Synthesis of pyrazino[1,2-b]indazoles via cascade cyclization of indazole aldehydes with propargylic amines.

An efficient intermolecular annulation of indazole aldehydes with propargylic amines has been developed for the synthesis of pyrazinoindazoles under catalyst- and additive-free conditions. This straightforward methodology was found to feature a wide substrate scope, high atom economy and environmental advantages. The bioactivity results of these new pyrazino[1,2-b]indazoles showed that some of them exhibited significant antifungal activity.

[Exploration of mechanism of total triterpenoids from fruits of Chaenomeles speciosa against senescent GES-1 cells induced by D-galactose based on Gln/GLS1/α-KG metabolic axis and mitochondrial apoptosis signaling pathway].

Total triterpenoids from the fruits of Chaenomeles speciosa(TCS) are active components in the prevention and treatment of gastric mucosal damage, which have potential anti-aging effects. However, it is still unclear whether TCS can improve gastric aging, especially its molecular mechanism against gastric aging. On this basis, this study explored the effect and mechanism of TCS on senescent GES-1 cells induced by D-galactose(D-gal) to provide scientific data for the clinical use of TCS to prevent gastric aging. GES-1 cells cultured in vitro and those transfected with overexpression GLS1(GLS1-OE) plasmid of glutaminase 1(GLS1) were induced to aging by D-gal, and then TCS and or GLS1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide(BPTES) were given. Cell survival rate, positive rate of ß-galactosidase(SA-ß-gal) staining, mitochondrial membrane potential(MMP), and apoptosis were investigated. GLS1 activity, levels of glutamine(Gln), glutamate(Glu), α-ketoglutarate(α-KG), urea, and ammonia in supernatant and cells were detected by enzyme-linked immunosorbent assay(ELISA) and colorimetric methods. The mRNA and protein expressions of GLS1 and the related genes of the mitochondrial apoptosis signaling pathway were measured by real-time fluorescence quantitative PCR and Western blot. The results manifested that compared with the D-gal model group and GLS1-OE D-gal model group, TCS significantly decreased the SA-ß-gal staining positive cell rate and MMP of D-gal-induced senescent GES-1 cells and GLS1-OE senescent GES-1 cells, inhibited the survival of senescent cells, and promoted their apoptosis(P<0.01). It decreased the activity of GLS1 and the content of Gln, Glu, α-KG, urea, and ammonia in supernatant and cell(P<0.01), reduced the concentration of cytochrome C(Cyto C) in mitochondria and the mRNA and protein expressions of GLS1 and proliferating nuclear antigen in cells(P<0.01). The mRNA expression of Bcl-2 and Bcl-xl, the protein expression of pro-caspase-9 and pro-caspase-3, and the ratio of Bcl-2/Bax and Bcl-xl/Bad in cells were decreased(P<0.01). Cyto C concentration in the cytoplasm, the mRNA expressions of Bax, Bad, apoptosis protease activating factor 1(Apaf-1), and protein expressions of cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 were increased(P<0.01). The aforementioned results indicate that TCS can counteract the senescent GES-1 cells induced by D-gal, and its mechanism may be closely related to suppressing the Gln/GLS1/α-KG metabolic axis, activating the mitochondrial apoptosis pathway, and thereby accelerating the apoptosis of the senescent cells and eliminating senescent cells.

Evolution of 101 Apocynaceae plastomes and phylogenetic implications.

