Exosomes are a kind of nanovesicles with a wide range of chemical components，which are enriched in a variety of bioactive molecules，such as lipids，proteins，nucleic acids，etc. Exosomes carry biologically active molecules that transmit different messages between cells，and play a role in human physiological and pathological processes. Compared with synthetic carriers such as liposomes and nanoparticles，by virtue of their natural endogenous attributes and cell-specific targeting capabilities，exosomes have broad application prospects in the fields of early disease diagnosis marker screening and targeted therapy drug carriers. This article reviews the role of exosomes in common children's diseases and their research progress，providing new ideas for pediatric clinicians to explore disease diagnosis and treatment.

Objective:To summarize the current research status, assessment tools, and influencing factors of fatigue in patients receiving maintenance hemodialysis (MHD) and provide a reference for the management of fatigue in this patient population.Methods:A literature search was conducted in databases including PubMed, Web of Science, ProQuest, Cochrane Library, Science Direct, Embase, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for studies related to fatigue in patients receiving MHD. The search timeframe was from establishing the databases to January 23, 2024.Results:A total of 46 studies were included. Various assessment tools for fatigue in patients receiving MHD were identified, though specific tools were limited. The Short Form 36 Vitality Subscale (SF-36 VS) was the most commonly used assessment tool. The main factors influencing fatigue in these patients included sociodemographic, dialysis-related, disease-related, physical, nutritional, and psychological factors.Conclusions:Fatigue is a significant symptom in patients receiving MHD. Healthcare professionals must develop specific tools for accurately assessing fatigue in this population and explore standardized management plans.

Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

[Abstract] Objective: To study the effect of Notch4 signaling pathway on the self-renewal capacity of cancer stem cells (CSCs) of oral squamous cell carcinoma PJ15 and PJ41 cells and its mechanism. Methods: The expression of Notch4 gene in head and neck tumors was analyzed using TCGA database. 2 μmol/L cisplatin was used to treat oral squamous cell carcinoma PJ15 and PJ41 cells for 48 h, following with the treatment of Notch pathway inhibitor DAPT for 24 h. Flow cytometry was used to detect the ratio of CSCs, Western blotting and qPCR were used to detect the expressions of CSCs markers (Sox2, Bmi-1, Oct4, Nanog) and downstream genes in Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1, HES2, DLL4, etc.). Notch4 was knocked down by siRNA technology. Notch4 was silenced with siRNA technology. Western blotting and qPCR were used to detect the effect of si-Notch4 and cisplatin on the expression level of CSCs markers. The stem cell pelletingtestwasusedtodetecttheself-renewalabilityof CSCs. Results: Notch4 gene was highly expressed in head and neck tumor tissues (P=0.046). After cisplatin treatment, compared with the control group, expressions of NICD4 and CSCs markers (Sox2, Bmi-1, Oct4, Nanog) as well as downstream genes of Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1,HES2, DLL4, etc.) increased significantly (all P<0.05), and the proportion of ALDH1 positive cells increased significantly (P<0.05); with the further addition of DAPT, the expressions of the above genes decreased significantly (P<0.05 or P<0.01). After knocking down Notch4, compared with the control group, the size and number of spheres of PJ15 cells [1.33±0.47] vs [8.00±0.82], P<0.01) and PJ41 cells ([1.00±0.82] vs [7.67±1.25], P<0.01) were significantly lower than that of the control group; after the addition of 2 μmol/L DDP for 24 h, there was no significant difference in the expressions of Nanog and Bmi-1 gene between si-Notch4 group and control group. Conclusion:Activation of Notch4 signaling pathway can enhance the self-renewal ability of CSCs in oral squamous cell carcinoma PJ15 and PJ41 cells.

