Single-cell sequencing: Current applications in various tuberculosis specimen types.

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (M.tb) and responsible for millions of deaths worldwide each year. It has a complex pathogenesis that primarily affects the lungs but can also impact systemic organs. In recent years, single-cell sequencing technology has been utilized to characterize the composition and proportion of immune cell subpopulations associated with the pathogenesis of TB disease since it has a high resolution that surpasses conventional techniques. This paper reviews the current use of single-cell sequencing technologies in TB research and their application in analysing specimens from various sources of TB, primarily peripheral blood and lung specimens. The focus is on how these technologies can reveal dynamic changes in immune cell subpopulations, genes and proteins during disease progression after M.tb infection. Based on the current findings, single-cell sequencing has significant potential clinical value in the field of TB research. Next, we will focus on the real-world applications of the potential targets identified through single-cell sequencing for diagnostics, therapeutics and the development of effective vaccines.

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway.

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances de novo cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.

The Impact of HIFU Ablation on the Histopathological Features of Locally Recurrent Fibroids Tissue Post-HIFU Treatment.

OBJECTIVE: To evaluate the impact of high-intensity focused ultrasound (HIFU) ablation on the histopathological features of locally recurrent fibroids tissue. METHODS: Patients who underwent transabdominal hysterectomy or myomectomy for uterine fibroids from January 1, 2021 to July 1, 2023 at a teaching hospital in China were enrolled in this prospective study. The patients who underwent surgery for local recurrence of uterine fibroids after HIFU ablation were categorized as the HIFU group, and patients who had not undergone HIFU ablation for uterine fibroids were the control group. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical staining were performed to analyze the counts of smooth muscle cells (SMCs), collagen content, microvascular count, and the expression levels of estrogen receptor (ER) and progesterone receptor (PR) in the fibroid tissue specimens. RESULTS: The mean SMC counts in the HIFU and control groups were 337.68/field and 328.52/field respectively. The mean collagen content in the HIFU group and control group were 46.06% and 41.69% respectively. The mean microvessel counts in the HIFU group and control group were 13.66/field and 14.08/field respectively. The mean ER scores in the HIFU and control groups were 6.9 and 7.47 respectively, and the mean PR scores were 7.3 and 7.56 respectively. Overall, there were no significant differences in the SMC counts, collagen content, microvascular counts, and the ER and PR expression levels between the HIFU group and control group (p > 0.05). CONCLUSIONS: HIFU ablation has no effect on the pathological characteristics of local recurrent fibroid tissue, and is an ideal non-invasive treatment option.

The safety and efficacy of myomectomy in the treatment of recurrent uterine fibroids after HIFU.

OBJECTIVE: To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation. METHODS: This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications. RESULTS: The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05). CONCLUSION: Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.

Achieving NPVR ≥ 80% as technical success of high-intensity focused ultrasound ablation for uterine fibroids: a cohort study.

OBJECTIVE: To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. MATERIALS AND METHODS: Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan-Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. MAIN RESULTS: A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR < 70% group, 31.0% in the NPVR 70-79% group, 18.2% in the NPVR 80-89% group and 17.8% in the NPVR ≥ 90% group (P < 0.05). However, no difference was found between the group of NPVR 80-89% and the group of NPVR ≥ 90% (P = 0.499). Age of patients and signal intensity on T2-weighted imaging (T2WI) of tumours were found to be independent risk factors for long-term re-intervention in the NPVR ≥ 80% group. A younger age and greater signal intensity on T2W images corresponded to a greater risk of re-intervention. CONCLUSION: USgHIFU, an alternative treatment for uterine fibroids, has reliable long-term efficacy. NPVR ≥ 80% can be used as a sign of technical success, which can reduce re-intervention rates. However, an important step is to communicate with patients in combination with the age of patients and the signal intensity on T2WI of fibroids. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee at our institution (Registration No. HF2023001; Date: 06/04/2023). The Chinese Clinical Trial Registry provided full approval for the study protocol (Registration No. CHiCTR2300074797; Date: 16/08/2023).

Interactions between CNS and immune cells in tuberculous meningitis.

