BACKGROUND:Ovarian cancer (OC) is a prevalent malignant tumor in the field of gynecology, exhibiting the third highest incidence rate and the highest mortality rate among gynecological tumors. Chromatin remodeling accomplishes specific chromatin condensation at distinct genomic loci and plays an essential role in epigenetic regulation associated with various processes related to cancer development. METHODS:Differentially expressed genes (DEGs) between OC and control samples were screened from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, combined with chromatin remodeling-related genes (CRRGs) obtained from the GeneCards database to identify differentially expressed CRRGs (DECRRGs). Enrichment analysis and protein-protein interaction (PPI) network were performed on the DECRRGs. Prognostic genes of OC were screened using univariate Cox and least absolute shrinkage and selection operator (Lasso) analyses. A risk model based on prognostic genes was developed, and the survival probability of OC patients in different risk groups was analyzed by Kaplan-Meier (KM) curve. Finally, the expression levels of prognostic genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS:In total, 7 potential prognostic genes associated with the progression of OC patients were obtained, including ARID1B, ATRX, CHRAC1, HDAC1, INO80, MBD2, and SS18. Based on the expression level of prognostic genes, OC patients were divided into high-risk group and low-risk group. Survival analysis indicated that patients classified into the high-risk group had higher mortality rates, which enables this prediction model to be utilized as an independent predictor of OC. Immunocorrelation analysis showed that low-risk patients were more likely to benefit from immunotherapy. CONCLUSION:In this study, we have identified 7 prognostic genes, including ARID1B, ATRX, CHRAC1, HDAC1, INO80, MBD2, and SS18. Overall, our findings provided a foundation for further comprehension of the potential molecular mechanisms underlying OC pathogenesis and progression.

Background:CD161, encoded by the killer cell lectin-like receptor B1 (KLRB1) gene, exhibits varied roles among different tumors. This study aimed to explore both the potential value of CD161 as a prognostic biomarker for hepatocellular carcinoma (HCC) and its association with immune cell infiltration. Methods:A total of 109 HCC patients who underwent surgery were retrospectively analyzed. Immunohistochemistry, bioinformatic analyses, and statistical measurements were used to investigate the associations between CD161 expression, immune cell infiltration, and clinical outcomes in both public databases and in-house cohorts. Results:CD161 was highly expressed at both protein and mRNA levels in adjacent normal tissues compared to tumor tissues of HCC patients. Meanwhile, CD161 was enriched in HCC cases characterized by smaller tumor sizes (≤5 cm) and the absence of portal vein tumor thrombus. Individuals with high CD161 expression showed extended overall survival (OS) and relapse free survival (RFS) compared to those with lower CD161 levels. CD161 was identified as an independent prognostic indicator for both OS and RFS. In addition, the enrichment analysis indicated a close correlation between CD161 and immune response, as well as between CD161 and the signaling pathways of cytokines and chemokines, implying its role in immune regulation during cancer development. Specifically, CD161 expression was positively associated with immunomodulators and tumor-infiltrating immune cells, especially CD8+T cells, CD4+T cells, and dendritic cells. Multiple public databases showed that patients with high CD161 expression were more likely to derive benefits from immunotherapy. Conclusion:CD161 was identified as a promising prognostic biomarker for HCC, as its expression indicates a favorable prognosis. Additionally, CD161 is closely linked to high infiltration of immune cells, participates in the regulation of the tumor immune microenvironment, and holds promise as a potential biomarker for predicting the efficacy of immunotherapy.

