ObjectiveTo explore the possible mechanism of action of Lifei Xiaoji Pill （理肺消积丸， LXP） in the treatment of non small cell lung cancer based on the Warburg effect and the USP47/BACH1 pathway. MethodsFifty C57BL/6 mice were randomly divided into five groups， model group， LXP group， inhibitor group， LXP + inhibitor group， and cisplatin group， with 10 mice in each group. A lung cancer mouse model was established by subcutaneously injecting Lewis cells. On the next day， the model group mice were given 0.2 ml of saline by gavage daily， the LXP group given 240 mg/（kg·d） of LXP solution once a day by gavage， the inhibitor group intraperitoneally injected with P22077 at a dose of 10 mg/（kg·d） every day， the LXP + inhibitor group given both LXP by gavage and P22077 by intraperitoneal injection once a day， and the cisplatin group received 0.5 mg/（kg·d） cisplatin intraperitoneally every other day. All treatments lasted for 14 days. On the day after the last dose， tumor weight and volume were measured， tumor histopathology was examined by HE staining， apoptosis in tumor tissues was detected by TUNEL staining， and proliferation cell nuclear antigen （PCNA） protein levels were detected by immunohistochemistry. Warburg effect indicators， including glucose concentration， lactate content， and adenosine triphosphate （ATP） production in tumor tissues， were measured. Western Blot and qRT-PCR were used to detect the protein and mRNA expression levels of USP47， BACH1， hexokinase 2 （HK2）， and glyceraldehyde 3-phosphate dehydrogenase （GAPDH）. ResultsCompared with the model group， all drug intervention groups showed reduced tumor weight and volume， improved tumor pathology， decreased PCNA positive rate， increased apoptosis rate， and reduced expression levels of USP47， BACH1， and HK2 proteins and mRNA （P＜0.05 or P＜0.01）. Except for lactate content in the cisplatin group， the glucose concentration in tumor tissues of other drug intervention groups increased， while lactate content and ATP production decreased （P＜0.05 or P＜0.01）. Compared with the LXP group， the LXP + inhibitor group showed more significant improvements in these indicators （P＜0.05 or P＜0.01）. Compared with the cisplatin group， the LXP + inhibitor group had lower mRNA expression of HK2 and GAPDH， and lower protein levels of USP47 and HK2 （P＜0.05 or P＜0.01）. Compared with the inhibitor group， the cisplatin group had higher HK2 protein levels， while the LXP + inhibitor group showed lower mRNA expression of BACH1， HK2， and GAPDH （P＜0.05 or P＜0.01）. ConclusionLXP significantly inhibits tumor growth in lung cancer mice， and its mechanism of action may be related to inhibiting the Warburg effect via the USP47/BACH1 pathway.

Suicide is one of the important causes of death among children and adolescents.Suicide can be prevented，and adolescence is a critical period for prevention.The manifestations and prevalence of suicidal ideation and suicidal behavior exhibit obvious demographic characteristics.Suicide behavior is influenced by various factors such as cultural acceptability，accessibility of suicide methods，and the lethality of suicide methods.Poor family environment，stressful life events，and negative social relationships are all risk factors for suicide.Prevention strategies can be classified based on different populations and suicide risks，including universal prevention strategies，selective prevention strategies，and indicated prevention strategies.