The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells, monocytes, and the barrier systems within the brain. Recently, advances in the immune cells in the CNS provided new insights to understand the development of tuberculous meningitis (TBM), which is the predominant form of Mycobacterium tuberculosis (M.tb) infection in the CNS and accompanied with high mortality and disability. The development of the CNS requires the protection of immune cells, including macrophages and microglia, during embryogenesis to ensure the accurate development of the CNS and immune response following pathogenic invasion. In this review, we summarize the current understanding on the CNS immune cells during the initiation and development of the TBM. We also explore the interactions of immune cells with the CNS in TBM. In the future, the combination of modern techniques should be applied to explore the role of immune cells of CNS in TBM.

Single-cell RNA profiling reveals classification and characteristics of mononuclear phagocytes in colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health problem worldwide. Mononuclear phagocytes are the main immune cells in the tumor microenvironment of CRC with remarkable plasticity, and current studies show that macrophages are closely related to tumor progression, invasion and dissemination. To understand the immunological function of mononuclear phagocytes comprehensively and deeply, we use single-cell RNA sequencing and classify mononuclear phagocytes in CRC into 6 different subsets, and characterize the heterogeneity of each subset. We find that tissue inhibitor of metalloproteinases (TIMPs) involved in the differentiation of proinflammatory and anti-inflammatory mononuclear phagocytes. Trajectory of circulating monocytes differentiation into tumor-associated macrophages (TAMs) and the dynamic changes at levels of transcription factor (TF) regulons during differentiation were revealed. We also find that C5 subset, characterized by activation of lipid metabolism, is in the terminal state of differentiation, and that the abundance of C5 subset is negatively correlated with CRC patients' prognosis. Our findings advance the understanding of circulating monocytes' differentiation into macrophages, identify a new subset associated with CRC prognosis, and reveal a set of TF regulons regulating mononuclear phagocytes differentiation, which are expected to be potential therapeutic targets for reversing immunosuppressive tumor microenvironment.

Long-term re-intervention after USgHIFU and prediction of NPVR in different ages of patients with uterine fibroids.

OBJECTIVE: Long-term re-intervention after ultrasound-guided high intensity focused ultrasound (USgHIFU) ablation was reported, and the prediction of non-perfusion volume ratio (NPVR) in differently aged patients with uterine fibroids (UFs) was explored. MATERIALS AND METHODS: Patients with UFs who underwent USgHIFU ablation from January 2012 to December 2019 were enrolled and divided into < 40-year-old and ≥ 40-year-old groups. Cox regression was used to analyze the influencing factors of re-intervention rate, and receiver operating characteristic (ROC) curve was used to analyze the correlation between NPVR and re-intervention rate. RESULTS: A total of 2141 patients were enrolled, and 1558 patients were successfully followed up. The 10-year cumulative re-intervention rate was 21.9%, and the < 40-year-old group had a significantly higher rate than the ≥ 40-year-old group (30.8% vs. 19.1%, p < 0.001). NPVR was an independent risk factor in both two groups. When the NPVR reached 80.5% in the < 40-year-old group and 75.5% in the ≥ 40-year-old group, the risk of long-term re-intervention was satisfactory. CONCLUSION: The long-term outcome of USgHIFU is promising. The re-intervention rate is related to NPVR in differently aged patients. Young patients need a high NPVR to reduce re-intervention risk.

Prediction of non-perfusion volume ratio for uterine fibroids treated with ultrasound-guided high-intensity focused ultrasound based on MRI radiomics combined with clinical parameters.

BACKGROUND: Prediction of non-perfusion volume ratio (NPVR) is critical in selecting patients with uterine fibroids who will potentially benefit from ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, as it reduces the risk of treatment failure. The purpose of this study is to construct an optimal model for predicting NPVR based on T2-weighted magnetic resonance imaging (T2MRI) radiomics features combined with clinical parameters by machine learning. MATERIALS AND METHODS: This retrospective study was conducted among 223 patients diagnosed with uterine fibroids from two centers. The patients from one center were allocated to a training cohort (n = 122) and an internal test cohort (n = 46), and the data from the other center (n = 55) was used as an external test cohort. The least absolute shrinkage and selection operator (LASSO) algorithm was employed for feature selection in the training cohort. The support vector machine (SVM) was adopted to construct a radiomics model, a clinical model, and a radiomics-clinical model for NPVR prediction, respectively. The area under the curve (AUC) and the decision curve analysis (DCA) were performed to evaluate the predictive validity and the clinical usefulness of the model, respectively. RESULTS: A total of 851 radiomic features were extracted from T2MRI, of which seven radiomics features were screened for NPVR prediction-related radiomics features. The radiomics-clinical model combining radiomics features and clinical parameters showed the best predictive performance in both the internal (AUC = 0.824, 95% CI 0.693-0.954) and external (AUC = 0.773, 95% CI 0.647-0.902) test cohorts, and the DCA also suggested the radiomics-clinical model had the highest net benefit. CONCLUSIONS: The radiomics-clinical model could be applied to the NPVR prediction of patients with uterine fibroids treated by HIFU to provide an objective and effective method for selecting potential patients who would benefit from the treatment mostly.