This study aimed to explore the correlation between primary tumors (PT) and paired metastatic lymph nodes (LN) and to develop a predictive model to provide evidence for forecasting patient prognoses. We obtained single-cell and bulk transcriptome data from the Gene Expression Omnibus database. Furthermore, mRNA transcriptomic data, encompassing 112 normal tissues and 1066 breast cancer samples, along with survival, clinical, and mutation information for breast cancer patients, were acquired from The Cancer Genome Atlas (TCGA). Employing a machine learning integration framework incorporating ten distinct algorithms, we developed and validated a prognostic model. We constructed a prognostic model named Lymph Node Metastasis-Related Scores (LMRS) using 26 differentially expressed genes trained on eight TCGA datasets. Across validation sets, the model demonstrated a high C-index, signifying its stability and effectiveness, outperforming 64 models from other studies. Notably, cytolytic activity and T cell co-stimulation were downregulated in the high LMRS group, alongside a downregulation of immune cells, including B cells, CD8 + T cells, iDCs, and TILs. Similarly, most immune checkpoints exhibited a decreasing trend with high LMRS expression. Finally, we selected the hub biomarkers PGK1 and HSP90 for pathological verification. Results indicated higher expression levels in PT and LN compared to normal and benign tumors, with higher expression levels in LN than in PT. This comprehensive analysis sheds light on gene expression differences between PT and LN in breast cancer, culminating in the development of a multiple-gene prognostic model with high clinical accuracy for prognosis prediction.

Epithelial ovarian cancer (EOC) is a lethal form of gynecological malignancy. Some EOC patients experience relapse after standard primary debulking surgery (PDS) and adjuvant chemotherapy (ACT). Identifying molecular residual disease (MRD) by circulating tumor DNA (ctDNA) detection can timely signal the potential for relapse. However, research on the usage of ctDNA for MRD detection in EOC is limited. Fifty-one EOC patients who received standard PDS and ACT were included. Targeted sequencing based on a panel of 1021 cancer-related genes, along with further validation using Enrich-rare-mutation sequencing, was performed on tumor tissues acquired during PDS and on plasma samples collected before and after PDS/ACT to identify variants reflecting tumor signals. Post-surgery MRD was associated with relapse (Log-rank p = 0.0006) and was identified as an independent prognostic factor (HR, 3.4; 95

前哨淋巴结是原发肿瘤引流区域中的一组淋巴结,对腋窝淋巴结状态的预测、指导手术方案及评估预后有重要意义[1].虽然冰冻切片诊断其转移情况存在局限性,但仍是目前较快捷的诊断方式,临床仍依据其结果决定腋窝淋巴结清扫术[2].一张高质量冰冻切片对确保术中病理诊断的准确性具有极重要作用,而前哨淋巴结细胞丰富,质地较脆,周围脂肪组织丰富,易出现误诊或漏诊.本研究通过对前哨淋巴结的冷冻切片制作进行总结,不断提高制片质量及诊断准确率.

Epithelial ovarian cancer (EOC) is classified into five major histotypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC), and mucinous (MOC). However, the landscape of molecular and immunological alterations in these histotypes, especially LGSOC, CCOC, ENOC, and MOC, is largely uncharacterized. We collected 101 treatment-naive EOC patients. The resected tumor tissues and paired preoperative peripheral blood samples were collected and subjected to target sequencing of 1021 cancer-associated genes and T cell repertoire sequencing. Distinct characteristics of mutations were identified among the five histotypes. Furthermore, tumor mutation burden (TMB) was found to be higher in CCOC and ENOC, but lower in LGSOC and HGSOC. Alterations associated with DNA damage repair (DDR) pathways and homologous recombination deficiencies (HRD) were prevalent in five histotypes. CCOC demonstrated increased level of T cell clonality compared with HSGOC. Interestingly, the proportion of the 100 most common T cell clones was associated with TMB and tumor neoantigen burden in CCOC, highlighting more sensitive anti-tumor responses in this histotype, which was also evidenced by the enhanced convergent recombination of T cell clones. These findings shed light on the molecular traits of genomic alteration and T cell repertoire in the five major EOC histotypes and may help optimize clinical management of EOC with different histotypes.

