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.

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.

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.

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.

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.

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.

The complete plastomes of red fleshed pitaya (Selenicereus monacanthus) and three related Selenicereus species: insights into gene losses, inverted repeat expansions and phylogenomic implications.

Selenicereus is a genus of perennial shrub from the family Cactaceae, and some of them play an important role in the food industry, pharmaceuticals, cosmetics and medicine. To date, there are few reports on Selenicereus plastomes, which limits our understanding of this genus. Here, we have reported the complete plastomes of four Selenicereus species (S. monacanthus, S. annthonyanus, S. grandifloras, and S. validus) and carried out a comprehensive comparative analysis. All four Selenicereus plastomes have a typical quartile structure. The plastome size ranged from 133,146 to 134,450 bp, and contained 104 unique genes, including 30 tRNA genes, 4 rRNA genes and 70 protein-coding genes. Comparative analysis showed that there were massive losses of ndh genes in Selenicereus. Besides, we observed the inverted repeat regions had undergone a dramatic expansion and formed a previously unreported small single copy/inverted repeat border in the intron region of the atpF gene. Furthermore, we identified 6 hypervariable regions (trnF-GAA-rbcL, ycf1, accD, clpP-trnS-GCU, clpP-trnT-CGU and rpl22-rps19) that could be used as potential DNA barcodes for the identification of Selenicereus species. Our study enriches the plastome in the family Cactaceae, and provides the basis for the reconstruction of phylogenetic relationships. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01121-z.

Comparative plastid genomics of four Pilea (Urticaceae) species: insight into interspecific plastid genome diversity in Pilea.

BACKGROUND: Pilea is a genus of perennial herbs from the family Urticaceae, and some species are used as courtyard ornamentals or for medicinal purposes. At present, there is no information about the plastid genome of Pilea, which limits our understanding of this genus. Here, we report 4 plastid genomes of Pilea taxa (Pilea mollis, Pilea glauca 'Greizy', Pilea peperomioides and Pilea serpyllacea 'Globosa') and performed comprehensive comparative analysis. RESULTS: The four plastid genomes all have a typical quartile structure. The lengths of the plastid genomes ranged from 150,398 bp to 152,327 bp, and each genome contained 113 unique genes, including 79 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. Comparative analysis showed a rather high level of sequence divergence in the four genomes. Moreover, eight hypervariable regions were identified (petN-psbM, psbZ-trnG-GCC, trnT-UGU-trnL-UAA, accD-psbI, ndhF-rpl32, rpl32-trnL-UAG, ndhA-intron and ycf1), which are proposed for use as DNA barcode regions. Phylogenetic relationships based on the plastid genomes of 23 species of 14 genera of Urticaceae resulted in the placement of Pilea in the middle and lower part of the phylogenetic tree, with 100% bootstrap support within Urticaceae. CONCLUSION: Our results enrich the resources concerning plastid genomes. Comparative plastome analysis provides insight into the interspecific diversity of the plastid genome of Pilea. The identified hypervariable regions could be used for developing molecular markers applicable in various research areas.

Comparative plastid genomics of Mazaceae: focusing on a new recognized genus, Puchiumazus.

MAIN CONCLUSION: Six Mazaceae plastomes were assembled in this study, including the newly recognized genus, Puchiumazus. Comparative plastid genomic analysis provided new insights into Mazaceae. The phylogenetic categorization of Mazus lanceifolius (Mazaceae) has long been uncertain. In 2021, the scholars Bo Li, D. G. Zhang, and C. L. Xiang republished M. lanceifolius as a new species Puchiumazus lanceifolius, within a new genus Puchiumazus. However, there is little plastome information on Mazaceae. Following the publishing of the new genus Puchiumazus, it is now necessary to study the Mazaceae plastome features to comprehensively understand this young family. The Mazaceae plastomes all have a typical quartile structure. The plastomes have a size ranging from 152,388 to 154,252 bp, and each plastome contains 112 unique genes, including 78 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. A comparative analysis showed that these plastome sequences are highly conserved. Furthermore, we identified four relatively hypervariable regions (trnQ-UUC-psbK, trnS-GCU- trnS-CGA, trnT-UGU-trnL-UAA and ycf1) that can be used as potential DNA barcodes for the identification of this clade. Phylogenetic relationships based on the whole plastome sequences of 25 samples of 14 genera of Lamiales placed M. lanceifolius in the basal clade of the family Mazaceae, with 100% bootstrap support. In summary, the M. lanceifolius results indicate that a new monotype genus (Puchiumazus) should be established at the whole-plastome level. This study provides plastid genomic resources for exploring the phylogeny of Mazaceae.

Favorable Alleles of GRAIN-FILLING RATE1 Increase the Grain-Filling Rate and Yield of Rice.

Hybrid rice (Oryza sativa) has been cultivated commercially for 42 years in China. However, poor grain filling still limits the development of hybrid japonica rice. We report here the map-based cloning and characterization of the GRAIN-FILLING RATE1 (GFR1) gene present at a major-effect quantitative trait locus. We elucidated and confirmed the function of GFR1 via genetic complementation experiments and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing in combination with genetic and molecular biological analyses. In addition, we conducted haplotype association analysis to mine the elite alleles of GFR1 among 117 rice accessions. We observed that GFR1 was constitutively expressed and encoded a membrane-localized protein. The allele of the rice accession Ludao (GFR1 Ludao) improved the grain-filling rate of rice by increasing Rubisco initial activity in the Calvin cycle. Moreover, the increased expression of the cell wall invertase gene OsCIN1 in the near isogenic line NIL-GFR1 Ludao promoted the unloading of Suc during the rice grain-filling stage. A yeast two-hybrid assay indicated that the Rubisco small subunit interacts with GFR1, possibly in the regulation of the rice grain-filling rate. Evaluation of the grain-filling rate and grain yield of F1 plants harboring GFR1 Ludao and the alleles of 20 hybrids widely cultivated commercially confirmed that favorable alleles of GFR1 can be used to further improve the grain-filling rate of hybrid japonica rice.

