BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective To investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

Objective:To investigate the complicated virus infection of infants with pertussis and its effect on the disease.Methods:From January 2019 to March 2020, a total of 100 hospitalized infants with pertussis were admitted to the Second Affiliated Hospital of Medical College of Shantou University, nasopharyngeal swabs were collected for detection of ten pathogens including pertussis, namely respiratory syncytial virus(RSV), parainfluenza virus(PIV), bordetella pertussis (BP), human rhinovirus(HRV), human bocavirus(HBoV), human metapneumovirus(hMPV), influenza B virus (INF-B), adenovirus, influenza A virus and cytomegalovirus(CMV). According to the results of pathogen detection, all infants were divided into single detection group of BP(single detection group) and co-detection group of BP combined with viruses(co-detection group). The clinical data of the two groups were retrospectively analyzed and compared to explore the differences of clinical characteristics and its impact on the course of disease.Results:Among 100 cases, there were 54(54.0%) boys and 46(46.0%)girls.The age ranged from 28 days to 2 years and 5 months, with a median age of 3.5 months.Fifty-six cases were classified as single detection group, while 44 cases were included into co-detection group.Among infants in co-detection group, fourteen cases were co-infected with CMV(31.8%, 14/44), seven cases with HRV(15.9%, 7/44), seven cases with PIV(15.9%, 7/44), four cases with RSV(9.1%, 4/44), one case with hMPV(2.2%, 1/44), eight cases with CMV+ HRV(18.2%, 8/44), one case with HRV+ HBoV (2.2%, 1/44), one case with CMV+ PIV(2.2%, 1/44)and one case with CMV+ PIV+ INF-B(2.2%, 1/44). The number of infants in the single detection group who had cyanosis before treatment, requiring repiratory support, PICU admission, severe pneumonia or abnormal myocardial enzymes were higher than those in the co-detection group( P<0.05), while the months of age were lower than that in the co-detection group( P<0.05). When comparing the clinical characteristics of infants over three months of age, only the number of cases of combined cyanosis before treatment and the number of days in hospital were higher in the single detection group than those in the co-detection group ( P<0.05), no statistically significant differences were found in the other clinical characteristics between the two groups( P>0.05). Conclusion:The cases of infants requiring repiratory support, complicated with severe pneumonia or abnormal myocardial enzymes in the single detection group are higher than those in the co-detection group, which may be attributed to the small age of months.

Objective:To improve accuracy of prediction amount of length of gastric tube placed through nose and reduce occurrence of adverse events thorough clinical observation of measurement of length of nasogastric tube placement in critically ill children.Methods:Using the convenient sampling method, critically ill children who were hospitalized and needed a nasogastric tube in Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital Affiliated to Capital Medical University were selected from April to September 2019. The prediction method of "nos-ear-xiphoid (NEX) increased by 5 cm" (NEX+5 cm) was adopted. The values of placed length in this study were collected and compared with those predicted by traditional measurement method (namely NEX) , improved "nose-ear-mid-umbilicus" (NEMU) and formula method.Results:A total of 52 critically ill children were enrolled in this study. The length of placed nasogastric tube was 31.5 (28.3, 35.8) cm, and 43 cases (82.7%) were determined to be qualified by X-ray. The length of gastric tube required to be placed in children was 27.0 (24.1, 31.0) cm according to the NEX method, and the length of gastric tube required to be placed in children was 26.1 (22.5, 29.0) cm measured by the formula method. Both were shorter than that measured by NEX+5 cm, and the differences were statistically significant ( P<0.01) . The NEMU method measured the length of gastric tube to be inserted into the child to be 31.0 (28.3, 36.0) cm. Compared with the length measured by NEX+5 cm, and the difference was not statistically significant ( P>0.05) . Conclusions:This study uses NEX+5 cm to predict the actual length of the gastric tube inserted through the nose. The accuracy is relatively high and the operation method is simple. It is necessary to consider individual differences in clinical applications, especially the large variability in infants and young children. After catheterization, abdominal ultrasound, X-ray and other auxiliary examination methods should be used to determine the location of catheterization, and individualized catheterization programs should be given to children according to different therapeutic objective.

According to multicenter randomized controlled trials, laparoscopic radical resection of colon cancer has the same short and long term clinical efficacy as traditional open surgery. In laparoscopic radical resection of right semicolon cancer, it is important to separate the embryonic plane of the root, and to ligate and cut off the central vascular roots. Only by separation along the membrane space can one achieve minimally invasive operation with no bleeding, and ensure the integrity of the excision of the mesangium and avoid damage of internal fascia and other organs. The mesangial distribution of the right semicolon is adjacent to the mesangium of the stomach and is connected to the mesentery of the small intestine. The pancreaticoduodenum locates between the right semicolon mesentery and the retroperitoneal subperitoneal fascia. In particular, the relationship between the anterior and posterior Treitz fascia of the pancreaticoduodenum and the Toldt space is complex, which is closely related to the feasibility of complete mesocolic excision(CME). This article introduces the distribution of intermembranous space and mesangial bed in the right semicolon, presenting the problem in CME surgery. In addition, there are key points in identifying the gap between the membranes based on the author’s experience and we propose a new evaluation criteria for membrane surgical specimens, which has certain guiding significance for radical CME surgery for right semicolon cancer.

According to multicenter randomized controlled trials, laparoscopic radical resection of colon cancer has the same short and long term clinical efficacy as traditional open surgery. In laparoscopic radical resection of right semicolon cancer, it is important to separate the embryonic plane of the root, and to ligate and cut off the central vascular roots. Only by separation along the membrane space can one achieve minimally invasive operation with no bleeding, and ensure the integrity of the excision of the mesangium and avoid damage of internal fascia and other organs. The mesangial distribution of the right semicolon is adjacent to the mesangium of the stomach and is connected to the mesentery of the small intestine. The pancreaticoduodenum locates between the right semicolon mesentery and the retroperitoneal subperitoneal fascia. In particular, the relationship between the anterior and posterior Treitz fascia of the pancreaticoduodenum and the Toldt space is complex, which is closely related to the feasibility of complete mesocolic excision(CME). This article introduces the distribution of intermembranous space and mesangial bed in the right semicolon, presenting the problem in CME surgery. In addition, there are key points in identifying the gap between the membranes based on the author’s experience and we propose a new evaluation criteria for membrane surgical specimens, which has certain guiding significance for radical CME surgery for right semicolon cancer.

According to multicenter randomized controlled trials, laparoscopic radical resection of colon cancer has the same short and long term clinical efficacy as traditional open surgery. In laparoscopic radical resection of right semicolon cancer, it is important to separate the embryonic plane of the root, and to ligate and cut off the central vascular roots. Only by separation along the membrane space can one achieve minimally invasive operation with no bleeding, and ensure the integrity of the excision of the mesangium and avoid damage of internal fascia and other organs. The mesangial distribution of the right semicolon is adjacent to the mesangium of the stomach and is connected to the mesentery of the small intestine. The pancreaticoduodenum locates between the right semicolon mesentery and the retroperitoneal subperitoneal fascia. In particular, the relationship between the anterior and posterior Treitz fascia of the pancreaticoduodenum and the Toldt space is complex, which is closely related to the feasibility of complete mesocolic excision(CME). This article introduces the distribution of intermembranous space and mesangial bed in the right semicolon, presenting the problem in CME surgery. In addition, there are key points in identifying the gap between the membranes based on the author’s experience and we propose a new evaluation criteria for membrane surgical specimens, which has certain guiding significance for radical CME surgery for right semicolon cancer.