Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: a retrospective observational study based on SEER.

PURPOSE: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. METHODS: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan-Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. RESULTS: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18-45, 46-55, 56-65, and 65-80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18-45 years: OS P = 0.019, BCSS P = 0.016; age group of 46-55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18-45 years: OS P = 0.473, BCSS P = 0.750; age group of 46-55 years: OS P = 0.380, BCSS P = 0.816, age group of 56-65 years: OS P = 0.484, BCSS P = 0.290; age group of 66-80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB. CONCLUSION: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT.

Efficacy and safety analysis of non-radical surgery for early-stage cervical cancer (IA2 ~ IB1): a systematic review and meta-analysis.

Objective: Radical hysterectomy has long been considered as the standard surgical treatment for early-stage cervical cancer (IA2 to IB1 stages), according to the 2009 International Federation of Obstetrics and Gynecology. This study aims to conduct an in-depth evaluation of the effectiveness and safety of non-radical surgery as an alternative treatment for patients with early-stage cervical cancer. Methods: A systematic search of online databases including PubMed, Embase, and the Cochrane Library was conducted to identify relevant literature on surgical treatment options for early-stage cervical cancer. Keywords such as "cervical cancer," "conservative surgery," "early-stage," "less radical surgery," and "simple hysterectomy" were used. Meta-analysis was performed using Stata 15.0 software, which included randomized controlled trials (RCTs) and cohort studies. Results: This meta-analysis included 8 eligible articles covering 9 studies, with 3,950 patients in the simple hysterectomy (SH) surgery group and 6,271 patients in the radical hysterectomy (RH) surgery group. The results indicate that there was no significant difference between the two groups in terms of the Overall Survival (OS) (HR = 1.04, 95% CI: 0.86-1.27, p = 0.671; Heterogeneity: I2 = 33.8%, p = 0.170), Disease Free Survival (DFS) (HR = 1.39, 95% CI: 0.59-3.29, p = 0.456; Heterogeneity: I2 = 0.0%, p = 0.374), Cervical Cancer Specific Survival (CCSS) (HR = 1.11, 95% CI: 0.80-1.54, p = 0.519; Heterogeneity: I2 = 11.9%, p = 0.287) and recurrence rate (RR = 1.16, 95% CI: 0.69-1.97, p = 0.583; Heterogeneity: I = 0.0%, p = 0.488). However, the mortality rate (RR = 1.35, 95% CI: 1.10-1.67, p = 0.006; Heterogeneity: I2 = 35.4%, p = 0.158) and the rate of postoperative adjuvant therapy (RR = 1.59, 95% CI: 1.16-2.19, p = 0.004; Heterogeneity: I2 = 92.7%, p < 0.10) were higher in the SH group compared to those in the RH group. On the other hand, the incidence of surgical complications was lower in the SH group (RR = 0.36, 95% CI: 0.21-0.59, p = 0.004; Heterogeneity: I2 = 0.0%, p = 0.857) than that in the RH group. Subgroup analysis revealed that patients in the IB1 stage SH group had a significantly higher mortality rate compared to those in the RH group (RR = 1.59, 95% CI: 1.23-2.07, p < 0.001; Heterogeneity: I2 = 0.0%, p = 0.332). However, there was no significant difference in mortality rates between the two groups for patients at stage IA2 (RR = 0.84, 95% CI: 0.54-1.30, p = 0.428; Heterogeneity: I2 = 26.8%, p = 0.243). In the subgroups positive for Lymphovascular Space Invasion (LVSI), patients in the SH group had a significantly higher mortality rate than those in the RH group (RR = 1.34, 95% CI: 1.09-1.65, p = 0.005; Heterogeneity: I2 = 41.6%, p = 0.128). However, in the LVSI-negative subgroups, there was no significant difference in mortality rates between the two groups (RR = 0.33, 95% CI: 0.01-8.04, p = 0.499). Conclusion: For patients with early-stage cervical cancer patients at IA2 without LVSI involvement, comparisons between the two groups in terms of OS, DFS, CCSS, recurrence rate, and mortality rates revealed no statistically significant differences, indicating that the choice of surgical approach does not affect long-term survival outcomes for this specific patient group. For patients at IB1 and IA2 stages with LVSI involvement, while there were no significant differences between the two groups in OS, DFS, CSS, and recurrence rate, a significant increase in mortality rates was observed in the SH group. This indicates a potential elevated risk of mortality associated with SH in this subset of patients. Notably, the incidence of surgical complications was significantly lower in the SH group compared to the RH group, highlighting the safety profile of SH in this context. Significantly, among patients in the SH group, an increase in the rate of postoperative adjuvant treatment is associated with a higher occurrence of treatment-related complications. To facilitate more precise patient selection for conservative surgical management, future prospective studies of superior quality are imperative to gain deeper insights into this matter. Systematic review registration: PROSPERO (CRD42023451609: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451609).

