[Role and mechanism of IL-6/STAT3/Th17 signaling pathway in the intervention of forsythia in acute lung injury of septic rats].

Objective: To investigate the mechanism of interleukin-6 (IL-6) /signal transducers and activators of transcriptional 3 (STAT3) /helper T cell 17 (Th17) signaling pathway in lung injury of rats with sepsis intervened by forsythia, with a view to provide experimental basis for the role and mechanism of forsythia in the treatment of sepsis. Methods: In July 2021, 30 healthy Wistar male rats were selected and randomly divided into sham operation group, model group and treatment group, with 10 rats in each group. The rat model of sepsis was established by cecal ligation and puncture. 2 h after recovery, the rats were given traditional Chinese medicine forsythia orally, twice a day at an interval of 12 h. The wet/dry mass ratio (W/D) of lung tissue was detected 24 h after surgery. The morphological changes of lung tissue were detected by HE staining. Flow cytometry was used to detect Th17 population in peripheral blood. The expression levels of IL-6 and interleukin-17A (IL-17A) in serum were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of IL-17A and IL-6 in lung tissues were detected by reverse transcription-polymerase chain reaction. The expression levels of STAT3 and IL-17A in lung tissue were determined by Western blotting. Results: Compared with model group, the W/D of lung tissue in treatment group was decreased, and the difference was statistically significant (P<0.05). HE staining of lung tissue showed that compared with the model group, the degree of lung lesion and injury was reduced in the treatment group. Compared with sham operation group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in model group was significantly increased (P<0.05). Compared with model group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in treatment group was significantly decreased (P<0.05). Compared with sham operation group, peripheral blood serum IL-6 and IL-17 of rats in model group were significantly increased (P<0.05). Compared with model group, IL-6 and IL-17 in peripheral blood serum of rats in treatment group were decreased (P<0.05). Compared with sham operation group, the expressions of IL-17A and IL-6 mRNA in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the expressions of IL-17A and IL-6 mRNA in lung tissue of rats in treatment group were significantly decreased (P<0.05). Compared with sham operation group, the protein expressions of STAT3 and IL-17A in lung tissue in model group were significantly increased (P<0.05). Compared with model group, the pritein expressions of STAT3 and IL-17A in lung tissue in treatment group were significantly decreased (P<0.05) . Conclusion: Forsythia plays a role in alleviating lung injury by down-regulating the expressions of the signaling pathway IL-6/STAT3/Th17, which providing a new target for the treatment of sepsis induced lung injury.

[A case of brucellosis complicated with capillary leak syndrome and multiple organ dysfunction syndrome].

Brucellosis can lead to pathological changes of multiple systems. Capillary leak syndrome (CLS) is a clinical syndrome caused by different reasons, mainly characterized by hypotension, hypoproteinemia and systemic edema. The condition is critical and the clinical manifestations are complex, and multiple organ dysfunction syndrome (MODS) may occur in severe cases. CLS caused by brucellosis is extremely rare. The diagnosis and treatment of a patient with brucellosis complicated with CLS and MODS was analyzed in this paper, in order to improve the knowledge of clinicians about brucellosis and its complications.

[Exploring the treatment of sepsis-associated acute lung injury with Liangge Powder via ERK1/2 and PI3K/AKT pathways: based on network pharmacology and whole animal experimentation].

