BACKGROUND AND AIMS:The repertoire of adhesion receptors and ligands is supported by molecules, which are primarily recognized for their roles in immunity. We have recently shown that the co-stimulatory molecule CD40 ligand (CD154/CD40L) is pro-atherogenic and serves as an adhesive ligand for cells expressing the integrin Mac-1 (CD11b/CD18). Here, we studied the role of endothelial CD40L in several models of cardiovascular inflammation. METHODS AND RESULTS:We generated mice with an endothelial cell-specific deficiency of CD40L, Bmx-CreERT2+Cd40lgfl/flApoe-/- (EC-CD40L-KO), and Cd40lgfl/flApoe-/- as controls. In a model of atherosclerosis, EC-CD40L-KO mice developed on average 39.4 ± 14.7 % smaller atherosclerotic plaques after 10 weeks of the conditional genetic deficiency compared to controls. Plaques from EC-CD40L-KO mice contained less macrophages, lipids and more collagen. In intravital microscopy of inflamed mesenteric venules, leukocyte adhesion was reduced 3.1-fold in EC-CD40L-KO mice with a similar effect on slow rolling. In a model of thioglycolate-induced peritonitis, leukocyte migration into the peritoneal cavity was reduced by 38.2 ± 16.2 % in EC-CD40L-KO mice compared to controls after 72 h. Furthermore, 7 days after a permanent surgical ligation of the Left Anterior Descending (LAD) coronary artery, significantly fewer Mac-1-expressing neutrophils and macrophages were detected in the infarcted myocardium in the absence of endothelial CD40L. CONCLUSIONS:In this functional validation study, we demonstrate that endothelial cell-expressed CD40L serves as an adhesion molecule in different models of acute inflammation in the aortic, peritoneal, mesenteric, and coronary vasculature. CD40L may therefore represent a promising therapeutic target at the interface of adaptive immunity and myeloid inflammation.

ABSTRACT The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host’s immunity against cancer. IMPORTANCE Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.

Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells. This interaction results from ERK2-mediated SUCLA2 S124 phosphorylation and subsequent PIN1-mediated cis-trans isomerization of SUCLA2. OXCT1-associated SUCLA2 generates succinyl-CoA, which not only serves as a substrate for OXCT1 but also directly succinylates OXCT1 at K421 and activates OXCT1. SUCLA2-regulated OXCT1 activation substantially enhances ketolysis, HCC cell proliferation, and tumor growth in mice. Notably, treatment with acetohydroxamic acid, an OXCT1 inhibitor used clinically for urinary infection, inhibits liver tumor growth in mice and significantly enhances lenvatinib therapy. Our findings highlight the role of SUCLA2-coupled regulation of OXCT1 succinylation in ketolysis and unveil an unprecedented strategy for treating HCC by interrupting ketolysis.

Autosomal dominant polycystic kidney disease (ADPKD) is marked by aberrant cell proliferation driven by cAMP-PKA and MAPK signaling pathways. EGR1, a transcription factor directly activated by the above two pathways, is critical in the over-proliferation of tumor cells, which share similarities with cystic epithelial cells in ADPKD. This study utilized in vitro cell models, three-dimensional (3D) cyst model, embryonic renal cystic model, and PKD mouse model to clarify the role of EGR1 in cyst development of ADPKD. We found the high expression and nuclear condensates of EGR1 in human ADPKD renal cyst epithelial cells and PKD mouse kidney tissue. Pharmacological inhibition of EGR1 retarded cyst enlargement in in vitro, ex vivo, and in vivo ADPKD models. Furthermore, EGR1 formed nuclear condensates with YAP1 and CBP via phase separation, leading to EGR1-specific transcriptional activation and upregulation of cell-cycle-related genes (e.g., CCND1, CCNE1, and CDK4/6), thus promoting abnormal renal cystic epithelial cell proliferation. Disruption of EGR1 phase separation significantly alleviated cyst growth in the forskolin-induced 3D spheroid model of mIMCD3 cells and MDCK cyst model. These findings demonstrate that phase separation-mediated EGR1 condensates facilitate renal cyst development in ADPKD.

