Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Dissolvable microneedles(DMNs)offer significant advantages for vaccine delivery,including pain relief,saving drug dose,no contamination of sharp instruments and autonomous operation.The review introduces the materials,fabri-cation processes and physical characteristics of DMNs,focusing on its application in delivering various vaccines,such as influenza vaccines,COVID-19 vaccines,viral hepatitis vaccines and the measles-rubella vaccine.Current research dem-onstrates that DMNs provide significant advantages in enhancing vaccine immunogenicity,boosting vaccine stability and reducing vaccination costs.Yet,challenges confronting the development of DMNs remain in terms of unclear material me-tabolism,skin safety,difficulties in large-scale production and lack of quality standards and regulations.With the continu-ous progress of microneedle technique and constant improvement of policies and regulations,DMNs are expected to play an important role in boosting the convenience of vaccination and raising the coverage rate of vaccination,thereby making significant contributions to human health undertakings.

Dissolvable microneedles(DMNs)offer significant advantages for vaccine delivery,including pain relief,saving drug dose,no contamination of sharp instruments and autonomous operation.The review introduces the materials,fabri-cation processes and physical characteristics of DMNs,focusing on its application in delivering various vaccines,such as influenza vaccines,COVID-19 vaccines,viral hepatitis vaccines and the measles-rubella vaccine.Current research dem-onstrates that DMNs provide significant advantages in enhancing vaccine immunogenicity,boosting vaccine stability and reducing vaccination costs.Yet,challenges confronting the development of DMNs remain in terms of unclear material me-tabolism,skin safety,difficulties in large-scale production and lack of quality standards and regulations.With the continu-ous progress of microneedle technique and constant improvement of policies and regulations,DMNs are expected to play an important role in boosting the convenience of vaccination and raising the coverage rate of vaccination,thereby making significant contributions to human health undertakings.

Objective:To investigate the correlation between serum lipoprotein (a) [LP(a)] and the severity of white matter hyperintensities (WMHs) in the middle-aged and elderly people in the community.Methods:Consecutive middle-aged and elderly residents residing in the community underwent physical examinations in the Affiliated Jiangning Hospital of Nanjing Medical University from June 2016 to August 2021 were retrospectively collected. Fasting venous blood was collected on the next day of admission to detect the level of Lp(a). During hospitalization, cranial MRI examination was performed and the severity of WMHs was graded using the Fazekas visual scoring method. Ordinal multivariate logistic regression analysis was used to determine independent related factors for the severity of WMHs.Results:A total of 1 752 patients were included in the analysis. There were 969 males (55.31%) and 783 females (44.69%). Their age was 66.18±10.32 years old. There were 1 167 patients (66.61%) in the mild WMHs group, 407 (23.23%) in the moderate WMHs group, and 178 (10.16%) in the severe WMHs group. Ordinal multivariable logistic regression analysis showed that after adjusting for confounding factors, a higher serum Lp(a) level was independently related to the severity of WMHs (with the first quartile as a reference, the third quartile: odds ratio 1.441, 95% confidence interval 1.050-1.976, P=0.023; the fourth quartile: odds ratio 1.717, 95% confidence interval 1.252-2.354, P=0.001). Conclusion:Serum Lp(a) is independently correlated with the severity of WMHs.

Objective:To analyze the site of vestibular nerve damaged in patients with acute vestibular neuritis. Methods:Fifty-seven patients with acute vestibular neuritis were recruited, and each patient underwent caloric irrigation test, video head impulse test（vHIT） and vestibular evoked myogenic potentials（VEMPs）. The results were further analyzed. Results:Analysis of abnormal rates of different vestibular function tests: the abnormal rate of caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and posterior semicircular canal vHIT were 92.98%, 92.98%, 92.98%, and 52.63%, respectively. The abnormal rate of cervical vestibular evoked myogenic potentials（cVEMP） and ocular vestibular evoked myogenic potentials（oVEMP） were 52.63% and 89.47%. The abnormal rate of caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and oVEMP were significantly higher than posterior semicircular canal vHIT and cVEMP（P<0.01）. Combination analysis of different vestibular function tests: there are twenty-six patients（45.61%, superior and inferior vestibular nerve） with abnormal caloric irrigation test, video head impulse test, and VEMPs. There are twenty-five patients（43.86%, superior vestibular nerve） with abnormal caloric irrigation test, horizontal semicircular canal vHIT, anterior semicircular canal vHIT, and oVEMP. There are 4 patients（7.02%, inferior vestibular nerve） with abnormal posterior semicircular canal vHIT and cVEMP. There are two patients（3.51%, ampullary vestibular nerve） with abnormal caloric irrigation test, horizontal semicircular canal vHIT, and anterior semicircular canal vHIT. The rate of superior and inferior vestibular neuritis and superior vestibular neuritis were significantly higher than inferior vestibular neuritis and ampullary vestibular neuritis（P<0.01）. Conclusion:Acute vestibular neuritis subtypes can be divided into four categories: superior and inferior vestibular neuritis, superior vestibular neuritis, inferior vestibular neuritis, and ampullary vestibular neuritis. Video head impulse test can accurately assess the site of vestibular nerve damage in patients with acute vestibular neuritis. In addition, vHIT combined with VEMPs can provide objective evidence for the diagnosis of ampullary vestibular neuritis.
Humans ; Vestibular Neuronitis/diagnosis* ; Vestibule, Labyrinth ; Vestibular Nerve ; Semicircular Canals ; Head Impulse Test/methods*