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study.

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Macrophage Migration Inhibitory Factor as a Potential Plasma Biomarker of Cognitive Impairment in Cerebral Small Vessel Disease.

As the pathogenesis of cerebral small vessel disease with cognitive impairment (CSVD-CI) remains unclear, identifying effective biomarkers can contribute to the clinical management of CSVD-CI. This study recruited 54 healthy controls (HCs), 60 CSVD-CI patients, and 57 CSVD cognitively normal (CSVD-CN) patients. All participants underwent neuropsychological assessments and multimodal magnetic resonance imaging. Macrophage migration inhibitory factors (MIFs) were assessed in plasma. The least absolute shrinkage and selection operator model was used to determine a composite marker. Compared with HCs or CSVD-CN patients, CSVD-CI patients had significantly increased plasma MIF levels. In CSVD-CI patients, plasma MIF levels were significantly correlated with multiple cognitive assessment scores, plasma levels of blood-brain barrier (BBB)-related indices, white matter hyperintensity Fazekas scores, and the mean amplitude of low-frequency fluctuation in the right superior temporal gyrus. Higher plasma MIF levels were significantly associated with worse global cognition and information processing speed in CSVD-CI patients. The composite marker (including plasma MIF) distinguished CSVD-CI patients from CSVD-CN and HCs with >80% accuracy. Meta-analysis indicated that blood MIF levels were significantly increased in CSVD-CI patients. In conclusion, plasma MIF is a potential biomarker for early identification of CSVD-CI. Plasma MIF may play a role in cognitive decline in CSVD through BBB dysfunction and changes in white matter hyperintensity and brain activity.

Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer.

Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.

Treatment for locally resectable stage IIIC1r cervical cancer: surgery or chemoradiotherapy?

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.

Minority stress, social support and mental health among lesbian, gay, and bisexual college students in China: a moderated mediation analysis.

BACKGROUND: The existing body of research exploring minority stressors and their impact on the mental health of Lesbian, Gay, and Bisexual (LGB) students in China remains limited in scope and often restricted to specific geographic regions.. METHODS: A combination of snowball and targeted sampling strategies was used to recruit lesbian, gay and bisexual students (N = 1,393) for a cross-sectional, online survey in China. Participants (Mage = 20.00 years; 60.23% assigned male at birth) were tasked with completing a comprehensive questionnaire designed to capture various dimensions, including gender expression, minority stressors (e.g., school bullying, internalized homophobia), social psychological resources (e.g., perceived social support), and mental health-related outcomes (e.g., depression, anxious and stress). Our analytical approach involved hierarchical multiple regression analyses, mediation and moderated mediation modeling to elucidate the intricate interplay among these factors. RESULTS: Our findings shed light on the pronounced mental health disparities afflicting LGB college students in China, with notable prevalence rates of depression (48.1%), anxiety (57.1%), and stress (37.5%). A significant positive correlation was observed between experiences of school-based victimization and internalized homophobia, which, in turn, exhibited a direct association with affective symptoms.School bullying was positive with internalized homophobia, which was positively associated with affective symptoms.In addition to unveiling the indirect effects of school bullying on affective symptoms, our study identified direct links in this complex relationship. Notably, the availability of social support emerged as a pivotal factor, serving as a moderator within the mediation model by mitigating the path from school-based victimization bullying to internalized homophobia (ß = -0.077, P = 0.040). CONCLUSIONS: This study underscores the pervasive and concerning mental health disparities experienced by LGB college students in China. In response, institutions of higher learning should intensify anti-bullying initiatives tailored to LGB students and implement comprehensive gender education programs. Moreover, concerted efforts should be directed at enhancing the accessibility of social support resources for LGB college students, with the aim of cultivating and sustaining favorable psychological well-being.

Potential Association of Neutrophil Extracellular Traps With Cognitive Impairment in Cerebral Small Vessel Disease.