Apocynaceae are one of the ten species-richest angiosperm families. However, the backbone phylogeny of the family is yet less well supported, and the evolution of plastome structure has not been thoroughly studied for the whole family. Herein, a total of 101 complete plastomes including 35 newly sequenced, 24 reassembled from public raw data and the rest from the NCBI GenBank database, representing 26 of 27 tribes of Apocynaceae, were used for comparative plastome analysis. Phylogenetic analyses were conducted using a combined plastid data matrix of 77 protein-coding genes from 162 taxa, encompassing all tribes and 41 of 49 subtribes of Apocynaceae. Plastome lengths ranged from 150,897 bp in Apocynum venetum to 178,616 bp in Hoya exilis. Six types of boundaries between the inverted repeat (IR) regions and single copy (SC) regions were identified. Different sizes of IR expansion were found in three lineages, including Alyxieae, Ceropegieae and Marsdenieae, suggesting multiple expansion events of the IRs over the SC regions in Apocynaceae. The IR regions of Marsdenieae evolved in two ways: expansion towards the large single copy (LSC) region in Lygisma + Stephanotis + Ruehssia + Gymnema (Cosmopolitan clade), and expansion towards both LSC and small single copy (SSC) region in Dischidia-Hoya alliance and Marsdenia (Asia-Pacific clade). Six coding genes and five non-coding regions were identified as highly variable, including accD, ccsA-ndhD, clpP, matK, ndhF, ndhG-ndhI, trnG(GCC)-trnfM(CAU), trnH(GUG)-psbA, trnY(GUA)-trnE(UUC), ycf1, and ycf2. Maximum likelihood and Bayesian phylogenetic analyses resulted in nearly identical tree topologies and produced a well-resolved backbone comprising 15 consecutive dichotomies that subdivided Apocynaceae into 15 clades. The subfamily Periplocoideae were embedded in the Apocynoid grade and were sister to the Echiteae-Odontadenieae-Mesechiteae clade with high support values. Three tribes (Melodineae, Vinceae, and Willughbeieae), the subtribe Amphineuriinae, and four genera (Beaumontia, Ceropegia, Hoya, and Stephanotis) were not resolved as monophyletic. Our work sheds light on the backbone phylogenetic relationships in the family Apocynaceae and offers insights into the evolution of Apocynaceae plastomes using the most densely sampled plastome dataset to date.

Taxonomy, comparative genomics of Mullein (Verbascum, Scrophulariaceae), with implications for the evolution of Verbascum and Lamiales.

BACKGROUND: The genus Verbascum L. (Scrophulariaceae) is distributed in Africa, Europe, and parts of Asia, with the Mediterranean having the most species variety. Several researchers have already worked on the phylogenetic and taxonomic analysis of Verbascum by using ITS data and chloroplast genome fragments and have produced different conclusions. The taxonomy and phylogenetic relationships of this genus are unclear. RESULTS: The complete plastomes (cp) lengths for V. chaixii, V. songaricum, V. phoeniceum, V. blattaria, V. sinaiticum, V. thapsus, and V. brevipedicellatum ranged from 153,014 to 153,481 bp. The cp coded 114 unique genes comprising of 80 protein-coding genes, four ribosomal RNA (rRNA), and 30 tRNA genes. We detected variations in the repeat structures, gene expansion on the inverted repeat, and single copy (IR/SC) boundary regions. The substitution rate analysis indicated that some genes were under purifying selection pressure. Phylogenetic analysis supported the sister relationship of (Lentibulariaceae + Acanthaceae + Bignoniaceae + Verbenaceae + Pedaliaceae) and (Lamiaceae + Phyrymaceae + Orobanchaceae + Paulowniaceae + Mazaceae) in Lamiales. Within Scrophulariaceae, Verbascum was sister to Scrophularia, while Buddleja formed a monophyletic clade from (Scrophularia + Verbascum) with high bootstrap support values. The relationship of the nine species within Verbascum was highly supported. CONCLUSION: Based on the phylogenetic results, we proposed to reinstate the species status of V. brevipedicellatum (Engl.) Hub.-Mor. Additionally, three genera (Mazus, Lancea, and Dodartia) placed in the Phyrymaceae family formed a separate clade within Lamiaceae. The classification of the three genera was supported by previous studies. Thus, the current study also suggests the circumscription of these genera as documented previously to be reinstated. The divergence time of Lamiales was approximated to be 86.28 million years ago (Ma) (95% highest posterior density (HPD), 85.12-89.91 Ma). The complete plastomes sequence data of the Verbascum species will be important for understanding the Verbascum phylogenetic relationships and evolution in order Lamiales.

Plastome structure of 8 Calanthe s.l. species (Orchidaceae): comparative genomics, phylogenetic analysis.