The dose of focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer is predictable: A multicenter retrospective study.

To analyze the influencing factors of energy efficiency factors (EEF) in focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer and build a dosimetry model. The patients with unresectable pancreatic cancer that underwent FUAS were enrolled from 3 clinical centers between June 2015 and June 2022 for retrospective analysis. The significance of the factors with the potential to affect the EEF was assessed, correlations among the factors were analyzed, and the accuracy of the prediction models established by the factors containing different imaging features was compared. From a total of 236 cases, 215 cases were screened for study, EEF was significantly correlated with mode of anesthesia, grayscale change, tumor volume, tumor location, the distance from the tumor center to skin, contrast-enhanced computer tomography enhancement type, T2-weighted imaging fat suppression signal intensity and contrast-enhanced T1-weighted imaging enhancement type on magnetic resonance imaging. The resultant multiple regression models of EEF achieved significance, contains predictors of Tumor volume, the distance from tumor center to skin, T2-weighted imaging fat suppression signal intensity, and contrast-enhanced T1-weighted imaging enhancement type had better goodness of fit. Compared with CT, the EEF prediction model established by adding magnetic resonance imaging features showed better prediction in FUAS treatment of unresectable pancreatic cancer.

Factors influencing USgHIFU ablation for adenomyosis with NPVR ≥ 50.

OBJECTIVE: To investigate the influencing factors of ultrasound-guided HIFU (USgHIFU) ablation for adenomyosis with a non-perfused volume ratio (NPVR)≥50%. METHODS: A total of 299 patients with adenomyosis who underwent USgHIFU ablation were enrolled. Quantitative signal intensity (SI) analysis was performed on T2WI and dynamic enhancement type. The energy efficiency factor (EEF) was defined as the ultrasound energy delivered for ablating 1 mm3 of tissue. NPVR ≥ 50% was used as the criterion for technical success. Adverse effects and complications were recorded. Logistic regression analyses of variables were conducted to identify the factors affecting NPVR ≥ 50%. RESULTS: The median NPVR was 53.5% (34.7%). There were 159 cases in the NPVR ≥ 50% group and 140 cases in the NPVR < 50% group. The EEF in NPVR < 50.0% group was significantly higher than that in NPVR ≥ 50% group (p < 0.05). The incidence of intraoperative adverse effects and postoperative adverse events in the NPVR < 50% group were higher than those in the NPVR ≥ 50% group (p < 0.05 for both). Logistic regression analysis showed that abdominal wall thickness, SI difference on T2WI between adenomyosis and rectus abdominis, and enhancement type on T1WI were protective factors for NPVR ≥ 50% (p < 0.05), while the history of childbirth was an independent risk factor (p < 0.001). CONCLUSIONS: Compared with NPVR < 50%, NPVR ≥ 50% did not increase the intraprocedural and postprocedural adverse reactions. The possibility of NPVR ≥ 50% was higher in patients with thinner abdominal walls, showed slight enhancement of adenomyosis on T1WI, with a history of childbirth, or in whom the SI difference on T2WI between adenomyosis and rectus abdominis was more minor.

Long-term outcomes of ultrasound guided high intensity focused ultrasound ablation for patients with uterine fibroids classified by T2WI: a multicenter retrospective study.

