Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl^-, Na⁺, K⁺, and Ca²⁺ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified.
Rats ; Animals ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Signal Transduction ; Cerebrospinal Fluid/metabolism*

Objective:To evaluate the clinical characteristics and prognosis of febrile convulsions (FS) in children during the epidemic period of novel coronavirus Omicron variant.Methods:A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with FS at Changsha Central Hospital Affiliated to University of South China from February 1, 2022 to January 31, 2023. The clinical characteristics and prognosis of FS patients caused by Omicron variant infection (observation group) were compared with those caused by non Omicron variant infection (control group).Results:A total of 131 cases in the observation group and 341 cases in the control group; The proportion of children aged 12-36 months in the observation group was lower than that in the control group ( P<0.05), and the proportion of children aged ≥60 months was higher than that in the control group ( P<0.05). Most of the FS in the observation group occurred within 24 hours of fever (128/131, 97.7%), with a statistically significant difference compared to the control group ( P<0.05), and most of them were generalized tonic clonic seizures (127/131, 96.9%), with only one seizure during the course of the disease (114/131, 87.0%), consistent with the characteristics of simple FS. The main clinical symptoms of FS patients in the observation group were upper respiratory tract infections (108/131, 82.5%), which were significantly higher than those in the control group (164/341, 48.1%), while the incidence of lower respiratory tract infections was lower than that in the control group ( P<0.05). 369 pediatric patients were followed up by phone or outpatient visits, with 98 cases in the observation group and 2 cases experiencing recurrence. There was no recurrence in the group aged ≥60 months; A total of 271 cases were followed up in the control group, with 9 cases experiencing recurrence. Conclusions:The number of children with FS caused by novel coronavirus Omicron variant has increased sharply, and the proportion of late onset FS patients has increased significantly. Most of them are upper respiratory tract infections. Convulsions usually occur within 24 hours of fever, and the prognosis is good.

Objective:To investigate the value of PET/CT imaging with 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-3 polyethylene glycol- D-Phe1-Tyr3-Thr8-octreotide Arg-Gly-Asp (NOTA-3P-TATE-RGD), a dual somatostatin receptor 2- and integrin α vβ 3- targeting tracer, in the evaluation of neuroendocrine neoplasms (NEN). Methods:From April 2021 to February 2022, 35 patients (19 males, 16 females; median age 54(41, 61) years) with histologically confirmed NEN in Peking Union Medical College Hospital were prospectively enrolled. All patients were scanned with both 68Ga-NOTA-3P-TATE-RGD and 68Ga-1, 4, 7, 1 0-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) PET/CT imaging within one week. The differences of the numbers of detected lesions, SUV max and tumor-to-background ratio (TBR) between the two imaging methods were compared by Wilcoxon signed-rank test. Results:Of the 35 patients, the total numbers of lesions detected by 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE were 1 190 and 1 106, respectively. 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE both detected 35 primary tumors and performed comparably in detecting lymph node metastases (4(1, 8) vs 4(1, 8); z=-0.45, P=0.655) and bone metastases (5(2, 60) vs 5(2, 66); z=-1.11, P=0.244). However, the number of liver lesions detected by 68Ga-NOTA-3P-TATE-RGD was significantly higher than that by 68Ga-DOTATATE (17(6, 27) vs 8(3, 26); z=-2.31, P=0.021). 68Ga-DOTATATE demonstrated higher SUV max than 68Ga-NOTA-3P-TATE-RGD (15.6(9.9, 24.9) vs 12.7(8.0, 18.4); z=-7.19, P<0.001), while the TBR of liver metastases was significantly lower (3.4(1.8, 5.5) vs 6.1(3.8, 10.8); z=-7.56, P<0.001). Conclusion:68Ga-NOTA-3P-TATE-RGD performs better than 68Ga-DOTATATE in the detection of liver metastases, while is comparable to 68Ga-DOTATATE in detecting lesions of other sites.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
Carcinoma, Squamous Cell ; Cell Proliferation ; Head and Neck Neoplasms ; Humans ; Mouth Neoplasms ; Oxidoreductases Acting on CH-CH Group Donors ; SOXB1 Transcription Factors ; Squamous Cell Carcinoma of Head and Neck

