Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9％NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P＜0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P＜0.05),and there were significant differences between CAR-L group and CAR-H group(all P＜0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P＜0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
Calcium ; Acupuncture Therapy ; Acupuncture ; Acupuncture Analgesia/methods* ; Acupuncture Points ; Technology

Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC₅₀ = 6.40 ± 0.34 μmol·L^-1) and Ⅱ-2 (IC₅₀ = 7.15 ± 0.51 μmol·L^-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To study the expression of long noncoding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA(lncRNA HAGLR)and its downstream target genes in osteoporosis(OP)-tibial fracture(TF)rats,and to explore the effect and mechanism of lncRNA HAGLR on osteogenic differentiation of rat bone marrow mesenchymal stem cells(MSCs).Methods A total of 30 SD female rats were randomly divided into the sham group,the OP group and the OP-TF group,with 10 rats in each group.Serum alkaline phosphatase(ALP)and tartrate-resistant acid phosphatase(TRAP)levels of rats were detected by ELISA.Rats MSC cell line R7500 was induced by osteogenic differentiation induction medium and divided into the MSC group and the Osteogenic-MSC group.R7500 was individually transfected with pcDNA-HAGLR,pcDNA-NC,miR-19a-3p mimic,mimic negative control(NC mimic),miR-19a-3p inhibitor and negative control of miR-19a-3p inhibitor(NC inhibitor),and divided into corresponding groups.The dual luciferase gene report experiment was used to verify the targeting relationship between lncRNA HAGLR and miR-19a-3p and bone morphogenetic protein 2(BMP2)and miR-19a-3p.The expressions of lncRNA HAGLR and miR-19a-3p in each group were detected by qRT-PCR.The expressions of BMP2,ALP,collagen Ⅰ(COL-Ⅰ),osteocalcin(OCN),and osteopontin(OPN)were detected by Western blot.ALP staining and AR staining were used to detect the osteogenic differentiation ability of MSC.Results The serum ALP and TRAP levels in the OP group and the OP-TF group were higher than those in the sham group,and the differences were statistically significant(P<0.05).There was no significant difference in the expression levels of lncRNA HAGLR,miR-19a-3p or BMP2 of tibia tissue between the OP group and the sham group(P>0.05),while the expression levels of lncRNA HAGLR and BMP2 of tibia tissue in the OP-TF group were significantly lower than those in the sham group and the OP group(P<0.05),the expression level of miR-19a-3p of tibia tissue in the OP-TF group was higher than those in the sham group and the OP group(P<0.05).Compared with the MSC group,the expression level of lncRNA HAGLR in the Osteogenic-MSC group was significantly increased(P<0.05),while the expression of miR-19a-3p was decreased(P<0.05).The dual luciferase gene report experiment verified that lncRNA HAGLR has a targeting relationship with miR-19a-3p,and miR-19a-3p has a targeting relationship with BMP2.The expression level of miR-19a-3p in the pcDNA-HAGLR group was lower than that in the pcDNA-NC group(P<0.05).There was no significant difference in the expression level of lncRNA HAGLR between the miR-19a-3p mimic group and the NC mimic group(P>0.05).Compared with the NC mimic group,the expression level of BMP2 protein in the miR-19a-3p mimic group was decreased(P<0.05),while the expression level of miR-19a-3p was increased(P<0.05).The cells in the pcDNA-HAGLR group had stronger osteogenic differentiation ability and higher ALP activity than those in the pcDNA-NC group(P<0.05).The cells in the miR-19a-3p inhibitor group had stronger osteogenic differentiation ability and higher ALP activity than those in the NC inhibitor group(P<0.05).Conclusion The expression of lncRNA HAGLR and BMP2 is decreased and the expression of miR-19a-3p is increased in rats with tibial fracture.Overexpression of lncRNA HAGLR promotes osteogenic differentiation of rat MSCs by targeting the miR-19a-3p/BMP2 axis.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.
Humans ; Klebsiella pneumoniae ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Peritoneal Dialysis/adverse effects* ; Peritonitis/drug therapy* ; Risk Factors ; Treatment Failure ; Escherichia coli

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.
Animals ; Male ; Mice ; Colonic Neoplasms/drug therapy* ; Diarrhea ; Fluorouracil/adverse effects* ; Hormones ; Metabolomics ; Mice, Inbred BALB C ; Polysaccharides/pharmacology*