BACKGROUND: Calanthe (Epidendroideae, Orchidaceae) is a pantropical genus distributed in Asia and Africa. Its species are of great importance in terms of economic, ornamental and medicinal values. However, due to limited and confusing delimitation characters, the taxonomy of the Calanthe alliance (Calanthe, Cephalantheropsis, and Phaius) has not been sufficiently resolved. Additionally, the limited genomic information has shown incongruences in its systematics and phylogeny. In this study, we used illumina platform sequencing, performed a de novo assembly, and did a comparative analysis of 8 Calanthe group species' plastomes: 6 Calanthe and 2 Phaius species. Phylogenetic analyses were used to reconstruct the relationships of the species as well as with other species of the family Orchidaceae. RESULTS: The complete plastomes of the Calanthe group species have a quadripartite structure with varied sizes ranging between 150,105bp-158,714bp, including a large single-copy region (LSC; 83,364bp- 87,450bp), a small single-copy region (SSC; 16,297bp -18,586bp), and a pair of inverted repeat regions (IRs; 25,222bp - 26,430bp). The overall GC content of these plastomes ranged between 36.6-36.9%. These plastomes encoded 131-134 differential genes, which included 85-88 protein-coding genes, 37-38 tRNA genes, and 8 rRNA genes. Comparative analysis showed no significant variations in terms of their sequences, gene content, gene order, sequence repeats and the GC content hence highly conserved. However, some genes were lost in C. delavayi (P. delavayi), including ndhC, ndhF, and ndhK genes. Compared to the coding regions, the non-coding regions had more sequence repeats hence important for species DNA barcoding. Phylogenetic analysis revealed a paraphyletic relationship in the Calanthe group, and confirmed the position of Phaius delavayi in the genus Calanthe as opposed to its previous placement in Phaius. CONCLUSION: This study provides a report on the complete plastomes of 6 Calanthe and 2 Phaius species and elucidates the structural characteristics of the plastomes. It also highlights the power of plastome data to resolve phylogenetic relationships and clarifies taxonomic disputes among closely related species to improve our understanding of their systematics and evolution. Furthermore, it also provides valuable genetic resources and a basis for studying evolutionary relationships and population genetics among orchid species.

[Clinical Characterization of Patients with Ovarian Mass Combined with Dysplasia of Secondary Sexual Characteristics].

Objective To investigate the clinical characteristics of preadolescent and adolescent female patients with ovarian mass combined with dysplasia of secondary sexual characteristics. Methods This study retrospectively analyzed 18 cases of ovarian mass combined with dysplasia of secondary sexual characteristics aged 0-19 years admitted to Peking Union Medical College Hospital from January 2012 to November 2019.By analyzing the clinical manifestations,surgical methods,postoperative pathology,therapies and prognosis of the cases,we summarized the diagnosis and treatment ideas. Results Among the 18 cases,7(7/18,38.9%)developed secondary sex signs before puberty,including 5 cases showing precocity(including 2 cases of juvenile granulosa cell tumor,1 case of gonadoblastoma,1 case of ovarian follicular cyst,and 1 case of 46,XY simple gonadal dysplasia combined with dysgerminoma)and 2 cases presenting masculine manifestations(1 case of steroid cell tumor and 1 case of sclerosing stromal tumor).The rest 11(11/18,61.1%)cases showed abnormal development of secondary sexual characteristics during puberty,including 8 cases with masculine manifestations or abnormal menstruation after menarche(7 cases with sex cord stromal cell tumor and 1 case with cystic granulosa cell tumor),2 cases with primary amenorrhea(1 case with androgen insensitivity syndrome combined with testicular sertoli cell tumor and 1 case with endometriosis cyst combined with reproductive tract malformation),and 1 case diagnosed as 46,XX gonadal dysplasia with serous cystadenoma and no secondary sexual development during puberty. Conclusions Sex hormone levels should be actively tested in the case of prepubertal secondary sexual characteristics appearing early,pubertal secondary sexual characteristics being abnormal(underdevelopment),and/or menstrual abnormalities.Imaging examination should be performed to exclude ovarian organic lesions,and chromosome karyotype analysis should be performed if necessary.The diagnosis of ovarian mass in preadolescent and adolescent females with related symptoms should first be alerted to cord stromal cell tumor.It is recommended to rule out the possibility of combined reproductive tract malformation in the adolescent patients with primary amenorrhea.Chromosome examination should be conducted to rule out the possibility of gonadal dysplasia in the adolescent patients with primary amenorrhea and/or no development of secondary sexual characteristics.

