Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Phosphorylation ; Porphyromonas gingivalis ; Signal Transduction

Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.

Objective:To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO 2/FiO 2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO 2, SpO 2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. Results:Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ β values were -15.827, 1.202, 95% confidence interval (95% CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. Conclusion:Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

【Objective】 To investigate the function and molecular mechanism of osteosarcoma cells derived exosome on microenvironment of target organs. 【Methods】 The osteosarcoma derived exosomes were extracted and injected into nude mice through tail vein after PKH26 fluorescence staining. The liver, spleen, lung, kidney and brain tissues were extracted 24 hours later and then the amount of red fluorescence in different fields was counted under fluorescence microscope. The uptake of exosomes in different types of cells was detected by immunofluorescence. 143B derived exosomes were co-cultured with human lung fibroblasts, and the uptake was detected by fluorescence microscopy. The expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were detected by RT-qPCR, while the changes of p-p65 in inflammatory signaling pathway of NF- κB and p-ERK, p-p38 in MAPK signaling were detected by western blotting. 【Results】 TSG101, Flotillin-1, CD63 and CD9 were expressed in 143B derived exosomes, and Calnexin expression was absent(P<0.05). The exosomes presented a saucer-like structure under electron microscope. The size of the exosomes is(141.92± 52.85) nm. The exosomes distributed more in lung tissue than liver, kidney, spleen and brain after injection through the tail vein of nude mice(P<0.05). The mRNA levels of inflammatory cytokines IL-1β, IL-6and TNF-α were significantly increased in human lung fibroblast cells after incubation with 143B exosomes(P<0.05). p-p65, p-ERK and p-p38MAPK were significantly up-regulated(P<0.05) . 【Conclusions】 Osteosarcoma cells derived exosomes could activate inflammatory signaling pathway NF-κB and MAPK, and up-regulate the expression of the inflammatory cytokines IL-1β, IL-6 and TNF-α in lung fibroblast cells.

The aim of the present study was to investigate the effect of Sophoral flavones on proliferation of cardiac fibroblasts (CFb) induced by high glucose and its underlying mechanism. Cardiac fibroblasts were exposed to different concentration of D-glucose (15, 25 and 35 mmol·L^-1) at different time point (24, 48 and 72 h) in order to determine cell proliferation, and the model group was established by culturing CFb with 25 mmol·L^-1D-glucose for 48 h. Sophoral flavones (12.5, 25 and 50 mg·L^-1) were employed for intervention. The cell viability was measured by MTT assay, and the levels of transforming growth factor-β₁ (TGF-β₁), matrix metalloproteinase-2 (MMP-2), collagen Ⅰ and collagen Ⅲ were measured by ELISA. In addition, flow cytometry was employed to detect the cell cycle; while the protein expression of prohibitin (PHB) was observed via immunocytochemistry and Western blot. This animal experiment had been approved by Jilin Medical University Experiment Animal Ethics Review Committee. The results showed that 25 mmol·L^-1 glucose could promote the proliferation of CFb; and the contents of TGF-β₁, MMP-2, collagen Ⅰ and collagen Ⅲ in the model group were higher than that of control (P<0.05). The number of cells in S and G₂ phase increased under high glucose condition. In the model group, PHB translocation occurred at 6 h and protein expression decreased at 48 h (P<0.01). Compared with the model group, 12.5-50 mg·L^-1 Sophoral flavones reduced the contents of TGF-β₁, MMP-2, collagen Ⅰ and collagen Ⅲ, increased the number of G₁ phase cells, and increased the expression of PHB protein at 48 h (P<0.05), with no effect on the nuclear translocation of PHB. These results indicated that Sophoral flavones could prevent the proliferation of CFb induced by high glucose, the mechanism of which may be related to increasing the expression of PHB protein.

Objective    To investigate the clinical manifestations of patients with cardiac myxoma and the factors affecting the occurrence of embolic events. Methods     A retrospective study of 38 patients with cardiac myxoma diagnosed and surgically removed from January 2010 to December 2017 was performed. There were 11 males and 27 females at age of 32-75 (50.00±16.12) years. The patients were divided into a non-embolized group and an embolized group. The clinical manifestations of the patients were summarized and the factors leading to embolism were analyzed. Rseults    Of the 26 patients in the non-embolized group, 22 patients (84.62%) had dyspnea, 14 patients (53.85%) had palpitations, 4 patients (15.38%) had angina pectoris, and 1 patient (3.85%) had heart failure. Of the 12 patients in the embolized group, 4 patients (33.33%) had dyspnea, 3 patients (25%) had palpitations, and 1 patient (8.33%) had angina pectoris. The mean diameter of the non-embolized group was 5.71±1.63 cm, and the maximum diameter of the tumor in the embolized group was 4.52±1.88 cm. There was no significant difference between the maximum diameter of the tumor in the embolized group and the maximum diameter of the non-embolized group (P>0.05). Atrial fibrillation occurred in 2 patients in the non-embolized group before operation. Atrial fibrillation occurred in 5 patients in the embolized group. Atrial fibrillation was more likely to occur in the embolized group (P<0.05). Conclusion     Atrial fibrillation in the patients with cardiac myxoma is closely related to embolic events. The size of myxoma is not related to the occurrence of embolic events.

