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Objective@#To investigate the breakfast consumption of middle school students and to analyze its relationship with physical fitness, so as to provide reference for improving physical fitness of middle school students.@*Methods@#A total of 2 732 middle school students from Shangrao City were selected in September 2021 by random cluster stratified sampling. The breakfast consumption behaviors of middle school students were investigated by questionnaire, and the general information, family information and other lifestyle behaviors were collected. The physical fitness test includes grip strength, standing long jump, 1 minute sit up, sit forward bend, 50 m run and 20 m shuttle run test (20 m SRT) to evaluate the strength, flexibility, speed and endurance of middle school students. χ 2 tests were used to compare the correlation between different demographic characteristics, breakfast behavior and physical fitness,and Logistic regression analysis was used to infer the correlation strength between breakfast behavior and physical fitness.@*Results@#The detection rate of physical fitness failure among middle school students was 21.5%. There were statistically significant differences between breakfast frequency and grip strength and 20 m SRT( χ 2=8.27, 13.90, P < 0.05 ). Logistic regression analysis results showed that 20 m SRT was positively correlated with breakfast frequency (sometimes eat breakfast, OR =1.51, skip or occasionally eat breakfast OR =2.08, P <0.05).@*Conclusion@#The low frequency of breakfast consumption of middle school students is associated with low performance on 20 m SRT. Schools and families should pay attention to the breakfast consumption of middle school students to ensure adequate daily nutrition intake.
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Objective@#To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke.@*Methods@#Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI.@*Results@#A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke.@*Conclusion@#Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.
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Objective:To study the efficacy of nasal intermittent positive pressure ventilation (NIPPV) and minimally invasive surfactant therapy (MIST) in very preterm infants with respiratory distress syndrome (RDS).Methods:From January to December 2020, very preterm infants (gestation age ≤30 weeks) with RDS born and treated in our hospital were randomly assigned into NIPPV group and nasal continuous positive airway pressure (NCPAP) group. Both groups were treated with MIST technique. The following items were compared between the two groups:adverse reactions during MIST, partial pressure of carbon dioxide (PaCO 2) at 2 h after MIST, the incidences of intubation within 72 h, two or more doses of pulmonary surfactant (PS), frequent apnea, other complications and the parameters of respiratory support treatment. Results:A total of 62 cases were included, with 32 in the NIPPV group and 30 in the NCPAP group. Compared with the NCPAP group, the NIPPV group had lower incidences of bradycardia (6.3% vs. 30.0%), decreased oxygen saturation (12.5% vs. 40.0%) and apnea (6.3% vs. 30.0%) during MIST ( P<0.05). No significant difference existed in the incidence of regurgitation ( P>0.05). PaCO 2 at 2 h after MIST [40.1(38.2,43.8)mmHg vs. 48.3(44.1,50.0)mmHg], the incidences of intubation within 72 h (6.3% vs. 30.0%), two or more doses of PS (6.3% vs. 30.0%)and frequent apnea (6.3% vs. 30.0%) in NIPPV group were lower than NCPAP group ( P<0.05). No significant differences existed between the two groups on the following items: the durations of invasive ventilation, non-invasive ventilation, oxygen therapy, the incidences of bronchopulmonary dysplasia, intraventricular hemorrhage (≥Ⅲ), periventricular leukomalacia, retinopathy of prematurity (≥Ⅱ), necrotizing enterocolitis (≥Ⅱb), nasal injury, air leak and death ( P>0.05). Conclusions:Combining NIPPV and MIST can reduce the incidence of adverse reactions during PS administration without increasing respiratory support duration and common complications in preterm infants. It is recommended for clinical use.
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Prenatal examinations are of great significance to promoting maternal and child health. This article reviews research progress of Centering Pregnancy at home and abroad, including its main content, application in special groups, benefits of implementation, and leads to some enlightenment of this model to the field of midwifery in China, which provides reference for a new model nationally applied in prenatal care.