Prolonged conservative treatment in patients with recurrent endometrial cancer after primary fertility-sparing therapy: 15-year experience.

OBJECTIVE: To evaluate the efficacy and prognosis of repeated treatment on patients with recurrent endometrial cancer (EC) after complete remission for primary fertility-preserving therapy. MATERIALS AND METHODS: We performed a retrospective study of patients with presumed stage IA endometrial cancer who had recurrence after achieving complete remission by fertility-preserving management at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2003 to April 2018. For each patient, medical records and pathology reports were reviewed. The demographic features, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed. RESULTS: Of the 41 recurrent patients with a median disease-free interval period of 16 months (range, 5-55 months), 23 were diagnosed at recurrence as EC, and 18 were diagnosed as atypical hyperplasia (AH) or endometrial intraepithelial neoplasia (EIN). 26 patients received repeated fertility-preserving treatment, and 23 patients were evaluable for efficacy. The complete response (CR) rate of repeated treatment (19/23, 82.6%) was lower than that of primary fertility-preserving treatment (161/170, 94.7%) with borderline significance (P = 0.053). The CR rate of AH/EIN patients was higher than that of EC patients with no statistical difference (92.9% vs 66.7%, P = 0.260). Among 19 patients achieved CR, 3 got pregnant and delivered successfully, while 3 had a second relapse. Four cases failed to response to the repeated treatment and underwent definitive surgery. 15 patients referred to definitive surgery directly after recurrence and one of them had a pelvic recurrence after 120 months. All patients are alive without evidence of disease at last follow-up. CONCLUSIONS: For patients with recurrent EC after primary fertility-preserving treatment, repeated fertility-preserving treatment can still achieve a promising response and patients have possibilities of completing childbirth.

Comparison of Iodine-125 seeds implantation and afterloading radiotherapy in murine models of human cervical cancer.

OBJECTIVE: To compare the efficacies and side effects of Iodine-125 (125I) seeds implantation with afterloading radiotherapy on tumor xenografts derived from Hela cells. METHODS: Mice bearing Hela cells were randomly divided into three groups: two therapeutic groups receiving four 125I seeds implantation and afterloading therapy, respectively, and the one control group without any intervention. Comparisons were evaluated in aspects of curative efficacies (tumor volume, tumor inhibition rate and metastasis) and side effects (body weight, ovarian endocrine functions, skin lesion surrounding the tumor). RESULTS: The xenografts tumor volume of therapeutic groups were significantly smaller than that of controls(p < 0.05),both of the 125I seeds implantation and afterloading therapy showed excellent tumor inhibition rate. Furthermore, 125I seeds implantation had milder side effects on skin, weight loss, ovarian endocrine functions. CONCLUSIONS: (125)I seed implantation may be an alternative minimally invasive therapy for cervical cancer.

The emerging role of extracellular vesicles in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by restricted, repetitive behavioral patterns and deficits in social interactions. The prevalence of ASD has continued to rise in recent years. However, the etiology and pathophysiology of ASD remain largely unknown. Currently, the diagnosis of ASD relies on behavior measures, and there is a lack of reliable and objective biomarkers. In addition, there are still no effective pharmacologic therapies for the core symptoms of ASD. Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted by almost all types of cells. EVs play a vital role in cell-cell communications and are known to bear various biological functions. Emerging evidence demonstrated that EVs are involved in many physiological and pathological processes throughout the body and the content in EVs can reflect the status of the originating cells. EVs have demonstrated the potential of broad applications for the diagnosis and treatment of various brain diseases, suggesting that EVs may have also played a role in the pathological process of ASD. Besides, EVs can be utilized as therapeutic agents for their endogenous substances and biological functions. Additionally, EVs can serve as drug delivery tools as nano-sized vesicles with inherent targeting ability. Here, we discuss the potential of EVs to be considered as promising diagnostic biomarkers and their potential therapeutic applications for ASD.

