Surufatinib combined with transarterial embolization versus surufatinib monotherapy in patients with liver metastatic neuroendocrine tumors: Study protocol for a prospective, randomized, controlled trial.

BACKGROUND: More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. METHODS: This is a prospective, multicenter, open-label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression-free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator-assessed PFS, liver-specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. DISCUSSION: This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.

Successful pregnancy and delivery after HiPorfin photodynamic therapy for cervical high-grade squamous intraepithelial lesion.

OBJECTIVE: The study analyzed HiPorfin-Photodynamic therapy (PDT) for young women with cervial high-grade squamous intraepithelial lesion (HSIL) and evaluated the impact of PDT on their pregnancy and delivery. METHODS: Retrospective analysis of 4 patients (21-33 years old) were treated with HiPorfin® (2 mg/kg) PDT in 2019-2022. 1 patient suffered from cervical intraepithelial neoplasia (CIN)Ⅱ and 3 patients from CIN Ⅲ. 630 nm laser light irradiated the cervical surface and endocervical canal with light dose of 150 J/cm2 and 100-120 J/cm2 respectively. RESULTS: The median observation time period was 40.5 months. Cure rate, HPV eradication rate and negative conversion rate of cytology were all 100.0 % at 3, 6 and 12 months. All cervical canal lesions completely turned negative. No recurrence occurred during the long-term follow-up period. None of patients suffered from infertility. Three patients delivered vaginally and one delivered by C-section to healthy infants at term. CONCLUSION: HiPorfin® PDT for cervical HSIL was proved to be a safe method without adverse effects on female fertility and allowing these women to have healthy, full-term children.

Case report: Diverse immune responses in advanced pancreatic ductal adenocarcinoma treated with immune checkpoint inhibitor-based conversion therapies.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, presenting limited therapeutic options and a grim prognosis due to its aggressive nature. Despite ongoing exploration of various combination therapies, a standardized treatment approach after the first-line treatment progress remains elusive. This report details the cases of two patients with unresectable advanced PDAC who underwent distinct conversion treatment regimens involving immune checkpoint inhibitors (ICIs). Remarkably, both patients became eligible for surgery following different anti-PD-1 antibody-based conversion therapies, ultimately achieving R0 resection. In essence, our findings highlight the efficacy of the anti-PD-1 antibody combined with a tyrosine kinase inhibitor (TKI) regimen and chemotherapy alongside anti-PD-1 antibody as viable conversion therapies for preoperative advanced PDAC. Tumor immune microenvironment (TIME) analysis underscores the intratumoral and intertumoral heterogeneity observed in the postoperative immune landscape of surgical specimens. This insight contributes to a deeper understanding of the potential benefits of these conversion therapies in addressing the challenging landscape of advanced PDAC.

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder.

Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of autism spectrum disorder (ASD). The purpose of this study was to characterize gut microbiota and serum amino acid metabolome profiles in children with ASD. A non-randomized controlled study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with ASD (n = 30) compared with neurotypical controls (NC) (n = 30) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles. Compared with children in the NC group, those in the ASD group showed lower richness, higher evenness, and an altered microbial community structure. At the class level, Deinococci and Holophagae were significantly lower in children with ASD compared with TD. At the phylum level, Deinococcus-Thermus was significantly lower in children with ASD compared with TD. In addition, the functional properties (such as galactose metabolism) displayed significant differences between the ASD and NC groups. Five dominant altered species were identified and analyzed (LDA score > 2.0, P < 0.05), including Subdoligranulum, Faecalibacterium_praushitzii, Faecalibacterium, Veillonellaceae, and Rumminococcaceae. The peptides/nickel transport system was the main metabolic pathway involved in the differential species in the ASD group. Decreased ornithine levels and elevated valine levels may increase the risk of ASD through a metabolic pathway known as the nickel transport system. The microbial metabolism in diverse environments was negatively correlated with phascolarctobacterium succinatutens. Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in ASD and the underlying mechanisms between metabolite and ASD.

Photodynamic therapy with HiPorfin for cervical squamous intraepithelial lesion at childbearing age.

