Structural basis for activity regulation of MLL family methyltransferases.

The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.

[Clinical and gene mutation features of cystic fibrosis: an analysis of 8 cases]. / 8ä¾‹å›Šæ€§çº¤ç»´åŒ–æ‚£å„¿ä¸´åºŠåŠåŸºå› çªå˜åˆ†æž.

OBJECTIVES: To study the clinical features and gene mutation sites of children with cystic fibrosis (CF), in order to improve the understanding of CF to reduce misdiagnosis and missed diagnosis. METHODS: A retrospective analysis was performed on the medical records of 8 children with CF who were diagnosed in Hebei Children's Hospital from 2018 to 2021. RESULTS: Among the 8 children with CF, there were 5 boys and 3 girls, with an age of 3-48 months (median 8 months) at diagnosis, and the age of onset ranged from 0 to 24 months (median 2.5 months). Clinical manifestations included recurrent respiratory infection in 7 children, sinusitis in 3 children, bronchiectasis in 4 children, diarrhea in 8 children, fatty diarrhea in 3 children, suspected pancreatic insufficiency in 6 children, pancreatic cystic fibrosis in 1 child, malnutrition in 5 children, and pseudo-Bartter syndrome in 4 children. The most common respiratory pathogens were Pseudomonas aeruginosa (4 children). A total of 16 mutation sites were identified by high-throughput sequencing, multiplex ligation-dependent probe amplification, and Sanger sequencing, including 5 frameshift mutations, 4 nonsense mutations, 4 missense mutations, 2 exon deletions, and 1 splice mutation. CFTR mutations were found in all 8 children. p.G970D was the most common mutation (3 children), and F508del mutation was observed in one child. Four novel mutations were noted: deletion exon15, c.3796_3797dupGA(p.I1267Kfs*12), c.2328dupA(p.V777Sfs*2), and c.2950G>A(p.D984N). CONCLUSIONS: p.G970D is the most common mutation type in children with CF. CF should be considered for children who have recurrent respiratory infection or test positive for Pseudomonas aeruginosa, with or without digestive manifestations or pseudo-Bartter syndrome.

[Epidemiological features of severe acute respiratory syndrome coronavirus 2 infection in children in Shijiazhuang, China: an analysis of 133 cases].

OBJECTIVE: To study the epidemiological features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Shijiazhuang, China. METHODS: Based on the information officially announced on the official website of the Health Commission of Hebei Province, epidemiological data were collected from 133 children, aged 0-18 years, who were diagnosed with SARS-CoV-2 infection in Shijiazhuang from January 2 to January 30, 2021. A statistical analysis was performed for general status, regional distribution, presence or absence of clusters, and results of SARS-CoV-2 nucleic acid tests. RESULTS: Among the 133 children with SARS-CoV-2 infection, there were 65 boys and 68 girls, with a male/female ratio of 0.96:1. The youngest age of onset was 3 months and 7 days, and the mean age of onset was (9±5) years. Of all the 133 children, 90(67.7%) were the first confirmed case of SARS-CoV-2 infection among their family members. Of all the children, 108(81.2%) came from the Gaocheng District in Shijiazhuang, among whom 38(28.6%) were from Xiaoguozhuang Village where the first patient with a confirmed diagnosis lived. SARS-CoV-2 nucleic acid test at week 2 after the outbreak showed positive results in 88 children (66.2%), and only 5 children had clinical symptoms before positive SARS-CoV-2 results were obtained. Of all the 133 children, 19(14.3%) were found positive in the first SARS-CoV-2 nucleic acid test after the outbreak, and 70(52.6%) had positive results for ≥4 times. There were 98 school students with infection, among whom 74(75.5%) were the first confirmed case in their family, and among 35 non-school students, 16(45.7%) were the first confirmed case in their family (P < 0.05). CONCLUSIONS: Among the children confirmed with SARS-CoV-2 infection in Shijiazhuang, there is a high proportion of children who are the first confirmed case in their family, and the children are mainly distributed in the rural areas of Gaocheng. Most of these children are students, so the prevention and control of cluster infection in schools should be taken seriously. There are often no symptoms before SARS-CoV-2 nucleic acid test, with a low positive rate of the first nucleic acid test, which increases the difficulty of early discovery of the epidemic.

[Efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia complicated by airway mucus obstruction].