Ecotoxicological assessment, oxidative response, and enzyme activity disorder of the rotifer Brachionus asplanchnoidis exposed to a toxic cocktail of spent lithium-ion battery leachate.

Spent lithium-ion batteries (LIBs) have emerged as a major source of waste due to their low recovery rate. The physical disposal of spent LIBs can lead to the leaching of their contents into the surrounding environment. While it is widely agreed that hazardous substances such as nickel and cobalt in the leachate can pose a threat to the environment and human health, the overall composition and toxicity of LIB leachate remain unclear. In this study, a chemical analysis of leachate from spent LIBs was conducted to identify its primary constituents. The ecotoxicological parameters of the model organism, rotifer Brachionus asplanchnoidis, were assessed to elucidate the toxicity of the LIB leachate. Subsequent experiments elucidated the impacts of the LIB leachate and its representative components on the malondialdehyde (MDA) level, antioxidant capacity, and enzyme activity of B. asplanchnoidis. The results indicate that both the LIB leachate and its components are harmful to individual rotifers due to the adverse effects of stress-induced disturbances in biochemical indicators, posing a threat to population development. The intensified poisoning phenomenon under combined stress suggests the presence of complex synergistic effects among the components of LIB leachate. Due to the likely environmental and biological hazards, LIBs should be strictly managed after disposal. Additionally, more economical and eco-friendly recycling and treatment technologies need to be developed and commercialized.

Crucial roles of specialized chitinases in elytral and hindwing cuticles construction in Leptinotarsa decemlineata.

BACKGROUND: The Colorado potato beetle (CPB), Leptinotarsa decemlineata, is a major potato (Solanum tuberosum) pest, infesting over 16 million km2 and causing substantial economic losses. The insect cuticle forms an apical extracellular matrix (ECM) envelope covering exposed organs to direct morphogenesis and confer structural protection. While select chitinase (Cht) genes have proven essential for larval development, their potential activities directing ECM remodeling underlying adult wing maturation remain undefined. RESULTS: We investigated the expression patterns and performed an oral RNA interference (RNAi) screen targeting 19 LdChts in late-instar L. decemlineata larvae. Subsequently, we assessed their effects on adult eclosion and wing characteristics. Knockdown of LdCht5, LdCht7, LdCht10, LdIDGF2, and LdIDGF4, as well as others from Group IV (LdCht15, LdCht12, LdCht17, and LdCht13) and Groups VII-X (LdCht2, LdCht11, LdCht1, and LdCht3), resulting in shrunken, misshapen elytra with reduced areal density, as well as transverse wrinkling and impaired wing-tip folding in hindwings. Scanning electron micrographs revealed eroded elytral ridges alongside thinned, ruptured hindwing veins, indicative of mechanical fragility post-LdCht suppression. Spectroscopic analysis uncovered biomolecular alterations underlying the elytral anomalies, including decreases in peaks representing chitin, proteins, and lipids. This loss of essential ECM components provides evidence for the fragility, wrinkling, and shrinkage observed in the RNAi groups. CONCLUSION: Our findings elucidate the crucial role of chitinases in the turnover of chitinous cuticles on beetle wings, offering insights into RNAi-based control strategies against this invasive pest. © 2024 Society of Chemical Industry.

Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis.

OBJECTIVES: To explore the differences between women with endometriosis associated ovarian cancer and typical epithelial ovarian cancer. STUDY DESIGN: The medical charts of total 226 patients with epithelial ovarian cancer treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histology evaluation determined endometriosis associated ovarian cancer (n = 17) or non-endometriosis associated ovarian cancer (n = 209). RESULTS: Compared with non-endometriosis associated ovarian cancer, patients with endometriosis associated ovarian cancer were proved: (1) to be younger and more likely to be premenopausal at diagnosis of epithelial ovarian cancer (P = .03 and .005, respectively); (2) to have lower preoperative serum level of Ca125 (mean: 122.9 vs 1377.5 U/mL, P < .001) and more likely to display normal Ca125 level (P < .001); (3) to be identified at the earlier stage (stage I, P < .001); (4) to have completely different distribution of histological subtypes (significant overrepresentation of clear cell and endometrioid carcinoma). CONCLUSION: As such, patients with endometriosis associated ovarian cancer differ from non-endomertiosis associated ovarian cancer in many of their critical clinical and biologic characteristics.