No acceptable biomarker can facilitate the early identification of cognitive impairment associated with cerebral small vessel disease (CSVD) in the older persons. The neutrophil extracellular traps (NETs) in the inflammation response of circulatory and central systems are essential in destroying the blood-brain barrier. The present study aims to explore the potential associations of plasma NETs with cognitive performance in CSVD. We recruited 146 CSVD patients and 66 healthy controls (HCs), and comprehensive neuropsychological assessments and multimodal magnetic resonance imaging were conducted. Three NETs markers, namely citrullination of histone H3, neutrophil elastase-DNA, and myeloperoxidase (MPO)-DNA, and 4 oxidative stress-related indexes in plasma samples, were measured. The plasma levels of 3 NETs markers were more significantly elevated in CSVD patients than in HCs. Significant correlations of the 3 NETs markers were observed with multiple cognitive domain scores. Furthermore, higher plasma malondialdehyde and NETs levels were significantly associated with the worse Montreal Cognitive Assessment scores among CSVD patients. Moreover, plasma MPO-DNA levels significantly mediated the effect of the amplitude of low-frequency fluctuation value within the bilateral caudate and the scores of global cognitive function, executive function, and information processing speed. Additionally, a panel of 3 NETs markers had the highest area under the curve value to distinguish the cognitively impaired CSVD patients from HCs and nonimpaired ones. Therefore, plasma NETs may be potential biomarkers for early diagnosis of CSVD-related cognitive impairment. Activated lipid peroxidation in circulation and impaired caudate function support potential associations of plasma NETs in cognitively impaired CSVD patients.

Dual-Interface Engineering in Perovskite Solar Cells with 2D Carbides.

Passivating the interfaces between the perovskite and charge transport layers is crucial for enhancing the power conversion efficiency (PCE) and stability in perovskite solar cells (PSCs). Here we report a dual-interface engineering approach to improving the performance of FA0.85 MA0.15 Pb(I0.95 Br0.05 )3 -based PSCs by incorporating Ti3 C2 Clx Nano-MXene and o-TB-GDY nanographdiyne (NanoGDY) into the electron transport layer (ETL)/perovskite and perovskite/ hole transport layer (HTL) interfaces, respectively. The dual-interface passivation simultaneously suppresses non-radiative recombination and promotes carrier extraction by forming the Pb-Cl chemical bond and strong coordination of π-electron conjugation with undercoordinated Pb defects. The resulting perovskite film has an ultralong carrier lifetime exceeding 10 µs and an enlarged crystal size exceeding 2.5 µm. A maximum PCE of 24.86 % is realized, with an open-circuit voltage of 1.20 V. Unencapsulated cells retain 92 % of their initial efficiency after 1464 hours in ambient air and 80 % after 1002 hours of thermal stability test at 85 °C.

LAX1, functioning with MADS-box genes, determines normal palea development in rice.

Normal floral organ development in rice is necessary for grain formation. Many MADS-box family genes that belong to ABCDE model have been widely implicated in rice flower development. The LAX1 allele encodes a plant-specific basic helix-loop-helix (bHLH) transcription factor, which is the main regulator of axillary meristem formation in rice. However, the molecular mechanisms of LAX1 allele together with MADS-box family genes underlying palea development have not been reported. We found a short palea mutant plant in a population of indica rice variety 9311 treated with cobalt 60. We report the map-based cloning and characterization of lax1-7, identified as a new mutant allele of the LAX1 locus, and the role of its wild-type allele LAX1 in rice palea development. Through complementary experiments, combined with genetic and molecular biological analyses, the function of the LAX1 allele was determined. We showed that LAX1 allele is expressed specifically in young spikelets and encodes a nucleus-localized protein. In vitro and in vivo experiments revealed that the LAX1 protein physically interacts with OsMADS1, OsMADS6 and OsMADS7. The LAX1 allele is pleiotropic for the maintenance of rice palea identity via cooperation with MADS-box genes and other traits, including axillary meristem initiation, days to heading, plant height, panicle length and spikelet fertility.

Alteration and clinical potential in gut microbiota in patients with cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients. Methods: Sixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing. Results: Based on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm. Conclusion: The evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately.