OBJECTIVE: To study the efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus obstruction. METHODS: According to the time from admission to the treatment via fiber bronchoscope, the children with MPP who were found to have airway mucus obstruction under a fiber bronchoscope were randomly divided into early intervention group (≤3 days; n=40) and late intervention group (>3 days; n=56). The two groups were compared in terms of clinical data and imaging recovery.The children were followed for 1-3 months. RESULTS: Of the 96 children, 38 were found to have the formation of plastic bronchial tree, among whom 10 were in the early intervention group and 28 were in the late intervention group (P=0.01). Compared with the late intervention group, the early intervention group had a shorter duration of fever, length of hospital stay, and time to the recovery of white blood cell count and C-reactive protein (P<0.05), as well as a higher atelectasis resolution rate (P<0.05). Compared with the late intervention group, the early intervention group had a higher percentage of children with a ≥ 60% absorbed area of pulmonary consolidation at discharge. After 3 months of follow-up, the early intervention group had a higher percentage of children with a ≥ 90% absorbed area of pulmonary consolidation than the late intervention group (80% vs 55%; P=0.01), and the early intervention group had a lower incidence rate of atelectasis than the late intervention group (P<0.05). CONCLUSIONS: Early treatment via fiber bronchoscope can shorten the course of the disease and reduce complications and sequelae in MPP children with airway mucus obstruction.

Correlation analysis of serum thyroglobulin, thyroid-stimulating hormone levels, and thyroid-cancer risk in thyroid nodule surgery.

BACKGROUND: Thyroglobulin (Tg) is one of the markers of thyroid cancer, and its concentration may be elevated in patients with malignant thyroid tumors. Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland, which has a significant impact on thyroid gland function. Excessively high or low TSH levels may be associated with an increased risk of thyroid cancer. Thus, in-depth studies on the association of serum Tg and TSH levels with thyroid cancer risk in patients with thyroid nodules are warranted. This can help determine whether Tg and TSH levels can predict the degree of malignancy of thyroid nodules, which can in turn guide doctors in making accurate diagnoses and treatment decisions. Furthermore, such studies can provide more accurate diagnostic methods for thyroid nodules and help patients become aware of the presence of thyroid cancer as early as possible, thereby improving the success rate of treatment and prognosis. AIM: To investigate the association of serum Tg and TSH levels with the risk of thyroid cancer in patients undergoing thyroid nodule surgery. METHODS: The clinical data and laboratory examination results of 130 patients who underwent thyroid nodule surgery were retrospectively analyzed. Furthermore, their preoperative serum Tg and TSH levels were recorded. Histopathological examination conducted during follow-up revealed the presence of thyroid cancer. Correlation analysis were used to analyze the association of Tg and TSH levels with the risk of thyroid cancer. RESULTS: Of the 130 patients, 60 were diagnosed with thyroid cancer. Statistical analysis revealed a significant positive correlation between serum Tg levels and the risk of thyroid cancer (P < 0.05). This suggests that high serum Tg levels are associated with an increased risk of thyroid cancer. However, no significant correlation was observed between serum TSH levels and the risk of thyroid cancer (P > 0.05). CONCLUSION: In patients who underwent thyroid nodule surgery, serum Tg levels exhibited a significant correlation with the risk of thyroid cancer but serum TSH levels did not. These findings suggest that serum Tg can serve as an important biomarker for assessing the risk of thyroid cancer in these patients.

[Risk factors for infection with extended-spectrum beta-lactamase-producing strains in children].

OBJECTIVE: To study the risk factors for infection with extended-spectrum beta-lactamase (ESBL) producing strains in children. METHODS: The clinical data of 242 pediatric in-patients with lower respiratory tract infections from February 2009 to January 2011 were retrospectively analyzed. The risk factors of ESBL-producing strain infections were investigated using univariate analysis and multivariate logistic regression analysis. RESULTS: Univariate analysis showed that six factors were related with ESBL-producing strain infections: repeated sucking of phlegm (OR: 2.279, P<0.01), tracheal intubation(OR: 3.101, P<0.01), administration of the third generation cephalosporin for more than three days (OR: 3.628, P<0.01), admission to the pediatric intensive care unit (PICU) (OR: 2.378, P<0.01), indwelling of nasogastric tube (OR: 2.460, P<0.01), prophylactic use of antibiotics (OR: 1.747, P<0.05). Multivariate logistic regression showed that the application of the third-generation cephalosporin for more than three days (OR: 5.672, P<0.01), repeated sucking of phlegm (OR: 3.917, P<0.01), tracheal intubation (OR: 3.717, P<0.01), indwelling of nasogastric tube (OR: 2.961, P<0.01), and admission to PICU (OR: 3.237, P<0.01) were the independent risk factors for the infections. CONCLUSIONS: The infections of ESBL-producing strains are caused by many factors, among which the application of the third-generation cephalosporin for more than three days, invasive operations, and admission to PICU are the independent risk factors.

