Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology / 中华血液学杂志

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

Subnational inequalities of early marriage and fertility among Chinese females from 1990 to 2010 / 北京大学学报(医学版)

OBJECTIVE@#To analyze the inequality of early marriage and adolescent fertility with respect to local economic development among Chinese females aged 15-19 years from 1990 to 2010.@*METHODS@#Aggregated data were extracted from the Chinese National Census from 1990 to 2010. We calculated the ever-married rate and fertility rate of female adolescents aged 15-19 years. Using gross domestic product (GDP) per capita as an indicator for socio-economic status of a province, we calculated the slope index of inequality (SII) and the concentration index (CI) to analyze the subnational inequalities of early marriage and adolescent fertility. Weighted linear regression models were also established to assess the associations between GDP per capita and the ever-married rate/fertility rate.@*RESULTS@#The ever-married rate for Chinese female adolescents aged 15-19 years decreased from 4.7% in 1990 to 1.2% in 2000, and rebounded to 2.1% in 2010. From 1990 to 2000, the fertility rate decreased from 22.0 per 1 000 to 6.0 per 1 000, and further decreased to 5.9 per 1 000 in 2010. In 1990, the socio-economic inequalities of the ever-married rate and fertility rate for female adolescents aged 15-19 years were not statistically significant (P for SII or CI>0.05). The values of SII revealed that, in 2000 and 2010, female adolescents with the lowest GDP per capita had an ever-married rate 2.4% (95%CI: 0.4-4.4) and 2.3% (95%CI: 0.3-4.2) higher than those with the highest GDP per capita, respectively. In the meantime, in 2000 and 2010, female adolescents with the lowest GDP per capita had a fertility rate 12.9 per 1 000 (95%CI: 5.4-20.5) and 9.3 per 1 000 (95%CI: 4.6-14.0) higher than those with the highest, respectively. In 2000 and 2010, the CIs for marriage were -0.32 (P=0.02) and -0.17 (P=0.03), respectively, and the CIs for childbirth were -0.37 (P<0.01) and -0.26 (P<0.01), respectively. In 2000, the ever-married rate and the fertility rate were estimated to increase by 1.4% (95%CI: 0.1-2.7) and 7.9 per 1 000 (95%CI: 2.9-12.8) with 100% increase in GDP per capita, respectively; in 2010, the numbers were 1.5% (95%CI: 0.1-2.9) and 6.7 per 1 000 (95%CI: 3.2-10.1), respectively.@*CONCLUSION@#Subnational socio-economic inequality of early marriage and adolescent fertility existed in 2000 and 2010. Female adolescents residing in less-developed areas were more likely to engage in early marriage and childbirth. Reducing income inequality and increasing education investment for poverty-stricken areas seem to be effective measures to reduce this inequality.

Trends of prevalence of excellent health status and physical fitness among Chinese Han students aged 13 to 18 years from 1985 to 2014 / 北京大学学报(医学版)

OBJECTIVE@#To analyze the trends of prevalence of excellent health status and physical fitness among Chinese Han students aged 13 to 18 years from 1985 to 2014.@*METHODS@#In the study, 738 523 students aged 13 to 18 years were extracted from the 1985 to 2014 Chinese National Survey on Students' Constitution and Health. Height, weight, vital capacity and indicators of physical fitness were measured for each student. According to National Standards for Students' Physical Health (2014 Revision), students meeting an overall score ≥ 90.0 were considered to be of excellent health status and physical fitness. We used the Chi-square test to compare the differences in prevalence of excellent health status and physical fitness among different subgroups and draw maps of regional distribution of prevalence by using ArcGIS.@*RESULTS@#From 1985 to 2014, the average height, weight, and BMI for Chinese Han students aged 13 to 18 years increased consistently, while the average vital capacity and indicators of physical fitness fluctuated largely. The overall prevalence of excellent health status and physical fitness increased from 2.7% in 1985 to 4.4% in 1995, dropped consistently to 1.1% in 2005, rebounded 0.6 percentage points in 2010, and increased to 2.2% in 2014. In each survey year, the prevalence for the boys was always higher than for the girls (P<0.001), the prevalence for middle school students aged 13 to 15 years was always higher than for high school students aged 16-18 years (P<0.001), and the prevalence for students in eastern region was higher than in western and central regions (P<0.001). In 1985 and 1995, the prevalence in certain provinces in eastern and central regions was <1%. In 2005, almost half provinces (14/30) had a prevalence <1%. In 2014, provinces in eastern coastal areas had relatively high prevalence of excellent health status and physical fitness in students aged 13 to 18 years, while provinces in central and western regions had relatively low prevalence.@*CONCLUSION@#A fluctuating trend of the prevalence of excellent health status and physical fitness has been observed among Chinese Han students aged 13 to 18 years during the past three decades. There is great difference between the current prevalence of excellent health status and physical fitness and the goal of Outline of the Healthy China 2030 Plan, thus, the effective interventions and strategies for promoting students' physical activity and physical fitness are urgently needed in China.

