OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

In the field of substance detection,ion dissociation techniques have become crucial for enhancing qualitative accuracy.By applying external energy to induce dissociation of ions in the substance being analyzed,the internal structural information can be obtained,thereby improving qualitative capabilities.Current research on ion dissociation techniques primarily focuses on tandem mass spectrometry,which typically requires a vacuum environment.However,research on ambient ion dissociation techniques is less developed,with some progress made in the field of tandem ion mobility spectrometry.Recently,the development of field-induced dissociation(FID)in this area has enabled ambient dissociation of various explosive and volatile alcohol ions.Nevertheless,the limitation imposed by the maximum breakdown field of air restricts the energy of the electric field,making it challenging to dissociate ions with high energy requirements,such as those of drugs.To address this issue,in this work,an ambient heat-induced dissociation(HID)technique based on high temperatures was proposed,in which an ambient ion heat-induced dissociation unit was developed and integrated into a home-made ion trap mass spectrometer.Experiments were conducted on four representative drug samples,e.g.methamphetamine,heroin,cocaine,and ketamine.The parent ions mass spectra,low vacuum collision-induced dissociation(CID)mass spectra and ambient HID mass spectra for each sample were obtained.By analyzing and comparing the fragmentation products from ambient and low vacuum dissociation,the feasibility of the ambient HID technique was verified.This technique provided a method for ion dissociation in single mass analyzers without tandem mass spectrometry capability and offered a new research direction for the future development of tandem ion mobility spectrometry.

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.

Objective To explore the clinical efficacy and safety of Xuefu Zhuyu decoction as an adjuvant chemotherapy in patients with advanced cervical cancer.Methods This study recruited advanced cervical cancer patients who underwent TP regimen(paclitaxel+cisplatin)chemotherapy in Luzhou District People's Hospital in Changzhi City from January 2019 to January 2021.According to the random number table method,patients with advanced cervical cancer were divided into a control group(treated with TP regimen)and an test group(treated with TP regimen combined with Xuefu Zhuyu decoction).The serum tumor marker levels(carcinoembryonic antigen,squamous cell carcinoma antigen and carbohydrate antigen 125),traditional Chinese medicine syndrome scores and clinical efficacy[objective response rate,disease control rate and overall survival time]between two groups of patients were observed and compared.The occurrence of adverse drug reactions was assessed according to the Common Terminology Standard for Adverse Events(CTCAE 4.03).Results A total of 92 cases of advanced cervical cancer were included in this study,with 46 cases in each group.Before treatment,there was no significant statistical difference in the serum tumor marker levels and traditional Chinese medicine syndrome scores between the control group and the test group with advanced cervical cancer(P>0.05).After treatment,the serum tumor marker levels and traditional Chinese medicine syndrome scores in the test group and the control group significantly decreased compared to before(P<0.05),and they were significantly lower in the test group than those in the control group(P<0.05).In terms of clinical efficacy,there was no significant difference in objective response rate between two groups(P>0.05),while the disease control rate and median overall survival time of the test group were significantly higher than those of the control group(P<0.05).In terms of safety,no fatal adverse events were observed,and most adverse events were mild and controllable.In addition,there was no significant difference in the incidence of nausea and vomiting,anemia,thrombocytopenia and renal dysfunction between two groups(P>0.05),while the incidence of leukopenia and liver function injury in the test group were significantly lower than those in the control group(P<0.05).Conclusion Xuefu Zhuyu decoction can significantly improve the efficacy of chemotherapy patients with advanced cervical cancer,reduce serum tumor marker expression levels,improve traditional Chinese medicine syndrome scores,increase disease control rate,prolong overall survival,and has high safety.

Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

Objective To compare the effects of levo-praziquantel (L-PZQ) and dextro-praziquantel (D-PZQ) on the proliferation and activation of the human hepatic stellate cell line LX-2 in vitro. Methods LX-2 cells were stimulated with transforming growth factor-β (TGF-β). LX-2 cell proliferation was measured using the CCK-8 assay after 24 h stimulation with 0 to 50 μg/mL concentrations of praziquantel, and the gene and protein expression of type Ⅰ collagen (collagen Ⅰ), type Ⅲ collagen (collagen Ⅲ) and α-smooth muscle actin (α-SMA) was quantified in LX-2 cells using quantitative real-time PCR (qPCR) and Western blotting assays 24 h and 48 h following stimulation with 15 μg/mL praziquantel to detect LX-2 cell activation. Results There were significant differences in the survival rate of LX-2 cells between L-PZQ and D-PZQ treatments at all concentrations (F = 6.119 and 79.180, both P values < 0.05). Either L-PZQ or D-PZQ at a concentration of < 30 μg/mL showed no remarkableeffectsonthe LX-2 cell proliferation (both P values > 0.05), and L-PZQ at a concentration of > 50 μg/mL and D-PZQ at a concentration of > 40 μg/mL inhibited the LX-2 cell proliferation (both P values < 0.05), while D-PZQ at concentrations of 40 μg/mL and 50 μg/mL showed greater inhibition on LX-2 cell proliferation than L-PZQ (t = 3.419 and 8.776, both P values < 0.05). There were significant differences in the collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both transcriptional (F = 21.55, 79.99 and 46.70, all P values < 0.05) and translational levels (F = 20.12, 30.29 and 32.93, all P values < 0.05) among the blank control group, TGF-β stimulation group, L-PZQ treatment group and D-PZQ treatment group. L-PZQ treatment resulted in remarkable inhibition on collagen Ⅲ and α-SMA gene expression in LX-2 cells (both P values < 0.05); however, the treatment showed no remarkable inhibition collagen Ⅰ gene expression or collagen Ⅰ, collagen Ⅲ or α-SMA protein expression in LX-2 cells (all P values > 0.05). In addition, D-PZQ treatment resulted in significant inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both translational and transcriptional levels (all P values < 0.05), and D-PZQ showed higher inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA gene expression in LX-2 cells than L-PZQ (all P values < 0.05). Conclusions Both L-PZQ and D-PZQ inhibit the proliferation and activation of LX-2 cells, and D-PZQ shows a higher inhibitory activity than L-PZQ.

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ² = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.
Adenosine Diphosphate/pharmacology* ; Adenosine Triphosphate ; Animals ; Molluscacides/pharmacology* ; Silica Gel/pharmacology* ; Snails ; Streptomyces ; Water

Ultra-high performance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS/MS) has been used to detect the metabolites of schaftoside in plasma, bile, urine and feces of mice after oral administration. The study was approved by the Experimental Animal Ethics Committee from Xuzhou Medical University (No. XZMULL201612024). Compounds were identified by analyzing their high-resolution mass spectrometry data, mass spectra, and comparison with reference substances and the literatures. The parent compound and 29 metabolites were detected in the plasma, bile, urine and feces samples of mice. The main metabolic pathways of schaftoside in mice include deglycosylation/glycosylation, hydroxylation/dehydroxylation, hydrogenation, methylation, acetylation, sulfation, and glucuronidation. This study provides references for the material basis of schaftoside in vivo.

Objective:To investigate the efficacy of the posterior axillary approach in the treatment of some scapular fractures.Methods:Retrospectively analyzed were the data of 41 patients with scapular fracture who had been treated through the posterior axillary approach at Department of Traumatology, The Second Hospital of Jilin University from April 2018 to July 2021. There were 32 males and 9 females, aged from 24 to 83 years (average, 52.4 years). Of them, 7 were complicated with multiple injuries, 16 with other fractures, and 4 with brachial plexus injury. Recorded were length of surgical incision, intraoperative blood loss, operation time, and range of shoulder motion, Disability of Arm Shoulder and Hand (DASH) score, Constant shoulder score and postoperative complications at the last follow-up.Results:In this cohort, length of incision ranged from 7 to 12 cm (average, 9.3 cm), intraoperative blood loss from 80 to 150 mL (average, 110.5 mL), exposure time of the posterior axillary approach from 5 to 10 min (average, 7.9 min), and fracture operation time from 85 to 140 min (average, 110.8 min). The 41 patients were followed up for 6 to 36 months (mean, 14.3 months) after surgery. At the last follow-up, the average ranges of shoulder motion were 177° (from 150° to 180°) in flexion, 175° (from 140° to 180°) in abduction and 47° (from 30° to 50°) in extension, the average DASH score was 36.4 points (from 34 to 46 points), and the average Constant score 96.0 points (from 84 to 100 points). There were no complications like loss of fracture reduction, loosening or breakage of plate or screw during follow-up. Incision healing was delayed in 2 patients and mild heterotopic ossification occurred in 2 patients.Conclusion:As a new surgical approach for some scapular fractures, the posterior axillary approach allows internal fixation of the fractures of the scapular glenoid, neck and body under direct vision, leading to good-looking postoperative wound and reliable curative effects.