BACKGROUND AND AIMS:Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS:ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS:It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 μg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1β, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS:This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.

Although it has been more than 20 years since the first aquaporin was discovered, the specific functions of many aquaporins are still under investigation, because various mice lacking aquaporins have no significant phenotypes. And in many studies, the function of aquaporin is not directly related to its transport function. Therefore, this chapter will focus on some unexpected functions of aquaporins, such the decreased tumor angiogenesis in AQP1 knockout mice, and AQP1 promotes cell migration, possibly by accelerating the water transport in lamellipodia of migrating cells. AQP transports glycerol, and water regulates glycerol content in epidermis and fat, thereby regulating skin hydration/biosynthesis and fat metabolism. AQPs may also be involved in neural signal transduction, cell volume regulation, and organelle physiology. AQP1, AQP3, and AQP5 are also involved in cell proliferation. In addition, AQPs have also been reported to play roles in inflammation in various tissues and organs. The functions of these AQPs may not depend on the permeability of small molecules such as water and glycerol, suggesting AQPs may play more roles in different biological processes in the body.

Nonalcoholic fatty liver disease (NAFLD), which is the most common liver disease, is associated with type 2 diabetes mellitus and metabolic syndrome. Although there is no consensus on the treatment of NAFLD, growing evidence suggests that tight glycemic control would contribute to the improvement of NAFLD. However, some insulin sensitizers cannot improve NAFLD, especially nonalcoholic steatohepatitis (NASH). Whether insulin-independent hypoglycemic drug dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, may improve NAFLD keeps unclear. Therefore, 12-week-old male C57BL/6 wild-type and db/db mice were treated with 1 mg/kg dapagliflozin or vehicle for 12 weeks. Dapagliflozin alleviated NASH, manifesting as decreased alanine aminotransferase and NAFLD activity score in db/db mice. Also, dapagliflozin reduced de novo lipogenesis by the upregulation of FXR/SHP and downregulation of LXRα/SREBP-1c in the liver of db/db mice. Moreover, dapagliflozin treatment reduced inflammatory response by inhibiting the NF-κB pathway and alleviated fibrosis by restoring the balance between fibrogenesis and fibrolysis in the liver of db/db mice. In summary, dapagliflozin alleviates NASH mostly by reducing lipid accumulation, inflammation, and fibrosis. These findings provide new insights for understanding the protective effect of dapagliflozin in NASH and suggest that dapagliflozin may be used to treat NASH.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

Aging is a major risk factor for chronic diseases and disability in humans. Nowadays, no effective anti-aging treatment is available clinically. In this study, oridonin was selected based on the drug screening strategy similar to Connectivity MAP (CMAP) but upon transcriptomes of 102 traditional Chinese medicines treated cell lines. Oridonin is a diterpenoid isolated from Rabdosia rubescens. As reported, Oridonin exhibits a variety of pharmacological activities, including antitumor, antibacterial and anti-inflammatory activities. Here, we found that oridonin inhibited cellular senescence in human diploid fibroblasts (2BS and WI-38), manifested by decreased senescence-associated β-galactosidase (SA-β-gal) staining. Compared with the elderly control group, the positive cell rate in the oridonin intervention group was reduced to 48.5%. Notably, oridonin prolonged the lifespan of yeast by 48.9%, and extended the average life span of naturally aged mice by 21.6%. Our mice behavior experiments exhibited that oridonin significantly improved the health status of naturally aged mice. In addition, oridonin also delayed doxorubicin-induced cellular senescence and mouse senescence. Compared with the model group, the percentage of SA-β-gal positive cells in the oridonin treatment group was reduced to 59.8%. It extended the average lifespan of mice by 53.8% and improved healthspan. Mechanistically, we showed that oridonin delayed aging through the AKT signaling pathway and reversed the genetic changes caused by doxorubicin-induced cell senescence. Therefore, oridonin is a potential candidate for the development of anti-aging drugs.

