa. Early diagnosis is likely to preserve ovarian function. Objective: The purpose of this review is to review the current findings of ovarian torsion including clinical presentations, diagnostic criteria, surgical procedures, and prognosis. Evidence Acquisition: The literature search is mainly available in PubMed and Web of Science platforms by searching "ovarian torsion" combined with one or several terms including "diagnosis" "risk factors" "surgery" and "torsion recurrence." Results: Abdominal pain, nausea, and vomiting were normal clinical presentations. In order to increase the accuracy of diagnosis, it is necessary to integrate clinical presentation and the findings of imaging and laboratory examinations. Computed tomography findings, plasma d-dimer level, and the time from pain onset play a critical role in distinguishing ovarian necrosis. The efficiency of oophoropexy on preventing recurrent ovarian torsion is controversial. Conclusion: Most patients with early diagnosis of ovarian torsion may have a better prognosis with conservative surgery. Relevance: Better understanding of ovarian torsion is critical for gynecologists to promote accuracy of diagnosis and select the optimal surgical procedure.

Correction: MiR-181b-5p Downregulates NOVA1 to Suppress Proliferation, Migration and Invasion and Promote Apoptosis in Astrocytoma.

[This corrects the article DOI: 10.1371/journal.pone.0109124.].

Artificial intelligence in dentistry: A bibliometric analysis from 2000 to 2023.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Role of Branched-Chain Amino Acids in Metabolic Changes of Polycystic Ovary Syndrome.

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of menstrual disorders in women of childbearing age. It has been found that branched-chain amino acids (BCAAs), a class of essential amino acids that cannot be synthesized by the human body, play a significant role in the metabolic changes of PCOS, which may be involved in the pathogenesis of PCOS. Objective: The purpose of this review is to summarize the relevance between BCAAs and metabolic abnormalities in PCOS and to explore their possible mechanisms. Evidence Acquisition: The evidence is mainly obtained by reviewing the literature on PubMed related to PCOS, BCAAs, and related metabolic abnormalities and conducting summary analysis. Results: The metabolism of BCAAs can affect the homeostasis of glucose metabolism, possibly by disrupting the balance of gut microbiota, activating mTORC1 targets, producing mitochondrial toxic metabolites, and increasing the expression of proinflammatory genes. The correlation between obesity and BCAAs in PCOS patients may be related to the gene expression of BCAA metabolism-related enzymes in adipose tissue. The association between BCAA metabolic changes and nonalcoholic fatty liver disease in PCOS patients has not been fully clarified, which may be related to the lipid accumulation caused by BCAAs. At present, it is believed that hyperandrogenism in patients with PCOS is not related to BCAAs. However, through the study of changes in BCAA metabolism in prostate cancer caused by hyperandrogenism, we speculate that the relationship between BCAAs and hyperandrogenism may be mediated by mTORC1 and amino acid transporters. Conclusions and Relevance: Review of prior articles reveals that BCAAs may be related to insulin resistance, obesity, nonalcoholic fatty liver, and hyperandrogenism in PCOS patients, and its mechanisms are complex, diverse, and interrelated. This review also discussed the mechanism of BCAAs and these metabolic disorders in non-PCOS patients, which may provide some help for future research.

Nomogram based on immune-inflammatory indicators and age-adjusted charlson comorbidity index score to predict prognosis of postoperative parotid gland carcinoma patients.

BACKGROUND: Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. METHOD: All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. RESULT: The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup. CONCLUSION: The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies.

Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells.