Prognostic analysis of endometrioid epithelial ovarian cancer with or without endometriosis: a 12-year cohort study of Chinese patients.

OBJECTIVE: Clinicopathological characteristics and possible prognostic factors among women with endometrioid epithelial ovarian cancer (EEOC) with or without concurrent endometriosis were investigated. STUDY DESIGN: A search of medical charts at Peking Union Medical College Hospital from 2000 through 2012 identified patients with EEOC with or without endometriosis. RESULTS: Of 188 patients with EEOC, concurrent endometriosis was identified in 32 (17.0%). Patients with concurrent endometriosis were approximately 5 years younger, more likely to be premenopausal, more likely to have an early stage of EEOC, and less likely to have high-grade tumors compared to those without endometriosis. The univariate analysis showed that concurrent endometriosis was a significant prognostic factor for disease-free survival, but this association did not remain in the multivariate analysis. CONCLUSION: Women with EEOC and concurrent endometriosis showed distinct characteristics and had longer disease-free survival when compared to those without endometriosis.

[Pregnant rate and pregnancy-relating factors of patients with early endometrial carcinoma and severe atypical hyperplasia of endometrium after fertility-preserving treatment by progestin].

OBJECTIVE: To summarize the pregnant rate of patients with early endometrial carcinoma and severe atypical hyperplasia after fertility-preserving treatment and analyze their pregnancy-relating factors. METHODS: Endometrial curettage was used to evaluate the therapy response of endometrium after every 3 months of administration of high-dose progestin as fertility-sparing treatment for 51 patients with stage I endometrial carcinoma or severe endometrial atypical hyperplasia from Jun. 1996 to Jan. 2010. Individualized maintained treatment was given to patients after achieving complete remission of the endometrium. Pregnant results and pregnancy-relating factors were analyzed retrospectively. RESULTS: The median age of all the 51 patients was 29 years old. Forty-five (88%, 45/51) achieved complete response. Of the 34 cases who desired to conceive after complete response, 16 of them had 22 pregnancies, the pregnant rate was 47% (16/34); and 12 women obtained healthy live birth baby, the fertility rate was 35% (12/34). The pregnant rate of patients at age >35 or ≤ 35 was 0/2 and 50% (16/32) respectively (P > 0.05). The pregnant rate of patients with or without infertility was 40% (8/20) and 8/14, with endometrial cancer or severe atypical hyperplasia was 40% (10/25) and 6/9, respectively (all P > 0.05). The pregnant rate of patients who received in vitro fertilization-embryo transfer, ovulation promotion, or no treatment was 7/7, 6/16 and 3/11 respectively (P < 0.01). CONCLUSIONS: Fertility-preserving treatment for early endometrial cancer and severe atypical hyperplasia with high-dose progestin could achieve higher response rate. Assisted reproductive technologies could significantly increase the chance of conception.

[Multicenter randomized controlled clinical study for the operative treatment of malignant ovarian germ cell tumors].

OBJECTIVE: To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. METHODS: The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. RESULTS: (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. CONCLUSIONS: Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

Risk factors and predictors of acute gastrointestinal injury in stroke patients.

