Objective:To analyze clinical characteristics of patients within 48 hours in pediatric intensive care unit（PICU）,and investigate causes and prognosis of extubation failure in reintubation children.Methods:A single-center retrospective study was conducted.Patients who were reintubated within 48 hours after extubation in PICU at Children's Hospital of Fudan University from January 1，2019 to December 31，2022 were retrospectively enrolled.Patients with unplanned extubation for various reasons which include re-intubation due to surgery and replacement of tracheal intubation were excluded.We analyzed the clinical characteristics，causes of extubation failure and prognosis.Main outcome measures included principal diagnosis，pediatric critical illness score（PCIS），the reason of intubation，the glasgow coma scale（GCS），the direct cause of reintubation，aeration time，hospitalization period，outcomes at PICU discharge and whether to extubate successfully.Results:During the study period，a total of 2 652 patients were extubated in PICU,and a total of 87 children were enrolled.Finally，63（72.4%）patients survived at PICU，nine（10.3%）patients died in hospital，and 15（17.2%）patients were discharged automatically.In the survival group，38（60.3%）patients were decannulated and 25（39.7%）patients underwent tracheotomy.The top three principal diagnosis in 87 cases were central nervous system disease[34（39.1%）cases]，lower airway disease[18（20.7%）cases] and sepsis[nine（10.3%）cases].Of the 87 children，28（32.2%）patients were reintubated due to central respiratory failure，21（24.1%）patients were reintubated due to lower airway disease，20（23.0%）patients were reintubated due to upper airway obstruction，14（16.1%）patients were reintubated due to cough weakness and/or swallowing disturbance，and four（4.6%）patients were reintubated for other reasons.In children with mechanical ventilation duration ≥7 days before first extubation，central nervous system diseases were the most common primary diseases，and it accounts for 55.6%.Central respiratory failure was the main direct cause of reintubation，accounting for 40.0%，and more patients(40.0%) had GCS scores＜8 before the first intubation.Compared with the successful decannulation group，the extubation failure group had the higher proportion of children with GCS＜8（32.7% vs.10.5%， P＜0.05），the longer median duration of mechanical ventilation before the first extubation[239（123，349）h vs.68.5（19，206）h， P＜0.05]and the longer median length of ICU stay[38（23，54）d vs.24（12，43）d， P＜0.05].After comparing the three groups including survival group，in-hospital death group and automatic discharge group，the PCIS score of the survival group was the highest，and the in-hospital death group was the lowest( P＜0.05). Conclusion:The rate of reintubation at 48 h after extubation in PICU is 3.3%.The immediate causes of reintubation mainly included central respiratory failure，lower airway disease，upper airway obstruction，cough weakness and/or dysphagia.The mortality rate of reintubation in critically ill children is high and the prognosis is poor.

Objective:To analyze the safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids.Methods:The clinical data of 60 patients with uterine fibroids who were admitted to Zhejiang Veteran Hospital from February 2020 to February 2022 were retrospectively analyzed. These patients were divided into a control group and an observation group ( n = 30/group) according to different surgical methods. The control group underwent conventional surgery. The observation group underwent superselective embolization of the uterine arteries. Uterine size, uterine fibroid size, postoperative hormone level, and complications were compared between the two groups. Results:There was no significant difference in total response rate between the observation and control groups [93.33 (28/30) vs. 83.33 (25/30), χ2 = 1.46, P > 0.05]. After surgery, serum estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone levels in the observation group were (164.14 ± 19.97) ng/L, (2.43 ± 1.47) IU/L, (2.51 ± 1.14) IU/L, and (5.05 ± 0.43) μg/L, respectively, which were significantly lower than (190.23 ± 21.62) ng/L, (3.78 ± 1.63) IU/L, (3.94 ± 1.23) IU/L, (8.22 ± 1.35) μg/L in the control group ( t = 4.86, 3.37, 4.67, 12.25, all P < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group [3.33% (1/30) vs. 20.00% (6/30), χ2 = 4.04, P < 0.05). Conclusion:Compared with conventional surgery, superselective embolization of the uterine arteries is more effective on uterine fibroids, better keep postoperative hormone level stable, and reduce or avoid short- and long-term complications. Therefore, superselective embolization of the uterine arteries for the treatment of uterine fibroids deserves the clinical promotion.

