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.

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).

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.

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.

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.

Tolerance and efficacy of HIFU ablation for uterine fibroids NPVR ≥ 90%: a nested case-control study.

OBJECTIVE: To investigate the tolerance and efficacy of HIFU ablation for uterine fibroids with a non-perfused volume ratio (NPVR) ≥ 90%. METHODS: A prospective cohort study of 2411 patients from 20 clinical centers was available. Contrast-enhanced MRI was used to assess the non-perfused volume ratio (NPVR). The International Society of Interventional Radiotherapy (SIR) complication grading system was used as the tolerance index. Uterine Fibroids-related Symptoms-Quality of Life (UFS-QoL) was used to evaluate the efficacy. RESULTS: A total of 1352 patients underwent USgHIFU ablation treatment enrolled, NPVR was median 91.9% (IQR, 81.4%,100.0%). There was 761 case (56.3%) in the NPVR ≥ 90% group in which 17.5% case experienced SIR-B abdominal pain, 591 cases (43.7%) in NPVR < 90% group in which 9.3% case had SIR-B abdominal pain. There were statistically differences in the improvement degree of UFS at 12 months among the four subgroups (NPVR < 70%, 70%-80%, 80%-90%, 90%-100%) (all p < 0.05). CONCLUSIONS: Patients with NPVR ≥ 90% had a higher incidence of SIR-B lower abdominal pain. NPVR was positively correlated with the degree of symptom relief at 12 months, and NPVR ≥ 90% was more likely to obtain better clinical symptom relief.

Potential Application of Low-Intensity Pulsed Ultrasound in Delaying Aging for Mice.

INTRODUCTION: The low-intensity pulsed ultrasound (LIPUS) is one of the popular treatment modalities allowing to boost the proliferation, differentiation, and migratory activity of cells, which might be a powerful strategy for anti-aging. Seeking a novel setup for LIPUS would benefit the development of ultrasound therapeutics. METHODS: Here, we proposed a novel underwater exposure setup of LIPUS. C57BL/6 mice were reared in the designated age-groups, which consisted of a middle-aged group (12-14 months) and an old-age group (20-23 months). The age-related changes of body composition, imbalance of energy supply and demand, imbalance of signal network maintaining internal stability, and representative phenotypes of neurodegeneration and neuroplasticity with the presence and absence of underwater LIPUS in middle-aged and aged groups were evaluated. RESULTS: The results showed that there were obvious aging changes, imbalance of energy supply and demand, imbalance of signal network maintaining homeostasis, neurodegeneration, and damage of neural plasticity in the middle-aged and aged group with or without the LIPUS. Although middle-aged group and aged group responded differently to LIPUS, they mostly generated positive results in relieving bone loss, improving ovarian structure, regulated immune system, and enhanced endurance ability, which should have declined over age. DISCUSSION: These findings indicate that underwater extracorporeal LIPUS exposure could be employed as single or combined anti-aging strategies that generated positive outcomes against the process of aging.

Adaptability and clinical applicability of UFS-QoL in Chinese women with uterine fibroid.

OBJECTIVE: To demonstrate the applicability and adaptability of uterine fibroid symptoms and quality of life (UFS-QoL) in assessing the efficacy of treatment in Chinese populations. METHODS: This is a secondary analysis of a prospective cohort study involving 20 Chinese hospitals and 2,411 Chinese women with fibroids. Patients completed UFS-QoL and short form-36 (SF-36) at pre-surgery, 6-month and 12-month post-treatments. Internal consistency of the quality of life assessed by the UFS-QoL questionnaire using Cronbach's α coefficient (α). Principal axis factor analysis with orthogonal rotation was established to investigate relationships between items and subscales. Concurrent validity refers to the Spearman's correlation estimate of the correlation between UFS-QoL and SF-36. Using effect size and standardized response mean, the ability to detect change was evaluated by comparing pre- and post-6-month and post-12-month treatment scores. RESULTS: Exploratory factor analysis yielded six subscales (concern, activities, energy/mood, control, self-consciousness, and sexual function) with eigenvalues > 1 in UFS-QoL. A 63.61% total variance was explained by the test items. Ceiling effects of self-consciousness and sexual functioning subscales from UFS-QoL were > 15%. UFS-QoL showed a positive and moderate correlation with SF-36 to establish good concurrent validity. And showed good consistency reliability (Cronbach α > 0.7 in all subscales), ability to detect change after treatment. This excluded self-consciousness (α = 0.56), which demonstrated the lowest effect size (0.38) and standardized response means (0.38) 6- and 12-months post-treatment. CONCLUSIONS: Symptom severity, activity, and mood subscales of the Chinese UFS-QoL were valid and reliable. However, the self-consciousness domain needs further investigation on cultural adaptation, such as cognitive debriefing for how Chinese interpret these questions.