Objective: To investigate the therapeutic effect and mechanism of Liangge Powder against sepsis-induced acute lung injury (ALI) . Methods: From April to December 2021, the key components of Liangge Powder and its targets against sepsis-induced ALI were analyzed by network pharmacology, and to enrich for relevant signaling pathways. A total of 90 male Sprague-Dawley rats were randomly assigned to sham-operated group, sepsis-induced ALI model group (model group), Liangge Powder low, medium and high dose group, ten rats in the sham-operated group and 20 rats in each of the remaining four groups. Sepsis-induced ALI model was established by cecal ligation and puncture. Sham-operated group: gavage with 2 ml saline and no surgical treatment. Model group: surgery was performed and 2 ml saline was gavaged. Liangge Powder low, medium and high dose groups: surgery and gavage of Liangge Powder 3.9, 7.8 and 15.6 g/kg, respectively. To measure the wet/dry mass ratio of rats lung tissue and evaluate the permeability of alveolar capillary barrier. Lung tissue were stained with hematoxylin and eosin for histomorphological analysis. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1ß in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The relative protein expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-protein kinase B (AKT), and p-ertracellular regulated protein kinases (ERK) were detected via Western blot analysis. Results: Network pharmacology analysis indicated that 177 active compounds of Liangge Powder were selected. A total of 88 potential targets of Liangge Powder on sepsis-induced ALI were identified. 354 GO terms of Liangge Powder on sepsis-induced ALI and 108 pathways were identified using GO and KEGG analysis. PI3K/AKT signaling pathway was recognized to play an important role for Liangge Powder against sepsis-induced ALI. Compared with the sham-operated group, the lung tissue wet/dry weight ratio of rats in the model group (6.35±0.95) was increased (P<0.001). HE staining showed the destruction of normal structure of lung tissue. The levels of IL-6 [ (392.36±66.83) pg/ml], IL-1ß [ (137.11±26.83) pg/ml] and TNF-α [ (238.34±59.36) pg/ml] were increased in the BALF (P<0.001, =0.001, <0.001), and the expression levels of p-PI3K, p-AKT and p-ERK1/2 proteins (1.04±0.15, 0.51±0.04, 2.31±0.41) were increased in lung tissue (P=0.002, 0.003, 0.005). The lung histopathological changes were reduced in each dose group of Liangge Powder compared with the model group. Compared with the model group, the wet/dry weight ratio of lung tissue (4.29±1.26) was reduced in the Liangge Powder medium dose group (P=0.019). TNF-α level [ (147.85±39.05) pg/ml] was reduced (P=0.022), and the relative protein expression levels of p-PI3K (0.37±0.18) and p-ERK1/2 (1.36±0.07) were reduced (P=0.008, 0.017). The wet/dry weight ratio of lung tissue (4.16±0.66) was reduced in the high-dose group (P=0.003). Levels of IL-6, IL-1ß and TNF-α[ (187.98±53.28) pg/ml, (92.45±25.39) pg/ml, (129.77±55.94) pg/ml] were reduced (P=0.001, 0.027, 0.018), and relative protein expression levels of p-PI3K, p-AKT and p-ERK1/2 (0.65±0.05, 0.31±0.08, 1.30±0.12) were reduced (P=0.013, 0.018, 0.015) . Conclusion: Liangge Powder has therapeutic effects in rats with sepsis-induced ALI, and the mechanism may be related to the inhibition of ERK1/2 and PI3K/AKT pathway activation in lung tissue.

[Progress in the development of treprostinil for the treatment of pulmonary hypertension].

Pulmonary arterial hypertension is a progressive pulmonary vascular disease, which can cause right heart failure and even death in severe cases. Treprostinil is a stable prostacyclin analogue and a powerful drug for dilating pulmonary vessels. It can be administered in different ways, with a long half-life, good stability and is suited for diverse types of PAH. It is approved for the treatment of Group 1 PAH, but some studies show that treprostinil is effective in patients with Group 3 or Group 4 PAH. Therefore, this article will review the progress of evidence-based medicine evidence of traprostanil in the treatment of type 1, 3 and 4 pulmonary hypertension.

[T lymphocyte subsets combined with inflammatory indicators for auxiliary diagnosis and prognosis evaluation of sepsis].