OBJECTIVE: To evaluate the long-term outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids classified by T2-weighted magnetic resonance imaging (T2WI-MRI). MATERIALS AND METHODS: The data of 1427 premenopausal women with symptomatic uterine fibroids who underwent USgHIFU at four teaching hospitals in China were analyzed retrospectively. The uterine fibroids were classified based on their T2WI-MRI signal intensities relative to that of skeletal muscle, myometrium and endometrium as: hypointense, isointense, heterogeneous hyperintense fibroids (HHF), slightly HHF (sHHF) and markedly HHF (mHHF), respectively. The rates of symptom relief and reintervention post-USgHIFU ablation were compared between the classified groups. RESULTS: A total of 1303 patients were followed up for 44 (40, 49) months. The symptom relief rate of the hypointense and isointense fibroids was 83.3% and 79.5%, respectively, which were significantly higher (p < .05) compared to that of HHF, sHHF and mHHF (58.3%, 44.2% and 60.4%), respectively. sHHF had the lowest symptom relief rate (p < .05). The cumulative reintervention rate for hypointense, isointense, HHF, sHHF and mHHF types were 8.8%, 10.8%, 21.4%, 39.9% and 19.8%, respectively. The reintervention rate of hypointense/isointense fibroids was significantly lower than that of HHF/mHHF/sHHF (p < .01), while sHHF had the highest re-intervention rate (p < .01). Thus, reintervention rate is inversely correlated to the rate of symptom relief. CONCLUSIONS: USgHIFU ablation is effective for hypointense, isointense, HHF and mHHF with acceptable long-term follow-up outcomes. However, sHHF is associated with a higher reintervention rate.

Sacral injury and influencing factors after ultrasonic ablation of uterine fibroids ≤30 mm from the sacrum

PURPOSE: To study sacral injuries and influencing factors after ultrasonic ablation of uterine fibroids no more than 30 mm from the sacrum. METHODS: A total of 406 patients with uterine fibroids who underwent percutaneous ultrasound ablation were analyzed retrospectively. All patients underwent contrast-enhanced magnetic resonance imaging (MRI) scans before and after high-intensity focused ultrasound. The abnormal signal intensity (low signal intensity on T1WI and high signal intensity on T2WI) on the postoperative MRIs was indicative of a sacral injury. The patients were divided into a sacrum injury group and a sacrum non-injury group. The relationship between fibroid characteristics, ultrasound ablation parameters, and injury was analyzed using univariate and multivariate analyses. RESULTS: There were 139 cases of sacral injury (34.24%). When the distance from the fibroid's dorsal side to the sacrum was 0-10 mm, the risk assessment showed that the danger of sacral injury increased by 1.85 times and 3.03 times compared with that at a distance of 11-20 or 21-30 mm. Furthermore, the risk of sacral injury increased by 1.89 times and 3.23 times when the therapeutic dose (TD) of a fibroid was >500 KJ compared with that of a fibroid with TD= 250-500 KJ and <250 KJ. CONCLUSION: A distance of 10 mm or less and a TD of >500 KJ were significantly correlated with sacral injury. The distance from the fibroid's dorsal side to the sacrum and the TD were the main causes of injury to the sacrum. A distance of 10 mm or less and a TD of >500 KJ carried higher injury risks, while a distance of 21-30 mm and a TD of <250 KJ were the most appropriate circumstances to reduce the risk of sacral injury.

Clinical efficacy and re-pregnancy outcomes of patients with previous cesarean scar pregnancy treated with either high-intensity focused ultrasound or uterine artery embolization before ultrasound-guided dilatation and curettage: a retrospective cohort study.