The Role of Exosomes in Pancreatic Cancer.

Pancreatic cancer remains one of the deadliest cancers in the world, as a consequence of late diagnosis, early metastasis and limited response to chemotherapy, under which conditions the potential mechanism of pancreatic cancer progression requires further study. Exosomes are membrane vesicles which are important in the progression, metastasis and chemoresistance in pancreatic cancer. Additionally, they have been verified to be potential as biomarkers, targets and drug carriers for pancreatic cancer treatment. Thus, studying the role of exosomes in pancreatic cancer is significant. This paper focuses on the role of exosomes in the proliferation, metastasis and chemoresistance, as well as their potential applications for pancreatic cancer.

Chemoresistance in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.

Identification of putative markers linked to grain plumpness in rice (Oryza sativa L.) via association mapping.

BACKGROUND: Poor grain plumpness (GP) is one of the main constraints to reaching the yield potential of hybrid rice. RESULTS: In this study, the GP of 177 rice varieties was investigated in three locations across 2 years. By combining the genotype data of 261 simple sequence repeat (SSR) markers, association mapping was conducted to identify the marker-GP association loci. Among 31 marker-GP association loci detected in two or more environments and determined using general linear model (GLM) analyses, seven association loci were also detected using mixed linear model (MLM) analyses. The seven common loci detected by the two analytical methods were located on chromosomes 2, 3 (2), 7, 8 and 12 (2) and explained 7.24~22.28% of the variance. Of these 7 association loci, five markers linked to GP were newly detected: RM5340 on Chr2, RM5480 and RM148 on Chr3, RM1235 on Chr8, and RM5479 on Chr12. CONCLUSIONS: Five marker-GP association loci were newly detected using both the GLM and MLM analytical methods. Elite allele RM505-170 bp had the highest average phenotypic effect on increasing the GP, and the typical carrier variety was 'Maozitou'. Based on the distribution of the elite alleles among the carrier varieties, the top 10 parental combinations for improving the GP in rice via cross-breeding were predicted.

Designing a Beryllium-Free Deep-Ultraviolet Nonlinear Optical Material without a Structural Instability Problem.

A beryllium-free deep-ultraviolet (deep-UV) nonlinear optical (NLO) material K3Ba3Li2Al4B6O20F is developed mainly by the element substitution of Be for Al and Li from Sr2Be2B2O7 that was considered as one of the most promising deep-UV NLO materials. K3Ba3Li2Al4B6O20F preserves the structural merits of Sr2Be2B2O7 and thus exhibits no layering growth tendency and possesses the optical properties required for deep-UV NLO applications, including deep-UV transparency, phase-matchability, and sufficiently large second-harmonic generation (1.5 × KH2PO4). Furthermore, it overcomes the structural instability problem of Sr2Be2B2O7, which is confirmed by the obtainment of large single crystals and phonon dispersion calculations. These attributes make it very attractive for next-generation deep-UV NLO materials. The substitution of Be for Al and Li in beryllium borates provides a new opportunity to design beryllium-free deep-UV NLO materials with good performance.

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.

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).

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.

[Application of transvaginal external fascia trachelectomy in the treatment of CIN and micro-invasive cervical cancer].

OBJECTIVE: To explore the feasibility and safety of transvaginal external fascia trachelectomy to conservatively treat patients with stage Ia1 squamous carcinoma of the uterine cervix (SCC) and cervical intraepithelial neoplasia (CIN) III, who are not suitable to take cold knife conization (CKC). METHODS: From July 2002 to September 2010, those patients who had a strong desire to preserve the uterus or fertility but also are confronted with following situations received transvaginal external fascia trachelectomy: CIN III with large area lesion (colposcopically observed lesion area was larger than 3/4 of the cervix), or patients with CIN II-III suffered recurrence or had persistent lesion or positive margin after CKC or LEEP, or patients with CIN II-III upgraded into stage Ia1 SCC through LEEP and pathological confirmation (except for those with lymphovascular space invasion), or CIN III patients complicated with upper vaginal intraepithelial neoplasia (VAIN). Their clinical information and data were reviewed and analyzed. RESULTS: Among the 79 cases, who underwent transvaginal external fascia trachelectomy, six were stage Ia1 SCC, 61 were CIN III with a large area lesion (23 cases had glandular involvement), three were CIN III complicated with VAIN, six were CIN III with persistent lesion after LEEP, two were CIN III with positive margins after LEEP, and one case had recurrence after conization. The median age of these patients was 33 years old, ranging from 23 to 40 years old. The mean operation time was 39 min (rang 20-60 min), the average amount of bleeding was 40 ml (rang 1-300 ml) and the mean hospital stay was 10 d ( rang 6-17 d). The CIN III patients complicated with VAIN received this surgery with resection of the adjacent vaginal mucosa more than 2 cm in 3.8% (3/79). The median follow-up time was 49 months (8-85 months) and none of these patients had ureteral injury or large amount of intraoperative or postoperative bleeding or post-operative recurrence. No patient complained any effect on their sexual life. Among the five patients with reproductive desire, one was at her 22 w gestation after one induced abortion and one spontaneous abortion, four patients experienced term birth in which three were cesarean section and one was natural labour. CONCLUSIONS: Transvaginal external fascia trachelectomy is a safe and effective conservative treatment for stage Ia1 SCC, CIN III with large area lesion, CIN III complicated with VAIN and CIN II-III suffering recurrence, persistent lesion or positive margins after CKC and others that are not suitable to take CKC.