Objective: To explore the application value of T lymphocyte subsets combined with procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and white blood cell count (WBC) in the auxiliary diagnosis and prognosis evaluation of sepsis. Methods: In a retrospective study, seventy-two patients with sepsis diagnosed and treated in Tianjin First Central Hospital from June 2018 to April 2021 were selected as the research objects, and included in the sepsis group were 46 males and 26 females, aged 68 (57.3, 80.3) years. In addition, 111 patients with local infection admitted to hospital during the same period were included in the local infection group, including 62 males and 49 females, aged 68 (51, 77) years. Sepsis patients were divided into survival group (43 cases) and death group (29 cases) according to the 28-day outcome. CD3+, CD4+, CD8+, CD4+/CD8+ ratio were detected by flow cytometry within 24 h after admission, PCT was detected by ELISA, CRP was detected by immunoturbidimetry, blood routine examination, blood lactic acid (Lac) and oxygen partial pressure (PO2) were detected by instrumental method. Multivariate Logistic regression analysis was used to evaluate the correlation between each indicator and sepsis, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of each indicator for sepsis. Multivariate Logistic regression analysis and Kaplan Meier survival analysis were used to evaluate the prognostic value of each index for patients with sepsis. Results: Peripheral blood CD3+, CD4+, CD8+, CD4+/CD8+ ratio and PLT in sepsis group were significantly lower than those in local infection group(Z=-8.184,P<0.001;Z=-7.210,P<0.001;Z=-5.936,P<0.001;Z=-2.700,P=0.007;Z=-6.381,P<0.001); PCT, CRP, NLR and Lac levels were significantly higher than those in local infection group(Z=-8.262,P<0.001;Z=-3.094,P=0.002;Z=-9.004,P<0.001;Z=-4.770,P<0.001). Multivariate Logistic regression model showed that PCT, NLR, CD3+, CD8+, CD4+/CD8+ were independent risk factors for sepsis. According to ROC curve analysis, AUC of sepsis patients diagnosed by each indicator were 0.862, 0.894, 0.858, 0.760 and 0.618, respectively. The cut-off values were 3.075 ng/ml, 10.715, 44.935×109/L, 27.463×109/L and 0.750, respectively. The NLR sensitivity was 80.6%, and the CD3+ specificity was 94.6%. The AUC of combined detection of PCT and NLR was 0.947, sensitivity was 87.5% and specificity was 91.9%. The combined detection AUC of PCT, NLR, CD3+, CD4+/CD8+ was 0.958, the sensitivity and specificity were 90.3% and 91.0% respectively(P<0.001). PCT and Lac in death group were significantly higher than those in survival group(Z=-2.302,P=0.021;Z=-3.095,P=0.002);Peripheral blood CD4+/CD8+ levels were significantly lower than those in survival group(Z=-3.691,P<0.001),Multivariate Logistic regression model showed that CD4+/CD8+ ratio was an independent risk factor for 28 d mortality in patients with sepsis (P<0.001). The ROC curve showed that the AUC was 0.758, and the Youden index reached the maximum when the cut-off value was 1.27, the sensitivity and specificity were 79.3% and 60.5%, respectively. Compared with patients with CD4+/CD8+ ≥1.27, 28-day mortality was significantly increased in patients with CD4+/CD8+<1.27 (P=0.032). Conclusion: The combined detection of PCT, NLR, CD3+ and CD4+/CD8+ can improve the auxiliary diagnostic efficiency of sepsis, and the ratio of CD4+/CD8+ in peripheral blood may have certain predictive value for the prognosis of sepsis.

[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].

Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.

[The importance of occupational history in clinical thinking from the diagnosis and treatment of a case of Tsutsugamushi disease].

A farm worker in Baodi District of Tianjin was diagnosed with Tsutsugamushi disease due to fever and intermittent cough for more than 3 months.The patient's diagnosis and treatment process was complicated, and the diagnosis was delayed in the early stage of the disease because the clinician neglected the occupational history and lacked knowledge about the prevention and control of tsutsugamushi disease. As an important part of the epidemiological history, occupational history is crucial for the diagnosis of occupational related diseases. Clinical thinking runs through the whole process of clinical diagnosis and disease treatment, and correct clinical thinking can effectively reduce the occurrence of misdiagnosis.Clinicians should ask and record career history in detail to improve the quality of health care.

[Estimation on the individual treatment effect among heterogeneous population, using the Causal Forests method].

