Functional mechanism and clinical implications of LINC00339 in delayed fracture healing.

OBJECTIVE: Delayed fracture healing is a common complication of fractures that significantly impacts human health. This study aimed to explore the role of LINC00339 (lncRNA) in delayed fracture healing to provide new directions for its treatment. METHODS: This study included 82 patients with fractures healing in a normal manner and 90 patients experiencing delayed fracture healing. Levels of LINC00339, miR-16-5p, and osteogenic marker-related mRNAs were measured using RT-qPCR. The predictive potential of LINC00339 for delayed fracture healing was validated using ROC curve analysis. The interaction between LINC00339 and miR-16-5p was validated using dual-luciferase reporter assays and RIP experiments. CCK-8 was used to assess cell proliferation, and apoptosis rates were measured by flow cytometry. RESULTS: LINC00339 was significantly upregulated in delayed fracture healing patients and exhibited strong predictive ability for this condition. Overexpression of LINC00339 inhibited osteoblast proliferation, promoted apoptosis, and reduced mRNA levels of osteogenic markers (P < 0.05). miR-16-5p was recognized as a target mRNA of LINC00339, with LINC00339 exerting negative regulation on miR-16-5p, while overexpression of miR-16-5p mitigated the inhibitory effects of LINC00339 on fracture healing (P < 0.05). CONCLUSION: This research indicated that LINC00339 may serve as a diagnostic marker for delayed fracture healing and revealed the function of the LINC00339/miR-16-5p axis on fracture healing by regulating osteoblasts.

Joint use of population pharmacokinetics and machine learning for prediction of valproic acid plasma concentration in elderly epileptic patients.

BACKGROUND: Valproic acid (VPA) is a commonly used broad-spectrum antiepileptic drug. For elderly epileptic patients, VPA plasma concentrations have a considerable variation. We aim to establish a prediction model via a combination of machine learning and population pharmacokinetics (PPK) for VPA plasma concentration. METHODS: A retrospective study was performed incorporating 43 variables, including PPK parameters. Recursive Feature Elimination with Cross-Validation was used for feature selection. Multiple algorithms were employed for ensemble model, and the model was interpreted by Shapley Additive exPlanations. RESULTS: The inclusion of PPK parameters significantly enhances the performance of individual algorithm model. The composition of categorical boosting, light gradient boosting machine, and random forest (7:2:1) with the highest R2 (0.74) was determined as the ensemble model. The model included 11 variables after feature selection, of which the predictive performance was comparable to the model that incorporated all variables. CONCLUSIONS: Our model was specifically tailored for elderly epileptic patients, providing an efficient and cost-effective approach to predict VPA plasma concentration. The model combined classical PPK with machine learning, and underwent optimization through feature selection and algorithm integration. Our model can serve as a fundamental tool for clinicians in determining VPA plasma concentration and individualized dosing regimens accordingly.

Role of atmospheric rivers in shaping long term Arctic moisture variability.

Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.

Extracellular Membrane Vesicles of Escherichia coli Induce Apoptosis of CT26 Colon Carcinoma Cells.

Escherichia coli (E. coli) is commonly utilized as a vehicle for anti-tumor therapy due to its unique tumor-targeting capabilities and ease of engineering modification. To further explore the role of E. coli in tumor treatment, we consider that E. coli outer membrane vesicles (E. coli-OMVs) play a crucial role in the therapeutic process. Firstly, E. coli-OMVs were isolated and partially purified by filtration and ultracentrifugation, and were characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western Blot (WB). The obtained extracellular nanoparticles, containing OMVs, were found to inhibited the growth of CT26 tumor in mice, while the expression of Bax protein was increased and the expression of Bcl-2 protein decreased. In vitro experiments showed that E. coli-OMVs entered CT26 cells and inhibited cell proliferation, invasion and migration. In addition, in the presence of E. coli-OMVs, we observed an increase in apoptosis rate and a decrease in the ratio of Bcl-2/Bax. These data indicate that E. coli-OMVs inhibits the growth of CT26 colon cancer by inducing apoptosis of CT26 cells. These findings propose E. coli-OMVs as a promising therapeutic drug for colorectal cancer (CRC), providing robust support for further research in related fields.

Electronic symptom monitoring after lung cancer surgery: establishing a core set of patient-reported outcomes for surgical oncology care in a longitudinal cohort study.

BACKGROUND: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. MATERIALS AND METHODS: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. RESULTS: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). CONCLUSION: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.