内质网应激(ERS)是机体维持细胞稳态的重要机制,在ERS状态下,内质网中未折叠蛋白反应(UPR)被激活,参与细胞蛋白稳态调节,维持细胞稳态,而IRE1α-XBP1通路是UPR的主要通路之一,在ERS中发挥重要作用.近来研究发现,ERS与肿瘤增殖、免疫逃逸及耐药密切相关,肿瘤细胞与免疫细胞中IRE1α-XBP1通路被激活,可导致细胞蛋白稳态发生改变,肿瘤细胞凋亡减少,促进肿瘤增殖,同时影响免疫细胞的功能,诱导免疫逃逸和细胞耐药.本文对IRE1α-XBP1通路在肿瘤增殖、免疫逃逸及耐药方面的相关机制进行综述.

随着病理新技术的不断进展,胸、腹水等液体的诊断也需要通过免疫组化或分子病理检测来进行判读,为下一步的精准治疗提供依据.因此细胞蜡块的制作就尤为重要,细胞蜡块可以很好地保持组织细胞的完整性,细胞蜡块中细胞的分布保留与实体组织有类似的排列结构,可提高诊断的准确性,并可以重复切片进行多项组织检测.但由于胸、腹水等液体的细胞成分有限,离心后细胞经多道脱水处理细胞分散不易包埋制作蜡块,为了最完整的保持细胞成分,有效防止细胞的丢失或与包埋纸的粘连,提高细胞蜡块的制作质量及提高肿瘤细胞的检出率,我们试验了多种办法,最终摸索出最简单有效的使用截断的一次性试管(或滴管)来完整保存细胞成分的方法,在此与大家共享.

Ovarian cancer has the highest death rate in gynecologic tumors and the main therapy for patients with advanced is chemotherapy based on cisplatin. Additionally, hyperthermic intraperitoneal has been used in clinic to obtain better efficacy for patients. Hence, combined photothermal therapy with platinum drugs in a new delivery system might bring new hope for ovarian cancer. A reduction sensitive polymer encapsulating a Pt (IV) prodrug and a near infrared II (NIR II) photothermal agent IR1048 to form nanoparticles were reported to enhance the efficacy of ovarian cancer treatment. At the same time, endoplasmic reticulum stress indicates an imbalance in proteostasis which probably caused by extrinsic stress such as chemotherapy and the temperature changed. The efficacy of nanoparticles containing Pt (IV) and IR1048 under NIR II light might be caused via increased DNA damage and endoplasmic reticulum (ER) stress.

盆腔廓清术是针对盆腔恶性肿瘤的一种根治性外科手术,主要适用于局部晚期或中央型复发性妇科恶性肿瘤、结直肠癌、泌尿系肿瘤等盆腔恶性肿瘤患者.早在1948年Brunschwig[1]报道应用盆腔廓清术治疗局部复发性子宫颈癌,而后应用于局部复发性直肠癌,逐渐扩展至盆腔的多种恶性肿瘤.盆腔廓清术因具有手术难度大、并发症多、有较高的复发率和死亡率以及医疗花费相对高等特点,恰当的选择手术适应证尤为重要.近年来,随着手术与功能重建等技术的重大进展,盆腔廓清术更加彻底和个体化,其适应证和禁忌证亦随之有所改变.

HE染色是最基本也是最重要的病理学染色技术[1].质量优良和规范化的HE染色切片是病理医生做出正确诊断的基础[2].随着电子信息技术的飞速发展及现代病理诊断的精细化要求,HE染色技术已由传统的手工操作模式转为全自动染色工作系统,目前全自动染色主要用浸染式与单独滴染式染色平台,全自动浸染平台因成本相对较低、试剂开放及出片效率高等特点,在病理科应用较普遍;而全自动单独滴染平台则更具交叉污染低、染色稳定均一、有效降低诊断误诊率的优势,真正实现了全过程无人干预的全自动染色平台模式而受到病理技术人员的青睐.

出现五大症状需注意 宫外孕是妇产科和急诊科医生最头痛的一种致命的疾病,这种疾病发病率高,一般能达到2％～3％,也就是说每100个孕妇当中就有2个是宫外孕,而且极具隐蔽性,它的症状和肠胃炎、月经不调等疾病非常类似.宫外孕是刚刚怀孕的孕妇最主要的死亡原因.官外孕都会产生哪些症状呢?

