OBJECTIVE: To retrospectively analyze the clinical characteristics of 15 children with B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, and summarize the efficacy and safety of blinatumomab in the treatment of pediatric B-ALL. METHODS: Fifteen children who received treatment with blinatumomab from February 2022 to January 2023 were enrolled in this study. One course (28 days) of blinatumomab concurrent with intrathecal chemotherapy was given according to the standard regimen, except for 2 cases who had shortened course of treatment due to hematopoietic stem cell transplantation (HSCT) and did not receive combined intrathecal chemotherapy, and 1 case had a shortened course of treatment due to economic problems. The efficacy and safety of the treatment were evaluated. RESULTS: In terms of efficacy, for the children who had achieved complete molecular remission (CMR) before treatment, blinatumomab treatment could effectively maintain CMR status; For the children who did not achieve CMR, the CMR rate after one standard course of treatment with blinatumomab reached 66.7%(4/6); For the children with relapsed/refractory ALL (R/R ALL) who had minimal residual disease (MRD), the MRD clearance rate reached 75.0%(3/4). The statistical results of the incidence of adverse events showed that 13.3%(2/15) of the children did not experience any adverse events. The most common adverse events were cytokine release syndrome (CRS) (73.3%, 11/15) and transaminase elevation (26.7%, 4/15); 33.3%(5/15) of the children experienced grade 3 or higher adverse events. All the adverse events were resolved after symptomatic treatment.The level of IgG decreased significantly after 4-7 weeks of treatment with blinatumomab, and gradually recovered after 8 weeks of treatment. CONCLUSION Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy.
Humans ; Antibodies, Bispecific/therapeutic use* ; Child ; Retrospective Studies ; Female ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction ; Treatment Outcome ; Child, Preschool ; Adolescent ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To explore the safety and management mode of hysteroscopy in three different modes:outpatient,daily and inpatient.Methods The quality control data of patients who underwent hysteroscopic surgery in Hysterscopy Centre,Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2021 were collected through the electronic information system of the hospital and the monthly quality control report of hysteroscopy center.The amount of surgery,the proportion of grade Ⅳsurgery,the analysis of operation types,the indicator including complications,and unanticipated secondary surgery were retrospectively analyzed.Results From 2019 to 2021,5 162 outpatient hysteroscopic patients,15 331 daily hysteroscopic patients and 5 942 inpatient hysteroscopic patients were admitted in our hospital.The age of inpatient hysteroscopic patients was significantly older than those of outpatient and daily patients(P<0.001).In the past three years,the proportion of daily hysteroscopy gradually increased,and the proportion of inpatient hysteroscopy gradually decreased(P<0.001).The total percentage of grade Ⅳ hysteroscopic surgery was 12.9%,in which inpatient was higher than daily,and daily was higher than outpatient(P<0.001).The incidence of complications and accidents during hysteroscopy was 0.117%(31/26 435),including 17 cases of uterine perforation,7 cases of hysteroscopy failure,3 cases of excessive intraoperative bleeding,2 cases of fluid overload,1 case of intestinal injury,and 1 case of anesthesia accident.The incidence of hysteroscopy in outpatient,daily and inpatient were 0.020%(1/5 162),0.137%(21/15 331)and 0.151%(9/5 942)respectively.Conclusion Hysteroscopy in outpatient,daily and inpatient are all safe and reliable.Outpatient and daily hysteroscopy can improve the efficiency of medical services,which has gradually become a trend.

