In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To study the factors influencing the blood concentration of caspofungin(CPFG),construct a prediction model,and validate the predictive effect of the model,so as to provide reference for the individualised dosing of patients with fungal infections in haematology.Methods Seventy-five patients admitted to the Department of Haematology,General Hospital of Tianjin Medical University,who were treated with CPFG for antifungal therapy during the period of March 2021 to June 2022 were selected as the study subjects,and CPFG blood concentration monitoring was carried out to explore the influencing factors of CPFG blood concentration and to construct a prediction model accordingly.Hosmer-Lemeshow(H-L)was used to test the goodness-of-fit of the model,and another 30 patients were selected as the verification group,and the predictive effect of the model was verified by the receiver's operating characteristics(ROC)curve.Results The mean blood concentrations of the patients at 0.5,9 and 24 h were(12.54±4.38),(6.80±2.76),(4.13±2.16)μg·mL-1,and the mean AUC0-24h were(152.05±57.60)μg·mL-1·h.AUC0-24h was lower than the reference value(98 μg·mL-1·h)in two patients.The results of correlation analysis showed that gender showed a correlation with 0.5 h blood concentration(P＜0.05),and there was no correlation with the rest of the two time points blood concentration and AUC0-24h(P＞0.05).Body weight and albumin(Alb)concentration showed correlation with 0.5,9,24 h blood drug concentration and AUC0-24 h(P＜0.05),and the rest of the indicators showed no correlation with blood drug concentration and AUC0_24h at each time point(P＞0.05).The results of multifactorial analysis showed that the factors influencing the patients'0.5 h blood concentration were gender,Alb concentration and body weight,and the factors influencing the 9 and 24 h blood concentration and AUC0-24h were Alb concentration and body weight(P＜0.05).Correlation analysis showed that the daily dose was positively correlated with the plasma concentration of CPFG at 0.5,9 and 24 h and AUC0-24h(P＜0.05).The results of multivariate analysis showed that the daily dose was also one of the influencing factors of the plasma concentration of CPFG(P＜0.05).ROC curve shows that the model has good prediction ability.Conclusion Body weight and Alb are significantly associated with CPFG blood concentrations and area under the drug-time curve,which can be used as a basis for preventive risk avoidance.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Acute myocardial infraction(AMI)has now become a threat to human health worldwide.Therefore,it is urgent to construct the standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI.The Intensive Care Unit(ICU)team of the Second Clinical Medical School of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)has taken up the mission of exploring the prevention and treatment of AMI with traditional Chinese medicine and promoting and the construction of the diagnosis and treatment system of integrated traditional Chinese and western medicine for AMI.The team pioneered the trinity mode of'saving heart,treating heart and nourishing heart'for AMI,focusing on the construction of standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI,creating the key technology system of Yiqi Huoxue Huatan method(the therapy mainly for replenishing qi,activating blood and dissolving phlegm)for AMI and putting it into the practice,which highlighted the achievements in the construction of the standardized platform.

Objective:To identify the types of fear of progression in patients after percutaneous coronary intervention (PCI) based on latent profile analysis, and to explore the influencing factors of different types.Methods:Cross-sectional survey method was used to select the patients with coronary heart disease and underwent PCI in Anhui Public Health Clinical Center from April to December 2023 as the research object. The general information questionnaire, Fear of Progression Questionnaire-Short Form, Ruminative Response Scale and Brief Illness Perception Questionnaire were used to investigate them. Mplus8.3 software was used to construct the latent profile model.Results:A total of 240 patients with complete data were enrolled, including 176 males and 64 females, aged 28-84 (62.94 ± 11.20) years. The results of latent profile analysis showed that the fear of progression of patients after PCI could be divided into three latent categories: There were 59 cases (24.6%) in the low fear group, 111 cases (46.3%) in the medium fear group, and 70 cases (29.1%) in the high fear-worried family group. The results of multiple logistic regression analysis showed that compared with the low fear group, the probability of having primary school education or below was higher in the medium fear group ( OR=4.054, 95% CI 1.370-11.996) and the high fear-worry family group ( OR=5.996, 95% CI 1.562-23.014), secondary school was more likely in the moderate fear group ( OR=3.096, 95% CI 1.104-8.682, all P<0.05);Living in rural areas were more likely to be in the moderate fear group ( OR=2.587, 95% CI 1.187-5.637) and the high few-worry family group ( OR=6.958, 95% CI 2.567-18.856, all P<0.05); The probability of the first interventional therapy was higher in the moderate fear group ( OR=2.496, 95% CI 1.107-5.630) and the high fear-worry family group ( OR=4.924, 95% CI=1.809-13.402, all P<0.05). In addition, compared with the low fear group, patients with higher rumination were more likely to belong to the high few-worry family working group ( OR=1.130, 95% CI 1.055-1.210, P<0.05);Moderate fear group ( OR=1.181, 95% CI 1.046-1.334) and high fear family working group ( OR=1.349, 95% CI 1.164-1.562, all P<0.05) had a higher level of illness perception. Conclusions:There is significant heterogeneity in the fear of progression among patients after PCI. Medical staff can implement precise intervention according to the potential category characteristics of patients′ fear of progression, so as to reduce the level of fear of disease progression.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Mesenchymal stem cells (MSC) possess unique immunomodulatory properties and have enormous potential in the treatment of graft-versus-host disease (GVHD). However,the low implantation and survival rates of MSC in vivo,coupled with their weak immunosuppressive functions,have resulted in unstable clinical efficacy in the treatment of GVHD. Preconditioning of MSC with hypoxia,active molecules and gene modification can enhance the function of MSC and improve the implantation rate,survival rate and therapeutic effect of MSC. This review summarized the strategies for enhancing the efficacy of MSC in the treatment of hematopoietic stem cell transplantation complicated with GVHD in recent years,aiming to provide new strategies for optimizing the application of MSC in the prevention and treatment of GVHD.