The prognostic genes model of breast cancer drug resistance based on single-cell sequencing analysis and transcriptome analysis.

Breast cancer (BC) represents a multifaceted malignancy, with escalating incidence and mortality rates annually. Chemotherapy stands as an indispensable approach for treating breast cancer, yet drug resistance poses a formidable challenge. Through transcriptome data analysis, we have identified two sets of genes exhibiting differential expression in this context. Furthermore, we have confirmed the overlap between these genes and those associated with exosomes, which were subsequently validated in cell lines. The investigation screened the identified genes to determine prognostic markers for BC and utilized them to formulate a prognostic model. The disparities in prognosis and immunity between the high- and low-risk groups were validated using the test dataset. We have discerned different BC subtypes based on the expression levels of prognostic genes in BC samples. Variations in prognosis, immunity, and drug sensitivity among distinct subtypes were examined. Leveraging data from single-cell sequencing and prognostic gene expression, the AUCell algorithm was employed to score individual cell clusters and analyze the pathways implicated in high-scoring groups. Prognostic genes (CCT4, CXCL13, MTDH, PSMD2, and RAB27A) were subsewoquently validated using RT-qPCR. Consequently, we have established a model for predicting prognosis in breast cancer that hinges on drug resistance and ERGs. Furthermore, we have evaluated the prognostic value of this model. The genes identified as prognostic markers can now serve as a reference for precise treatment of this condition.

Frequency-Domain Robust PCA for Real-Time Monitoring of HIFU Treatment.

High intensity focused ultrasound (HIFU) is a thriving non-invasive technique for thermal ablation of tumors, but significant challenges remain in its real-time monitoring with medical imaging. Ultrasound imaging is one of the main imaging modalities for monitoring HIFU surgery in organs other than the brain, mainly due to its good temporal resolution. However, strong acoustic interference from HIFU irradiation severely obscures the B-mode images and compromises the monitoring. To address this problem, we proposed a frequency-domain robust principal component analysis (FRPCA) method to separate the HIFU interference from the contaminated B-mode images. Ex-vivo and in-vivo experiments were conducted to validate the proposed method based on a clinical HIFU therapy system combined with an ultrasound imaging platform. The performance of the FRPCA method was compared with the conventional notch filtering method. Results demonstrated that the FRPCA method can effectively remove HIFU interference from the B-mode images, which allowed HIFU-induced grayscale changes at the focal region to be recovered. Compared to notch-filtered images, the FRPCA-processed images showed an 8.9% improvement in terms of the structural similarity (SSIM) index to the uncontaminated B-mode images. These findings demonstrate that the FRPCA method presents an effective signal processing framework to remove the strong HIFU acoustic interference, obtains better dynamic visualization in monitoring the HIFU irradiation process, and offers great potential to improve the efficacy and safety of HIFU treatment and other focused ultrasound related applications.

A Comparison of Quality of Life, Cosmesis and Cost-Utility of Open Surgery, Vacuum-Assisted Breast Biopsy and High Intensity Focused Ultrasound for Breast Fibroadenoma.

RATIONALE AND OBJECTIVES: To compare the quality of life (QOL), cosmesis and cost-utility of open surgery (OS), vacuum-assisted breast biopsy (VABB) and high intensity focused ultrasound (HIFU) for fibroadenoma (FA). MATERIALS AND METHODS: A total of 162 patients with 267 FAs were enrolled. Baseline characteristics and treatment information were recorded. Patients were followed up at 3-, 6- and 12-month post-treatment. QOL was evaluated by health survey. Breast cosmesis was evaluated by self-rating survey and Harvard Scale. A decision-analytic model was established and incremental cost was calculated for cost-utility analysis. RESULTS: For QOL evaluation, there was no difference of physical component summary (PCS) score in three groups (P > 0.05), while the mental component summary (MCS) score was significantly higher in HIFU group than the other two groups at 3- and 6-month post-treatment (P < 0.05). The proportion of patients satisfied with breast cosmesis was significantly higher in HIFU group (96.49%) than in VABB group (54.90%) and OS group (49.99%) (P < 0.05). By Harvard Scale, 27.78%, 78.42% and 100.00% of patients were rated as excellent and good in OS group, VABB group and HIFU group, respectively (P < 0.05). To acquire a quality-adjusted life year (QALY), cost of OS, VABB and HIFU was 1034.31 USD, 1776.96 USD and 1277.67 USD, respectively. When compared to OS, incremental cost analysis showed HIFU was cost-effective, while VABB was not. CONCLUSION: OS, VABB and HIFU were all effective and safe for FA, but among these three treatments, HIFU had the best QOL improvement, breast cosmesis and cost-effectiveness.