The Therapeutic Value of Adjuvant Chemotherapy after Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to evaluate the therapeutic value and treatment-related complications of adjuvant chemotherapy after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). DESIGN: The medical records of LACC patients who underwent CCRT were reviewed retrospectively. METHODS: A total of 1,138 patients with LACC who had been treated at our hospital between January 2013 and December 2017 were included in the study and classified into two groups: the CCRT group, comprising 726 patients who had received only CCRT, and the CCRT + adjuvant chemotherapy (ACT) group, comprising 412 patients who had received three cycles of adjuvant chemotherapy after CCRT. 39 patients in the CCRT group and 50 patients in the CCRT + ACT group had undergone lymphadenectomy, which revealed pathology-positive lymph nodes in 22 patients and 35 patients, respectively. Progression-free survival (PFS), overall survival (OS), and adverse events were compared. RESULTS: The median follow-up time was 61 months (range: 2-96 months). No significant differences in PFS and OS were found between the two groups (p > 0.05), but more grade 3-4 acute hematologic toxicities were observed in the CCRT + ACT group than in the CCRT group (24.8% vs. 31.8%, p = 0.01). A subgroup analysis of patients with pathology-positive lymph nodes showed that the 5-year PFS and OS rates were 76.5% and 74.9%, respectively, for the CCRT + ACT group and 45.0% and 49.2%, respectively, for the CCRT group; the differences were statistically significant (p = 0.015 and 0.042, respectively). LIMITATIONS: First, the sample size of the subgroup of patients with pathology-positive lymph nodes was too small for a confirmative conclusion. The heterogeneous population and the selection bias resulting from the retrospective design were the other flaws of our study. CONCLUSION: The application of adjuvant chemotherapy after CCRT may be worth investigating further for women with LACC and pathology-positive lymph nodes, but this approach is associated with an increase in acute hematology toxicities.

Disturbance of neuron-microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron-microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron-microglia crosstalk and is involved in the pathogenic process of NPSLE. METHODS: Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. RESULTS: The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. CONCLUSION: GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron-microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.

Plastome variations reveal the distinct evolutionary scenarios of plastomes in the subfamily Cereoideae (Cactaceae).

BACKGROUND: The cactus family (Cactaceae) has been reported to have evolved a minimal photosynthetic plastome size, with the loss of inverted-repeat (IR) regions and NDH gene suites. However, there are very limited genomic data on the family, especially Cereoideae, the largest subfamily of cacti. RESULTS: In the present study, we assembled and annotated 35 plastomes, 33 of which were representatives of Cereoideae, alongside 2 previously published plastomes. We analyzed the organelle genomes of 35 genera in the subfamily. These plastomes have variations rarely observed in those of other angiosperms, including size differences (with ~ 30 kb between the shortest and longest), dramatic dynamic changes in IR boundaries, frequent plastome inversions, and rearrangements. These results suggested that cacti have the most complex plastome evolution among angiosperms. CONCLUSION: These results provide unique insight into the dynamic evolutionary history of Cereoideae plastomes and refine current knowledge of the relationships within the subfamily.

Efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent and refractory ovarian cancer: A systematic review and a meta-analysis.

Objective: To explore the efficacy and safety of PD-1/PD-L1 inhibitors in treating recurrent/refractory ovarian cancer (OC). Methods: The online databases, including PubMed, Embase and Cochrane Library, were searched for relevant literatures on exploring the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The keywords are as follows: Ovarian neoplasms, programmed death receptor, PD-1, PD-L1, immunotherapy, and immune checkpoint inhibitor. Furthermore, qualified studies were screened for further meta-analysis. Results: In this study, 11 studies (990 patients) were analyzed to evaluate the efficacy of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The combined results proved that the objective response rate (ORR) was 6.7%, 95% CI (4.6%,9.2%), disease control rate (DCR) was 37.9%, 95% CI (33.0%, 42.8%), median overall survival (OS) was 10.70 months, 95% CI (9.23, 12.17), and median progression free survival (PFS) was 2.24 months, 95% CI (2.05, 2.43). In addition, in terms of the safety of patients suffering from recurrent/refractory OC and receiving PD-1/PD-L1 inhibitors, the combined treatment related adverse events (TRAEs) were 70.9% (61.7%-80.2%), and the combined immune related adverse events (iAEs) were 29%, 95% CI (14.7%, 43.3%). Conclusion: In patients with recurrent/refractory OC, PD-1/PD-L1 inhibitors were used alone and there was no obvious evidence of improved efficacy and survival. As for safety, the incidences of TRAEs and iAEs are high, so PD1/PD-L1 inhibitors should be applied according to individual conditions. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367525, identifier CRD42022367525.