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Objective:To analyze the genetic characteristics of Group A Streptococcus (GAS) isolated from the pharynx of children with scarlet fever-like erythema. Methods:Pharyngeal GAS isolates were collected retrospectively from children with scarlet fever-like erythema admitted in the Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from June 2019 to February 2020.PCR and sequencing were used to detect emm genotyping and superantigen genes( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, ssa and smeZ) of the isolates.Data were compared by the chi-square test or Fisher′ s exact test between groups. Results:A total of 147 GAS strains were collected.The main emm genotypes were emm1.0 in 76 strains (51.70%) and emm12.0 in 60 strains (40.82%). Other 7 emm genotypes were all found in less than 5 strains.The detection rate of speF, smeZ, speG, speC, speB and ssa were as high as 100.00%(147/147 strains), 100.00%(147/147 strains), 99.32%(146/147 strains), 95.24%(140/147 strains), 94.56%(139/147 strains) and 92.52%(136/147 strains), respectively. speA, speJ, speI, speH and speM had a low detection rate of 51.70%(76/147 strains), 49.66%(73/147 strains), 32.65%(48/147 strains), 23.81%(35/147 strains) and 4.08%(6/147 strains), respectively.No speK and speL were detected.The frequencies of speA and speJ in emm1.0 strains (65/76 strains, 85.53% and 64/76 strains, 84.21%) were significantly higher than those in emm12.0 strains (4/60 strains, 6.67% and 6/60 strains, 10.00%). However, the frequencies of speH and speI in emm1.0 strains (7/76 strains, 9.21% and 2/76 strains, 2.63%) were significantly lower than those in emm12.0 strains (28/60 strains, 46.67% and 45/60 strains, 75.00%) (all P<0.001). Conclusions:At present, emm1.0 and emm12.0 are the main GAS strains isolated from the throat of children with scarlet fever-like erythema in Beijing, and emm1.0 is more common.There is a correlation between emm genotyping and the superantigen gene profile.Type 1 superantigen gene profile is significantly more frequently detected in emm1.0 strains than in emm12.0 strains.Type 2, 3 and 4 superantigen gene profiles are significantly more frequently detected in emm12.0 strains than in emm1.0 strains.
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Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.
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Objective:To analyze the clinical characteristics and pathogenic distribution of severe pneumonia in adults in order to provide basis for clinical diagnosis and treatment.Methods:From June 2021 to April 2022, 145 patients with pneumonia admitted to the Department of Respiratory and Critical Care Medicine of the Second People's Hospital of Guangdong Province. According to whether they meet the diagnostic criteria for severe pneumonia, they were divided into severe ( n=63) and mild ( n=82) groups, and the clinical features between the two groups were compared. At the same time, the role of FilmArray detection in severe pneumonia was discussed. The measurement data were tested using independent sample t test or Mann-Whitney U test, and the counting data were tested using Chi-square test or Fisher exact probability method. Results:The age of the patients in the severe group was (72.67±1.71) years, male patients accounted for 84.1%, and the median hospitalization time was 16 days. Nine patients died in hospital; most of them had fever, shortness of breath, and change of consciousness, accompanied by hypertension, diabetes, cerebrovascular disease, chronic kidney disease, and tumor history. Compared with the mild group, the total number of leukocytes, neutrophil ratio, procalcitonin, and C-reactive protein were higher in the severe group, but the CD3 +, CD4 +, and CD8 + cell counts were lower ( P<0.05). The positive rate of FilmArray detection in the severe group was 81%, and the mixed infection of multiple bacteria accounted for 50%, which was higher than that of traditional culture ( P<0.05). The top four pathogens in severe group were Pseudomonas aeruginosa, Acinetobacter baumannii complex, Klebsiella pneumoniae, and Staphylococcus aureus, which were significantly higher than that in the mild group ( P<0.05). Resistance genes were detected in patients with severe disease, which was significantly higher than that in patients with mild disease (70.7% vs. 17.5%, P<0.05). Conclusions:Severe pneumonia is more common in elderly men, with more basic diseases and poor immunity. FilmArray has a high positive rate and can detect multiple pathogens, which may have a role in the rapid diagnosis of severe pneumonia.
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SoxC transcription factors are a group of important protein molecules involved in gene transcription, translation and expression, which can regulate gene expression by specifically binding to corresponding target genes or proteins. The SoxC gene family has unique molecular structure features. Its members Sox4, Sox11 and Sox12 are abnormally expressed in a variety of tumors, and can be used as diagnostic and prognostic markers for different tumors. Investigating the pathogenic mechanisms of the SoxC transcription factor family and their clinical significance can increase the evidence for SoxC as a therapeutic target for tumors.