Objective:To analyze the expression levels and clinical significance of interferon (IFN)-α/β in the renal cortex and serum of children with lupus nephritis (LN).Methods:A total of 32 children with LN diagnosed in the pediatric nephrology department of the Second Xiangya Hospital of Central South University from December 2017 to September 2020 were selected as the study subjects (LN group). The normal kidney control group consisted of 3 normal kidney transplant volunteers who underwent biopsy of kidney tissue (normal kidney control group), while 14 healthy children who underwent physical examination were collected as the normal control group. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), LN patients were divided into mild activity group ( n=8), moderate activity group ( n=9), and severe activity group ( n=15). According to the International Society of Nephrology/Society of Nephrology (ISN/RPS) 2003 LN classification criteria, pathological classification was performed (3 cases in the mild pathological damage group, 8 cases in the moderate pathological damage group, and 11 cases in the severe pathological damage group); Immunohistochemistry was used to detect the expression and distribution of IFN-α/β in glomeruli and renal interstitium; Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of IFN-α/β in serum samples and analyze its correlation with the pathological classification and disease activity of LN patients. Results:The serum and renal cortex IFN-α/β levels in the LN group were higher than those in the normal control group and normal kidney control group, respectively (all P<0.05). The average level of serum IFN-α/β in the heavy activity group was higher than that in the light and moderate activity groups (all P<0.05). The serum and renal cortex IFN-α/β levels in the severe pathological damage group were significantly higher than those in the mild and moderate pathological damage groups (all P<0.05). Conclusions:IFN-α/β in the renal cortex is closely related to renal injury in LN; Serum IFN-α/β can assist in evaluating the disease activity level of LN to a certain extent.

Objective To explore the effect of stereotactic hematoma puncture aspiration (SHPS) combined with edaravone in the treatment of patients with cerebral hemorrhage in the Neurosurgery Intensive Care Unit (NICU). Methods A total of 98 patients with cerebral hemorrhage in NICU were divided into experimental group and control group by drawing lots, with 49 cases in each group. The control group was treated with SHPS and conventional therapy, while the experimental group was treated with edaravone on the basis of the control group. The clinical efficacy, the quality of life[the National Institute of Health Stroke Scale (NIHSS) score, the Ability of Daily Living (ADL) score and the China Stroke Scale (CSS) score], glucose and lipid metabolism indicators[jugular venous oxygen saturation (SjvO₂), arteriovenous lactate (A-VLac) and arteriovenous glucose (A-VGlu)], inflammatory factors[interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)]levels as well as incidence of complications were compared between the two groups. Results The total effective rate of the experimental group was 91.84%, which was significantly higher than 77.55% of the control group (P < 0.05). After treatment, the NIHSS score and CSS score of the experimental group were significantly lower than those of the control group, while the ADL score was significantly higher than that of the control group (P < 0.05). After treatment, the SjvO₂ level in the experimental group was significantly higher than that in the control group, while the levels of A-VGlu and A-VLac were significantly lower than those in the control group (P < 0.05). After treatment, the IL-8, IL-6 and TNF-α levels in the experimental group were significantly lower than those in the control group (P < 0.05). The incidence of complications in the experimental group was 12.24%, which was significantly lower than 30.61% in the control group (P < 0.05). Conclusion The combination of SHPS and edaravone can reinforce the clinical efficacy of patients with cerebral hemorrhage in NICU, improve neurological function, and reduce the incidence of postoperative complications.