Advance in Mechanism and Self-reported Measures of Functional Ankle Instability (review) / 中国康复理论与实践

This article reviewed the mechanism of functional ankle instability and the progress in the diagnosis and screening of functional ankle instability using self-reported measures. The subjects with functional ankle instability demonstrated def-icits in ankle joint proprioception, muscle strength, peroneal reaction time and postural stability. The self-reported mea-sures had been widely used as diagnostic and screening methods. It is recommended to use Ankle Instability Instrument or Cumberland Ankle Instability Tool with investigation of ankle injury as selection criteria for patients with functional ankle instability.

Fearful imagery induces hyperventilation and dyspnea in medically unexplained dyspnea / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Medically unexplained dyspnea refers to a condition characterized by a sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without underlying cardiopulmonary pathology. We were interested to know how anxiety triggers hyperventilation and elicits subjective symptoms in those patients. Using an imagery paradigm, we investigated the role of fearful imagery in provoking hyperventilation and in eliciting symptoms, specifically dyspnea.</p><p><b>METHODS</b>Forty patients with medically unexplained dyspnea and 40 normal subjects matched for age and gender were exposed to scripts and asked to imagine both fearful and restful scenarios, while end-tidal PCO(2) (PetCO(2)) and breathing frequency were recorded and subjective symptoms evaluated. The subject who had PetCO(2) falling more than 5 mmHg from baseline and persisting at this low level for more than 15 seconds in the imagination was regarded as a hyperventilation responder.</p><p><b>RESULTS</b>In patients with medically unexplained dyspnea, imagination of fearful scenarios, being blocked in an elevator in particular, induced anxious feelings, and provoked a significant fall in PetCO(2) (P < 0.05). Breathing frequency tended to increase. Eighteen out of 40 patients were identified as hyperventilation responders compared to 5 out of 40 normal subjects (P < 0.01). The patients reported symptoms of dyspnea, palpitation or fast heart beat in the same fearful script imagery. Additionally, PetCO(2) fall was significantly correlated with the intensity of dyspnea and palpitation experienced during the mental imagery on one hand, and with anxiety symptoms on the other.</p><p><b>CONCLUSIONS</b>Fearful imagery provokes hyperventilation and induces subjective symptoms of dyspnea and palpitation in patients with medically unexplained dyspnea.</p>

Medically unexplained dyspnea in children: a review of 34 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported.</p><p><b>METHODS</b>The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy.</p><p><b>RESULTS</b>Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified.</p><p><b>CONCLUSION</b>The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.</p>

Medically unexplained dyspnea: psychophysiological characteristics and role of breathing therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients.</p><p><b>METHODS</b>A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years.</p><p><b>RESULTS</b>Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased.</p><p><b>CONCLUSIONS</b>Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".</p>

Influence of Different Nebulization Inhalation Methods on Blood Oxygen Degree of Saturation in Infants with Asthma / 实用儿科临床杂志

Objective To evaluate the effect of different nebulization inhalation methods on blood oxygen degree of saturation(SaO2) in infants with asthma.Methods Sixty-two infants with asthma were randomly assigned into 3 groups: air-high-frequency flow stonized inhalation group(n=22),oxygen-high-frequency flow stonized inhalationthe group(n=20) and ultrason jet nebulization group(n=18).Three groups all were gived budesonide suspl.SaO2 was monitored during nubulization.Results There were significant differences of SaO2 levels between oxygen-high-frequency flow stonized inhalationthe group and air-high-frequency flow stonized inhalationthe group,ultrason jet ne-bulization group after 10 min and during inhalation(Pa