Female ; Humans ; Adenocarcinoma in Situ ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; Cervix Uteri/pathology* ; Adenocarcinoma/pathology* ; Papillomaviridae ; DNA, Viral

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Skin Neoplasms/pathology* ; Prognosis ; Retrospective Studies ; In Situ Hybridization, Fluorescence ; China ; Melanoma/diagnosis* ; Nail Diseases/pathology* ; Antigens, Neoplasm

Animals ; Mice ; Colon ; Histological Techniques

Humans ; Adamantinoma/surgery* ; Bone Diseases, Developmental ; Bone Neoplasms/surgery* ; Tibia/surgery*

Toxoplasma gondii, a ubiquitous pathogen that infects nearly all warm-blooded animals and humans, can cause severe complications to the infected people and animals as well as serious economic losses and social problems. Here, one local strain (TgPIG-WH1) was isolated from an aborted pig fetus, and the genotype of this strain was identified as ToxoDB #3 by the PCR RFLP typing method using 10 molecular markers (SAG1, SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, C22-8, C29-2 and Apico). A comparison of the virulence of this isolate with other strains in both mice and piglets showed that TgPIG-WH1 was less virulent than type 1 strain RH and type 2 strain ME49 in mice, and caused similar symptoms to those of ME49 such as fever in piglets. Additionally, in piglet infection with both strains, the TgPIG-WH1 caused a higher IgG response and more severe pathological damages than ME49. Furthermore, TgPIG-WH1 caused one death in the 5 infected piglets, whereas ME49 did not, suggesting the higher virulence of TgPIG-WH1 than ME49 during piglet infection. Experimental infections indicate that the virulence of TgPIG-WH1 relative to ME49 is weaker in mice, but higher in pigs. This is probably the first report regarding a ToxoDB #3 strain from pigs in Hubei, China. These data will facilitate the understanding of genetic diversity of Toxoplasma strains in China as well as the prevention and control of porcine toxoplasmosis in the local region.

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

To improve the accuracy of prenatal diagnosis for coarctation of the aorta ( CoA ) by comparatively analyzing the relevant factors and their application value . Methods Cases of disproportion of ventricles and great vessels were selected between January 2011 and July 2018 . Only liveborn fetuses with complete postnatal follow‐up were included in the study . One hundred and twelve cases were retrieved and analyzed . According to the postnatal ultrasound and CT results ,the patients were divided into gruop A and goup B . Different fetal echocardiography parameters and features were selected to evaluate the diagnostic value . Logistic regression analysis was used to select the best predictors of CoA and optimal cut‐offs for these parameters were identified by ROC analysis . Results One hundred and thirty eight fetuses were suspected to be CoA ,and 112 of them were born . T hey included 59 cases ( 52 .9% ) with CoA ( Group A ) and 53 cases ( 47 .3% ) without CoA ( Group B ) . T here were statistically significant differences between the two groups in gestational age ,Z‐score of diameter of left ventricle ,ascending aorta ( AAO ) and aortic arch isthmus ,main pulmonary artery ( M PA )/AAO diameters ratio ,and arterial duct/isthmus diameters ratio . T he parameters most predictive of postnatal CoA selected by logistic regression and the cut‐off values identified by ROC analysis were :gestational age at first diagnosis ≤34 .5 weeks ,Z‐score of diameter of left ventricle ＜ －1 .8 ,Z‐score of diameter of isthmus ＜ －2 .7 ,M PA/AAO diameters ratio＞1 .6 . AUC yielded by these parameters in combination was 0 .94 ( 95% CI :0 .89 －0 .99) . T he study group were divided into two subgroups by gestational age at first diagnosis .T he parameters and cut‐off values in subgroups were selected by the same analysis as above :Group Ⅰ ( ≤ 34 .5 weeks ) ,Z‐score of diameter of right ventricle ＞2 .1 ,M PA/AAO diameters ratio＞1 .6 ; Group Ⅱ( ＞34 .5 weeks) ,M PA/AAO diameters ratio ＞ 1 .7 ,arterial duct/isthmus diameters ratio ＞ 2 .3 . Meanw hile ,some ultrasound features ( including aortic arch hypoplasia ,retrograde blood flow of aortic isthmus ) should also be considered to improve diagnostic accuracy . Conclusions Combined with the use of different ultrasound parameters and features at different gestational weeks can improve the accuracy of the prenatal diagnosis of CoA in the right heart dominant fetus .

A motion unit for sucking robot with a stable motion, convenient operation and process simulation is introduced. The key parameters and process data of the sucking operation were obtained from the clinical work, which provided the basis for the design of the sucking robot motion unit. According to the points of sucking action, robotic thumb, forefinger and metacarpophalangeal joints were used to grip the suction tube, and the servo and arm structure were used to simulate the motion of the wrist and elbow to complete the rotation and push of the sputum suction tube. The feasibility is verified through the advanced sputum suction training model. The movement unit is stable in movement, and can smoothly complete the clamping, feeding, back off protection and rotating tube removal of the sputum suction tube, so as to achieve effective sputum suction.
Catheterization ; Intubation, Intratracheal ; Robotics ; Suction