Structural insights into NDH-1 mediated cyclic electron transfer.

NDH-1 is a key component of the cyclic-electron-transfer around photosystem I (PSI CET) pathway, an important antioxidant mechanism for efficient photosynthesis. Here, we report a 3.2-Å-resolution cryo-EM structure of the ferredoxin (Fd)-NDH-1L complex from the cyanobacterium Thermosynechococcus elongatus. The structure reveals three ß-carotene and fifteen lipid molecules in the membrane arm of NDH-1L. Regulatory oxygenic photosynthesis-specific (OPS) subunits NdhV, NdhS and NdhO are close to the Fd-binding site whilst NdhL is adjacent to the plastoquinone (PQ) cavity, and they play different roles in PSI CET under high-light stress. NdhV assists in the binding of Fd to NDH-1L and accelerates PSI CET in response to short-term high-light exposure. In contrast, prolonged high-light irradiation switches on the expression and assembly of the NDH-1MS complex, which likely contains no NdhO to further accelerate PSI CET and reduce ROS production. We propose that this hierarchical mechanism is necessary for the survival of cyanobacteria in an aerobic environment.

Morphometry of the Hand Knob Region and Motor Function Change in Eloquent Area Glioma Patients.

PURPOSE: The hand knob area is the cortical representation of motor hand function. The current study aimed to investigate the effects of eloquent area gliomas on the morphometry of the hand motor cortex and preoperative hand motor function. METHODS: A retrospective study of 320 glioma patients was conducted. Seventy-eight patients with gliomas involving motor functional area were finally enrolled. Using axial T2-weight magnetic resonance images, the width and height of the hand knob were measured in both hemispheres, and differences were compared between the affected and unaffected hemispheres. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to estimate the degree of correlation between distance measurements and motor impairment. RESULTS: The width and height of the hand knob in the affected and unaffected hemispheres were significantly different (p < 0.0001). The width, height and distance from the tumor to hand knob were reduced in the functionally impaired group compared to the unimpaired group (p = 0.0003, p < 0.0001, p = 0.0005, respectively). The three parameters were significantly correlated and remained significant in ROC and logistic regression analysis. The optimal cut-off value of width, height and distance for identifying preoperative hand muscle strength were 5.73 mm, 5.80 mm and 5.92 mm, respectively. CONCLUSION: The morphometry of the hand knob is often changed by the infiltration or extrusion of the tumors that were located in or near the hand knob. The width, height of hand knob and the distance from tumor to hand knob could serve as anatomic biomarkers related to preoperative neurological motor deficits.

Influencing factors for the prognosis of patients with drug-induced liver injury and establishment of a nomogram model / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

The Electrochemical Performance of Silicon Nanoparticles in Concentrated Electrolyte.