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14–21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

Cyst development in polycystic kidney disease (PKD) involves abnormal epithelial cell proliferation, which is believed to be affected by the primary cilia mediated signal transduction in the epithelial cells. Herein is reported that a natural compound 1-Indanone retard cyst development in in vitro and in vivo models of PKD, including MDCK cyst model, embryonic kidney cyst model, and a neonatal, kidney-specific Pkd1 knockout mouse model. It was found 1-Indanone significantly inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and down-regulating expression of anterograde transport motor protein KIF3A and IFT88. 1-Indanone down-regulated ciliary coordinated WNT/β-catenin, Hedgehog signaling remarkably. The experimental results indicate that 1-Indanone inhibited cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, which suggests that 1-Indanone may hold therapeutic potential to reduce cyst development in PKD. And reducing primary cilia length will become a potent strategy for ADPKD treatment.Funding Information: This work was supported by the National Natural Science Foundation of 356 China grants [81974083, 81620108029, 81330074, 81873597 and 81800388], the Beijing 357 Natural Science Foundation grant [7212151]Declaration of Interests: All the authors declared no competing interests.Ethics Approval Statement: All animal experiments were approved by the relevant government authorities and ethics committees, in compliance with the local regulations for the care and use of laboratory animals. All animal experiments were approved by the Care and Use of Laboratory Animals of China Association for Laboratory Animal Science, in compliance with the Institutional Animal Care and Use Committee at the Peking University Health Science Center (26 Febrary 2021; protocol no. LA2021080).

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originatingfromrenal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways. Methods We established the forskolin (FSK)-induced three-dimensional (3D) Madin-Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3',5'-cyclic monophosphate-stimulated cyst formation in ex vivo embryonic kidney culture. Cultured human renal cyst-lining cells (OX-161) and normal tubular epithelial cells were treated with FAK inhibitors or transfected with green fluorescent protein-tagged FAK mutant plasmids for proliferation study. Furthermore, we examined the role of FAK in two transgenic ADPKD animal models, the kidney-specific Pkd1 knockout and the collecting duct-specific Pkd1 knockout mouse models. Results FAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in ex vivo and 3D cyst models. In tissue-specific Pkd1 knockout mouse models, FAK inhibitors retarded cyst development and mitigated renal function decline. Mechanically, FSK stimulated FAK activation in tubular epithelial cells, which was blocked by a protein kinase A (PKA) inhibitor. Inhibition of FAK activation by inhibitors or transfected cells with mutant FAK constructs interrupted FSK-mediated Src activation and upregulation of ERK and mTOR pathways. Conclusions Our study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA-regulated proliferation.

目的:探讨盆腔放线菌病的临床病理特点及诊治要点。方法:对2017年12月至2019年8月于首都医科大学附属北京友谊医院及北京大学人民医院诊治的3例盆腔放线菌病患者的临床病理资料进行回顾性分析。结果:3例盆腔放线菌病患者中有2例有久置宫内节育器病史；3例的临床症状均无特异性，表现为腹痛、发热或泌尿系统症状；其中2例患者伴有消瘦，术前盆腔CT检查均显示盆腔包块与周围组织界限不清，误诊为生殖系统恶性肿瘤；另1例患者表现为尿频、尿急及阴道排出异物，形成膀胱-子宫瘘。3例患者均行手术治疗，3例均盆腔粘连严重，1例行子宫全切除及双侧附件切除术，1例行子宫全切除+双侧输卵管切除+右侧卵巢肿物剥除+膀胱瘘口修补术，1例因盆腔粘连严重仅行左侧附件切除及盆腔病灶部分切除术；术后病理检查均见到典型放线菌团形成的“硫磺颗粒”确诊。术后给予抗生素治疗，随访1~2年，3例患者均无复发。结论:盆腔放线菌病术前诊断困难，易误诊为恶性肿瘤，组织病理学检查见到放线菌即可确诊，抗生素是首选的治疗方案，必要时需联合手术治疗。