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Objective:To investigate the predictive value of CT perfusion imaging (CTP) parameters on the outcome after mechanical thrombosis (MT) in patients with anterior circulation acute ischemic stroke due to large vessel occlusion (LVO-AIS).Methods:The clinical data of patients with LVO-AIS received MT treatment in Taizhou People’s Hospital from July 2019 to June 2021 and achieved modified Thrombolysis in Cerebral Infarction (mTICI) blood flow grade 2b or above were retrospectively enrolled. RAPID software was used to automatically conduct image post-processing to obtain CTP parameters. The patients were divided into good outcome group (≤2) and poor outcome group (>2) according to the modified Rankin Scale score at 90 days after procedure. Multivariate logistic regression analysis was used to screen the CTP parameters that affect the outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of CTP parameters for poor outcomes. Results:A total of 88 patients with LVO-AIS were enrolled, including 52 males (59.1%), with a median age of 71 years (range 58-78 years), and the median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14 (range, 11-17). Eleven patients (12.5%) received intravenous thrombolytic bridging MT, and 77 (87.5%) received direct MT. Forty-seven patients (53.4%) had good outcomes and 41 (46.6%) had poor outcomes at 90 d after procedure. Univariate analysis showed that there were significant differences in baseline NIHSS score, vascular occlusion site, baseline Alberta Stroke Program Early CT Score, the number of retrieval attempts, V CBF<30%, V Tmax>6 s, V CBF>30%/mismatch volume and hypoperfusion intensity ratio (HIR) between the poor outcome group and the good outcome group (all P<0.05). Multivariable logistic regression analysis showed that atrial fibrillation (odds ratio [ OR] 6.200, 95% confidence interval [ CI] 1.225-31.374; P=0.027), baseline NIHSS score ( OR 1.188, 95% CI 1.00-1.404; P=0.043) and V CBF<30% ( OR 1.079, 95% CI 1.03-1.123; P=0.027) were the independent influencing factors of poor outcomes. ROC curve analysis showed that the areas under the curve of atrial fibrillation, baseline NIHSS score, V CBF<30% and their combined for predicting the poor outcoms were 0.675, 0.739, 0.882 and 0.914, respectively. V CBF<30% had the highest diagnostic efficiency in predicting poor outcomes of the single factor. When the cutoff value was 16 ml, the sensitivity and specificity were 82.9% and 78% respectively. Conclusions:RAPID software analysis parameters based on CTP can be used to predict the clinical outcomes after MT in patients with LVO-AIS. V CBF<30% >16 ml has a higher predictive value for poor outcomes after MT.
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Objective To perform an epidemiological investigation on a case with visceral leishmaniasis in Zhengzhou City, Henan Province, and to identify the source of infection, so as to illustrate the transmission chain and assess the risk of local leishmaniasis transmission. Methods The medical data were collected from a case with visceral leishmaniasis in Zhengzhou City, and the patient’s bone marrow smears were detected by microscopy. Serum anti-Leishmania antibody test and PCR assay were performed among high-risk residents and all dogs in the village where the patient lived. Sandflies were captured using light traps and artificial traps, and the captured female Phlebotomus chinensis was subjected to PCR assay. The internal transcribed spacer 1 (ITS1) gene was amplified with a nested PCR assay using the genomic DNA extracted from visceral leishmaniasis patients, positive dogs and sandflies, and the sequences were aligned with those download from NCBI. In addition, a phylogenetic tree was created based on the ITS1 gene. Results The visceral leishmaniasis patient had recurrent irregular fever, reduced complete blood counts, low hemoglobin, and a large number of Leishmania amastigotes in bone marrow smears, and was therefore diagnosed as visceral leishmaniasis. Both rk39 rapid diagnostic test and PCR assay tested negative among 324 residents living neighboring the patient’s residence, while 21.39% (43/201) dogs were positive for rk39 rapid diagnostic test and 13.93% (28/201) positive for PCR assay. There were 17 female Ph. chinensis tested positive for Leishmania (0.82%) by PCR assay, and the ITS gene sequences from visceral leishmaniasis patients, positive dogs and sandflies shared a 100% homology with L. infantum. The Leishmania species was therefore characterized as L. infantum. Conclusions L. infantum infection occurs in visceral leishmaniasis patients, dogs and sandflies in Zhengzhou City, indicating a complete transmission chain and a high transmission risk of visceral leishmaniasis by L. infantum. Intensified control measures are required to prevent local transmission of leishmaniasis in Zhengzhou City.