Silicon is a promising material for anodes in energy-storage devices. However, excessive growth of a solid-electrolyte interphase (SEI) caused by the severe volume change during the (de)lithiation processes leads to dramatic capacity fading. Here, we report a super-concentrated electrolyte composed of lithium bis(fluorosulfonyl)imide (LiFSI) and propylene carbonate (PC) with a molar ratio of 1:2 to improve the cycling performance of silicon nanoparticles (SiNPs). The SiNP electrode shows a remarkably improved cycling performance with an initial delithiation capacity of approximately 3000 mAh g-1 and a capacity of approximately 2000 mAh g-1 after 100 cycles, exhibiting about 6.8 times higher capacity than the cells with dilute electrolyte LiFSI-(PC)8 . Raman spectra reveal that most of the PC solvent and FSI anions are complexed by Li+ to form a specific solution structure like a fluid polymeric network. The reduction of FSI anions starts to play an important role owing to the increased concentration of contact ion pairs (CIPs) or aggregates (AGGs), which contribute to the formation of a more mechanically robust and chemically stable complex SEI layer. The complex SEI layer can effectively suppress the morphology evolution of silicon particles and self-limit the excessive growth, which mitigates the crack propagation of the silicon electrode and the deterioration of the kinetics. This study will provide a new direction for screening cycling-stable electrolytes for silicon-based electrodes.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Correlation of mucin1 and Ki67 expression with clinical pathological characteristics and prognosis of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To analyze the expression of mucin 1 (MUC1) and Ki67 in intrahepatic cholangiocarcinoma (ICC), and to explore the correlations between the expression of MUC1 and Ki67 and the clinicopathological features and prognosis of ICC patients.Methods:Clinical data of 398 patients with ICC admitted to Henan Provincial People's Hospital from January 2013 to March 2020 were retrospectively analyzed. A total of 104 patients were included in this study, including 67 males and 37 females, aged (56.6±9.3) years. Immunohistochemistry was used to detect the expression of MUC1 and Ki67 in cancer tissues. Univariate and multivariate Cox regression analysis were used to study the prognostic factors of ICC patients.Results:The expression of MUC1 was low in 65 patients and high in 39 patients. Ki67 expression was low in 52 patients and high in 52 patients. High expression of MUC1 was correlated with lymph node metastasis ( P<0.05), while high expression of Ki67 was correlated with tumor nodes number, lymph node metastasis and vascular invasion (all P<0.05). Multivariate analysis showed that ICC patients with high MUC1 expression ( HR=2.321, 95% CI: 1.420-3.792, P<0.001) and high Ki67 expression ( HR=2.012, 95% CI: 1.247-3.247, P=0.004) showed a poor prognosis after hepatectomy. ICC patients with high MUC1 expression ( HR=1.664, 95% CI: 1.058-2.618, P=0.028) and high Ki67 expression ( HR=1.883, 95% CI: 1.168-3.035, P=0.009) had a poor prognosis after hepatectomy. Conclusion:High expression of MUC1 and Ki67 is correlated with tumor growth and metastasis. MUC1 and Ki67 are independent risk factors for prognosis of ICC patients after hepatectomy.

Neuroendocrine carcinoma of gallbladder: a report on 17 patients from a single institution / 中华肝胆外科杂志

Objective:To analyze the clinicopathological features, diagnosis and treatment of neuroendocrine carcinoma of gallbladder (GB-NEC).Methods:The clinical data of 17 patients with GB-NEC confirmed by postoperative pathology managed at the People's Hospital of Zhengzhou University from March 2013 to January 2020 were analyzed retrospectively. There were 9 males and 8 females, with an age of (68.9±11.2) years. The clinical and follow-up data were analyzed.Results:The main clinical manifestations were abdominal pain ( n=9, 52.9%), anorexia ( n=5, 29.4%), jaundice ( n=2, 11.8%), abdominal mass ( n=2, 11.8%), and asymptomatic ( n=2, 11.8%). Radical resection of gallbladder carcinoma was performed in 9 patients, and palliative resection in 8 patients. Postoperative chemotherapy was given to 4 patients. Postoperative pathology showed small cell type in 11 patients and large cell type in 6 patients. Immunohistochemical staining showed synaptophysin positivity in 17 patients (100.0%), chromogranin A positivity in 12 (70.6%), Ki67 positivity in 17 patients (100%, >50% was defined as positive). All 17 patients were followed-up from 78 to 745 days, with a median of 237 days. At the time of censor of this study, 13 patients had died. The 1-and 2-year cumulative survival rates were 26.5% and 19.9%, respectively. The 1- and 2-year cumulative survival rates of radical gallbladder carcinoma resection ( n=9) were 44.4% and 33.3%, respectively. Eight patients underwent palliative resection, and the longest follow-up time was 276 days. Conclusion:This study showed the incidence of GB-NEC was low. There was no specific clinical manifestations, and the diagnosis mainly depended on immunohistochemistry. Patients with GB-NEC had high expressions of Ki67 and had poor prognosis. Early radical resection was helpful to improve survival of these patients.

The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST complex.