Objective To compare the changes of the Chinese Materia Medica resources(CMMR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2011-2022).Methods Using new techniques,after field investigation,collection and identification of the specimens of the animals,plants and minerals.The data of the CMMR in Sichuan found in the 4th CMMRI were analysed and compared with the data of 3rd CMMRI.Results ①9055 species of CMMR were found in Sichuan during the 4th CMMRI,including 8272 species of medicinal plants,745 species of medicinal animals and 38 species of medicinal minerals.Compared with the 3rd CMMRI,the number of CMMR found in Sichuan have greatly increased.The number of medicinal plants increased 5018 species,the number of medicinal animals increased 637 species and the number of medicinal minerals increased 5 species,too.②The medicinal plants is the main part of the CMMR,and the higher plants(7774 species)has the absolute advantage of the CMMR.The top 20 families which have plenty of plant species include Compositae,Rosaceae,Leguminosae,Ranunculaceae,etc.③ Based on the data of the CMMR of the 183 counties in Sichuan,the reserves of 235 species of wild CMMR in Sichuan is about 36.72 million ton.There were 49 CMMR which have reserves beyond 100 thousand tons,such as Arisaematis rhizoma,Epimedii folium,Cimicifugae rhizoma,Acori tatarinowii rhizoma,Gentianae macrophyllae radix,Polygoni multiflori radix etc.④In 2021,there were 215 species of CMMR cultivated in Sichuan,the main species were Aurantii fructus,Chuanxiong rhizoma,Polygonati rhizome,Salviae miltiorrhizae radix et rhizome.The planting area was 8.17 million and the production was 1.26 million ton.⑤All 183 countries were found CMMR,the number of the species of CMMR in 30 countries exceeded 800,including 16 countries which had more than 1000 kinds of CMMR,such as Emeishan,Hongya,Muli etc.The total types of the CMMR(up 118.31%),the reserves of the wild CMMR(up 119 times)and the number of the counties(up 3 times)which had plenty of CMMR,showed a marked increase over the 3rd CMMRI.8 new species were found in the the 4th CMMRI,such as Codonopsis atriplicifolia,Tongoloa tagongensis,Allium xinlongense,etc.Conclusion The species,the reserves of the CMMR and the resource rich countries in Sichuan are the top 3 in China and Sichuan is worthy of the title of"Hometown of Traditional Chinese Medicine".The compositions and types of the family,genus and species of the CMMR in Sichuan have significantly increased.The basic information of the CMR in Sichuan was clearly found out during the 4th CMMRI,and beneficial for the sustainable development and utilization of the CMMR in Sichuan.

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.
Humans ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Lymphatic Metastasis/pathology* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Lymph Nodes/pathology* ; Hypopharyngeal Neoplasms/surgery* ; Prognosis ; Head and Neck Neoplasms/pathology* ; Neoplasm Staging

ObjectiveTo construct a human ovarian cancer cell line SKOV3 （SK-Luc-EGFP） stably co-expressing luciferase （Luc） and enhanced green fluorescent protein （EGFP） and to explore its application in ovarian cancer research both in vitro and in vivo. MethodsThe recombinant plasmid pCDH-Luc-T2A-EGFP-Puro was constructed by introducing a Luc-T2A-EGFP fusion gene fragment amplified by Overlap PCR into plasmid vector. The three-plasmid lentivirus packaging system was transfected into HEK 293T cells and the viral supernatant was harvested to infect SKOV3 cells. SK-Luc-EGFP cell line with the highest fluorescence intensity of EGFP was obtained by puromycin selection and flow cytometry assessment， and the Luc expression of the cell line was subsequently validated by in vitro bioluminescent assay. SK-Luc-EGFP cells were further explored for the following applications： distinguishing SK-Luc-EGFP cells from non-tumor cells in ascites by flow cytometry and confocal microscopy； visualizing adhesion of SK-Luc-EGFP cells to mesothelial cells or omentum by fluorescence microscopy； monitoring process of SK-Luc-EGFP tumorigenesis by in vivo bioluminescence imaging. ResultsA recombinant lentiviral expression plasmid pCDH-Luc-T2A-EGFP-Puro was constructed and packaged into lentiviral particles that were then transfected into SKOV3 cells to generate SK-Luc-EGFP cell line. The purity of SK-Luc-EGFP cells based on EGFP expression was 100% as validated by fluorescence microscopy and flow cytometry； SK-Luc-EGFP cells could be visually distinguished from non-tumor cells in ascitic fluid by flow cytometry and confocal imaging. Moreover， Luc expression in SK-Luc-EGFP cells was verified by in vitro bioluminescence assay， and a linear relationship with a correlation coefficient of 0.997 9 was found between cell number and the bioluminescent signal. Adhesion of SK-Luc-EGFP cells to mesothelial cells was directly observed by fluorescence imaging in in vitro adhesion assay； peritoneal adhesion of SK-Luc-EGFP cells to omentum was also observed after intraperitoneal （i.p.） injection of SK-Luc-EGFP cells in nude mice； in the peritoneal metastasis mouse model established by i.p. injection of SK-Luc-EGFP cells， monitoring of tumorigenesis process was achieved by in vivo bioluminescence imaging. ConclusionSK-Luc-EGFP cell line is a useful tool for investigating ovarian cancer in vitro and in vivo.

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.
Humans ; Rats ; Male ; Animals ; Interleukin-10 ; Rats, Sprague-Dawley ; Interleukin-4/metabolism* ; Bombyx ; Interleukin-6/metabolism* ; Microglia/metabolism* ; Saline Solution/metabolism* ; Reperfusion Injury/metabolism* ; Brain Ischemia/metabolism* ; Cerebral Infarction ; Reperfusion ; Neurons