OBJECTIVE: To evaluate the clinical efficacy and safety of HiPorfin® photodynamic therapy (PDT) in the treatment of young women at reproductive age with high-grade squamous intraepithelial lesion (HSIL) of the cervix. METHODS: Prospective study of 41 patients aged 28.8 ± 4.6 years old with cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ at Peking University Shenzhen Hospital from March 2019 to January 2023. HiPorfin® (2 mg/kg) was infused intravenously, and 48-72 h later, 630-nm laser irradiation was performed in cervical canal and cervical surface with an irradiation dose of 100-120 J/cm2 and 150 J/cm2 respectively. RESULTS: All 41 patients with no recurrence had been observed at least 12 months follow-up period after PDT. The number of nulliparous women was 30 (30/41, 73.2 %). CIN Ⅱ were 22 cases (22/41,53.7 %) and CIN Ⅲ were 19 cases (19/41,46.3 %). Complete response (CR) was in 95.5 % (21/22) patients with CIN Ⅱ and 78.9 % (15/19) patients with CIN Ⅲ at 6 months follow-up. Meanwhile, CR rate was 100.0 % (22/22) and 84.2 % (16/19) in CIN Ⅱ and CIN Ⅲ group respectively at 12 months. Pre-treatment, all patients (41/41,100 %) were Human papilloma virus (HPV) positive. HPV eradication rate was 63.4 % (26/41), 73.2 % (30/41) and 92.7 % (38/41) at 3, 6 and 12 months after PDT respectively. Before treatment, cytology ≥ atypical squamous cells of undetermined significance (ASCUS) was 78.0 % (32/41). Negative conversion ratio of cytology was 75.0 % (24/32), 90.6 % (29/32) and 100.0 % (32/32) at 3, 6 and 12 months after PDT respectively. There were no serious adverse effects in patients during and after PDT. CONCLUSION: HiPorfin-PDT is a promising and organ-saving approach for cervical HSIL, which also eradicates HPV infection effectively and can be a beacon of hope for the young women with fertility preservation requirement.

The application of P-modified biochar in wastewater remediation: A state-of-the-art review.

Phosphorus modified biochar (P-BC) is an effective adsorbent for wastewater remediation, which has attracted widespread attention due to its low cost, vast source, unique surface structure, and abundant functional groups. However, there is currently no comprehensive analysis and review of P-BC in wastewater remediation. In this study, a detailed introduction is given to the synthesis method of P-BC, as well as the effects of pyrolysis temperature and residence time on physical and chemical properties and adsorption performance of the material. Meanwhile, a comprehensive investigation and evaluation were conducted on the different biomass types and phosphorus sources used to synthesize P-BC. This article also systematically compared the adsorption efficiency differences between P-BC and raw biochar, and summarized the adsorption mechanism of P-BC in removing pollutants from wastewater. In addition, the effects of P-BC composite with other materials (element co-doping, polysaccharide stabilizers, microbial loading, etc.) on physical and chemical properties and pollutant adsorption capacity of the materials were investigated. Some emerging applications of P-BC were also introduced, including supercapacitors, CO2 adsorbents, carbon sequestration, soil heavy metal remediation, and soil fertility improvement. Finally, some valuable suggestions and prospects were proposed for the future research direction of P-BC to achieve the goal of multiple utilization.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

SLC31A1 Identifying a Novel Biomarker with Potential Prognostic and Immunotherapeutic Potential in Pan-Cancer.

Solute carrier family 31 member 1 (SLC31A1) encodes a protein that functions as a homotrimer for the uptake of dietary copper. As a vital member of the cuproptosis gene family, it plays an essential role in both normal tissues and tumors. In this study, we analyzed SLC31A1 across human cancer types to gain a better understanding of SLC31A1's role in cancer development. We searched for information using online databases to analyze, systematically and comprehensively, the role of SLC31A1 in tumors. Amongst nine cancer types, the expression of SLC31A1 was significantly different between tumors and normal tissues. According to further analysis, pancreatic cancer had the highest mutation rate of the SLC31A1 gene, and the methylation levels of the gene were significantly reduced in seven tumors. The expression of SLC31A1 is also linked to the infiltration of tumors by immune cells, the expression of immune checkpoint genes, and immunotherapy markers (TMB and MSI), suggesting that SLC31A1 may be of particular relevance in immunotherapy. This thorough analysis of SLC31A1 across different types of cancer gives us a clear and comprehensive insight into its role in causing cancer on a systemic level.

Case report: Immunotherapy plus chemotherapy and stereotactic ablative radiotherapy (ICSABR): a novel treatment combination for Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma.

Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (EBVa LEL-ICC) is a rare tumor, characterized by a rich tumor immune microenvironment (TIME). While this tumor is reportedly sensitive to immunotherapy, its response has been inconsistent. This decreased sensitivity was associated with reduced TIME abundance. We report the case of a 53-year-old woman with EBVa LEL-ICC having reduced TIME abundance. The patient presented with a liver lesion, which was detected using ultrasound. Initially, the tumor was sensitive to immunotherapy and chemotherapy (IC), but resistance developed after a short interval. Subsequently, stereotactic ablative radiotherapy (SABR) was added to the patient's treatment, which now consisted of ICSABR. Successful tumor shrinkage was achieved with the combination therapy regimen. Thus, surgery and ICSABR are effective adjuncts to the first-line IC therapy in improving the survival rate of patients with EBVa LEL-ICC. The results of this study support multidisciplinary treatment as a viable treatment strategy for EBVa LEL-ICC.

Multistage utilization of soybean straw-derived P-doped biochar for aquatic pollutant removal and biofuel usage.

Biochar is of great importance to realizing solid biowastes reduction and environmental remediation. Modifying biochar for better performance is also of great concern to achieve property improvement. P-doped biochar from soybean straw is prepared for multistage utilization to realize water pollutant removal and biofuel usage. The results suggest that the prepared biochar is adequate for sulfadiazine adsorption and has stable performance under coexisting ions and aquatic pH. Furthermore, the higher heating value of the biochar is close to coal and thus can be an alternative to fossil fuel. The maximum sulfadiazine adsorption amount of P-doped biochar is 252.24 mg·g-1, and the P-doped biochar HHV is 24 MJ·kg-1 which can be an alternative to coal. The greenhouse gas and pollutant emission potential are also considered to explore the environmental impact of P-doped biochar production and usage. Overall, the optimal ratio of soybean straw: K3PO4 is 3:1.

Application of symbolic play test in identification of autism spectrum disorder without global developmental delay and developmental language disorder.

BACKGROUND: Children with autism spectrum disorders (ASD) usually experience difficulty regarding symbolic play. However, studies on whether symbolic play test (SPT) can differentiate between ASD and other developmental disorders are inconsistent, and evaluating the application value of the SPT in the identification of ASD without global developmental delay (GDD) and developmental language disorder (DLD) is necessary. METHODS: A total of 200 children were selected as the research participants. There were 100 cases of ASD without GDD and 100 cases of DLD. All children were tested by SPT and Children Neuropsychological and Behavioral Scale-Revision (CNBS-R2016). Binomial logistic regression was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of SPT in identifying ASD without GDD and DLD. RESULTS: SPT equivalent age was lower than chronological age in the two groups, the difference between the ASD without GDD group was greater than that in the DLD group, and the proportion of SPT equivalent age retardation was higher than that in the DLD group; the differences were statistically significant. Logistic regression analysis showed that there was a difference in SPT equivalent age between DLD and ASD without GDD. When the cut-off value of the SPT was 8.5, the largest area under the ROC curve was 0.723, and the sensitivity and specificity for the diagnosis of ASD without GDD were 0.720 and 0.620 respectively. CONCLUSIONS: Symbolic play ability in ASD children is worse than that of DLD children at comparable development levels. SPT may be helpful to distinguish ASD without GDD from children with DLD.

A Phase I Study of Gemcitabine/Nab-Paclitaxel/S-1 Chemotherapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. METHODS: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients` body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. RESULTS: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. CONCLUSION: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]).

Carbon dot-based molecularly imprinted fluorescent nanopomegranate for selective detection of quinoline in coking wastewater.

Quinoline, as a refractory and toxic organic pollutant in coking wastewater, causes great harm to the environment and human health even in trace amount. To realize the selective and sensitive detection of quinoline in coking wastewater, a novel molecularly imprinted fluorescent nanopomegranate with carbon dots (CDs) as seeds and fluorescence source (CD-MIP) was prepared, using quinoline as the template, and N-(ß-aminoethyl)-γ-aminopropyl trimethoxysilane (KH792) as the monomer. The preparation and detection conditions of CD-MIP were systematically optimized. The structure and detection performance of CD-MIP were investigated in detail. The resulting CD-MIP exhibits excellent photoluminescence performance, high detection sensitivity, good selectivity and reproducibility towards quinoline. Under the optimized conditions, the fluorescence intensity of CD-MIP shows a satisfying linearity with quinoline concentration in the range of 20-200 mg/L with a detection limit of 6.7 mg/L. Owing to the existence of imprinted cavities that highly match with quinoline, a high imprinting factor (3.46) for CD-MIP was obtained. In addition, CD-MIP represents a greater affinity towards quinoline than towards other analogues, as well as an outstanding anti-interference capability. For trace analysis in real coking wastewater, CD-MIP also gives satisfactory results. Therefore, CD-MIP shows promising application in the selective detection of trace quinoline in wastewater.