目的:探讨术前尿动力学检查(UDS)对术后新发压力性尿失禁(de novo SUI)的阴性预测价值.方法:对北京大学人民医院妇科2014年1月至2016年12月因盆腔脏器脱垂住院并手术、术前行UDS的177例患者进行回顾性研究.结果:177例患者,UDS对de novo SUI的阴性预测值(NPV)为89.9％;UDS无SUI的138例患者中,术前无SUI症状者83例,术中未行抗SUI手术,10例患者术后发生了de novo SUI,其中1例需手术治疗,做了抗SUI手术,再手术率1.2％(1/83).98例行经阴道网片置入的盆底重建术(TVM),UDS对这部分患者de novo SUI的NPV 89.6％;UDS无SUI,但有SUI症状患者36例,19例术中同时行尿道中段悬吊术手术,17例未做,前者de novo SUI发生率10.5％,后者无de novo SUI发生.结论:术前UDS对de novo SUI有较高的阴性预测价值,对术前有SUI症状的患者,UDS也可作为协助决定是否同时抗尿失禁手术的方法.

子宫内膜浆液性癌（ESC）因其恶性度高，近年来受到极大重视，然而对其发病机制的认识不足，且患者通常无明显症状，死亡率高，预后差，因此，明确ESC的发生、发展过程对精确分期、指导治疗具有重要意义。本文复习国内外关于ESC发病起源的研究结果，提出两种假设，即子宫内膜起源学说和输卵管起源学说，并论述两种学说的科学依据，为进一步探索ESC的发病机制提供思路。

子宫内膜癌是常见的女性生殖系统恶性肿瘤，对于复发性子宫内膜癌患者，即使无法完整切除病灶，不同程度的减瘤术也能缩小肿瘤体积，延长生存时间，改善预后。本文报道了1例低分化子宫内膜样癌Ⅲc期术后腹腔复发侵及下腔静脉行减瘤术及下腔静脉人工血管置换术患者，围术期风险可控，无特殊并发症发生，术后短期随访病情缓解。

Objective: To investigate the perioperative situation and recent effect of pelvic exenteration for patients with locally recurrent cervical cancer. Methods: A total of 17 patients with locally recurrent cervical cancer who underwent pelvic exenteration in Peking University People's Hospital from October 2015 to May 2018 were retrospectively analyzed for their clinical and pathological characteristics, surgical conditions, hospitalization costs, postoperative complications, and survival situation. Results: (1) The median age of 17 patients with locally recurrent cervical cancer was 51 years (range 27-64 years). Pathological type: 13 cases of squamous cell carcinoma, 2 cases of adenocarcinoma, and 2 cases of adenosquamous carcinoma. Thirteen patients received radiotherapy during the initial treatment and 4 patients did not receive radiotherapy. (2) Pelvic exenteration was performed in 17 patients with locally recurrent cervical cancer, of which 9 cases were performed with total pelvic exenteration (operation range including radical cystectomy, partial urethrectomy rectectomy and partial vaginalectomy), and 8 cases with anterior pelvic exenteration operation (operation range including: radical cystectomy, part of urethrectomy and part of vaginalectomy). Of the 17 patients successfully completed the operation. The median operation time was 450 minutes (range 240-760 minutes), the median intraoperative blood loss was 2 200 ml (range 200- 8 400 ml), the median postoperative hospital stay was 17 days (range 9-55 days), the median hospital cost was 83 857 yuan (range 41 588-296 354 yuan). (3) Of the 17 patients underwent pelvic exenteration, 16 of them had early complications, the most common one was fever (14 cases). Fourteen of them had late complications, and the most common one was a urinary system infection (12 cases). (4) The median overall survival time was 26.0 months (range 3-44 months), the median progression-free survival (PFS) time was 9.0 months (range 2-44 months). Among them, 13 patients received radiation therapy during the initial treatment, the median PFS time was 9.0 months (range 2-30 months); 4 patients did not receive radiation therapy in the initial treatment, the median PFS time was 10.5 months (range 2-44 months).Eleven patients received adjuvant therapy after pelvic exenteration, the median PFS time was 12.0 months (range 2-44 months); 6 patients did not receive adjuvant therapy, the median PFS time was 5.0 months (range 2-9 months). Conclusions: Pelvic exenteration has a wide range of operations, many postoperative complications, and high hospitalization costs. Adjuvant treatment after pelvic exenteration could improve the PFS time for some patients. Its clinical value and health economic value need to be further explored.