In recent years, due to the emergence of ultrafast ultrasound imaging technology, the sensitivity of detecting slow and micro blood flow with ultrasound has been dramatically improved, and functional ultrasound imaging (fUSI) has been developed. fUSI is a novel technology for neurological imaging that utilizes neurovascular coupling to detect the functional activity of the central nervous system (CNS) with high spatiotemporal resolution and high sensitivity, which is dynamic, non-invasive or minimally invasive. fUSI fills the gap between functional magnetic resonance imaging (fMRI) and optical imaging with its high accessibility and portability. Moreover, it is compatible with electrophysiological recording and optogenetics. In this paper, we review the developments of fUSI and its applications in neuroimaging. To date, fUSI has been used in various animals ranging from mice to non-human primates, as well as in clinical surgeries and bedside functional brain imaging of neonates. In conclusion, fUSI has great potential in neuroscience research and is expected to become an important tool for neuroscientists, pathologists and pharmacologists.
Animals ; Mice ; Ultrasonography/methods* ; Brain/physiology* ; Magnetic Resonance Imaging ; Optogenetics ; Hemodynamics

Objective:To provide objective basis for the diagnosis on liver metastasis from lung cancer by analysing contrast-enhanced ultrasonography(CEUS) characteristics.Methods:In a reprospective study, CEUS was performed in 78 cases with liver metastasis from lung cancer in Renmin Hospital of Wuhan University from January 2014 to March 2019. Patients were divided into three groups: the adenocarcinoma group( n=30), squamous cell carcinoma group ( n=20), and neuroendocrine neoplasm group( n=28). Conventional ultrasound and CEUS features were analyzed and the distinctions among the three groups were compared. Results:CEUS showed that 85.9%(67/78) of the liver metastasis from lung cancer with pattern of rapid wash-in and 89.7%(70/78) of rapid wash-out, so there was no statistical difference among the three groups( P>0.05). In the adenocarcinoma and squamous cell carcinoma group, 53.3%(16/30) and 55.0%(11/20) of cases were rim-like enhancement. And 71.4%(20/28) of the neuroendocrine neoplasm group with global enhancement that was different from the other groups(all P<0.05). At the peak of enhancement, most cases were hyperenhancement among the three groups, and the difference was not statistically significant( P>0.05). During the lesions of hyperenhancement, 73.7%(14/19) was global enhancement in the neuroendocrine neoplasm, compared to 75.0% (12/16) of the adenocarcinoma group and 72.7%(8/11) of the squamous cancer group with rim-like enhancement, which the differences was statistically significant(all P<0.05). At the peak of enhancement, 67.9%(19/28) lesions of the neuroendocrine neoplasm group were homogeneous enhancement, and only 21.4%(6/28) of the lesions was observed non-enhanced area, which was different from the other groups(all P<0.05). The times to iso-echogenity and hypo-echogenity were (33.2±7.6)s and (45.1±10.8)s respectively in the neuroendocrine neoplasm group, which were more than the other groups(all P<0.05). Capsule enhancement appeared in 32.1%(9/28) of the neuroendocrine neoplasm group in the delay phase, which was higher than 13.3%(4/30) of the adenocarcinoma group and 10.0%(2/20) of squamous cell carcinoma group (all P<0.05). Conclusions:CEUS can provide more diagnostic information for liver metastasis from lung cancer and may be a beneficial technique for differential diagnosis.