Objective: This project aimed to explore the effectiveness of estimating individual treatment effect on real data, among the heterogeneous population, with Causal Forests (CF) method, to find out the characteristics of heterogeneous population. Methods: We designed and conducted four computer simulation schemes to verify the effect of estimating on individual treatment, using the CF under four different environments of the treatment effects. Real data was then analyzed for the catheterization on right heart. Results: Results from the simulation process showed that the values on individual treatment effect that were estimated by causal forests were consistent with the population effect as well as in line with the expected distribution under the setting of four different effect values. Results of real data analysis showed that values of individual treatment effect among most patients appeared positive, so the use of RHC could cause an increase of the '180-day mortality rate' in the sampled population. Patients with lower predicted probability of 2-mo survival and albumin were more likely to have a lower risk of death after using the RHC. Conclusion: CF method could be effectively used to estimate the individual treatment effect and helping the individuals to make decision on the receipt of treatment.

Phylogenetic analysis of HA and NA genes of influenza H1N1 viruses from 1918 to 2017.

The 1918 "Spanish" pandemic is the earliest known influenza H1N1 virus. Since then H1N1 viruses circulated between humans and animals continuously. With the increased amount of samples of H1N1 viruses and technology development, researchers have been studying how the viruses evolved. Here, we analyzed HA and NA genes of H1N1 viruses from three aspects: host distribution, geographical distribution and phylogenetic analysis. The data showed hosts were predominantly human, swine and poultry, and other hosts were mainly cat, ferret, wild bear, canine, cheetah and seal. In terms of geographical distribution, the North America and Eurasia were the main H1N1 influenza pandemic areas. Of them, the United States, China, Japan, Canada, the United Kingdom, India and Singapore were the most affected. The phylogenetic analysis of surface genes of influenza H1N1 viruses from 1918 to 2017 worldwide revealed the distribution of all avian influenza viruses (AIVs) showed a clear geographical difference, mainly concentrated in Eurasia and America. American and Eurasian swine viruses might be the ancestors of the 2009 pandemic virus' HA and NA genes. Swine influenza viruses played an important role in the spread of influenza viruses across species. To our knowledge, this is the first large-scale phylogenetic analysis of HA and NA genes of influenza H1N1 viruses worldwide until now. Our findings further emphasize the importance of surveillance of the genetic diversity of influenza H1N1 viruses in different hosts and raised more concerns about the long-time monitoring. Keywords: influenza H1N1 viruses; HA genes; NA genes; phylogenetic analysis; evolution.

[Current status of reproductive health and its occupational influencing factors among female medical staff in a provincial maternal and child health hospital].

Objective: To investigate the current status of reproductive health among the female medical staff in a provincial maternal and child health hospital and analyze the occupational influencing factors for reproductive health, particularly the effects of high-intensity work, work shift, chemical poisons, and physical and biological factors on reproductive health, and to provide a scientific basis for developing related intervention measures and promoting the reproductive health of professional females. Methods: A reproductive health questionnaire was designed in terms of age, type of work, professional title, education level, working hours, working strength, and the reproductive health of female staff to analyze the current status of reproductive health, working strength, and occupational hazardous factors. The female medical staff in the provincial maternal and child health hospital completed the questionnaire on the internal network of the hospital voluntarily. Results: Of all respondents, 19.46% had a history of miscarriage, 5.90% visited the hospital due to infertility, 21.31% had irregular menstruation within the last 3 months, and 30.57% had reproductive system disease; 72.28% of the investigated medical staff often worked at night, 47.25% often worked overtime (more than 3 days a week) , and 22.27% worked over 8 hours daily. The respondents who often worked overtime had a significantly higher prevalence of reproductive system disease than those who did not often work overtime (χ(2)= 58.65, P<0.01) . The respondents who often worked at night had a significantly higher rate of miscarriage than those who did not work at night (χ(2)=41.57, P<0.01) . In all respondents, 87.08% were often exposed to chemical injuries such as disinfectants, and 78.15% had contact with noise, radiation, and other physical injuries; the medical staff exposed to chemical and physical injuries had a significantly higher proportion of individuals with a history of miscarriage than the unexposed staff (χ(2)=10.04, P<0.01; χ(2)=13.30, P<0.01) . Conclusion: Much attention should be paid to the reproductive health of female medical staff in the provincial maternal and child health hospital, who have high working strength. The occupational hazard factors can be avoided by reasonably arranging the work schedule and creating a supportive environment to improve the reproductive health of female medical staff.

[Mental health problems among female staff in a provincial maternal and child health hospital: an investigation of 647 individuals].