Objective:To summarize the clinical characteristics of suicidal behavior in children and provide a reference for further developing strategies for preventing childhood suicide.Methods:The medical records of children hospitalized in the pediatric intensive care unit（PICU）at Beijing Children's Hospital for suicidal behavior in the electronic medical record system from January 1,2018,to December 31,2022 were retrospectively selected.Clinical data of children with suicidal behavior were collected.Results:A total of 3 249 patients were admitted to the PICU,including 62 suicide patients.There were 20(32.3%) males,and 42(67.7%) females,with a male-to-female ratio of 1:2.1.The average age was (13.1 ± 1.5) years old,with a minimum age of 7.9 years and a maximum age of 15.7 years.There were 17 (27.4%) children with previously diagnosed mental illnesses.Notably 58.1% children had triggering factors for suicidal behavior.Analysis of suicide methods,53(85.5%) cases were intentional drug ingestion,six(9.7%) cases were jumping from height,and three(4.8%) cases were hanging.Additionally 26.4% cases of poisoning were male,while 66.7% of cases of jumping from height and hanging were male.There was a statistical difference in suicide methods between genders (χ 2=5.704, P=0.025).The poisoning ingestions were classified as 20(37.7%) cases of toxins; 14(26.4%) cases of antidepressants; 10(18.9%) cases of over-the-counter drugs; five(9.4%) cases of other prescription drugs; three(5.7%) cases of sedative drugs; one(1.9%) case of daily chemical.Sources of ingestions: 18(34.0%) cases were purchased personally (pharmacies or online shopping); 16(30.2%) cases were storing medicines at home; 13(24.5%) cases were daily taking antidepressants.Compared with non-poisoning patients,poisoning patients had a significantly shorter PICU duration (Z=-2.884, P=0.004).The total mortality rate of children admitted to PICU due to suicide was 16.1%(10/62).There was a statistical difference in the mortality rate among different suicide methods (χ 2=7.883, P=0.019). Conclusion:School aged children and boys are more likely to choose impulsive and more harmful suicide behaviors such as jumping from heights and hanging,and adolescent girls are more likely to choose intentional poisoning as their suicide method.Attention should be paid to the suicide risk of different age and gender groups.Intentional drug ingestion is the main method of suicide in children.Herbicide poisoning and antidepressant drug poisoning are the leading causes of suicide death.The death risk of suicidal behavior in children may be reduced by controlling the way of getting pesticides (especially herbicides) and obtaining maximum doses of antidepressants.

ObjectiveTo analyze the development status and quality of clinical practice guidelines for the treatment of dominant diseases with Chinese patent medicines （CPMs）. MethodsDatabases were searched from Jan. 2019 to Dec.2023 to collect the published clinical practice guidelines of CPMs for the treatment of dominant diseases. The information about the title， the participants， clinical problems， outcomes， evidence grade， recommendations， and recommendation strength in the included clinical practice guidelines were collected， for which the development status was analyzed， and the quality was evaluated with the Scientific， Transparent and Applicable Rankings （STAR） tool for clinical practice guidelines. ResultsTotally， 34 guidelines were included， involving 273 kinds of CPMs. One to ten （with the medium five） clinical problems were proposed from 29 clinical practice guidelines respectively. All the guidelines divided the evidence into four grades according to Grade of Recommendation Assessment， Deve-lopement an Evaluation. And 28 guidelines had five levels of recommendation strength. A total of 344 recommendations were extracted， including 86 strong-recommendations， 191 weak-recommendations （including 36 weak recommendations only based on expert consensus） and 67 recommendations with unclear recommendation strength. All guidelines had high scores in the three areas of “clinical questions （94.20%）”， “evidence （91.45%）” and “recommendations （89.06%）”， while the scores in the three areas of “registry （22.06%）”， “protocol （19.00%）” and “accessibility （31.51%）” were low. The STAR recommended stars of 8 guidelines were 5.0~4.0 stars， while that of 18 guidelines were 3.5~2.5 stars， and 8 guidelines were 2.0~1.0 stars. The three guidelines with the highest recommended stars were depressive disorder， community-acquired pneumonia， and influenza in adult. ConclusionThere is a certain gap in the quality of the published clinical practice guidelines of CPMs， and the quality of the guidelines could be further improved in registry， protocols， funds， and accessibility.

Suicide is one of the important causes of death among children and adolescents.Suicide can be prevented，and adolescence is a critical period for prevention.The manifestations and prevalence of suicidal ideation and suicidal behavior exhibit obvious demographic characteristics.Suicide behavior is influenced by various factors such as cultural acceptability，accessibility of suicide methods，and the lethality of suicide methods.Poor family environment，stressful life events，and negative social relationships are all risk factors for suicide.Prevention strategies can be classified based on different populations and suicide risks，including universal prevention strategies，selective prevention strategies，and indicated prevention strategies.

Vasculitis, involving any levels of vessels throughout the body, has variable nonspecific clinical presentation and complicated classification, hence, the diagnose is difficult. The liver is not the major organ involved, so it is prone to overlook vasculitis-associated liver injuries. The main manifestations of vasculitis involving the liver include abnormal liver biochemistry test (mainly increase of cholestatic liver enzymes), portal hypertension, and hepatic occupying lesions. Treatment principles are primarily directed at systemic immunosuppressive therapy for vasculitis. This review summarized the classification of vasculitis, major presentations of liver involvement in vasculitis, and the principles of treatment, to improve the awareness of the rare vascular diseases.