BACKGROUND: Cesarean scar pregnancy (CSP) treated with either high-intensity focused ultrasound ablation (HIFU-a) or uterine artery embolization (UAE) combined with ultrasound-guided dilation and curettage (USg-D&C) was effective. However, there is insufficient comparative research evidence on clinical efficacy and subsequent pregnancy outcomes after previous CSP treatment. This study aims to investigate the efficacy, safety, and subsequent pregnancy outcomes of HIFU-a compared to UAE before USg-D&C for the treatment of CSP. METHODS: Between January 2016 and July 2020, a total of 272 patients received the pretreatment with HIFU-a or UAE(HIFU-a group: n = 118; UAE group: n = 154). The clinical characteristics, treatment success rate, postoperative pregnancy rate and outcome of the two groups were compared and analyzed. RESULTS: The demographic characteristics of the two groups were similar. After pretreatment, the adverse events rate of HIFU-a group was lower than that of UAE group (10.40% (16/154) vs. 40.70% (48/118), P = 0.00). All patients received the USg-D&C. The HIFU-a group was of less intraoperative blood loss (10.00 (5.00-20.00) vs. 12.50 (5.00-30.00) ml, P = 0.03). There was no statistically significant difference between the two groups in success rates. However, the HIFU-a group was of a shorter duration of postoperative vaginal bleeding (12.00 (9.00-13.00) vs. 14.00 (12.00-15.00) days, P = 0.00). There was no significant difference between the two groups in terms of subsequent pregnancy rates (P = 0.317). However, the recurrent CSP (rCSP) rate in the HIFU-a group was lower than that in the UAE group (7.70% (6/78) vs. 19.70%(13/66), P = 0.03). CONCLUSIONS: CSP treated with either HIFU-a or UAE combined with USg-D&C was safe and effective. Although no significant difference was found in the subsequent pregnancy outcomes of the two groups, the rCSP was more common in the UAE group. So, we recommend HIFU-a combined with USg-D&C treatment modality.

Comparison efficacy of ultrasound-guided HIFU for adenomyosis-associated dysmenorrhea with different signal intensity on T2-weighted MR imaging.

AIM: To compare the therapeutic efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) in the treatment of adenomyosis with different signal intensity (SI) on T2-weighted images (T2WI). METHODS: A total of 299 adenomyosis patients who underwent HIFU and completed a one-year follow-up were retrospectively reviewed. Based on the SI values of adenomyosis relative to myometrium and endometrium on T2WI MRI, the patients were classified into three groups: the hypointense adenomyosis (Hypo-AM) group, the isointense adenomyosis (Iso-AM) group, and the hyperintense adenomyosis (Hyper-AM) group. The non-perfused volume ratio (NPVr) and relief of dysmenorrhea were used to assess the therapeutic efficacy. Optimal cutpoints (CPs) of NPVr were determined using the postoperative dysmenorrhea score as an anchor. Logistic regression analysis was used to test the relationship between the NPVr and SI. RESULTS: The clinical effectiveness rate was significantly lower in the Hyper-AM group than in the Hypo-AM and Iso-AM groups (P < 0.05 for both). The NPVr in the Hypo-AM and Iso-AM groups were significantly higher than that in the Hyper-AM group (P < 0.05 for both). The optimal CP was 54.0% for NPVr. Logistic regression analysis showed that the SI on T2WI was an effect factor for NPVr (P < 0.05), and the probability of NPVr ≥54.0% decreased continuously as the SI of adenomyosis increased. CONCLUSIONS: The NPVr of 54.0% has a clinically significant impact on dysmenorrhea scores in patients. The efficiency of the Hypo-AM and Iso-AM was better than that of the Hyper-AM.

The effectiveness of single ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation in managing placenta accreta spectrum (PAS) disorder.

OBJECTIVE: To evaluate the feasibility and effectiveness of single ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation in managing placenta accreta spectrum (PAS) disorder. MATERIALS AND METHODS: We retrospectively analyzed 40 PAS patients between April 2017 and October 2021. All the patients received one session of HIFU treatment. Regular follow-up was done after HIFU treatment until normal menstruation returned and placental tissue disappeared. The patient's reproductive-related outcomes were obtained through telephone interviews. RESULTS: The median follow-up time for the 40 patients was 30.50 (15.75-44.00) months and the mean placental tissue elimination time was 45.29 ± 33.32 days. The mean duration of bloody lochia was 13.43 ± 10.01 days, with no incidences of severe bleeding. Notably, Linear regression analysis showed that the residual placenta volume before HIFU was a factor affecting the duration of bloody lochia after HIFU (R2 = 0.284, B = 0.062, P = 0.000). The normal menstrual return time was 58.71 ± 31.14 days. One (2.50%) patient developed an infection. Two (5.00%) patients were subjected to ultrasound-guided suction curettage for persistent vaginal discharge for more than one month without infection. Notably, 7 of the 18 patients who expressed reproductive plans became pregnant during the 4 to 53 months of follow-up without placental abnormalities. The remaining 11 patients were on contraceptives. CONCLUSIONS: Single HIFU is an effective treatment option for managing PAS. However, future studies on further treatment strategies to reduce complications and promote patient recovery after HIFU ablation are desirable.

Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells.

Cholesterol dependence is an essential characteristic of pancreatic ductal adenocarcinoma (PDAC). Cholesterol 25-hydroxylase (CH25H) catalyzes monooxygenation of cholesterol into 25-hydroxycholesterol, which is implicated in inhibiting cholesterol biosynthesis and in cholesterol depletion. Here, we show that, within PDAC cells, accumulation of cholesterol was facilitated by the loss of CH25H. Methylation of the CH25H gene and decreased levels of CH25H expression occurred in human pancreatic cancers and was associated with poor prognosis. Knockout of Ch25h in mice accelerated progression of Kras-driven pancreatic intraepithelial neoplasia. Conversely, restoration of CH25H expression in human and mouse PDAC cells decreased their viability under conditions of cholesterol deficit, and decelerated tumor growth in immune competent hosts. Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Re-expression of CH25H in PDAC cells combined with immune checkpoint inhibitors notably inhibited tumor growth. We discuss additional benefits that PDAC cells might gain from inactivation of CH25H and the potential translational importance of these findings for therapeutic approaches to PDAC. IMPLICATIONS: Loss of CH25H by pancreatic cancer cells may stimulate tumor progression and interfere with immunotherapies.

Tumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer.

Activities of dendritic cells (DCs) that present tumor antigens are often suppressed in tumors. Here we report that this suppression is induced by tumor microenvironment-derived factors, which activate the activating transcription factor-3 (ATF3) transcription factor and downregulate cholesterol 25-hydroxylase (CH25H). Loss of CH25H in antigen presenting cells isolated from human lung tumors is associated with tumor growth and lung cancer progression. Accordingly, mice lacking CH25H in DCs exhibit an accelerated tumor growth, decreased infiltration and impaired activation of intratumoral CD8+ T cells. These mice do not establish measurable long-term immunity against malignant cells that undergo chemotherapy-induced immunogenic cell death. Mechanistically, downregulation of CH25H stimulates membrane fusion between endo-phagosomes and lysosomes, accelerates lysosomal degradation and restricts cross-presentation of tumor antigens in the intratumoral DCs. Administration of STING agonist MSA-2 reduces the lysosomal activity in DCs, restores antigen cross presentation, and increases therapeutic efficacy of PD-1 blockade against tumour challenge in a CH25H-dependent manner. These studies highlight the importance of downregulation of CH25H in DCs for tumor immune evasion and resistance to therapy.

Factors influencing treatment decisions in HIFU treatment of adenomyosis: A retrospective study.

Objective: To explore the influencing factors of decision-making in patients with adenomyosis, who are receiving high-intensity focused ultrasound (HIFU) treatment. Methods: A total of 776 patients with adenomyosis were enrolled into HIFU group (241 cases) and hysterectomy group (535 cases) according to the treatment methods. The general data, clinical symptoms, marital and childbearing history, and economic status were compared between the two groups, and factors with P < 0.05 were introduced into multivariate logistic regression analysis to determine the determinants of patients choosing HIFU. Results: The average age of the patients in the HIFU group was 39.1 ± 5.2 years, which was lower than that in the hysterectomy group, which was 45.1 ± 3.9 years (P < 0.05). The basic medical insurance for urban workers in the HIFU group was more than the hysterectomy group (P < 0.05). 95.9% of the hysterectomy group had no desire to have children, compared to 60.6% of the HIFU group, the difference was significant (P < 0.05). The treatment costs of HIFU group were significantly lower than that of hysterectomy group (P < 0.05). The main symptoms of the two groups were dysmenorrhea, menorrhagia, and secondary anemia. The results of multivariate logistic regression analysis showed that 31-40 years old, fertility desire, dysmenorrhea, menorrhagia, anemia and dizziness and fatigue were the influencing factors for the decision-making of HIFU for patients with adenomyosis. Conclusion: 31-40 years old, fertility desire, dysmenorrhea, menorrhagia, anemia and dizziness and fatigue were the influencing factors for patients to choose HIFU treatment. HIFU therapy has emerged as a new option for patients with adenomyosis as an alternative to hysterectomy.