Objective To provide a reference for differential diagnosis of orbit tumors in extraconal compartment by analyzing the parameters of contrast‐enhanced ultrasonography ( CEUS) . Methods A total of 76 patients with orbit tumors in extraconal compartment w ho underwent CEUS examination were retrospectively analyzed . T hese patients were divided into two groups depending on histological diagnosis including 27 cases with malignant tumor and 49 cases with benign tumor . CEUS images were analyzed using Sonoliver software . T he time‐intensity curve ( T IC ) and dynamic vascular pattern curve ( DVPC ) were acquired and the characteristics of the arterial flow infusion of these were analyzed . T he related parameters such as time of arrival time( AT ) ,rise time ( RT ) ,time to peak( T T P) ,mean transit time( mT T ) ,slope of rise( K1 ) ,the absolute value for slope of down ( K 2 ) were also obtained . T he differences of DVPC ,TIC and quantitative parameters between the two groups were compared . Receiver operating curve analysis was used to acquire the cut‐off values of these parameters for differential diagnosis . Results ① T ICs of the benign tumors were mainly fast rise and slow drop and DVPCs were mainly positive biphasic ,w hile T ICs of the malignant tumors were mainly fast rise and fast drop and DVPCs were mainly biphasic . ② T he differences of quantitative parameters IM AX ,K 1 ,K2 ,mT T and RT of T ICs were statistically significant between the two groups ( P ＜0 .05) ,w hile those of A T and T T P were not ( P ＞ 0 .05 ) . ③ IM AX＝ 456 .2% ,K1 ＝109 .6 ,K2 ＝35 .2 ,RT＝7 .9 s ,mT T＝28 .1 s were the best cut‐off values for differential diagnosis . Among these parameters ,mT T with 28 .1 s had the highest diagnostic value ( sensitivity :81% ,specificity :77% ) . Conclusions The quantitative CEUS parameters can provide effective reference for differential diagnosis of orbit tumors in extraconal compartment .

OBJECTIVE: explore the expression of miR-155-5p in Wilms tumor and its effect in regulating the proliferation, migration and apoptosis of Wilms tumor cells. METHODS: Specimens of tumor tissues and paired adjacent tissues were obtained from 40 patients with Wilms tumor for detection of the expression levels of miR-155-5p using RT-qPCR. Wilms tumor cell line G401 was transfected with miR-155-5p mimics and miR-155-5p inhibitor to induce miR-155-5p over-expression and its inhibition, respectively, and the changes in the cell proliferation, migration and apoptosis were assessed using cell counting kit-8 (CCK-8), wound healing assay and fl ow cytometry. RESULTS: RT-qPCR showed that the expression of miR-155-5p decreased significantly in Wilms tumor tissues as compared with normal kidney tissues and was significantly associated with TNM stage ( < 0.05). In G401 cells, over-expression of miR-155-5p significantly inhibited the cell proliferation and migration and promoted cell apoptosis ( < 0.05), and down-regulation of miR-155-5p obviously enhanced the proliferation and migration and suppressed apoptosis of the cells ( < 0.05). CONCLUSIONS miR-155-5p is down-regulated in Wilms tumor and its expression level is correlated with TNM stage. miR-155-5p participates in the progression of Wilms tumor by inhibiting the proliferation and migration and promoting apoptosis of the tumor cells, and may serve as a novel biomarker for diagnosis, therapy and prognostic evaluation of Wilms tumor.
Apoptosis ; Cell Movement ; Cell Proliferation ; Humans ; Kidney Neoplasms ; genetics ; MicroRNAs ; genetics ; Neoplasm Invasiveness ; Wilms Tumor ; genetics

Objective: To provide a reference for differential diagnosis of orbit tumors in extraconal compartment by analyzing the parameters of contrast-enhanced ultrasonography (CEUS). Methods: A total of 76 patients with orbit tumors in extraconal compartment who underwent CEUS examination were retrospectively analyzed. These patients were divided into two groups depending on histological diagnosis including 27 cases with malignant tumor and 49 cases with benign tumor. CEUS images were analyzed using Sonoliver software. The time-intensity curve (TIC) and dynamic vascular pattern curve (DVPC) were acquired and the characteristics of the arterial flow infusion of these were analyzed. The related parameters such as time of arrival time(AT), rise time (RT), time to peak(TTP), mean transit time(mTT), slope of rise(K₁), the absolute value for slope of down (K₂) were also obtained. The differences of DVPC, TIC and quantitative parameters between the two groups were compared. Receiver operating curve analysis was used to acquire the cut-off values of these parameters for differential diagnosis. Results: ①TICs of the benign tumors were mainly fast rise and slow drop and DVPCs were mainly positive biphasic, while TICs of the malignant tumors were mainly fast rise and fast drop and DVPCs were mainly biphasic. ②The differences of quantitative parameters IMAX, K₁, K₂, mTT and RT of TICs were statistically significant between the two groups (P<0.05), while those of AT and TTP were not (P>0.05). ③IMAX=456.2%, K₁=109.6, K₂=35.2, RT=7.9 s, mTT=28.1 s were the best cut-off values for differential diagnosis. Among these parameters, mTT with 28.1 s had the highest diagnostic value(sensitivity: 81%, specificity: 77%). Conclusions The quantitative CEUS parameters can provide effective reference for differential diagnosis of orbit tumors in extraconal compartment.