Objective To determine the effect of rapamycin(Rapa) on JAK2, ABCA3, and the immune checkpoint PD-1/PD-L1 in exosomes derived from JAK2 V617F positive HEL cells. Methods Human erythroleukemia HEL cells (JAK2 V617F mutation-positive) were cultured in vitro, and rapamycin was added at concentrations of 10, 50, and 100 nmol/L. The control group was established and cell proliferation inhibition rate was detected by CCK-8. Based on the inhibition rate of cell proliferation, cells intervened with 10 and 50 nmol/L Rapa were selected. Exosomes were extracted using a kit and identified by Western blot and flow cytometry. JAK2, ABCA3, and PD-1/PD-L1 mRNA changes in exosomes were detected by fluorescent quantitative PCR. The expression of exosome PD-1/PD-L1 protein was determined by flow cytometry. Results The exosomes extracted with the exosome kit all expressed characteristic CD9, CD63, and CD81 proteins, which were consistent with the general characteristics of exosomes. JAK2 mRNA can be detected in exosomes from HEL cells; Rapa reduced exosome production by HEL cells, and dose-dependently decreased gene expression of JAK2, ABCA3, and PD-L1 in exosomes. In addition, Rapa inhibited exosomal PD-L1 protein expression and had no significant effect on PD-1 protein expression. Conclusion HEL cells may transmit JAK2 mutant gene signals via exosomes. Rapa can reduce the production of exosomes and inhibits JAK2 mutated signals delivered by exosomes and suppresses PD-L1 protein expression.

Objective:To establish a risk prediction model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) using regression analysis and verify the model.Methods:The risk factors and acute exacerbation of 1 326 patients with chronic obstructive pulmonary disease (COPD) who entered the stable phase and followed up for 6 months in the four completed multi-center large-sample randomized controlled trials were retrospectively analyzed. Using the conversion-random number generator, about 80% of the 1 326 cases were randomly selected as the model group ( n = 1 074), and about 20% were the verification group ( n = 252). The data from the model group were selected, and Logistic regression analysis was used to screen independent risk factors for AECOPD, and an AECOPD risk prediction model was established; the model group and validation group data were substituted into the model, respectively, and the receiver operating characteristic (ROC) curve was drawn to verify the effectiveness of the risk prediction model in predicting AECOPD. Results:There were no statistically significant differences in general information (gender, smoking status, comorbidities, education level, etc.), body mass index (BMI) classification, lung function [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), etc.], disease status (the number and duration of acute exacerbation in the past year, duration of disease, etc.), quality of life scale [COPD assessment test (CAT), etc.] and clinical symptoms (cough, chest tightness, etc.) between the model group and the validation group. It showed that the two sets of data had good homogeneity, and the cases in the validation group could be used to verify the effectiveness of the risk prediction model established through the model group data to predict AECOPD. Logistic regression analysis showed that gender [odds ratio ( OR) = 1.679, 95% confidence interval (95% CI) was 1.221-2.308, P = 0.001], BMI classification ( OR = 0.576, 95% CI was 0.331-1.000, P = 0.050), FEV1 ( OR = 0.551, 95% CI was 0.352-0.863, P = 0.009), number of acute exacerbation ( OR = 1.344, 95% CI was 1.245-1.451, P = 0.000) and duration of acute exacerbation ( OR = 1.018, 95% CI was 1.002-1.034, P = 0.024) were independent risk factors for AECOPD. A risk prediction model for AECOPD was constructed based on the results of regression analysis: probability of acute exacerbation ( P) = 1/(1+ e- x), x = -3.274 + 0.518×gender-0.552×BMI classification + 0.296×number of acute exacerbation + 0.018×duration of acute exacerbation-0.596×FEV1. The ROC curve analysis verified that the area under ROC curve (AUC) of the model group was 0.740, the AUC of the verification group was 0.688; the maximum Youden index of the model was 0.371, the corresponding best cut-off value of prediction probability was 0.197, the sensitivity was 80.1%, and the specificity was 57.0%. Conclusion:The AECOPD risk prediction model based on the regression analysis method had a moderate predictive power for the acute exacerbation risk of COPD patients, and could assist clinical diagnosis and treatment decision in a certain degree.