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Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q1, Q3). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q1, Q3) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ2=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ2=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ2=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.
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Female , Humans , Male , Enhanced Recovery After Surgery , Gastrectomy , Length of Stay , Pain , Patient Outcome Assessment , Postoperative Complications/surgery , Prospective Studies , Retrospective Studies , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
Objective:To construct a training system of the professional postgraduate degree of general practice using the Delphi method.Methods:On the basis of consulting relevant policies and literature, and drawing lessons from foreign general practice training systems, the index system of training professional postgraduate medical students of general practice was preliminarily developed. After two rounds of Delphi expert consultation, using the threshold method to select evaluation indexes, the training system was finally established. Excel 2010 and SPSS 19.0 were used to make data entry and statistical analysis.Results:The active coefficients of experts in the two rounds of Delphi consultation were 75.0% (12/16) and 91.7% (11/12) respectively, both the two rounds of the degree of specialist authority were 0.87, and the final coordination coefficient of the specialists' opinion was 0.452. The index system was composed of 5 first-level indexes including training objectives, theoretical curriculum setting, clinical practice setting, teaching staff and graduation requirements and 31 second-level indexes.Conclusion:The experts have great initiative and authority on research subjects. The opinions of all experts tend to be uniform after two rounds of consultation, and the results are reliable. A relatively complete and credible training index system of professional postgraduate degree of general medicine has been built.
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Objective:To study the effects of quality improvement project of respiratory support in delivery room on the short-term clinical outcomes of very/extremely low birth weight infant (VLBWI/ELBWI).Methods:The clinical data of VLBWI/ELBWI before and after the implementation of the quality improvement project of respiratory support in delivery room in our hospital were retrospectively analyzed. The incidences of endotracheal intubation in delivery room, total endotracheal intubation within 72 h after birth, mechanical ventilation duration, total oxygen therapy duration, bronchopulmonary dysplasia (BPD) and other complications were compared between pre-improvement group (from January to October 2019) and post-improvement group (from January to December 2020).Results:A total of 85 cases were included in pre-improvement group and 85 in post-improvement group. The gestational age of the two groups were (29.2±1.4) weeks and (29.1±1.5)weeks and the birth weight were (1 180±195) g and (1 186±207) g, without significant differences ( P>0.05). After the implementation of the quality improvement project, the incidence of endotracheal intubation in the delivery room decreased from 32.9% to 2.4%, and the total incidence of endotracheal intubation within 72 h after birth decreased from 58.8% to 27.1%. The usage of pulmonary surfactant significantly decreased from 54.1% to 38.8% ( P<0.05) and the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) also significantly decreased from 17.6% to 5.9% ( P<0.05).No significant differences existed among other complications ( P>0.05). Conclusions:The quality improvement project of respiratory support in the delivery room can significantly reduce the incidence of endotracheal intubation in VLBWI/ELBWI without increasing short-term adverse outcome.