Objective: To investigate the current status of depression and anxiety among female staff in a maternal and child health hospital, and to provide a basis for developing related prevention and intervention measures and promoting the mental health of female staff. Methods: The female staff from a provincial maternal and child health hospital completed a psycho-health questionnaire survey on Internet from June to October, 2016. The questionnaires used in the survey consisted of Patient Health Questionnaire (PHQ-9) , Generalized Anxiety Disorder Scale (GAD-7) , and Symptom Checklist-90 (SCL-90) . The distribution features of mental health problems such as depression and anxiety were analyzed according to the results: of the questionnaire survey. Results Of all female staff surveyed, 42.04% showed depression symptoms, 28.90% showed anxiety symptoms, and 26.12% showed comorbid symptoms of depression and anxiety. Moderate or severe depression (anxiety) was mainly distributed among the female staff with comorbid symptoms (90.63% and 97.01%, respectively) . There were significant differences in the distribution of moderate or severe anxiety symptoms between the medical staff and nursing staff (χ(2)= 5.81, P=0.05) and between those with intermediate and junior professional titles (χ(2)=7.99, P=0.018) . As for SCL-90 results, the total score, total average score, and scores on factors of somatization, compulsion, interpersonal sensitivity, depression, and anxiety in the female staff with comorbid symptoms, moderate or severe depression, and moderate or severe anxiety were significantly higher than the national norm (P<0.01) , while the scores on paranoid and psychotic factors were significantly lower than the national norm (P<0.01) . The numbers of cases of positive factors were significantly higher in the female staff with comorbid symptoms than in the female staff with a single symptom and asymptomatic female staff (both P<0.01) , and positive cases were mainly distributed in depression, interpersonal sensitivity, compulsion, anxiety, and somatic factors. Conclusion: The prevalence of depression and anxiety is high among female staff in the maternal and child health hospital, mainly characterized by comorbid symptoms of moderate or severe depression and anxiety. Comorbidity is accompanied by mental health problems such as interpersonal sensitivity, obsessive compulsion, and physical discomfort. Corresponding measures are needed for the prevention and intervention of mental health problems among female staff in the maternal and child health hospital.

CT features differentiating pre- and minimally invasive from invasive adenocarcinoma appearing as mixed ground-glass nodules: mass is a potential imaging biomarker.

AIM: To investigate the differential diagnosis value of preoperative computed tomography (CT) features between pre/minimally invasive and invasive adenocarcinoma in pulmonary mixed ground glass nodules (mGGNs). MATERIALS AND METHODS: The histopathological data and CT images of 146 mGGNs in 141 patients were reviewed retrospectively. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to identify the CT features differentiating between pre/minimally invasive and invasive adenocarcinoma and to evaluate their accuracy. RESULTS: In univariate analysis, there were significant differences (p<0.05) in the nodule diameter, volume, density, mass, solid portion volume, shape, margin, air bronchogram, and pleural retraction between pre/minimally invasive and invasive adenocarcinoma. Multivariate logistic regression analyses revealed that nodule mass and volume were statistically significant independent differentiators. ROC curve analysis was performed to evaluate the differentiators. According to the corresponding ROC curve, the optimal cut-off mass to differentiate pre/minimally invasive adenocarcinoma from invasive adenocarcinoma was 254.87 mg, with a sensitivity of 84.52%, a specificity of 88.71%, and an accuracy of 86.30%. Compared with the area under the ROC curve (AUC) for mass, volume, and diameter, the differential diagnosis value of mass was higher than those of volume and diameter. CONCLUSION: Nodule mass and volume were significant differentiators of pre/minimally invasive adenocarcinoma from invasive adenocarcinoma in mGGN, and mass had a higher differential diagnosis value.

[A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study].

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10(9)/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10(9)/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10(9)/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10(9)/L) at 4(th) week, 8(th) week and 12(th) week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10(9)/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion: Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Exon 19 deletion was associated with better survival outcomes in advanced lung adenocarcinoma with mutant EGFR treated with EGFR-TKIs as second-line therapy after first-line chemotherapy: a retrospective analysis of 128 patients.