Multidrug resistance (MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here, based on the previous research of -(2-hydroxypropyl)methacrylamide (HPMA) polymer-drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin (Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide (MPP) and then attached to (HPMA) copolymers (P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species (ROS) as well as reduction of adenosine triphosphate (ATP) production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.

Objective To evaluate the reliability and clinical practicality of colony PCR in rapid detection of pathogenic fungi causing tinea capitis.Methods Totally,17 children with tinea capitis were enrolled from the Department of Dermatology of Wuxi No.2 People's Hospital between January 2016 and March 2017.Colony PCR was performed to detect pathogenic fungi.The results of colony PCR were compared with those of routine PCR and morphological identification,so as to evaluate the reliability of colony PCR in the identification of pathogenic fungi causing tinea capitis.Results After clinical specimens (broken hairs and scales) from the 17 patients were subjected to fungal culture,the mycelia were collected and successfully amplified by colony PCR.The time of clony PCR (mean,3.82 ± 0.50 days) for DNA template preparation was short than that of traditional morphological identification (14 days).Based on the results of conventional PCR,the accuracy of colony PCR for fungal identification was 100％,which was superior to that of conventional PCR (88.2％).Conclusions Colony PCR can be applied to the clinical detection of pathogenic fungi causing tinea capitis at specy level,and is a kind of rapid,economic and reliable molecular detection technique.

PURPOSE: C-end rule (CendR) peptides are found to enhance the penetration of chemotherapeutic agents into tumor cells, while GX1 is a peptide that homes to gastric cancer (GC) vasculature. This study aimed to synthesize a novel peptide GX1-RPAKPAR (GXC) and to explore the effect of GXC on sensitizing GC cells to chemotherapeutic agents. MATERIALS AND METHODS: Intracellular Adriamycin concentration analysis was applied to conform whether GXC peptide increases the penetration of chemotherapeutic agents into GC cells in vitro. The effect of GXC peptide on sensitizing GC cells to chemotherapeutics was validated by apoptosis assay and in vitro/vivo drug sensitivity assay. The specificity of GXC to GC tissue was validated by ex vivo fluorescence imaging. RESULTS: In vitro, administration of GXC significantly increased Adriamycin concentrations inside SGC-7901 cells, and enhanced the efficacy of chemotherapeutic agents by decreasing the IC50 value. In vivo, FITC-GXC specifically accumulated in GC tissue. Moreover, systemic co-injection with GXC peptide and Adriamycin statistically improved the therapeutic efficacy in SGC-7901 xenograft models, surprisingly, without obviously increasing side effects. CONCLUSION: These results demonstrated that co-administration of the novel peptide GXC with chemotherapeutic agents may be a potential way to enhance the efficacy of anticancer drugs in GC treatment.
Apoptosis ; Doxorubicin ; Drug Therapy* ; Heterografts ; In Vitro Techniques ; Inhibitory Concentration 50 ; Optical Imaging ; Peptides ; Sensitivity and Specificity ; Stomach Neoplasms*

Objective:To investigate the effect of poly (lactic acid)(PLA)electrospun membranes loaded with cisplatin and chloroquine on the oral squamous cell carcinoma CAL-27 cells,and to explore the method to prevent the recurrence of oral cancer.Methods: The DDP/PLA membranes, CQ/DDP/CQ/PLA membranes and CQ/DDP/PLA membranes were prepared by electrospinning.Then the micro morphology of three kinds of membranes were observed by scanning electron microscope (SEM);the degradation rate of PLA membrane was measuredby UV spectrophotometric.The LC3-Ⅱ expression level in CAL-27 cells was detected by laser scanning confocal microscope.The survival rate of CAL-27 cells was detected by MTT method.Results:The SEM results showed that the nanofibers of DDP/PLA,CQ/DDP/PLA and CQ/DDP/CQ/PLA membranes were continuous and smooth with uniform diameters.The degrated time of membranes was about 21 d.The MTT result showed that compared with control group,at first,the effects of cell killing of DDP/PLA membranes,CQ/DDP/CQ/PLA membranes and CQ/DDP/PLA membranes were not obvious;as the extension of time,the survival rates of CAL-27 cells in DDP/PLA membranes group,CQ/DDP/CQ/PLA membranes group and CQ/DDP/PLA membranes group were decreased (P <0.05).The immunofluorescence results showed that the fluorescence intensity of LC3-Ⅱ in CQ/DDP/CQ/PLA membranes group and CQ/DDP/PLA membranes group were lower than that in DDP/PLA membranes group.Conclusion:CQ/DDP/PLA membranes with sustained-release effect can increase the sensitivity of CAL-27 cells to DDP and enchance the killer effect of DDP on the CAL-27 cells.