目的 探讨经脐单孔腹腔镜卵巢囊肿剥除术的安全性和临床价值.方法 对2017年3月 ～2019年8月我院87例良性卵巢囊肿剥除术进行回顾性分析,其中单孔腹腔镜卵巢囊肿剥除术43例(单孔腹腔镜组),传统腹腔镜卵巢囊肿剥除术44例(传统腹腔镜组),比较2组手术时间、术中囊肿破裂率、术后血红蛋白(hemoglobin,Hb)下降幅度、术后24 h疼痛视觉模拟评分(Visual Analogue Scale,VAS)、排气时间、住院时间.结果 2组患者均无中转开腹和手术并发症发生.单孔腹腔镜组囊肿破裂率81.3％,明显高于传统腹腔镜组56.8％(χ2=6.137,P=0.013),术后24 h疼痛VAS评分单孔腹腔镜组明显低于传统腹腔镜组[1(0～2)分vs.2(0～3)分,Z=-3.575,P=0.000],排气时间明显早于传统腹腔镜组[(26.5±11.1)hvs.(33.1±11.8)h,t=-2.654,P=0.009].2组手术时间、术后Hb下降幅度和住院时间差异均无统计学意义(P>0.05).结论 经脐单孔腹腔镜良性卵巢囊肿剥除术是安全和可行的,但囊肿破裂率明显增高,应重视术前良恶性肿瘤的评估,交界性或恶性肿瘤慎用此术式.

压力性尿失禁(stress urinary incontinence,SUI)是指喷嚏、咳嗽、大笑或运动时腹压增高后出现不自主的尿液自尿道口漏出.SUI限制了女性日常活动及运动,严重影响其生活质量,并导致巨大心理压力.SUI的危险因素有:年龄、遗传 因素、雌激素水平降低、便秘、慢性咳嗽及肥胖等[1],其中肥胖是SUI的独立危险因素[2].

冷冻切片主要用于术中的病理诊断,病理医师利用冷冻切片在最短的时间内对送检术中标本进行良、恶性的鉴别,为临床医师进一步的手术方案和手术范围提供可靠的依据[1,2].术中快速冷冻切片的特点是:时间紧迫,高质量,要求准确.因此,时效性快而优质的冷冻切片迫切亟待.本实验旨在探讨OCT包埋剂在缩短冷冻时间,提高冷冻切片的可实用性.

由于乳腺癌治疗观念和方法的变化,保乳治疗成为越来越多乳腺癌患者的选择,而保乳手术的关键之一是术中快速冷冻切片能否对切缘性质作出准确判断,需要确定手术切缘有无癌浸润及前哨淋巴结是否有癌转移.冷冻切片完成的时间和质量不仅直接影响着病理诊断的及时性、准确性,而且对临床医师的确定手术范围及患者预后起着至关重要的作用.保乳术中冷冻由于需要的冷冻切片数量多、技术流程多、切片困难等原因,需要在人力、设备条件有限的情况下不断优化送检及技术流程,保证冷冻切片质量的同时提高速度,这就要求病理技术人员能够熟练地掌握冷冻切片技术,为病理医师快速诊断提供可靠保证.