OBJECTIVE: To determine whether the specific genotype of exon 19 deletion has a better survival outcome than that of exon 21 substitution in advanced lung adenocarcinoma with EGFR mutant patients that were treated with EGFR-TKIs as second-line therapy after first-line chemotherapy. METHODS: Between April 1, 2010 and December 31, 2012, the detailed clinical information of 128 patients was screened from the hospital information database of the First Affiliated Hospital and the Third Affiliated Hospital of Kunming Medical University by inclusion/exclusion criteria. Then, a telephone follow-up and a review of all patients' image data were done to obtain the survival information of all patients. After that, all patients' data were processed by IBM(®) SPSS(®) version 19.0. RESULTS: There were correlations between EGFR mutation status, gross tumor type and PFS or OS according to the Kaplan-Meier survival analyses and log-rank tests. The exon 19 deletions had significantly better survival outcomes in comparison to exon 21 substitutions (median PFS: 8.1 vs. 6.8 months, P = 0.002; median OS: 17.6 vs. 12.5 months, P = 0.000). Stratification analyses of PFS and OS revealed that exon 19 deletions had a survival superior to exon 21 substitutions. CONCLUSION: Compared with L858R mutation, the genotype of exon 19 deletion had a better survival outcome in terms of PFS and OS in patients with advanced lung adenocarcinoma treated with EGFR-TKIs as second-line therapy after first-line chemotherapy.

Inferior alveolar nerve function recovers after decompression of large mandibular cystic lesions.

OBJECTIVE: The treatment of large mandibular cystic lesions (diameter > 35 mm) is controversial. Few studies determine the inferior alveolar nerve function after decompression which is one of the major options for treating such lesions. We aim to investigate the recovery of inferior alveolar nerve function after decompression. METHODS: Twenty-two patients with large mandibular cystic lesions, diagnosed as keratocystic odontogenic tumor, ameloblastoma, or dentigerous cyst, were included. Inferior alveolar nerve function was observed by monitoring the pulp vitality of involved teeth (n = 64) with electric pulp test before decompression and 1, 3, 6, 9, 12, and 24 months after decompression, respectively. RESULTS: The pulp vitality of the involved teeth was significantly decreased before decompression. Recovery of pulp vitality could be observed after decompression, indicating the recovery of inferior alveolar nerve function. A majority (96.9%) of the vital pulp was preserved in the involved teeth after decompression. CONCLUSIONS: Recovery of inferior alveolar nerve function was remarkable in patients with large mandibular cystic lesions after decompression, indicated by the recovery of pulp vitality of involved teeth. When decompression is preferred, conservative therapy rather than root canal therapy is recommended for the teeth with root tip exposed in the cystic lesions and without pulposis.

Efficient Q-switched Ho:GdVO4 laser resonantly pumped at 1942 nm.

An efficient 2 µm room-temperature Q-switched Ho:GdVO4 laser end-pumped by a 1942 nm Tm-fiber laser is demonstrated. To our knowledge, this is the first report of Q-switched performance of Ho:GdVO4 crystal. A maximum CW output power of 6.85 W under the absorbed pump power of 24.1 W was obtained with a slope efficiency of 39.5% at a temperature of 17°C. With the same absorbed pump power, a maximum output energy per pulse of about 0.9 mJ and minimum pulse width of 4.7 ns were obtained at the pulsed repetition frequency (PRF) of 5 kHz, corresponding to a peak power of approximately 187.2 kW.

Activated protein C ratio, plasma tissue factor activity and activated factor VII in Chinese patients with coronary heart disease.