Correlation between postpartum pelvic floor dysfunction and vaginal microecological imbalance in late pregnancy. / äº§åŽç›†åº•åŠŸèƒ½éšœç¢ä¸Žå¦Šå¨ æ™šæœŸé˜´é“å¾®ç”Ÿæ€å¤±è¡¡çš„ç›¸å ³æ€§ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Pelvic floor dysfunction (PFD) seriously affects women's physical and mental health. Pregnancy and childbirth are recognized as high-risk factors for PFD, and studies have shown that vaginal microenvironmental disorders can promote the development of pelvic organ prolapse. In this study, we intend to investigate whether the changes in vaginal microecology during pregnancy affect the pelvic floor function and participate in the development of postpartum PFD, and provide a basis for the prevention and treatment of PFD. METHODS: A total of 358 full-term mothers who delivered in Third Xiangya Hospital, Central South University from November 2019 to April 2020 were selected and underwent review 6 to 8 weeks after delivery. The pelvic floor structures were examined using pelvic floor ultrasound, and ultrasound values were measured at rest and at maximum Valsalva maneuver. One hundred and seventy women with PFD were assigned in a PFD group, and 188 women without PFD were assigned in a control group. The clinical data of all mothers were collected, and the clinical data and the results of microecological testing for vaginal secretions after 36 weeks of gestation and before delivery were compared between the 2 groups. The correlation of PFD with leucorrhoea cleanliness, lactobacillus level, bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) was analyzed, and logistic regression analysis was used to screen for independent risk factors for PFD. RESULTS: The incidences of VVC, BV, Lactobacillus vaginalis deficiency, and leucorrhoea cleanliness ≥III° were all higher in the PFD group than those in the control group (P<0.05). Among them, leukocyte cleanliness ≥III°and lack of Lactobacilli in the vagina were independent risk factors for the development of PFD, while VVC and BV were not independent risk factors for the development of PFD. CONCLUSIONS: Postpartum PFD is related to vaginal microecological imbalance in late pregnancy, among which Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° are independent risk factors for the occurrence of PFD. Therefore, pregnant women with Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° in late pregnancy should pay attention to the occurrence of postpartum PFD, and early diagnosis and effective intervention of postpartum PFD should be enhanced.

Spontaneous rupture of an ovarian artery during pregnancy: A case report and literature review. / å¦Šå¨ æœŸåµå·¢åŠ¨è„‰è‡ªå‘æ€§ç ´è£‚1ä¾‹åŠæ–‡çŒ®å¤ä¹ .

Spontaneous rupture of the ovarian artery is very rare and can cause retroperitoneal hemorrhage, which is seriously life-threatening. Herein, we reported a case of massive retroperitoneal hematoma caused by spontaneous rupture of the right ovarian artery during pregnancy and intrauterine fetal death. A 32-year-old woman, gravida 6 para 5, had non-specific right lower abdomen and low back pain in the third trimester. Emergency cesarean section was performed due to the increased pain and decreased fetal heart rate. A huge retroperitoneal hematoma and intrauterine fetal death were found. Then, the abdomen was closed due to unknown source of bleeding and unstable vital signs. Computed tomography scan was conducted to clarify the extent of the retroperitoneal hematoma. Digital subtraction angiography confirmed the rupture of the right ovarian artery. A transcatheter artery embolization was successfully performed to control the bleeding. The patient ultimately recovered well after surgery.