Giant vesicles form in physiological saline and encapsulate pDNA by the modified electroformation method.

Giant vesicles (GVs) are used to study the structures and functions of cells and cell membranes. Electroformation is the most commonly used method for GV preparation. However, the electroformation of GVs is hindered in highly concentrated ionic solutions, limiting their application as cell models for research under physiological conditions. In this study, giant multilayer vesicles were successfully generated in physiological saline using a modified electroformation device by adding an insulating layer between the two electrode plates. The influence of the electric frequency and strength on the electroformation of GVs in physiological saline was explored, and a possible mechanism for this improvement was assessed. It has been shown that an insulating layer between the two electrodes can improve the electroformation of GVs in physiological saline by increasing the electrical impedance, which is weakened by the saline solution, thereby restoring the reduced effective electric field strength. Furthermore, macromolecular plasmid DNA (pDNA) was successfully encapsulated in the electroformed GVs of the modified device. This modified electroformation method may be useful for generating eukaryotic cell models under physiological conditions.

Long-term outcome and risk factors of reintervention after high intensity focused ultrasound ablation for uterine fibroids: a systematic review and meta-analysis.

OBJECTIVES: To quantify the reintervention rate and analyze the risk factors for reintervention after high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: Eighteen studies were selected from the seven databases. A meta-analysis was applied to synthesize the reintervention rates for fibroids across various follow-up durations. Subgroup-analysis was conducted based on the year of surgery, sample size, guide methods, and non-perfusion volume ratio (NPVR). Signal intensity of T2-weighted imaging (T2WI) was independently evaluated for reintervention risk. RESULTS: The study enrolled 5216 patients with fibroids treated with HIFU. There were 3247, 1239, 1762, and 2535 women reaching reintervention rates of 1% (95% confidence interval (CI): 1-1), 7% (95% CI: 4-11), 19% (95% CI: 11-27), and 29% (95% CI: 14-44) at 12, 24, 36, and 60-month after HIFU. The reintervention rates of patients treated with US-guided HIFU (USgHIFU) were significantly lower than those of patients treated with MR-guided focused ultrasound surgery (MRgFUS). When the NPVR of fibroids was over 50%, the reintervention rates at 12, 36 and 60-month after HIFU were 1% (95% CI: 0.3-2), 5% (95% CI: 3-8), and 15% (95% CI: 9-20). The reintervention risk for hyper-intensity fibroids on T2WI was 3.45 times higher (95% CI: 2.7-4.39) for hypo-/iso-intensity fibroids. CONCLUSION: This meta-analysis showed that the overall reintervention rates after HIFU were acceptable and provided consultative suggestions regarding treatment alternatives for patients with fibroids. Subgroup-analysis revealed that USgHIFU, NPVR ≥ 50%, and hypo-/iso-intensity of fibroids on T2WI were significant factors in reducing reintervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023456094.

Factors associated with thermal injury of abdominal skin in focused ultrasound ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). METHOD: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal-Wallis H. RESULTS: (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242-3.849), abdominal wall thickness (p < .001, OR = 1.042, 95% CI: 1.019-1.067), fundus fibroids (p = .038, OR = 1.790, 95% CI: 1.033-3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p = .022, OR = 1.843, 95% CI: 1.091-3.115), average sonication power (AP) (p = .025, OR = 1.021, 95% CI: 1.003-1.039), and treatment time (TT) (p < .001, OR = 1.017, 95% CI: 1.011-1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p = .002, OR = 0.775, 95% CI: 0.661-0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. CONCLUSIONS: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed.

The impact of Sars-Cov-2 infection on the wound healing of cervical treatment in patients with squamous intraepithelial lesions: a retrospective cohort study.

