Intrauterine adhesions, also known as Asherman’s syndrome, can have an impact on both reproductive outcomes and gynaecologic symptoms. Surgical management with hysteroscopic lysis of adhesions is the ...gold standard for treatment.
The following techniques are described in this presentation for cases with severe occlusive cavity and should be performed by experienced surgeons.
1.
The use of 3D ultrasound played an important role in the preoperative workup of the patient, it could be used to evaluate the severity of intrauterine adhesion and predict the complexity of the cases.
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Transabdominal 2D ultrasound guidance can help to delineate the location and extent of the adhesions and reduce the risk of uterine perforation and the formation of false passage. Laparoscopic guidance for severe cases has been advocated for immediate treatment of uterine perforation and minimizing extrauterine trauma.
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In patients with severe intrauterine adhesion, a “myometrial scoring technique” could be used by bipolar electrode need with score 6 to 8, 4-mm-deep incisions from the fundus to the cervix and a transverse incision at the uterine fundus. Or the “ploughing technique” could be used by scissors, both methods aim to remove the fibrotic tissue, expose any underlying healthy basal endometrial tissue capable of regeneration. It remains to be seen whether “ploughing technique” using cold scissors or a “myometrial scoring technique” by bipolar electrode produces similar or different results, which could only be resolved by RCT in the future.
4.
Surgical management offers favourable fertility outcomes and is often successful in restoring menstruation. Endometrial thickness and volume assessed by 3D-TVUS may have important predictive value for pregnancy after hysteroscopic adhesiolysis.
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Prevention of reformation of adhesions remains challenging and no single method for preventing recurrence has shown superiority.
Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell ...RNA sequencing and spatial transcriptomics. Strikingly, the metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as
M2-like macrophages. We further developed scMetabolism, a computational pipeline for quantifying single-cell metabolism, and observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status and restore the antitumor immune balance in responsive patients, whereas the nonresponsive patients deteriorated into a more suppressive one. Our work described the immune evolution of metastasis and uncovered the black box of how tumors respond to neoadjuvant chemotherapy. SIGNIFICANCE: We present a single-cell and spatial atlas of colorectal liver metastasis and found the highly metabolically activated
M2-like macrophages in metastatic sites. Efficient neoadjuvant chemotherapy can slow down such metabolic activation, raising the possibility to target metabolism pathways in metastasis.
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Background and Aims
We previously demonstrated that cancer‐associated fibroblasts (CAFs) promote tumor growth through recruitment of myeloid‐derived suppressor cells (MDSCs). 5‐lipoxygenase (5‐LO) is ...highly expressed in myeloid cells and is critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression by activating its receptor leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC).
Approach and Results
RNA‐sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from patients with ICC. Co‐injection of ICC patient‐derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF‐educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF‐CM stimulation increased expression and activity of 5‐LO in MDSCs, while 5‐LO inhibitor impaired the stemness‐enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL‐6 and IL‐33 primarily expressed by CAFs mediated hyperactivated 5‐LO metabolism in MDSCs. We identified the LTB4‐BLT2 axis as the critical downstream metabolite signaling of 5‐LO in promoting cancer stemness, as treatment with LTB4 was elevated in CAF‐educated MDSCs, or blockade of BLT2 (which was preferentially expressed in stem‐like ICC cells) significantly reduced stemness‐enhancing effects of CAF‐educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient‐derived xenograft models.
Conclusions
Our study reveals a role for CAFs in orchestrating the optimal cancer stemness‐enhancing microenvironment by educating MDSCs, and suggests the 5‐LO/LTB4‐BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.
Mitochondria lie at the heart of innate immunity, and aberrant mitochondrial activity contributes to immune activation and chronic inflammatory diseases, including liver cancers. Mitophagy is a ...selective process for removing dysfunctional mitochondria. The link between mitophagy and inflammation in tumorigenesis remains largely unexplored. We observed that FUN14 domain‐containing 1 (FUNDC1), a previously characterized mitophagy receptor, accumulates in most human hepatocellular carcinomas (HCCs), and we thus explored the role of FUNDC1‐mediated mitophagy in HCC initiation and progression in a mouse model in which HCC is induced by the chemical carcinogen, diethylnitrosamine (DEN). We showed that specific knockout of FUNDC1 in hepatocytes promotes the initiation and progression of DEN‐induced HCC, whereas FUNDC1 transgenic hepatocytes protect against development of HCC. Hepatocyte‐specific FUNDC1 ablation results in the accumulation of dysfunctional mitochondria and triggers a cascade of events involving inflammasome activation and hyperactivation of Janus kinase/signal transducer and activator of transcription signaling. Specifically, cytosolic mitochondrial DNA (mtDNA) release and caspase‐1 activation are increased in FUNDC1‐depleted hepatocytes. This subsequently results in the elevated release of proinflammatory cytokines, such as interleukin‐1β (IL1β) and hyperproliferation of hepatocytes. Conclusion: Our results suggest that FUNDC1 suppresses HCC initiation by reducing inflammasome activation and inflammatory responses in hepatocytes, whereas up‐regulation of FUNDC1 expression at the late stage of tumor development may benefit tumor growth. Our study thus describes a mechanistic link between mitophagic modulation of inflammatory response and tumorigenesis, and further implies that FUNDC1‐mediated mitophagy and its related inflammatory response may represent a therapeutic target for liver cancer.