Fertility-sparing treatment for cervical mullerian adenosarcoma: A case report and literature review. / å­å®«é¢ˆè ºè‚‰ç˜¤ä¿ç•™ç”Ÿè‚²åŠŸèƒ½æ²»ç–—1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Currently, whole uterus and bilateral tubal resection and oophorectomy is the main treatment of cervical mullerian adenosarcoma. However, young patients generally wish to retain reproductive function. The clinical data of a patient with cervical mullerian adenosarcoma, who underwent fertility preservation surgery were collected. A 13-year-old girl with abnormal vaginal bleeding and a 1.0 cm flocculent echogenicity in the lower part of the uterine cavity to the cervical canal and a cervical mass of about 61 mm×37 mm was found in the pelvic MRI. After initial diagnosis of dysfunctional uterine bleeding in adolescence and cervical blood clot, the patient was treated with artificial cycle treatment, but her symptoms did not improve. Then she was transferred to the Third Xiangya Hospital of Central South University for uninjured virgin membrane hysteroscopy and cervical mass electrotomy, but a few pedicles remained after the operation, and the pathology suggested a cervical mullerian adenosarcoma. Because the patient was young and had not yet given birth, she was treated with primary IAP regimen of chemotherapy and subcutaneously injected with gonadotropin-releasing hormone analogue (GNRH-A) once every 28 days (6 times in total) to protect the ovarian function. After the chemotherapy, she was treated with uninjured virgin membrane hysteroscopy and pedicle electrotomy of cervical mullerian adenosarcoma. After the operation, she received chemotherapy with IAP regimen for 5 times. After discharge, she was treated with megestrol 200 mg per day for 3 years. During 5 years of regular follow-up, no abnormality was seen. Cervical mullerian adenosarcoma in non-sexual women is easily misdiagnosed as ovulation dysfunction abnormal uterine bleeding. The necessity of hysteroscopy should be emphasized, and for patients with low-grade early-stage lesions who wish to retain fertility, local resection could be chosen, but attention is paid to lifelong follow-up to exclude long-term recurrence.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

The efficacy and safety of secondary focused ultrasound therapy for recurrence of non-neoplastic epithelial disorders of the vulva.

OBJECTIVE: To investigate the efficacy, safety, and influencing factors of secondary focused ultrasound (FU) therapy for recurrence of non-neoplastic epithelial disorders of the vulva (NNEDV). METHODS: Patients with NNEDV who have relapsed after initial FU treatment were included in this study. They were treated with secondary FU therapy between July 2015 and July 2021. Outcome measures included the degree of symptom severity and operative complications. We further analyzed the relationships between age, course, time between relapse and initial treatment, menopause status, lesion size, pathological types, severity of symptoms, and curative rate. RESULTS: There were 98 patients enrolled in this study, with a mean age of 47.4 ± 11.4 years. All patients successfully underwent secondary FU therapy. Blisters developed among 16 (16.3%) patients, of whom 6 (6.1%) developed superficial skin ulcers. A curative response was observed among 46 (46.9%) patients, while an effective response was observed among 44 (44.9%) patients. Only 8 (8.2%) patients showed no improvement. The total response rate was 91.8%. A total of 12 (12.2%) cases recurred among all effective cases. Patients with a recurrence of NNEDV after more than 1.5 years following their first FU therapy demonstrated a higher response rate than those with a recurrence after less than 1.5 years. CONCLUSIONS: A second FU therapy remains effective for patients with recurrent NNEDV with no obvious side effects. The response rate, however, is higher for patients who experience recurrence of NNDEDV after more than 1.5 years.

Inositol 1, 4, 5-trisphosphate receptor is required for spindle assembly in Xenopus oocytes.

The extent to which calcium signaling participates in specific events of animal cell meiosis or mitosis is a subject of enduring controversy. We have previously demonstrated that buffering intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, a fast calcium chelator), but not ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA, a slow calcium chelator), rapidly depolymerizes spindle microtubules in Xenopus oocytes, suggesting that spindle assembly and/or stability requires calcium nanodomains-calcium transients at extremely restricted spatial-temporal scales. In this study, we have investigated the function of inositol-1,4,5-trisphosphate receptor (IP3R), an endoplasmic reticulum (ER) calcium channel, in spindle assembly using Trim21-mediated depletion of IP3R. Oocytes depleted of IP3R underwent germinal vesicle breakdown but failed to emit the first polar body and failed to assemble proper meiotic spindles. Further, we developed a cell-free spindle assembly assay in which cytoplasm was aspirated from single oocytes. Spindles assembled in this cell-free system were encased in ER membranes, with IP3R enriched at the poles, while disruption of either ER organization or calcium signaling resulted in rapid spindle disassembly. As in intact oocytes, formation of spindles in cell-free oocyte extracts also required IP3R. We conclude that intracellular calcium signaling involving IP3R-mediated calcium release is required for meiotic spindle assembly in Xenopus oocytes.