PURPOSE: This prospective study investigates the incidence, risk factors, biological markers, and predictors of acute gastrointestinal injury (AGI) in patients with stroke. METHODS: The study involved a total of 98 patients with acute cerebrovascular disease were included. According to the ESICM, the definition of AGI in intensive care patients is classified as grade 0, I, II and III. Patients' demographics, serological indicators (e.g., urea nitrogen, albumin, D-lactate, α-GST, neutrophil count and lymphocyte count), relevant scores (NIHSS score, GCS score, APACHE II score), length of hospital stay as well as the 7-day and 28-day mortality were recorded. RESULTS: In 98 patients, the incidence of AGI was 90.8 %. The APACHE II, NIHSS, GCS and Hs-mGPS scores significantly increased the odds of a higher AGI grade (P < 0.05). Also, current use of antibiotics and the presence of pneumonia significantly increased the probability of a higher AGI grade (P < 0.05). NLR, diabetes and dehydrating drugs increased the probability of AGI grade II and III (P < 0.05). Finally, an early commencement of endovascular treatment significantly reduced the incidence of AGI class III (P < 0.05). Patients with higher AGI grades had longer hospital stays and higher 28-day mortality (P < 0.05). CONCLUSION: The degree of the neurological deficit in stroke patients (high NIHSS score, low GCS score) in this study was associated with the development of AGI. The patients' gastrointestinal barrier function continued to deteriorate during the week of onset. The APACHE II score, NRL score and HS-mGPS score have some predictive value for the occurrence of AGI in stroke patients.

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

Background: FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. Methods: We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. Results: A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. Conclusion: FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.

Prediction models for post-thrombectomy brain edema in patients with acute ischemic stroke: a systematic review and meta-analysis.

Objective: The objective of this study is to systematically evaluate prediction models for post-thrombectomy brain edema in acute ischemic stroke (AIS) patients. This analysis aims to equip clinicians with evidence-based guidance for the selection of appropriate prediction models, thereby facilitating the early identification of patients at risk of developing brain edema post-surgery. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, and Vip, aiming to identify studies on prediction models for post-thrombectomy brain edema in AIS patients up to January 2023. Reference lists of relevant articles were also inspected. Two reviewers independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines were employed to assess study bias and literature quality, respectively. We then used random-effects bivariate meta-analysis models to summarize the studies. Results: The review included five articles, yielding 10 models. These models exhibited a relatively high risk of bias. Random effects model demonstrated that the AUC was 0.858 (95% CI 0.817-0.899). Conclusion: Despite the promising discriminative ability shown by studies on prediction models for post-thrombectomy brain edema in AIS patients, concerns related to a high risk of bias and limited external validation remain. Future research should prioritize the external validation and optimization of these models. There is an urgent need for large-scale, multicenter studies to develop robust, user-friendly models for real-world clinical application. Systematic review registration: https://www.crd.york.ac.uk, unique Identifier: CRD42022382790.

Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage.

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage (ICH). Withaferin A (WFA), a natural compound, exhibits a positive effect on a number of neurological diseases. However, the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown. In this study, we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis. We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH. WFA was injected intracerebroventricularly at 0.1, 1 or 5 µg/kg once daily for 7 days, starting immediately after ICH operation. WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage. Through in vitro experiments, cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury. Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde, an oxidative stress marker, and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH. Western blot assay, quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis, promoted translocation of Nrf2 from the cytoplasm to nucleus, and increased HO-1 expression. Silencing Nrf2 with siRNA completely reversed HO-1 expression, oxidative stress and protective effects of WFA. Furthermore, WFA reduced hemin-induced ferroptosis. However, after treatment with an HO-1 inhibitor, the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened. MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury. Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway, which may highlight a potential role of WFA for the treatment of ICH.

An all-cellulose sponge with a nanofiller-assisted hierarchical cellular structure for fruit maintaining freshness.

Cellulose sponges with compressibility and resilience are an ideal packaging material for fruits with fragile skin. Here, a soft and elastic all-cellulose sponge (CS) with a hierarchical cellular structure was fabricated, where the long molecular chain cellulose constructed major pores, the cellulose at nanoscale acted as an elastic nanofiller to fill the gaps of long molecular chain cellulose fibers and constructed minor pores. With these two kinds of pores, this structure can absorb strain hierarchically. The sponge can protect fruits from mechanical damage when dropped or repeated vibration. Furthermore, the CS modified with chlorogenic acid (C-CGAS) had excellent antibacterial and antifungal abilities. Therefore, C-CGAS could extend the storage time of strawberries to 18 days without any microbial invasion, which is the longest storage time reported thus far. This study provides a new idea for the preparation of polymer sponges and a new design for the development of antimicrobial packaging materials.