Objective: To investigate the value of Cytomegalovirus(CMV) DNA real-time quantitative-polymerase chain reaction(RT-PCR) in different body fluids for diagnosing CMV pneumonia in immunocompetent infants. Methods: The clinical data of immunocompetent infants with CMV pneumonia who were treated in Pediatric Intensive Care Unit of Guangdong Women and Children′s Hospital from January 1^st, 2016 to February 5^th, 2018 were retrospectively analyzed.The clinical data included CMV DNA load of bronchoalveolar lavage fluid(BALF), urine, blood and cerebrospinal fluid(CSF); blood immunoglobulin(Ig)M CMV, alanine aminotransferase (ALT), X-ray and CT test of chest, combined infection, clinical manifestation and treatment. Results: Nine hundred and twenty-six infants received bronchoalveolar lavage by bronchoscope, and 34 cases were diagnosed as immunocompetent with CMV pneumonia.The infants with CMV pneumonia: the positive percentage of urine CMV DNA, blood CMV DNA, blood IgM CMV and ALT elevation were 100.0%(34/34 cases), 61.8%(21/34 cases), 52.9%(18/34 cases) and 20.6%(7/34 cases), respectively.There was no difference in positive percentage between blood CMV DNA and blood IgM CMV (χ²=0.5, P>0.05). Both the positive percentages of blood CMV DNA and blood IgM CMV were lower than those in the urine CMV DNA, and the differences were statistically significant (χ²=16.1, 20.9, all P<0.05). The positive percentages of ALT elevation were lower than those in the positive percentage of urine CMV DNA, blood CMV DNA and blood IgM CMV, and the differences were statistically significant (χ²=44.8, 11.9, 7.7, all P<0.05). Ten patients′ CSF CMV DNA were tested, and they were all negative.The median load of CMV DNA in BALF, urine and blood was 170.0×10⁵ copies/L, 130.0×10⁵ copies/L and 6.0×10⁵ copies/L.There was no difference in median load between BALF and urine (U=561, P>0.05). BALF CMV DNA load and blood CMV DNA load had a weak positive correlation (r=0.35, P<0.05), BALF CMV DNA load and age had a negative correlation (r=-0.42, P<0.05), and urine CMV DNA load and blood CMV DNA load had a positive correlation (r=0.52, P<0.05). No matter whether blood IgM CMV was positive, BALF CMV DNA load had no differences (U=92, P>0.05). The main radiographic signs were pulmonary interstitial lesions.Thirty-four immunocompetent infants with CMV pneumonia, 18 patients (52.9%) with symptoms lasted for over 2 weeks, 20 patients (58.8%) had complicated infections.They all received inductive treatment of Ganciclovir, 55.9%(19/34 cases) patients′ urine CMV DNA turned to be negative.When patients got combined infections by bacteria or mycoplasma, antibiotics were used.All discharged patients had symptoms relieved and signs improved. Conclusions BALF RT-PCR is instant, sensitive and distinctive method to diagnose CMV pneumonia.Urine RT-PCR gets specimens conveniently and safely, its positive percentage and DNA load are present well according to BALF, and is suitable for screening and monitoring CMV infection.Blood CMV DNA load and blood IgM CMV indicate viral dissemination and immunocompetence, but it is not recommended for diagnosing CMV pneumonia solely.

Integration of "5+3" training mode is to accelerate the construction of standardization of clinical medical personnel training system,and the establishment of the new training mode.The training goal is to make the students become the high-level clinicians with the ability of clinical thinking and clinical practice,and scientific research and teaching,who can independently and pro-fessionally prevent and treat the related common disease.Therefore,guided by the general training goal of our students,we designed and practiced a teaching mode centered on "immune disease mechanism analysis" in the teaching of medical immunology,aiming at improving students'ability of clinical thinking,self learning and team coorperation.