Tetrahymena telomerase holoenzyme subunits p75, p45 and p19 form a subcomplex (7-4-1) peripheral to the catalytic core. We report structures of p45 and p19 and reveal them as the Stn1 and Ten1 subunits of the CST complex, which stimulates telomerase complementary-strand synthesis. 7-4-1 binds telomeric single-stranded DNA, and mutant p19 overexpression causes telomere 3'-overhang elongation. We propose that telomerase-tethered Tetrahymena CST coordinates telomere G-strand and C-strand synthesis.

Dysphagia and its relationship with weight change in head and neck cancer patients treated with radiotherapy / 中华临床营养杂志

Objective To describe the characteristics of dysphagia in patients with head and neck cancer during radiotherapy,and analyze the cause of dysphagia and the relationship between dysphagia and weight change.Methods Patients with head and neck cancer treated with radiotherapy in Beijing Cancer Hospital from November 2017 to June 2018 were recruited.The M.D.Anderson Dysphagia Inventory (MDADI) was used to assess the dysphagia of patients before (T1),during (T2) and at the end (T3) of the radiotherapy.Meanwhile,the weight,dietary intake and radiation adverse effects were investigated.Generalized estimating equations were used to analyze the impact factors of dysphagia and the relationship among dysphagia,dietary intake and weight change.Results Ninety-six patients were completely investigated and the incidence of dysphagia were 6.3％ (6/ 96),80.2％ (77/96) and 85.4％ (82/96) in T1,T2 and T3.With the progress of radiotherapy,the total score and the scores of 4 dimensions of MDADI dropped and the dietary intake declined.The average weight loss was (5.09±3.31) kg,and 76.1％ of the patients had weight loss over 5％ at the end of radiotherapy.The occurrence of dysphagia was associated with the radiotherapy-related oral and laryngeal mucositis and the weight loss was closely associated with the site of radiation,dysphagia,and dietary intake decline.Conclusions The dysphagia of patients with head and neck cancer is affected by radiation adverse effects,and is most severe at the end of radiotherapy.Dysphagia might result in dietary intake decline and weight loss.Clinicians should pay close attention to the swallowing function of the patients and take measures earlier accordingly.

Taste alteration of head and neck cancer patients treated with radiotherapy: A longitudinal study / 中华临床营养杂志

Objective To investigate the taste alteration caused by radiotherapy and its relationship with nutritional status in head and neck cancer patients during and after radiotherapy.Methods From March to November 2017,172 patients with head and neck cancer receiving radiotherapy were recruited from Beijing Cancer Hospital including 86 patients completing all follow up visits.Chemotherapy-induced Taste Alteration scale was used to evaluate radiotherapy-induced taste alteration and the Patient-generated subjective global assessment (PGSGA) was used for nutrition evaluation at baseline,mid-treatment,post-treatment and 1-2 months after radiotherapy (follow-up).Generalized estimating equations was applied to analyze the influencing factors of taste alteration and its relationship with nutritional status.Results The incidence of taste alteration were 9.3％,84.9％,94.2％ and 77.9％ respectively at baseline,mid-treatment,post-treatment and 1-2 months after radiotherapy (follow-up).Taste alteration score increased with the increase of radiation dose,reached the highest at the posttreatment and decreased at follow-up visit which was still higher than the score at baseline.PG-SGA score increased with the increase of radiation dose.The incidence of severe malnutrition after radiotherapy was 95.3％,decreased to 45.3％ at follow up visit.Nutritional status was closely related to taste alteration.Total radiation dose and concurrent chemotherapy were the influencing factors of taste alteration.Conclusions The taste of patients with head and neck cancer is affected by radiotherapy.As radiotherapy continues,the taste alteration aggravates and PG-SGA score increases gradually,thus malnutrition becomes a prominent problem.Such effect will persist for a period of time after radiotherapy,which should be paid attention and interventions should be conducted to prevent or reduce this effect,in order that the lasting of malnutrition induced by taste alteration can be avoided.