Aim To investigate whether chronically un-predictable stress (CUS)-induced depression-like be-haviors of rats is associated with the variant expression of tryptophan hydroxylase (TPH)and tyrosine hydrox-ylase (TH).Methods 30 male SD rats were ran-domly divided into depression model group(MG)and control group (CG),the former was established using CUS plus solitary condition for 28 d,whereas the latter was fed normally as five rats per cage without CUS. The open field test(OFT)and the sucrose preference test were used to evaluate depressive behaviors.Both mRNA and protein expressions of TPH and TH in hip-pocampus and forebrain cortex were determined by re-al-time fluorescent quantitative PCR and western blot (WB),respectively.Results MG rats showed obvi-ous depressive behaviors with much lower locomotive activity and sucrose preference than CG.Meanwhile, the mRNA and protein expressions of TPH and TH also significantly decreased in MG rats,compared with CG rats.Conclusion The depression behaviors of rats in-duced by CUS may be associated with down-regulation of TPH and TH expression.

OBJECTIVETo investigate the molecular mechanism of the growth inhibitory effect of matrine on K562 cells in JAK/STAT3 mediated signal pathway.

METHODSWestern blot analyses were performed to investigate the differential expression of JAK2, STAT3, phosphor-STAT3 (Tyr705 & Ser727) and phosphor-JAK2 proteins after matrine treatment in K562 cells with or without human recombinant interleukin 6 (IL-6) pretreatment. The expression of STAT3 response gene products such as Bcl-xL, Cyclin D1 and c-Myc, were investigated by Western blot and quantitative real time RT-PCR (qRT-PCR). Expression of IL-6, a potent upstream activating factor of JAK/STAT3 pathway, was analyzed by both real time qRT-PCR and ELISA.

RESUTLSWestern blot revealed that matrine treatment resulted in a strong down-regulation of phosphor-STAT3 both in Tyr705 and Ser727 sites or phosphor-JAK2 proteins expression without significant effects on the total STAT3 and JAK2 proteins. The expression of phosphor-Tyr705 STAT3 and phosphor-Ser727 STAT3 was decreased to 0.370 ± 0.172 in K562 cells treated with 0.5 mg/ml matrine for 48 h, respectively, from 0.690 ± 0.119 and 1.150 ± 0.263 in control cells, accompanied with a dramatical down-regulation of phosphor-JAK2 from 0.670 ± 0.137 to 0.049 ± 0.057 (P<0.05). In addition, it was found that the expression of Bcl-xL, Cyclin D1, c-Myc was decreased both at the transcription and protein level in K562 cells after matrine treatment. Matrine treatment resulted in a significant decrease in the expression level of IL-6 in K562 cells from (35.1 ± 1.93) to (10.74 ± 1.83) and (8.66 ± 1.24) pg/ml at the dose of 0.5 and 0.8 mg/ml, respectively (p<0.05). Matrine treatment could diminish the up-regulation of STAT3, JAK2, phosphor-STAT3 and phosphor-JAK2 protein following pretreatment with IL-6 in K562 cells.

CONCLUSIONMatrine exerts its anti-leukemia effect by interfering with the JAK2/STAT3 signaling pathway. The inhibition of IL-6 expression may play a pivotal role in the disruption of JAK/STAT pathway by matrine.

Alkaloids ; Down-Regulation ; Humans ; Interleukin-6 ; Janus Kinase 2 ; K562 Cells ; Quinolizines ; STAT3 Transcription Factor ; Signal Transduction ; Up-Regulation

CD5 Antigens ; Humans ; Lymphoma, Mantle-Cell

Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.