Objective:To predict the risk of systolic anterior motion (SAM) after mitral valvuloplasty(MVP) by intraoperative transesophageal echocardiography (TEE) and its diagnostic value.Methods:From August 2016 to May 2020, 215 patients with mitral valve degeneration underwent MVP, including 182 patients without SAM (non-SAM group), and 33 patients with SAM (SAM group). TEE examination was performed immediately after operation to determine whether SAM phenomenon was relieved. According to the physiological basis of SAM, before cardiopulmonary bypass (CPB) and immediately after CPB, the parameters of SAM group and non-SAM group were measured and compared, including left atrial dimension(LAD), left ventricular end diastolic diameter(LVEDD), left ventricular end systolic diameter(LVESD), left ventricular ejection fraction(LVEF), basal septal diameter(basal-IVDd), left ventricular posterior wall thickness(LVPW), left ventricular outflow tract diameter(LVOTD), left ventricular outflow tract maximum velocity(LVOT-Vmax), left ventricular outflow tract pressure gradient(LVOTG), mitral valve maximum velocity(MV-Vmax), mitral valve mean pressure gradient(MVG-mean), mitral regurgitation area(MR-area), bulging subaortic septum, anterior leaflet length, posterior leaflet length, ratio between the lengths of the anterior and posterior leaflets, coaptation-septum distance(c-sept), nnular diameter of mitral valve, aorto-mitral angle (AMA) to screen the independent risk factors of SAM after MVP.Results:① Compared with the non-SAM group, LVEDd, LVESD, ratio between the length of the anterior and posterior leaflets, c-sep and AMA decreased in SAM group (all P<0.05), while basal-IVDd, LVEF, posterior leaflet length and bulging subaortic septum increased in SAM group (all P<0.05). ②Compared with that before the "edge to edge" technique, LVOT-Vmax decreased from (4.31±2.26)m/s to (2.55±1.39)m/s, LVOTG decreased from (43.58±10.89)mmHg to (23.36±12.76)mmHg, MVG-mean increased from (0.46±0.33)mmHg to (2.27±0.43)mmHg, and MR-area increased from (3.52±0.79)cm 2 to (0.96±0.57)cm 2 (all P<0.05). ③Multivariate logistic regression analysis showed that independent risk factors of SAM were LVEDd<45.430 mm ( OR=0.267, 95% CI=0.084-0.847), basal-IVDd>14.870 mm ( OR=12.049, 95% CI=1.619-89.661), length ratio of anterior and posterior leaflets of mitral valve>1.371 ( OR=0.159, 95% CI=0.045-0.562), angle of bulging angulated subaortic septum>62.330°( OR=18.246, 95% CI=2.824-117.896), c-sept<23.965 mm( OR=0.177, 95% CI=0.05-0.628), and AMA<123.730°( OR=0.197, 95% CI=0.098-0.396). Conclusions:Intraoperative TEE can evaluate the risk factors of SAM before MVP, and find the SAM phenomenon after MVP in time, which is helpful for surgeons to prevent and correct SAM after MVP and avoid secondary operation.

Objective:To identify clinical characteristics of slit ventricle syndrome (SVS) in children, thus improving pediatricians′ understanding of pediatric SVS.Methods:Clinical data of children diagnosed as SVS in the Emergency Department of Beijing Children′s Hospital, Capital Medical University from June 2015 to May 2019 were collected and retrospectively analyzed.Results:A total of 10 children with SVS were included, including 3 cases of arachnoid cyst, 3 cases of congenital hydrocephalus, 2 cases of Dandy-Walker syndrome, 1 case of idiopathic intracranial hypertension syndrome, and 1 case of hydrocephalus secondary to intracranial hemorrhage as the primary disease.The age of first shunting, and that at diagnosis of SVS were 1.3 (0.3-12.8) years, and 9.9 (3.8-13.3) years, respectively.SVS-associated symptoms appeared in 4.4 (0.5-12.0) years after shunting, including intermittent headache (10/10 cases), vomiting (10/10 cases), irritability (4/10 cases), seizures (5/10 cases), diminution of vision (2/10 cases), and intracranial hypertension (10/10 cases) at varying severities.When SVS occurred, the cerebral ventricle presented slit-like morphology.Three cases were relieved with mannitol treatment and 7 cases were treated with emergency lumbar-peritoneal shunt after mannitol failure.During 1-5 years of follow-up, 9 patients did not have SVS-associated symptoms and 1 case with medical therapy had recurrences.Conclusions:SVS is a rare complication after shunt surgery, with the clinical manifestations of intermittent headache and slow valve refilling conforming; imaging showed that the cerebral ventricle was slit-like morphology.When there are signs of intracranial hypertension after shunting and there is no cerebral ventricle dilatation in imaging, SVS should be highly vigilant.Once SVS is confirmed, surgical intervention should be introduced as early as possible after treatment failure of medication, so as to improve the prognosis.