The role of anti-tumor immunity of focused ultrasound for the malignancies: depended on the different ablation categories.

Improving anti-tumor immunity has promising outcomes in eradicating malignant tumors. Tumor cells can escape from immune surveillance and killing; therefore, various strategies are continuously developing to inhibit immune escape. Focused ultrasound (FUS) has recently emerged to play an important role in immune modulation. After FUS therapy, various tumor antigens and related signals are released. The non-thermal effect of FUS strengthens the blood and lymph circulation, increases cell permeability, and helps in crossing the physical barrier like the blood-brain barrier and blood-tumor barrier. However, the different ablation of FUS is proposed to have a different anti-tumor immune effect. Therefore, we categorized the FUS ablation into thermal and non-thermal ablation and summarized possible anti-tumor immunity mechanisms.

Doppler Imaging Assessment of Changes of Blood Flow in Adenomyosis After Higher-Dose Oxytocin: A Randomized Controlled Trial.

OBJECTIVES: To assess the changes of blood flow in adenomyosis (AM) after higher-dose oxytocin (OT) in different doses, and to evaluate the safety for patients. METHODS: A total of 124 patients with AM were randomly divided into 4 groups with continuous intravenous infusion of OT as 0.06, 0.12, 0.24 and 0.36 U/min, respectively. The changes of arteries of AM before and after intravenous infusion of OT were observed by color Doppler ultrasound. The changes of blood flow volume of the artery of AM before and after intravenous infusion of OT were compared among the 4 groups, and the vital signs and adverse drug reactions were monitored during intravenous drip. RESULTS: During the trial, no severe adverse reactions occurred and the vital signs of all the patients were stable. Among the 4 groups, it was found that there was a significant difference in the change of blood flow volume of blood artery in AM lesions between 0.06 U/min OT group and the other three groups after intravenous drip of OT (P < .05), but there was no significant difference in blood flow volume among the three groups (P > .05), and the difference of adverse drug reactions was statistically significant with the increase of OT dose (P < .05). CONCLUSION: OT can effectively reduce the blood flow volume of AM lesions, and continuous intravenous infusion of 0.12 U/min OT is an appropriate dose that can not only minimize the blood flow volume but also reduce the incidence of adverse drug reactions.

Learning Curve of USgHIFU Ablation for Uterine Fibroids: A Multi-Center Prospective Study.

OBJECTIVES: To verify the stability of high-intensity focused ultrasound (HIFU) technology and the feasibility of training programs with learning curve cumulative summation (LC-CUSUM). METHODS: A total of 12 physicians and 720 cases were equally assigned to the learning group and the control group, with 6 physicians and 360 cases per group. The learning group was treated by physicians without HIFU experience and the control group was treated by experienced physicians. Nonperfused volume (NPV) ratio was assessed by contrast-enhanced magnetic resonance imaging. Technical failure was defined as NPV ratio of uterine fibroids <70% and/or major complication, while <80% was set as a stricter standard of training qualification. LC-CUSUM was used to analyze the learning curve. RESULTS: Physicians with or without HIFU experience in both groups achieved matchable NPV ratios, where a NPV ratio of 92.52% (16.06) was achieved by experienced physicians and 93.82% (16.95) by inexperienced physicians. No major complication was observed. The results of LC-CUSUM analysis showed that, with the standards of the NPV ratio of 70% or 80%, the learning group mastered the technique on the 11th case and the 16th case, respectively, while the control group was stable. CONCLUSIONS: HIFU technology stayed stable in operation, with good safety and sound effectiveness, and was easy to learn. NPV ratio of 70% was considered as an appropriate indicator of training qualification. HIFU has remarkable prospects in achieving a NPV ratio of ≥80% without safety being compromised.

Potential Application of Low-Intensity Focused Ultrasound in Rapidly Relieving Delayed-Onset Muscle Soreness Induced by High-Intensity Exercise.