BACKGROUND: The high degree of intratumoral genomic heterogeneity is a major obstacle for glioblastoma (GBM) tumors, one of the most lethal human malignancies, and is thought to influence conventional therapeutic outcomes negatively. The proneural-to-mesenchymal transition (PMT) of glioma stem cells (GSCs) confers resistance to radiation therapy in glioblastoma patients. POLD4 is associated with cancer progression, while the mechanisms underlying PMT and tumor radiation resistance have remained elusive. METHOD: Expression and prognosis of the POLD family were analyzed in TCGA, the Chinese Glioma Genome Atlas (CGGA) and GEO datasets. Tumorsphere formation and in vitro limiting dilution assay were performed to investigate the effect of UCHL3-POLD4 on GSC self-renewal. Apoptosis, TUNEL, cell cycle phase distribution, modification of the Single Cell Gel Electrophoresis (Comet), γ-H2AX immunofluorescence, and colony formation assays were conducted to evaluate the influence of UCHL3-POLD4 on GSC in ionizing radiation. Coimmunoprecipitation and GST pull-down assays were performed to identify POLD4 protein interactors. In vivo, intracranial xenograft mouse models were used to investigate the molecular effect of UCHL3, POLD4 or TCID on GCS. RESULT: We determined that POLD4 was considerably upregulated in MES-GSCs and was associated with a meagre prognosis. Ubiquitin carboxyl terminal hydrolase L3 (UCHL3), a DUB enzyme in the UCH protease family, is a bona fide deubiquitinase of POLD4 in GSCs. UCHL3 interacted with, depolyubiquitinated, and stabilized POLD4. Both in vitro and in vivo assays indicated that targeted depletion of the UCHL3-POLD4 axis reduced GSC self-renewal and tumorigenic capacity and resistance to IR treatment by impairing homologous recombination (HR) and nonhomologous end joining (NHEJ). Additionally, we proved that the UCHL3 inhibitor TCID induced POLD4 degradation and can significantly enhance the therapeutic effect of IR in a gsc-derived in situ xenograft model. CONCLUSION: These findings reveal a new signaling axis for GSC PMT regulation and highlight UCHL3-POLD4 as a potential therapeutic target in GBM. TCID, targeted for reducing the deubiquitinase activity of UCHL3, exhibited significant synergy against MES GSCs in combination with radiation.

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway.

Objective: Oxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations. Materials and methods: Using streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured. Results: We demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition. Conclusion: Our findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma.

OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

Effects of long-term no-tillage and different stover mulching amounts on soil carbon and nitrogen contents and enzyme activities of carbon and nitrogen cycle in Mollisols.

To understand the effects of different stover mulching amounts in no-tillage on soil carbon and nitrogen contents and enzyme activities, finding a stover mulching amount which can meet the requirement of soil carbon and nitrogen accumulation while maximizing economic benefits, we conducted a long-term conservation tillage field experiment since 2007 in Mollisols area of Northeast China. We analyzed soil carbon and nitrogen contents, enzyme activities and economic benefits under conventional tillage (Control, CT), no-tillage without stover mulching (NT0), no-tillage with 33% stover mulching (NT33), no-tillage with 67% stover mulching (NT67), and no-tillage with 100% stover mulching (NT100) before planting in May 2020. The results showed that compared with CT, NT0 did not affect soil organic carbon (SOC) and total nitrogen (TN) contents, but increased soil organic carbon recalcitrance and decreased the availability of dissolved organic nitrogen (DON) and ammonium nitrogen. Compared with NT0, no-tillage with stover mulching significantly increased SOC contents in 0-10 cm layer and increased with the amounts of stover. In addition, NT67 and NT100 significantly increased SOC stocks, facilitating the accumulation of soil organic matter. The effects of different stover mulching amounts on soil nitrogen content in 0-10 cm layer were different. Specifically, NT33 increased DON content and DON/TN, NT67 increased DON content, while NT100 increased TN content. Compared with CT, NT0 decreased peroxidase (POD) activity in 0-10 cm layer. Compared with NT0, NT33 increased ß-glucosidase (ßG), cellobiase (CB), 1,4-ß-N-acetylglucosaminidase (NAG), polyphenol oxidase (PPO) and POD activities, while NT67 only increased CB, NAG and POD activities in 0-10 cm soil layer, both alleviated microbial nutrient limitation. NT100 increased PPO activity in 10-20 cm layer. NT33 increased carbon conversion efficiency of stover compared with NT100, and had the highest economic benefit. In all, no-tillage with 33% stover mulching was the optimal strategy, which could promote nutrient circulation, boost stover utilization efficiency, improve the quality of Mollisols, and maximize guaranteed income.