OBJECTIVE: There is close relationship between abnormal coagulation system and progression of coronary heart disease (CHD), our purpose is to evaluate the contribution of hematologic factors and some other risk factors to the development of coronary heart disease (CHD) in Chinese population. METHODS: 56 patients with CHD at admission and 54 controls were enrolled. Plasma levels of protein C, free protein S, total protein S, thrombomodulin, activated factor VII (FVIIa), factor VII:Ag, P-selectin, tissue-type plasminogen activator, plasminogen activator inhibitor-1 were measured by enzyme linked immunosorbent assay, activity of tissue factor (aTF) by chromogenic activity assay, and activated protein C (APC) ratio, prothrombin time, aPTT, fibrinogen, D-dimmer and thrombin time by full-automated coagulation analyzer. RESULTS: Compared with controls, plasma level of thrombomodulin, FVIIa, factor VII:Ag and aTF were raised in CHD group (p<0.05, 0.001, 0.05, and 0.05, respectively). The average APC ratio in CHD group was lower than that in controls (p<0.001). The result of binary logistic regression analysis showed that activated factor VII (OR2.680, 95%CI1.539-4.665) and tissue factor activity (OR1.019, 95%CI1.004-1.035) were risk factors and high density lipoprotein (OR0.008, 95%CI0-0.478) and activated protein C ratio (OR0.001, 95%CI0-0.011) were protective factors for CHD. CONCLUSIONS: Low activated protein C ratio, elevated tissue factor activity and increased activated factor VII in plasma may contribute to development of coronary heart disease.

Regulation of two key nuclear enzymatic activities by the 7SK small nuclear RNA.

7SK is a highly conserved small nuclear RNA (snRNA) in vertebrates. Since its discovery in 1968, little had been known about its function until recently, when 7SK was found to associate with the general transcription elongation factor P-TEFb. Together with the HEXIM1 protein, 7SK sequesters P-TEFb into a kinase-inactive complex, where it mediates HEXIM1's inhibition of P-TEFb. This helps maintain P-TEFb in a functional equilibrium to control transcription, cell growth, and differentiation. Although highly abundant, only a small fraction of 7SK is P-TEFb-bound. Using affinity purification, we have identified APOBEC3C as another 7SK-associated protein. As a member of the APOBEC family that functions in diverse processes through deaminating cytosine in DNA, it is unclear how APOBEC3C's activity is controlled to prevent its mutations of genomic DNA. We show that most of APOBEC3C interact with about half of nuclear 7SK, which suppresses APOBEC3C's deaminase activity and sequesters APOBEC3C in the nucleolus where it could be at a safe distance from most genomic sequences. Because the DNA substrate-binding site in APOBEC3C differs from the region for 7SK binding, 7SK does not act as a substrate competitor in inhibiting APOBEC3C. The demonstration of 7SK's suppression of yet another enzyme besides P-TEFb suggests a general role for this RNA in regulating key nuclear functions.

Cutaneous stimulation improves function of a chronic patient with cerebellar damage.

The prognosis of cerebellar hemorrhage with brain stem compression is known to be poor, and patients who can usually survive are severely disabled with limited benefit from conventional rehabilitation. An innovative cutaneous stimulation was administered to a chronic patient (2 years after the incidence) who has severe ataxia, gait imbalance and limb spasticity caused by cerebellar hemorrhage. After 8 months of intervention, patient's function as evaluated by two functional measures has improved by 40%. In addition, the patient's ataxia and hypotonia have improved significantly in which he has regained the abilities to grasp objects, sit upright, control his equilibrium, and monitor an electric wheelchair. The present case study demonstrated a significant improvement of a chronic severely disabled patient who received the intervention 2 years after the accident, suggesting that the cutaneous stimulation may be a possible effective neurologic intervention.

Eukaryotic elongation factor 2 can bind to the synthetic oligoribonucleotide that mimics sarcin/ricin domain of rat 28S ribosomal RNA.

Eukaryotic elongation factor 2 (eEF2) catalyzes the translocation of peptidyl-tRNA from the A site to P site by binding to the ribosome. In this work, the complex formation of rat liver eEF2 with a synthetic oligoribonucleotide (SRD RNA) that mimics sarcin/ricin domain of rat 28S ribosomal RNA is invested in vitro. Purified eEF2 can specifically bind SRD RNA to form a stable complex. tRNA competes with SRD RNA in binding to eEF2 in a less extent. Pretreatment of eEF2 with GDP or ADP-ribosylation of eEF2 by diphtheria toxin can obviously reduce the ability of eEF2 to form the complex with the synthetic oligoribonucleotide. These results indicate that eEF2 is likely to bind directly to the sarcin/ricin domain of 28S ribosomal RNA in the process of protein synthesis.