Objective:To explore the effect of Hsp22 on the activation of cardiac fibroblasts stimulated by TGFβ1 and its possible molecular mechanism.Methods:Cardiac fibroblasts of adult mice were isolated and cultured, and stimulated with TGFβ1 to induce fibroblast activation. Fibroblasts were incubated with Hsp22 of different concentrations (1, 2, 4, 8, 10 μg/mL) for 24 h, and their activation, proliferation and secretion were observed. CCK8 kit was used to detect cell proliferation. RT-PCR was used to detect the transcription of fibrogenic factor. Immunofluorescence was used to detect the expression of α-SMA protein. Immunoblotting was used to detect the possible signal protein.Results:CCK8 results showed that fibroblast increased significantly after TGFβ1 stimulation ( P<0.05). The expression of α-SMA in fibroblasts and the transcription of fibrosis-related genes increased significantly after TGFβ1 stimulation ( P<0.05). Different concentrations (1, 2, 4, 8, and 10 μg/mL) of Hsp22 all inhibited the proliferation of fibroblasts significantly (( P<0.05). Eight μg/mL and 10 μg/mL Hsp22 inhibited the expression of α-SMA ( P<0.05). and reduced the transcription of fibrosis-related genes ( P<0.05). Immunoblotting results indicated that after induced by TGFβ1, the expression of WNT and β-catenin, the phosphorylation level of GSK3β, and the nuclear translocation of β-catenin increased ( P<0.05). Ten μg/mL Hsp22 inhibited the expression of WNT and β-catenin, and reduced the phosphorylation of GSK3β the nuclear translocation of β-catenin and the phosphorylation of smad2 and smad3( P<0.05). Conclusions:Hsp22 could block TGFβ1-induced fibroblast activation, proliferation and secretion via inhibiting the WNT/β-catenin signaling pathway.

Objective: To explore the relationship between family cohesion, psychological resilience and non-suicidal self-injury among middle school students. Methods: By using the stratified random cluster sampling method, 2 065 students from 4 middle school from Fujian province were investigated with family cohesion scale, adolescent psychological resilience scale and adolescent self-injury behavior questionnaire. Results: The report rate of self-injury was 40.34%, which differed by childhood migration experiences, parenting style as well as academic pressure (χ2=11.66，29.45，12.48，P<0.01). Total scores and dimensional scales in family cohesion and psychological resilience showed significant differences in students with or without self-injury (t=-8.33，-12.08，-7.29，-11.53，-3.38，-7.37，-7.68，P<0.01). The family cohesion was positively correlated with the psychological resilience and each dimension (r=0.27-0.56, P<0.01), but negatively correlated with non-suicidal self-injury (r=-0.18, P<0.01). The psychological resilience and each dimension were negatively correlated with non-suicidal self-injury (r=-0.24--0.14, P<0.01). Psychological resilience had a partial mediating effect between family cohesion and non-suicidal self-injury, with mediating effect accounting for 61.11% of the total effect. Conclusion Psychological resilience played a mediating role between family cohesion and non-suicidal self-injury. By promoting family cohesion to improve psychological resilience, it is helpful to prevent non-suicidal self-injury among middle school students.

Clinical data of 93 patients with severe craniocerebral injury admitted in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2018 were retrospectively analyzed. Forty six patients received 10% hypertonic salt solution 60 ml (hypertonic salt group) and 47 patients received 20% mannitol 125 ml (mannitol group) for relieving early postoperation cerebral edema. The changes of intracranial pressure, central venous pressure, heart rate, mean arterial pressure (MAP), urine volume and serum sodium level at 2, 4 and 6 h after dehydrating agents were compared between two groups. There were no significant differences in the intracranial pressure, central venous pressure, heart rate and urine volume between two groups at 2, 4 and 6 h after the first dehydration treatment (all P>0.05). The MAP values of the two groups were (88±11) and (80±10), (85±10) and (78±9), (79±12) and (73±13) mmHg (1 mmHg=0.133 kPa) at 2, 4 and 6 h after the first dehydration treatment; and the serum sodium levels were (145±5) and (136±4), (144±6) and (133±5), (140±5) and (135±4) mmol/L, respectively. There were significant differences between two groups (all P<0.05). It is suggested that hypertonic salt can reduce intracranial pressure and increase cerebral perfusion better than mannitol in severe craniocerebral injury.