Efficacy and prognostic factors of intensity-modulated radiotherapy for large primary hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the efficacy of intensity-modulated radiotherapy (IMRT) in treating large primary hepatocellular carcinoma (LHCC) which is unsuitable for surgery or has poor response to radiofrequency ablation, interventional therapy, and other local treatments, and to identify the prognostic factors for survival. MethodsWe retrospectively analyzed the clinical data of 29 LHCC patients who received IMRT from April 2008 to August 2011. There were five fractions per week and the dose for each fraction was 2 to 6 Gy; the total dose was 50 to 70 Gy. The short-term efficacy and prognosis were observed and analyzed. The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis. Multivariate analysis was performed using the Cox regression model. ResultsThe complete remission, partial remission, stable disease, and disease progression rates were 3.57%, 32.14%, 53.57%, and 10.72%, respectively. The overall median progression-free survival (PFS) time was 6.43 months, and the median overall survival (OS) time was 11.43 months. The 1- and 2-year survival rates were 46.79% and 25.23%, respectively. Univariate analysis showed tumor response rate was an independent prognostic factor for PFS. The Cox proportional hazard model suggested the tumor response rate and prescribed dose were the independent prognostic factors for PFS. In addition, the independent prognostic factors for OS included tumor response rate, tumor diameter, and tumor volume. The common acute radiotherapy toxicities included gastrointestinal discomfort, radiation-induced liver damage, and myelosuppression. ConclusionIMRT is a safe and effective option for the LHCC patients who are unsuitable for surgery or in the cases that other local therapies fail.

Research of systolic blood pressure at admission on in-hospital outcomes in patients with ST elevated acute myocardial infarction / 中华急诊医学杂志

Objective To investigate the impact of systolic blood pressure (SBP) at admission on in-hospital outcomes in patients with ST elevated acute myocardial infarction (STEMI).Methods Data of 336 STEMI patients admitted from September 2008 to May 2011 were retrospectively analyzed.Total of 336 STEMI patients were classified into 4 groups as per the level of SBP at admission:group A (＜ 101 mmHg,n =59) ; group B (101-120 mmHg,n =109) ; group C (121-140 mmHg,n =98) and group D (＞ 140 mmHg,n =69).And clinical features,coronary angiography (CAG) findings,the strategy of treatment,complications and hospital mortality were compared among 4 groups with SPSS version 18.0 software.Results The mortality rates of the four groups were 18.64％,1.83％,4.08％,1.45％,respectively.The patients with SBP ＜ 106 mmHg were in greater risk of in-hospital mortality,Killip class ≥ 3 at admission,shock and refractory arrhythmias,and more patients in this group needed pacemaker and intraaortic balloon pump (IABP) treatment than patients in other 3 groups.While there was no significant difference in mortality rate between other three groups.Multivariate logistic regression analysis demonstrated SBP ＜ 101 mmHg (OR =6.368,P =0.002) and peak value of troponin Ⅰ (OR =3.781,P =0.008) were independent risk factors of in-hospital death in STEMI patients.Conclusions The STEMI patients with SBP ＜ 101 mmHg at admission had higher mortality rate and low SBP at admission had great prognostic value in short-term outcomes of STEMI.

Protective effects of recombinant human erythropoietin against acute liver injury induced by sepsis in rats / 中华急诊医学杂志

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute liver injury.Methods Ninety-six healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into 3 groups:normal control group (sham group,n =32),CLP model group (sepsis group,n =32) and rHuEPO treatment group (n =32).The rat model of sepsis was established by caecal ligation and puncture.In treatment group,rats were treated with rHuEPO 5000 U/kg administered through caudalis vein after CLP procedure.Continuous observation was carried out until 24 h after modeling.Of each group,8 rats were sacrificed at 2 h,6 h,12 h and 24 h,respectively,and then the liver tissue samples and blood samples were collected.Blood samples were assayed for determining the levels of serum cytokines [tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) by using the enzyme-linked immunoadsorbentassay (ELISA) method.The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected.Histopathological changes of liver tissues were observed under optical and transmission electron microscopy.Results (①)The levels of ALT,AST,TNF-a,iNOS in serum of rats in control group were lower than those in model group and rHuEPO group (P ＜0.01).The levels of TNF-α,IL-6 and iNOS in serum of rats in rHuEPO group were decreased significantly compared with model group (P ＜ 0.01).(②) The optical microscopy and the transmission electron microscopy showed hepatocyte edema,liver focal necrosis,inflammatory cell infiltration in portal area and severe congestion of interlobular veins,hepatocyte karyopyknosis,mitochondrial and endoplasmic reticulum (ER) obviously decreased in sepsis group at 24 h.Hepatic injury was attenuated after employment of rHuEPO.Conclusions Recombinant human erythropoietin can inhibit the levels of ALT,AST,TNF-a,iNOS in serum,thus modifying the inflammatory response and providing protective effects against acute liver injury in the wake of infection.