Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

The cognitive impairment of diabetes mellitus type 2(T2DM)is closely related to neurovascular coupling(NVC)changes,but the exact mechanism remains unclear.Functional MRI(fMRI)technology were able to jointly analyze NVC changes of T2DM,providing new ideas for revealing the mechanism of cognitive dysfunction caused by T2DM.The progresses of fMRI for exploring NVC changes in T2DM were reviewed in this article.

Objective:To explore the mediating role of kinesiophobia in the relationship between illness perception and cardiac rehabilitation willingness among patients with coronary heart disease.Methods:Using the convenient sampling method, a total of 255 patients with coronary heart disease who were admitted to Cardiovascular Department of the Second Affiliated Hospital of Chongqing Medical University from June to September 2022 were selected as the research objects. The survey was conducted using a general information questionnaire, Chinese version of the Tampa Scale for Kinesiophobia Heart (TSK-Heart-C) , Heart Rehabilitation Scale and Chinese version of Brief Illness Perception Questionnaire.Results:The total score of TSK-Heart-C in 255 patients with coronary heart disease was (38.53±9.27) , the total score of Heart Rehabilitation Scale was (49.90±12.53) , and the total score of Chinese version of Brief Illness Perception Questionnaire was (53.04±15.90) . Disease perception had a direct effect on heart rehabilitation willingness (β=-0.378, P<0.01) , kinesiophobia played a mediating role between illness perception and heart rehabilitation willingness (β=-0.254, P<0.01) , and the mediating effect accounted for 40.19% of the total effect. Conclusions:Kinesiophobia is a mediating variable between cardiac rehabilitation willingness and illness perception. Medical staff should pay attention to the level of kinesiophobia in patients with coronary heart disease, provide correct health education, improve patients' correct understanding and compliance with the disease, take correct cardiac rehabilitation measures and effectively improve quality of life of patients.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Objective:To explore the psychological status of female patients with mandibular angle hypertrophy before and after receiving mandibular angle osteotomy (MAO) using psychological measurement methods.Methods:The study included 36 female patients (age ranged 18-35 years, with mean age of 23 years) who underwent bilateral mandibular angle osteotomy at the Department of Burns and Plastic Surgery, Naval Medical University. Symptom Checklist-90 (SCL-90), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess the patients′ psychological status before and after surgery. SPSS 18.0 was used to compare the preoperative and postoperative data with the national norms.Results:According to the SCL-90 questionnaire, the scores of the six factors, including obsessive-compulsive symptoms (2.24±0.43 vs. 1.62±0.58, P<0.01), interpersonal sensitivity (1.85±0.46 vs. 1.65±0.61, P=0.02), depression (1.91±0.43 vs. 1.50±0.59, P<0.01), anxiety (1.75±0.42 vs. 1.39±0.43, P<0.01), hostility (1.86±0.45 vs. 1.46±0.55, P<0.01), and paranoia (2.18±0.46 vs. 1.43±0.57, P<0.01) of patients before surgery were significantly higher than the national norms. One month after surgery, there was a significant improvement in SAS and SDS scores compared to preoperative scores ( t=8.0, 10.4, P<0.01). The SAS score decreased from 43.0±9.8 to 37.5±6.8, and the SDS score decreased from 47.1±10.6 to 39.4±7.5. There was no statistically significant difference in the depression and anxiety indices of SCL-90 compared to the national norms ( P>0.05). Conclusions:Mandibular angle osteotomy significantly improves the psychological health of female patients with mandibular angle hypertrophy and can alleviate the symptoms of anxiety and depression.

INTRODUCTION: Fear of cancer recurrence (FCR) among cancer survivors is a persistent and distressing psychosocial concern that affects recovery and quality of life. The prevalence of FCR in Singapore is unknown. This cross-sectional study was designed to examine FCR and identify factors associated with FCR in mixed-cancer survivors locally. METHODS: Cancer survivors in remission (n = 404) were assessed for: FCR using the Fear of Cancer Recurrence Inventory (FCRI); emotional distress using the Hospital Anxiety and Depression Scale; and quality of life using the World Health Organization Quality of Life-BREF. Clinical and severe/pathological FCR was determined based on the severity scale of FCRI, known as FCRI-Short Form. Multivariate logistic regression was performed to examine factors associated with FCR. RESULTS: The mean score on the FCRI was 59.5 ± 30.4. 43.6% of cancer survivors had clinical FCR and 32.1% had severe/pathological FCR. Younger age (odds ratio [OR] 0.952, 95% confidence interval [CI] 0.911-0.995, p < 0.05), higher educational status (OR 2.55, 95% CI 1.15-5.65, p < 0.05) and higher levels of emotional distress (OR 1.17, 95% CI 1.10-1.24, p < 0.001) were significantly associated with severe/pathological levels of FCR. CONCLUSION The present study is the first to determine levels of FCR among cancer survivors in Singapore. While the total FCR scores were similar to those of international studies, severe/pathological levels of FCR were found to be four times higher. These findings highlight a problem that is not widely recognised or acknowledged, but which deserves greater attention.

Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.