Objective:To investigate the computed tomography (CT) features of adenocarcinoma of esophagogastric junction (AEG) after neoadjuvant chemotherapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 59 patients with AEG who underwent neoadjuvant chemotherapy in Peking University Cancer Hospital from February 2010 to November 2014 were collected. There were 51 males and 8 females, aged from 46 to 82 years, with a median age of 63 years. All the 59 patients underwent enhanced CT examination before and after neoadjuvant chemotherapy. Observation indicators: (1) pathological examination and neoadjuvant chemotherapy of patients with AEG; (2) results of CT examination in patients with AEG, including ① qualitative indicators of CT and ② quantitative indicators of CT. Measurement data with skewed distribution were represented as M( P25, P75) or M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Results:(1) Pathological examination and neoadjuvant chemotherapy of patients with AEG: of the 59 patients with AEG, high-differentiated adenocarcinoma was observed in 1 patient, moderate-differentiated adenocarcinoma in 40 patients, and low-differentiated adenocarcinoma in 18 patients. Effective response to neoadjuvant chemotherapy was observed in 13 patients, including 6 patients of pathological tumor regression grading (pTRG) 0 and 7 of pTRG 1; poor response was observed in 46 patients, including 12 patients of pTRG 2 and 34 patients of pTRG 3. (2) Results of CT examination in patients with AEG. ① Qualitative indicators of CT: for the 13 patients with effective response to neoadjuvant chemotherapy, 13 had the presence of ulcers, 5 had layered enhancement, 10 had infiltration of adventitia surface, and 2 had positive extramural venous invasion (EMVI) before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 13 had shallowed or disappeared ulcers, 7 patients had changed enhancement pattern, 3 had infiltration of adventitia surface, and 1 had positive EMVI. For the 46 patients with poor response to neoadjuvant chemotherapy, 28 had the presence of ulcers, 18 had layered enhancement, 37 had infiltration of adventitia surface, and 22 had positive EMVI before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 23 had shallowed or disappeared ulcers, 7 patients had changed layered enhancement pattern, 33 had infiltration of adventitia surface and 21 had positive EMVI, respectively. There was no significant difference in the layered enhancement or infiltration of adventitia surface before neoadjuvant chemotherapy between patients with different treatment response ( χ2=0.002, 0.000, P>0.05). There were significant differences in the presence of ulcers and positive EMVI before neoadjuvant chemotherapy between patients with different treatment response ( χ2=5.591, 4.421, P<0.05). After neoadjuvant chemotherapy, there were significant differences in the changes of layered enhancement pattern, infiltration of adventitia surface and positive EMVI between patients with different treatment response ( χ2=6.359, 10.090, 4.728, P<0.05); while there was no significant difference in the shallowed or disappeared ulcers between patients with different treatment response ( χ2=1.239, P>0.05). ② Quantitative indicators of CT: for the 13 patients with good response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy were 1.37 cm(0.94 cm, 1.88 cm), 8.9 cm 2 (4.7 cm 2, 9.9 cm 2), 53 HU(47 HU, 63 HU), respectively. After neoadjuvant chemotherapy, the above indicators were 1.17 cm(0.79 cm, 1.29 cm), 4.4 cm 2(2.5 cm 2, 6.1 cm 2), 30 HU(25 HU, 53 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -23%(-42%, 9%), -51%(-60 %, -21%), -44%(-51%, 19%), respectively. For the 46 patients with poor response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion were 1.57 cm(1.21 cm, 1.96 cm), 9.4 cm 2(6.6 cm 2, 13.1 cm 2), 60 HU(53 HU, 66 HU) before neoadjuvant chemotherapy, respectively. After neoadjuvant chemotherapy, the above indicators were 1.16 cm(0.94 cm, 1.37 cm), 6.2 cm 2(4.8 cm 2, 8.1 cm 2), 55 HU(47 HU, 65 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -27%(-38%, -9%), -33%(-47%, -12%), -9%(-22%, 9%), respectively. There was no significant difference in the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy between patients with different treatment response ( Z=-1.372, -1.372, -1.331, P>0.05). There was no significant difference in the maximum tumor height after neoadjuvant chemotherapy between patients with different treatment response ( Z=-0.503, P>0.05), while there were significant differences in the maximum tumor area and CT value of the lesion ( Z=-2.743, -3.049, P<0.05). There was no significant difference in the change rate of the maximum tumor height or the maximum tumor area between patients with different treatment response ( Z=0.000, -1.481, P>0.05), while there was a significant difference in the change rate of CT value of the lesion ( Z=-3.231, P<0.05). Conclusion:Effective response of AEG to neoadjuvant chemotherapy was characterized by the changes in tumor layered enhancement pattern, reduction in the maximum tumor area, reduced CT value of the lesion, negative infiltration of adventitia surface, and negative EMVI.