5543 Background: Circulating tumor DNA (ctDNA) analysis in epithelial ovarian cancer (EOC) was previously reported, however with limited samples or limited genes. Here, we reported an analysis of ctDNA in EOC cohort using targeted sequencing with a 1021-gene panel. Methods: Patients with EOC were enrolled, and treatment-naïve tumor tissues and blood samples were collected. We utilized a 1021-gene NGS panel in matched tissue DNA and ctDNA to identify somatic mutations with white blood cell DNA as a germline control. Results: Mutations were identified in all of the 65 tissues and in 53 (81.5%) ctDNA. The median ctDNA mutation allelic frequency was 2.5%, ranging from 0.1% to 36.2%. A median of 66.7% (12.5%-100.0%) of tissue derived mutations were observed in ctDNA. Besides, there were 91 ctDNA private mutations, including TP53 gene mutations. The most frequently mutated genes were TP53 (55.4%), PIK3CA (13.8%) and ARID1A (12.3%) in ctDNA analysis, which were consistent with tissue analysis (60.0%, 26.2% and 20.0% of tissues with TP53, PIK3CA and ARID1A mutations, respectively). Mutations of TP53 (37/42) in high-grade serous ovarian carcinoma (HGSOC), PIK3CA (10/11) and ARID1A (8/11) in ovarian clear cell carcinoma, BRAF (4/5) in low-grade serous ovarian carcinoma and PIK3CA (3/5), ARID1A (2/5) and PTEN (2/5) in endometrioid carcinoma were observed as the most commonly genetic aberrations in ctDNA in different sub-types of EOC, which located in different signal pathways and suggested different pathogenesis. In total, 90.5% (38/42) of HGSOC were ctDNA positive, comparing with 65.2% (15/23) of other EOC subtypes (p = 0.012). In addition, 56.5% (13/23) of stage I~II EOC were ctDNA positive, comparing with 94.7% (36/38) of stage III (p = 0.002). No association between ctDNA positivity and other clinic characteristics was observed, including pathological differentiation, CA125, lesion density (solid vs. cystic-solid and cystic). Multivariable analysis suggested FIGO stage III (p = 0.008) as an independent predictor of ctDNA detection. Conclusions: In summary, genomic characterization of EOC may offer insights into tumorigenesis and identify potential therapeutic targets in this disease.

妊娠相关子宫颈神经内分泌癌是发生于孕期或产后的子宫颈神经内分泌恶性肿瘤.由于其病理类型特殊,发病率极低,早期易发生转移,预后极差.目前报道病例数量少,缺乏诊治经验,对其治疗方案尚无统一定论.本文就妊娠相关子宫颈神经内分泌癌的诊疗进展进行探讨,以期为临床决策提供依据.

The goal of this work was to investigate the tumor mutational burden (TMB) in Chinese patients with gynecologic cancer. In total, 117 patients with gynecologic cancers were included in this study. Both tumor DNA and paired blood cell genomic DNA were isolated from formalin-fixed paraffin-embedded (FFPE) specimens and blood samples, and next-generation sequencing was performed to identify somatic mutations. TP53 , PTEN , ARID1A , and PIK3CA alterations were significantly different in various types of gynecologic cancers (p = 0.001, 1.15E-07, 0.004, and 0.009, respectively). The median TMB of all 117 gynecologic tumor specimens was 0.37 mutations/Mb, with a range of 0–41.45 mutations/Mb. Despite the lack of significant difference, endometrial cancer cases had a higher median TMB than cervical and ovarian cancer cases. Younger gynecologic cancer patients (age <40 years) had a significantly lower TMB than older patients (age ≥40 years) (p = 0.04). In addition, TMB was significantly increased with increasing clinical stage of disease (p = 0.001). PTEN alterations were commonly observed in patients with a moderate to high TMB (n = 8, 38.10%, p = 9.95E-04). Although limited by sample size, all of the patients with TSC2 (n = 3, p = 3.83E-11) or POLE (n = 2, p = 0.005) mutations had a moderate to high TMB. Further large-scale, prospective studies are needed to validate our findings.

术后快速康复(enhanced recovery after surgery,ERAS)指为使患者快速康复,在围手术期采用的、经循证医学证据证实有效的一系列优化处理措施,以减轻患者心理和生理的创伤应激反应,从而减少并发症,缩短住院时间,降低再入院及死亡风险,降低医疗费用.ERAS概念最初是针对胃肠道及盆腔手术,由丹麦哥本哈根大学、被誉为“快速康复外科之父”的Henrik Kehlet教授于1997年提出的.2001年欧洲率先成立了ERAS合作组,欧洲临床营养和代谢委员会(ESPEN)于2005年提出了统一的ERAS方案,随后Wind等提出了ERAS结肠外科方案,并成为当前的核心内容,逐渐拓展应用到大多数的普通外科手术.相对于ERAS在外科领域的广泛应用,其在妇科的应用相对滞后.现将ERAS在妇科中的研究进展综述如下.