[Clinical Efficacy and Safety of Ixazomib-Containing Regimens in the Treatment of Patients with Multiple Myeloma].

OBJECTIVE: To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma (MM). METHODS: A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022. Among the 32 patients, 15 patients were relapsed and refractory multiple myeloma (R/RMM) (R/RMM group), 17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events (AE) or other reasons (conversion treatment group). The treatment included IPD regimen (ixazomib+pomalidomide+dexamethasone), IRD regimen (ixazomib+lenalidomide+dexamethasone), ICD regimen (ixazomib+cyclophosphamide+dexamethasone), ID regimen (ixazomib+dexamethasone). RESULTS: Of 15 R/RMM patients, overall response rate (ORR) was 53.3%(8/15), among them, 1 achieved complete response (CR), 2 achieved very good partial response (VGPR) and 5 achieved partial response (PR). The ORR of the IPD, IRD, ICD and ID regimen group were 100%（3/3）, 42.9%（3/7）, 33.3%（1/3）, 50%（1/2）， respectively， there was no statistically significant difference in ORR between four groups (χ 2=3.375, P =0.452). The ORR of patients was 50% after first-line therapy, 42.9% after second line therapy, 60% after third line therapy or more, with no statistically significant difference among them (χ2=2.164, P =0.730). In conversion treatment group, ORR was 88.2%(15/17), among them, 6 patients achieved CR, 5 patients achieved VGPR and 4 patients achieved PR. There was no statistically significant difference in ORR between the IPD（100%， 3/3）, IRD（100%， 6/6）, ICD（100%， 3/3） and ID（60%， 3/5） regimen groups (χ2=3.737，P =0.184). The median progression-free survival (PFS) time of R/RMM patients was 9 months (95% CI : 6.6-11.4 months), the median overall survival (OS) time was 18 months (95% CI : 11.8-24.4 months). The median PFS time of conversion treatment group was 15 months (95% CI : 7.3-22.7 months), the median OS time not reached. A total of 10 patients suffered grade 3- 4 adverse event (AE). The common hematological toxicities were leukocytopenia, anemia, thrombocytopenia. The common non-hematological toxicities were gastrointestinal symptoms (diarrhea, nausea and vomit), peripheral neuropathy, fatigue and infections. Grade 1-2 peripheral neurotoxicity occurred in 7 patients. CONCLUSION: The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy, particularly for conversion patients who are effective for bortezomib therapy. The AE was manageable and safe.

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

E2F1-regulated USP5 contributes to the tumorigenic capacity of glioma stem cells through the maintenance of OCT4 stability.

Mesenchymal glioma stem cells (MES GSCs) are a subpopulation of cells in glioblastoma (GBM) that contribute to a worse prognosis owing to their highly aggressive nature and resistance to radiation therapy. Here, OCT4 is characterized as a critical factor in sustaining the stemness phenotype of MES GSC. We find that OCT4 is expressed intensively in MES GSC and is intimately associated with poor prognosis, moreover, OCT4 depletion leads to diminished invasive capacity and impairment of the stem phenotype in MES GSC. Subsequently, we demonstrated that USP5 is a deubiquitinating enzyme which directly interacts with OCT4 and preserves OCT4 stability through its deubiquitination. USP5 was additionally proven to be aberrantly over-expressed in MES GSCs, and its depletion resulted in a noticeable diminution of OCT4 and consequently a reduced self-renewal and tumorigenic capacity of MES GSCs, which can be substantially restored by ectopic expression of OCT4. In addition, we detected the dominant molecule that regulates USP5 transcription, E2F1, with dual luciferase reporter gene analysis. In combination, targeting the E2F1-USP5-OCT4 axis is a potentially emerging strategy for the therapy of GBM.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China.