Objective: SARS-CoV-2 infection has been associated with an increase in inflammatory factors, a weakening of the immune system, and a potentially delay in wound healing following surgery or ablative treatment. In this retrospective cohort study, we aimed to investigate the impact of SARS-CoV-2 infection on wound healing following cervical treatment in patients with squamous intraepithelial lesions (SIL). Method: From November 2022 to February 2023, patients with SIL who underwent cervical ablative treatment or loop electrosurgical excision procedure at the People's Hospital of Guangxi Zhuang Autonomous Region, China, were enrolled in the study. Of these, 29 patients who developed symptoms of SARS-CoV-2 infection and confirmed by an antigen test within one month after cervical treatment were included as experimental group, while the other 31 patients who received cervical treatment after recovering from SARS-CoV-2 infection were included in the control group. The cervical wound condition of all patients was documented using colposcopy immediately and one month after the procedure. Image J software was utilized to analyze the wound healing rate at one month post-treatment, and the wound healing status between two groups was compared. A vaginal discharge examination was performed before and one month after cervical treatment. Results: No significant differences in age, severity, treatment, or time between groups. Experimental group had significantly lower healing rate 83.77(62.04, 97.09) % than control 98.64(97.10, 99.46)%，p < 0.001, and a higher scab non-shedding rate (24.14% vs. 3.22%, p = 0.024). Among patients who were infected with SARS-CoV-2 after undergoing cervical treatment, we observed 5 out of 7 patients (71.43%) contracted SARS-CoV-2 within 2 weeks after cervical treatment. No significant correlation was found between white blood cell count or leukocyte esterase in vaginal discharge and delayed wound healing of the cervix (p = 0.947 and 0.970, respectively). Conclusion: SARS-CoV-2 infection may prolong the healing time of cervical treatment in patients with SIL. To minimize the risk of delayed healing, it's crucial for patients to avoid viral infections such as SARS-CoV-2 within the first month of treatment. Taking necessary precautions to prevent infection is essential for successful cervical treatment outcomes in patients with SIL.

Pregnancy outcomes of adenomyotic patients with primary infertility after high-intensity focused ultrasound treatment.

OBJECTIVE: To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) treatment for adenomyotic patients with primary infertility and to explore the factors that affect the pregnancy outcomes. MATERIALS AND METHODS: Twenty-seven adenomyotic patients with primary infertility who underwent HIFU at HUNAN Provincial Maternal and Child Health Care Hospital, China, between July 2018 and December 2022 were retrospectively reviewed. We evaluated the pregnancy outcomes and analyzed the factors that may affect pregnancy outcomes including time to conception, pregnancy approach, gestational age, delivery mode, neonatal outcomes, and complications during pregnancy and delivery. RESULTS: Among the 27 adenomyotic patients with primary infertility, 10 patients had a total of 11 pregnancies after HIFU treatment. Of these, eight (72%) cases were natural pregnancies and three (23%) were in vitro fertilization (IVF) pregnancies. The median time to conception was 10 (range 4-25) months. There were eight (72%) successful deliveries. The rate of full-term deliveries was 90%. Of the eight live births, four (50%) were born vaginally and four (50%) by cesarean section. No severe complications occurred. The mean birth weight of newborns was 3.1 (range: 2.3-3.9) kg; all newborns developed well without complications during postpartum and breastfeeding. CONCLUSIONS: HIFU treatment for adenomyosis could improve fertility of patients with primary infertility. HIFU is a promising therapeutic approach for patients with adenomyosis and infertility who wish to achieve pregnancy and have live birth deliveries.

Comparison of menstruation recovery after ultrasound-guided suction curettage in patients with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization.

OBJECTIVES: To investigate the menstruation recovery after two therapeutic regimens, high-intensity focused ultrasound (HIFU) or uterine artery embolization (UAE) combined with ultrasound-guided suction curettage, for premenopausal women with cesarean scar pregnancy (CSP). MATERIALS AND METHODS: Seventy patients with CSP treated with HIFU followed by ultrasound-guided suction curettage and 63 patients with CSP treated with UAE followed by ultrasound-guided suction curettage in our hospital were retrospectively reviewed. The treatment parameters and the menstrual blood loss (MBL) volume at 6 months after the two therapeutic regimens were compared between the two groups. RESULTS: There was no significant difference in treatment results between the two groups. With regard to postoperative MBL volume, 5 out of 70 patients in the HIFU group and 22 out of 63 patients in UAE group exhibited a reduction in MBL, respectively. Multivariate logistic regression revealed that hypomenorrhea was more likely to occur in the UAE group than in the HIFU group (UAE group vs. HIFU group; OR 11.328, 95% CI 3.158-55.871; p < 0.001). CONCLUSION: Compared to UAE, HIFU has less influence on postoperative MBL volume, which may be a fertility-sparing option for patients with CSP.

An in vitro and in vivo study on extracorporeal transducer optimization for high-intensity focused ultrasound to improve the safety and efficacy of breast tumor ablation.

OBJECTIVE: To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer. MATERIALS AND METHODS: Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared. RESULTS: The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer. CONCLUSIONS: The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.

Bifidobacterium-derived membrane vesicles inhibit triple-negative breast cancer growth by inducing tumor cell apoptosis.