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Objective:In order to Understand the cognition of breastfeeding needs in perinatal period among parturients, International Board Certified Lactation Consultants and obstetric nurses, and analyze their differences, provide a theoretical basis for the development of interventions.Methods:Using the objective sampling method, 10 parturients, 6 International Board Certified Lactation Consultants and 6 obstetric nurses from a tertiary A specialist hospital in Shanghai from February to June in 2021 were selected for semi-structured depth interviews. The inteniew focused on the needs of breastfeeding in different stages of perinatal period.Results:Through analysis and induction, the following three themes were finally condensed. Cognitive differences in prenatal education: post-hospital breastfeeding support. Parturients lack prenatal awareness of breastfeeding initiatives and prefer problem-oriented feedback after childbirth to be addressed in a timely manner, but healthcare professionals consider it necessary to provide prenatal breastfeeding education to pregnant women. Inpatient nursing supports cognitive similarities and differences: there was agreement between parturients and healthcare professionals on strengthening post-natal health education and assessing needs for psychological change. The difference is that parturients are more likely to have information and guidance on milking, however, healthcare professionals believe that the focus is on providing guidance on breastfeeding techniques and strengthening professional training for medical personnel. Breastfeeding supports cognitive similarities and differences after discharge: both parturient and healthcare professionals want family and peer support in post-hospital breastfeeding support. The difference is that parturients want to be able to keep in touch with healthcare professionals on feedback issues, but healthcare professionals believe that further community support is needed.Conclusion:Parturient and healthcare professionals have different cognition of perinatal breastfeeding needs. Targeted interventions and personalized breastfeeding plans should be developed for their different cognitions, with a view to further improving the rate of exclusive breastfeeding in China and achieving the goal of healthy development for all.
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N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.
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Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
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Objective To evaluate the clinical efficacy of liver transplantation in children with Alagille syndrome (ALGS). Methods Clinical data of 12 children with ALGS were collected and retrospectively analyzed. Clinical characteristics of children with ALGS, pathological characteristics of liver tissues, characteristics of liver transplantation, postoperative complications and follow-up of children with ALGS were analyzed. Results JAG1 gene mutation and typical facial features was present in all 12 children. Jaundice was the most common initial symptom, which occurred at 7 (3, 40) d after birth. Upon liver transplantation, the Z scores of height and body weight were calculated as -2.14 (-3.11, -1.83) and -2.32 (-3.12, -1.12). Five children developed severe growth retardation and 4 children with severe malnutrition. Eight of 12 children were diagnosed with cardiovascular abnormalities. Pathological examination showed that the lobular structure of the diseased livers of 4 children was basically maintained, and 8 cases of nodular liver cirrhosis in different sizes including 1 case of single early moderately-differentiated hepatocellular carcinoma. Three children were misdiagnosed with biliary atresia and underwent Kasai portoenterostomy. Eight children underwent living donor liver transplantation, three children underwent cadaveric donor liver transplantation (two cases of split liver transplantation and one case of cadaveric total liver transplantation), and one child underwent domino liver transplantation (donor liver was derived from a patient with maple syrup urine disease). during the follow-up of 30.0(24.5, 41.7) months, the survival rates of the children and liver grafts were both 100%. During postoperative follow-up, the Z scores of height and body weight were calculated as -1.24 (-2.11, 0.60) and -0.83 (-1.65, -0.43), indicating that the growth and development of the children were significantly improved after operation. Conclusions Liver transplantation is an efficacious treatment for children with ALGS complicated with decompensated cirrhosis, severe itching and poor quality of life. For children with ALGS complicated with cardiovascular abnormalities, explicit preoperative evaluation should be delivered, and consultation with pediatric cardiologists should be performed if necessary.
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Ventricular arrhythmias (VAs) and sudden cardiac death (SCD) are significant adverse events that affect the morbidity and mortality of both the general population and patients with predisposing cardiovascular risk factors. Currently, conventional disease-specific scores are used for risk stratification purposes. However, these risk scores have several limitations, including variations among validation cohorts, the inclusion of a limited number of predictors while omitting important variables, as well as hidden relationships between predictors. Machine learning (ML) techniques are based on algorithms that describe intervariable relationships. Recent studies have implemented ML techniques to construct models for the prediction of fatal VAs. However, the application of ML study findings is limited by the absence of established frameworks for its implementation, in addition to clinicians’ unfamiliarity with ML techniques.This review, therefore, aims to provide an accessible and easy-to-understand summary of the existing evidence about the use of ML techniques in the prediction of VAs. Our findings suggest that ML algorithms improve arrhythmic prediction performance in different clinical settings. However, it should be emphasized that prospective studies comparing ML algorithms to conventional risk models are needed while a regulatory framework is required prior to their implementation in clinical practice
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We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.
Subject(s)
Adolescent , Child , Female , Humans , Male , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Cunninghamella , Mucormycosis/etiologyABSTRACT
Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.