OBJECTIVES: To evaluate the efficacy of low-intensity focused ultrasound (LIFU) treatment on rapid relief of delayed-onset muscle soreness (DOMS) triggered by high-intensity exercise. METHODS: A total of 16 healthy male college students were randomly divided into two groups: the LIFU group (n = 8) and the Sham group (n = 8). After the exercise protocol, the LIFU group received treatment, which parameters included that the power output was 2.5 W/cm2 , the frequency was 1 MHz, and the treating time was 20 minutes. The Sham group was treated with LIFU without energy output. Visual analog scale was used to evaluate the level of DOMS in every participant. The activities of plasma creatine kinase, lactate dehydrogenase, and the plasma concentration were measured by spectrophotometry. Tumor necrosis factor-α and interleukin-6 of serum were analyzed by enzyme-linked immunosorbent assay. RESULTS: The visual analog scale of quadriceps femoris and/or calf muscles in the LIFU group decreased significantly at 24 hours (P < 0.01) and 48 hours (P < .01) after the exercise protocol. Both the accumulation of lactic acid (P < .01) in muscle and the activity of lactate dehydrogenase (P < .01) reduced immediately after LIFU treatment. The activities of tumor necrosis factor-α and interleukin-6 24 hours lowered in the LIFU group (P < .01). CONCLUSIONS: LIFU treatment could relieve muscle soreness rapidly and effectively in the early stages of DOMS. The application of LIFU may provide a potential strategy for clinical treatment for DOMS.

Gene expression profiling for the diagnosis of multiple primary malignant tumors.

BACKGROUND: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. METHODS: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. RESULTS: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins. CONCLUSIONS: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

Systematic review and trial sequential analysis of high-intensity focused ultrasound combined with chemotherapy versus chemotherapy in the treatment of unresectable pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to compare the survival benefits between high-intensity focused ultrasound (HIFU) combined with chemotherapy and chemotherapy alone in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). METHODS: All randomized clinical trials (RCTs) and observational studies were systematically searched through the databases of PubMed, EMBASE, CNKi and CQVIP up to December 2020. Case reports, case series and nonsystematic reviews were excluded. A meta-analysis was conducted to generate combined hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). RESULTS: Seven trials, containing a total of 992 patients, were included in this study. The meta-analysis showed that a combination of HIFU and chemotherapy increased overall survival compared with chemotherapy alone, with a pooled HR of 0.40 (95% confidence interval [CI], 0.28-0.58). The combined therapy group had a significant advantage in 1-year survival rate (OR: 0.35, 95% CI: 0.22-0.53, p = 0.00). The trial sequence analysis (TSA) showed that there were enough trials to control for random errors. CONCLUSION: Our analysis suggests that HIFU combined with chemotherapy intravenously will prolong survival for unresectable PDAC patients. The TSA showed that the survival benefit of combined therapy was definitive and there was no need to expand the sample size for repetitive exploration.

The safety and ablation efficacy of ultrasound-guided high-intensity focused ultrasound ablation for desmoid tumors.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs). METHOD: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure. RESULTS: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment. CONCLUSION: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.

Effects of Low-Intensity Pulsed Ultrasound on Myelosuppression of Rats Induced by Chemotherapy Drugs With Cell Cycle Specificity.

OBJECTIVES: To explore the ameliorating effects of low-intensity pulsed ultrasound (LIPUS) on Sprague Dawley rat myelosuppression induced by cell cycle specificity drugs (docetaxel, mitotic phase sensitive; and etoposide, gap 2 phase sensitive). METHODS: Rats were respectively administered docetaxel (100 mg/kg) or etoposide (110 mg/kg) by intraperitoneal injection for 4 consecutive days. Then the rats were divided randomly into a LIPUS group and a non-LIPUS group. In the LIPUS group, the right femoral metaphysis of rats was treated by LIPUS (acoustic intensity, 200 mW/cm2 ; frequency, 0.3 MHz; and duty cycle, 20%) for 20 minutes on 7 consecutive days from day 5. The rats of the non-LIPUS group were treated without ultrasound output. A blood cell count, an enzyme-linked immunosorbent assay, a real-time quantitative polymerase chain reaction, and hematoxylin-eosin staining were applied to detect the results. RESULTS: Low-intensity pulsed ultrasound significantly promoted the counts of bone marrow nucleated cells, white blood cells, immunoglobulin A (IgA), IgG, granulocyte colony-stimulating factor, stem cell factor, and intercellular cell adhesion molecule 1 and reduced the counts of vascular cell adhesion molecule 1 whether in the docetaxel or etoposide group (P < .05). Low-intensity pulsed ultrasound only increased the expression level of IgM in the docetaxel group but decreased the level of interleukin 6 in the etoposide group (P < .05). CONCLUSIONS: Low-intensity pulsed ultrasound has potential to be a noninvasive treatment for myelosuppression caused by different cell cycle-sensitive chemotherapy drugs.