More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for ...diagnosing hepatitis B virus (HBV) -related HCC.
Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.
We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively.
We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.
Aiming at the problem of displacement of collapse direction caused by the impact of the high-rise reinforced concrete chimney in the process of blasting demolition, combined with the monitoring ...methods such as high-speed photography observation, piezoelectric ceramic sensor, and blasting vibration monitor, the impact process of the 180 m high chimney was comprehensively analyzed. The results show that the chimney will experience multiple 'weight loss' and 'overweight' effects during the sit-down process, inducing compressive stress waves in the chimney. When the sit-down displacement is large, the broken reinforced concrete at the bottom can play a significant buffering effect, and the 'overweight' effect gradually weakens until the sit-down stops. The stress of the inner and outer sides of the chimney wall is obviously different in the process of collapsing and touching the ground. The waveform of the monitoring point of the piezoelectric ceramic sensor is divided into three stages, which specifically characterizes the evolution process of the explosion load and the impact of the chimney. The vibration induced by explosive explosion is mainly high-frequency vibration above 50 Hz, the vibration induced by chimney collapse is mainly low-frequency vibration below 10 Hz, and the vibration characteristics are obviously different. In the process of blasting demolition and collapse of high-rise reinforced concrete chimney, due to the impact of sitting down, the wall of the support tube is subjected to uneven force, resulting in the deviation of the collapse direction. In practical engineering, the control measures of chimney impact, blasting vibration, and collapse touchdown vibration should be fully strengthened to ensure the safety of the protection target around the blasting demolition object.
Anaerobic ammonium oxidation (anammox) is an energy saving and environmentally friendly technique for wastewater treatment. Sludge adsorption is an important process after organics enter the anammox ...reactor. The extracellular polymeric substances (EPS) of anammox sludge play a key role on the activity of anammox. This study utilized Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to investigate molecular-level compositional characteristics of the stratified EPS of the anammox sludge, and to explore the adsorption preference of each EPS layer to refractory dissolved organic matter (DOM) during anammox treatment. Results showed that the adsorbed component by the tightly bound EPS layer was dominantly composed of lipids and proteins, with nearly 80% of formulas being CHO and CHON. The outer layers (slime, loosely bound-EPS) preferentially adsorbed the compounds with comparatively higher aromatic and unsaturated degrees, with S-containing formulas and lignin being the predominant components. The newly produced formulas in the effluent were inferred to be associated with the anammox treatment performance. The refractory DOM, with smaller molecular weight and high reductive degree, seemed to experience a single adsorption by the stratified EPS, and became part of the anammox sludge.
•High removal efficiency shows preferential S-compound adsorption by Anammox EPS.•EPS outer layers show greater adsorptive ability for refractory DOM.•Small molecular weight, high saturated degree DOM formulas show environmental risk.
•High and rapid uptakes of Pb(II) and Cd(II) were achieved by MS biosorbent.•Multilayer adsorption of Pb(II)/Cd(II) occurred on the heterogeneous MS surface.•MS biosorbent maintained 96–97% of the ...adsorption capacity after desorption.•The mechanism was elucidated by coupling physicochemical and spectroscopic methods.•Carboxyl, hydroxyl, amine, and ether groups were the binding sites.
Abundant fruit waste materials can be utilized as sustainable biosorbents for heavy metal removal from aqueous solutions. In this study, mango seed (MS) comprising seed kernel and shell showed the maximum adsorption capacities of 263.4 mg-Pb/g at pH 5.0 and 93.7 mg-Cd/g at pH 7.5. The best fitting of the adsorption isotherms to the Redlich-Peterson model indicated multilayer adsorption of Pb(II) and Cd(II) on the heterogeneous surface of MS. The adsorption was rapid with 93% of Pb(II) and 78% of Cd(II) adsorption accomplished within 10 min. More than 99% of the sequestered Pb(II) and 88% of the sequestered Cd(II) were recovered by desorption using 0.2 M HNO3, and the regenerated MS maintained 96–97% of the adsorption capacities. A combination of physicochemical and spectroscopic approaches showed that carboxyl, hydroxyl, amine, and ether groups were the binding sites; electrostatic attraction, microprecipitation, complexation, and ion exchange (with Ca2+ and Mg2+) jointly contributed to the adsorption. The seed kernel which has a more amorphous structure and a higher ion exchange capability favored higher Pb(II) and Cd(II) adsorption compared with the seed shell which contains a higher content of crystalline cellulose. These findings imply the application potential of MS for heavy metal removal and provide important information for the (bio)sorbent development.
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