BACKGROUND: Bacterial outer membrane vesicles have gained increasing attention for its antitumor effect and application in drug delivery. However, the bacterial membrane vesicles (MVs) that are secreted by Gram-positive bacteria are rarely mentioned. Bifidobacterium has a certain anti-tumor effect, but there is a certain risk when injected into human body. Here we investigated the potential of Bifidobacterium-derived membrane vesicles (B-MVs) as therapeutic agents to treat triple-negative breast cancer. METHODS AND RESULTS: Firstly, we discovered that Bifidobacterium can produce B-MVs and isolated them. In vivo, we found that B-MVs can inhibit tumor growth in mice and the mice were in good state. H&E staining displayed extensive apoptotic cells in tumor tissues. Western blotting and immunohistochemistry showed that B-MVs increased the expression of Bax, while decreased the expression of Bcl-2. These results suggested that B-MVs may induce apoptosis of tumor cells in vivo. Furthermore, to further confirm this phenomenon, we conducted experiments in vitro. Hoechst 33,258 staining assay, flow cytometry and western blotting also demonstrated B-MVs promoted cell apoptosis in vitro. CONCLUSIONS: We speculate B-MVs may inhibit tumor growth by inducing tumor cell apoptosis in triple-negative breast cancer, which provided a new direction in the treatment of TNBC.

Recent Advances in Understanding Multi-scale Climate Variability of the Asian Monsoon.

Studies of the multi-scale climate variability of the Asian monsoon are essential to an advanced understanding of the physical processes of the global climate system. In this paper, the progress achieved in this field is systematically reviewed, with a focus on the past several years. The achievements are summarized into the following topics: (1) the onset of the South China Sea summer monsoon; (2) the East Asian summer monsoon; (3) the East Asian winter monsoon; and (4) the Indian summer monsoon. Specifically, new results are highlighted, including the advanced or delayed local monsoon onset tending to be synchronized over the Arabian Sea, Bay of Bengal, Indochina Peninsula, and South China Sea; the basic features of the record-breaking mei-yu in 2020, which have been extensively investigated with an emphasis on the role of multi-scale processes; the recovery of the East Asian winter monsoon intensity after the early 2000s in the presence of continuing greenhouse gas emissions, which is believed to have been dominated by internal climate variability (mostly the Arctic Oscillation); and the accelerated warming over South Asia, which exceeded the tropical Indian Ocean warming, is considered to be the main driver of the Indian summer monsoon rainfall recovery since 1999. A brief summary is provided in the final section along with some further discussion on future research directions regarding our understanding of the Asian monsoon variability.

A Theragnostic HIFU Transducer and System for Inherently Registered Imaging and Therapy.

OBJECTIVE: One big challenge with high intensity focused ultrasound (HIFU) is the difficulty in accurate prediction of focal location due to the complex wave propagation in heterogeneous medium even with imaging guidance. This study aims to overcome this by combining therapy and imaging guidance with one single HIFU transducer using the vibro-acoustography (VA) strategy. METHODS: Based on the VA imaging method, a HIFU transducer consisting of 8 transmitting elements was proposed for therapy planning, treatment and evaluation. Inherent registration between the therapy and imaging created unique spatial consistence in HIFU transducer's focal region in the above three procedures. Performance of this imaging modality was first evaluated through in-vitro phantoms. In-vitro and ex-vivo experiments were then designed to demonstrate the proposed dual-mode system's ability in conducting accurate thermal ablation. RESULTS: Point spread function of the HIFU-converted imaging system had a full wave half maximum of about 1.2 mm in both directions at a transmitting frequency of 1.2 MHz, which outperformed the conventional ultrasound imaging (3.15 MHz) in in-vitro situation. Image contrast was also tested on the in-vitro phantom. Various geometric patterns could be accurately 'burned out' on the testing objects by the proposed system both in vitro and ex vivo. CONCLUSION: Implementation of imaging and therapy with one HIFU transducer in this manner is feasible and it has potential as a novel strategy for addressing the long-standing problem in the HIFU therapy, possibly pushing this non-invasive technique forward towards wider clinical applications.

Focused ultrasound: a novel therapy for improving vaginal microecology in patients with high-risk HPV infection.

OBJECTIVES: To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. MATERIALS AND METHODS: We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. RESULTS: Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). CONCLUSION: FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology.

Temperature-Promoted Giant Unilamellar Vesicle (GUV) Aggregation: A Way of Multicellular Formation.

The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.