A case report: deep and durable response to low-dose lenvatinib and tislelizumab in an elderly patient with advanced intrahepatic cholangiocarcinoma.

Background: Older patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment. Case presentation: We report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months. Conclusion: The case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

Risk factors for regional lymph node metastasis in rectal neuroendocrine tumors: a population-based study.

Introduction: The identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis. Methods: Patient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model. Results: Univariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction. Discussion: The novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

Serplulimab combined with gemcitabine, nab-paclitaxel and stereotactic body radiotherapy as the first-line treatment for patients with metastatic pancreatic adenocarcinoma in China: a multicentre, single-arm, phase II trial (ICSBR) protocol.

INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion.

PURPOSE: We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). METHODS: Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48-72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. RESULTS: The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. CONCLUSIONS: HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

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.

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.

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.

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.

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.

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]).

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.

Efficacy of low extra-abdominal aortic block in cesarean section for placenta accreta spectrum disorders and its effect on the expression of MDA and SOD. / ä½Žä½è ¹ä¸»åŠ¨è„‰å¤–é˜»æ–­æœ¯åœ¨èƒŽç›˜æ¤å ¥æ€§ç–¾ç— å‰–å®«äº§æœ¯ä¸­çš„æ•ˆæžœåŠå¯¹MDA、SOD表达的影响.

OBJECTIVES: Placenta accreta spectrum disorders (PAS) refers to a group of abnormalities in placental adhesion and invasion, which may lead to serious complications such as intractable postpartum hemorrhage. The use of low-level extra-abdominal aortic temporary block during cesarean section may reduce intraoperative bleeding in patients with PAS, but it may also cause ischemia-reperfusion injury. In this study, we intend to investigate the efficacy of low extra-abdominal aortic block in cesarean section for placental implantation disease and its effect on malondialdehyde (MDA) level and superoxide dismutase (SOD) activity, and analyze the severity of ischemia-reperfusion injury caused by them. METHODS: Pregnant women with invasive placenta accreta spectrum disorders who delivered in the Department of Obstetrics and Gynecology of the Third Xiangya Hospital of Central South University from July 2017 to July 2021, were selected, and they were divided into 2 groups. Group A consisted of those who underwent low extra-abdominal aortic block during cesarean section (n=15) and group B consisted of those who did not undergo extra-abdominal aortic block (n=15). The intraoperative bleeding, blood transfusion, hysterectomy and complication rate, postoperative hospital stay and hospitalization expenses were compared between the 2 groups to analyze the efficacy of abdominal aortic block. The biochemical indexes related to ischemia-reperfusion, MDA content and total superoxide dismutase (T-SOD) activity, were measured at the corresponding time points in both groups. The time points of each test were: in group A, before the block of the low extra-abdominal aorta after delivery (A0), 0 h (A1, when the myometrium was started to be sutured), 0.5 h (A2), 2 h (A3), and 4 h (A4) after the open block; in group B, after delivery of the fetus (B0), 0 h (B1), 0.5 h (B2), 2 h (B3), and 4 h (B4) after the myometrium was started to be sutured. Total duration of abdominal aortic block in group A was also recorded. Both groups were observed for sings of edema, ischemia, necrosis and infection in the limbs after surgery. The severity of ischemia-reperfusion injury caused by abdominal aortic block were determined by detecting the relevant biochemical indexes at different moments of reperfusion. RESULTS: The intraoperative bleeding and blood transfusion in group A were less than those in group B, and the difference was statistically significant (P<0.05). There was no significant difference in postoperative hospital stay and hospitalization expenses between the 2 groups (P>0.05). Surgical complications: in group A, the uterus was preserved in all cases, there was 1 bladder injury and 2 pelvic infections; while in group B, there was 1 hysterectomy, 3 bladder injuries, and 3 pelvic infections. Changes in T-SOD and MDA values: compared with A0 before block, the MDA level was significantly elevated in blood at time points A1, A2, and A3, while SOD activity was significantly decreased (P<0.05), and the 2 observed indexes basically returned to A1 level (ischemic period) at 4 h after open block (A4). There was no significant difference in the changes of T-SOD and MDA in group B (P>0.05). Comparison of T-SOD and MDA levels between group A and B: the difference of the 2 indexes was not statistically significant between A0 and B0 (P>0.05), MDA level was not statistically significant between A1 and B1, T-SOD activity at A1 was lower than B1, the difference was statistically significant, at the rest of the same time point, MDA level in group A were higher than that in group B, T-SOD activity in group A were lower than that in group B, the difference was statistically significant (P<0.05). No postoperative limb edema, ischemia, necrosis, or infection occurred in both groups. CONCLUSIONS: Low-level extra-abdominal aortic block effectively reduces bleeding and transfusion during cesarean section for placenta accreta spectrum disorders, resulting in a transient MDA elevation and a decrease of SOD activity, which means causing transient ischemia-reperfusion injury without complications such as limb edema, ischemia, necrosis, and infection.

A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.

Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.

Prevalence of Human Papillomavirus Among Chinese Han and Mongols Minority Women in Inner Mongolia, China: Reflected by Self-Collected Samples in CHIMUST.

Background: The disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia. Methods: Genotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results. Results: The hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,-52,-18/-58,-31/-39, and-59 while in Mongols were-16,-31,-58,-18 and-52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40-44 (20.5%) and 55-59 (23.5%) years in Han women while three peaks were observed at age of 30-34 (22.1%), 45-49 (22.9%), and 55-59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively. Conclusion: The prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

Associations of benzotriazoles and benzothiazoles with estrogens and androgens among pregnant women: A cohort study with repeated measurements.

People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, which are environmental pollutants that may possess endocrine-disrupting potential; however, no epidemiological evidence is available on the associations of BTRs and BTHs with estrogens and androgens. This study aimed at investigating the associations of BTRs and BTHs with estrogens and androgens among pregnant women. Based on a prospective cohort study, we included 459 pregnant women who donated a complete serial of urine samples at each trimester and had repeated measurements of four BTRs, four BTHs, three estrogens (estrone, 17ß-estradiol, and estrio), and two androgens (dehydroepiandrosterone and testosterone) in the urine samples. Associations of repeatedly measured BTRs and BTHs with maternal urinary estrogens and androgens were analyzed, and the cross-sectional associations were also analyzed. Tolyltriazole (TTR) (≥59.3%) and benzothiazole (BTH) (≥93.5%) had the highest detection rate among the BTRs and BTHs, respectively. Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with 17ß-estradiol, estriol, and testosterone, while the trend of the associations with estrone and dehydroepiandrosterone was inconsistent. Among the positive associations with 17ß-estradiol, estriol, and testosterone, the percent of change in estriol associated with TTR was the most prominent [28.5% (95% confidential interval: 24.2%, 32.9%) for each doubling in TTR]. The significant associations with estrone, estriol, testosterone, and dehydroepiandrosterone were stronger among pregnant women who gave birth to a boy than those who gave birth to a girl. These findings add epidemiological evidence on the endocrine-disrupting potential of BTRs and BTHs and highlight the importance of focusing on the health outcomes of BTRs and BTHs related to disturbed estrogens and androgens. Future studies are needed to validate these findings and explore the underlying mechanisms.