[Molecular mechanism of the prefrontal cortex involved in electroacupuncture against myocardial ischemia based on metabolomics].

OBJECTIVE: To explore the effects of electroacupuncture(EA) on metabolic patterns of the prefrontal cortex in rats with acute myocardial ischemia. METHODS: Eighteen SD rats were randomly divided into sham group, model group and EA group, with 6 rats in each group. Rats in the model and EA groups were subject to acute myocardial ischemia by ligation of the left anterior descending coronary artery. For the EA group, EA stimulation (1 mA, 2 Hz/15 Hz, 30 min) was applied to "Shenmen"(HT7) -"Tongli"(HT5) once a day for 3 consecutive days. The histopathological changes of myocardial tissue and levels of ischemia modified albumin (IMA) in serum were determined by HE staining and ELISA, respectively. The LC-MS/MS technique was used to characterize the metabolic profiling of the prefrontal cortex. The differentially expressed metabolites were screened by principal component analysis(PCA) and partial least squares-linear discriminant analysis (PLS-LDA), and subsequently Kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was performed. RESULTS: Compared with the sham group, the myocardial fibers were disordered and fractured, and content of serum IMA was significantly increased in the model group (P<0.01), which, however, were significantly decreased in the EA group (P<0.01). With PCA and PLS-LDA, there were 18 differential metabolites between the model and sham groups. Forty-eight differential metabolites were emerged between the EA and model groups. Three metabolites associated to the sphingolipid metabolism were reversed by EA stimulation, as indicated by KEGG. CONCLUSION: The molecular mechanism of EA against myocardial ischemia is partially mediated by regulating sphingolipid-related metabolites in the prefrontal cortex.

Design, fabrication and application of self-spiraling pattern-driven 4D-printed actuator.

Self-spiraling actuators are widely found in nature and have high research and actuator-application value in self-lock and self-assembly. Four-dimensional (4D) printing is a new generation additive manufacturing of smart materials and has shown great potential for the fabrication of multi-functional and customized structures. The microarchitecture design of a bilayer actuator could bring flexible and diversified self-spiraling behaviors and more possibilities for practical application by combing 4D printing. This work investigates the stimuli effects of fiber patterns and fabrication parameters on self-spiraling behaviors of the bilayer actuator via both experimental and theoretical methods. This work may potentially provide pattern design guidance for 4D-printed self-spiraling actuators to meet different application requirements.

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients.

Background: Reliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD. Materials and methods: A prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers. Results: The gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R 2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients. Conclusion: Brain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

Limited Lithium Loading Promises Improved Lithium-Metal Anodes in Interface-Modified 3D Matrixes.

Confining Li metal in a three-dimensional (3D) matrix has been proven effective in improving the Li-metal anodes; however, in most studies, the loading of Li in the 3D matrix is far excessive, resulting in a dense bulk Li-metal anode with a low Li-utilization rate, forfeiting the effect of the 3D matrix. Here, we show that limiting the loading of Li metal within an interface-modified 3D carbon matrix not only increases the Li-utilization rate but also improves the electrochemical performance of the Li-metal anode. We use lithiophilic Fe2O3 granules anchored on a 3D carbon fiber scaffold to guide molten Li dispersion onto the fibers with controlled Li loading. Limiting Li loading maximizes the interface lithiophilic effect of the Fe2O3 granules while preserving sufficient space for electrolyte infusion, collectively ensuring uniform Li deposition and fast Li+ transport kinetics. The Li anode with limited Li dosage achieves remarkably improved Li-anode performances, including long lifespan, low voltage polarization, and low electrochemical resistance in both the symmetric cells and full cells. The improved electrochemical performance of the limited Li anode substantiates the importance to reduce Li loading from a fresh perspective and provides an avenue for building practical Li-metal batteries.

Efficacy and Safety of Minimally Invasive Surgery Versus Open Laparotomy for Interval Debulking Surgery of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A Systematic Review and A Meta-Analysis.

Objective: The selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC. Methods: Relevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: "ovarian neoplasms", "minimally invasive surgical procedures", "laparotomy", and "neoadjuvant therapy". Eligible studies were screened out for further meta-analysis. Results: Six eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59-1.23; heterogeneity: P = 0.051, I2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = -1.21; 95% CI = -1.78 to -0.64; heterogeneity: P < 0.001, I2 = 92.7%]. Conclusions: For IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298519, identifier CRD42022298519.