PURPOSE: This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. METHODS: Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. CONCLUSIONS: This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Efficacy and Safety of Children With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia After Anti-CD19 CAR T-Cell Therapy Without Bridging Transplantation.

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, a considerable number of patients experience relapse within 1 year after CAR T-cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation. MATERIALS AND METHODS: In our study, we investigated 42 children with R/R B-ALL who underwent anti-CD19 CAR T-cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity. RESULTS: The cohort that received the CAR T-cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% ± 8.5%, and the event-free survival (EFS) was 55.9% ± 7.9%, with a median follow-up duration of 50.1 months. Minimal residual disease (MRD) ≥1% was associated with inferior outcomes, resulting in lower 4-year OS (P = .033) and EFS (P = .014) compared to MRD<1%. The incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD≥1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity. CONCLUSION: These findings suggest that reducing the pre-infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T-cell therapy.

Effects of evidence-based nursing on surgical site wound infection in patients undergoing acute appendicitis surgery: A meta-analysis.

This study aimed to comprehensively evaluate the effects of evidence-based nursing (EBN) intervention on wound infection and postoperative complications in patients after appendectomy for acute appendicitis (AA), with the expectation of providing a theoretical basis for postoperative care in AA. Randomised controlled trials (RCTs) on the postoperative application of EBN in patients with AA were searched in PubMed, Web of Science, Cochrane Library, Embase, China Biomedical Literature Database, Wanfang and China National Knowledge Infrastructure from the inception of databases to October 2023. Two authors screened and evaluated the literature based on the inclusion and exclusion criteria, and data were extracted from the final included literature. Stata software (version 17.0) was employed for data analysis. In total, 29 RCTs involving 2848 patients with AA were included, with 1424 in the EBN group and 1424 in the conventional care group. The analyses revealed that patients with AA who experienced EBN were significantly less likely to develop postoperative wound infections (odds ratio [OR] = 0.23, 95% confidence intervals [CIs]: 0.14-0.38, p < 0.001) and postoperative complications (OR = 0.20, 95% CI: 0.15-0.26, p < 0.001) as opposed to conventional care. Available evidence suggests that EBN can effectively reduce the risk of wound infection and postoperative complications in patients undergoing appendectomy for AA, thereby improving patient prognosis. This finding is worth promoting in the clinical practice.

Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

Synthesis and characterization of iron clusters with an icosahedral [Fe@Fe12]16+ Core.

Iron-metal clusters are crucial in a variety of critical biological and material systems, including metalloenzymes, catalysts, and magnetic storage devices. However, a synthetic high-nuclear iron cluster has been absent due to the extreme difficulty in stabilizing species with direct iron-iron bonding. In this work, we have synthesized, crystallized, and characterized a (Tp*)4W4S12(Fe@Fe12) cluster (Tp* = tris(3,5-dimethyl-1-pyrazolyl)borate(1-)), which features a rare trideca-nuclear, icosahedral [Fe@Fe12] cluster core with direct multicenter iron-iron bonding between the interstitial iron (Fei) and peripheral irons (Fep), as well as Fep···Fep ferromagnetic coupling. Quantum chemistry studies reveal that the stability of the cluster arises from the 18-electron shell-closing of the [Fe@Fe12]16+ core, assisted by its bonding interactions with the peripheral tridentate [(Tp*)WS3]4- ligands which possess both S→Fe donation and spin-polarized Fe-W σ bonds. The ground-state electron spin is theoretically predicted to be S = 32/2 for the cluster. The existence of low oxidation-state (OS ∼ +1.23) iron in this compound may find interesting applications in magnetic storage, spintronics, redox chemistry, and cluster catalysis.