Search

With the dramatically increasing detection rate of ground-glass nodules (GGN), exact understanding and treatment strategy of them has become the hottest issue currently. More and more studies have begun to explore the underlying mechanisms of their indolent characteristics and favorable prognosis from the perspectives of molecular evolution and immune microenvironment. GGN has different dominating gene mutations at different evolutional stages. The pure GGN has a lower tumor mutation burden and genomic instability, while a gradually evolutionary feature of genomic mutation along with the pathological progression can be observed. GGN has less infiltration of immune cells, and they are under the pressure of immune surveillance with weakened immune escape. With the increase of solid components, an inhibitory immune microenvironment is gradually established and immune escape is gradually enhanced, leading to rapid tumor growth. Further exploration of the molecular characteristics of GGN will help to more precisely distinguish these highly heterogeneous lesions, which could be helpful to make personalized treatment plans.

Objective: To examine the efficiacy of a machine learning diagnostic model specifically for solid nodules in multiple pulmonary nodules constructed by combining patient clinical information and CT features. Methods: Totally 446 solid nodules resected from 287 patients with multiple pulmonary nodules in Department of Thoracic Surgery, Peking University People's Hospital from January 2010 to December 2018 were included. There were 117 males and 170 females, aging (61.4±9.9) yeras (range: 33 to 84 years). The nodules were randomly divided into training set (228 patients with 357 nodules) and test set (59 patients with 89 nodules) by a ratio of 4∶1. The extreme gradient boosting (XGBoost) algorithm was used to generate a predictive model (PKU-ML model) on the training set. The accuracy was verified on the test set and compared with previous published models. Finally, an independent single solid nodule set (155 patients, 95 males, aging (62.3±8.3) years (range: 37 to 77 years)) was used to evaluate the accuracy of the model for predictive value of single solid nodules. Area of receiver operating characteristic curve (AUC) was used to evaluate diagnostic values of models. Results: In the training set, the AUC of the PKU-ML model was 0.883 (95% CI : 0.849 to 0.917). In the test set, the performance of the PKU-ML model (AUC=0.838, 95% CI : 0.754 to 0.921) was better than the models designed for single pulmonary nodules (Brock model: AUC=0.709, 95% CI : 0.603 to 0.816, P= 0.04; Mayo model: AUC=0.756, 95% CI : 0.656 to 0.856, P= 0.01; VA model: AUC=0.674, 95% CI : 0.561 to 0.787, P< 0.01), similar with PKUPH model (AUC=0.750, 95% CI : 0.649 to 0.851, P= 0.07). In the independent single solid nodules set, the PKU-ML model also achieved good performance (AUC=0.786, 95% CI : 0.701 to 0.872). Conclusion: The machine learning based PKU-ML model can better predict the malignancy of solid nodules in multiple pulmonary nodules, and also achieved a good performance in predicting the malignancy of single solid pulmonary nodules compared to mathematical models.

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.

Objective: To estimate the probability of N2 lymph node metastasis and to assist physicians in making diagnosis and treatment decisions., Methods: We reviewed the medical records of 739 patients with computed tomography-defined stage I non-small cell lung cancer (NSCLC) that had an exact tumor-node-metastasis stage after surgery. A random subset of three fourths of the patients (n=554) were selected to develop the prediction model. Logistic regression analysis of the clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis. A prediction model was then built and externally validated by the remaining one fourth (n=185) patients which made up the validation data set. The model was also compared with 2 previously described models., Results: We identified 4 independent predictors of N2 disease: a younger age, larger tumor size, central tumor location, and adenocarcinoma or adenosquamous carcinoma pathology. The model showed good calibration (Hosmer-Lemeshow test: P=0.923) with an area under the receiver operating characteristic curve (AUC) of 0.748 (95% confidence interval, 0.710-0.784). When validated with all the patients of group B, the AUC of our model was 0.781 (95% CI: 0.715-0.839) and the VA model was 0.677 (95% CI: 0.604-0.744) (P =0.04). When validated with T1 patients of group B, the AUC of our model was 0.837 (95% CI: 0.760-0.897) and Fudan model was 0.766 (95% CI: 0.681-0.837) (P < 0.01)., Conclusion: Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined stage I NSCLC and was more accurate than the existing models. Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.

Objective: To study the clinical effect of the Gartland III humerus supracondylar fractures in children by manipulative reduction and Kirschner wire percataneous internal fixation., Methods: From July 2010 and July 2013, 60 patients with Gartland III humerus supracondylar fracture were selected and divided into treatment group and control group. In the treatment group 32 patients were treated with traditional bone setting tetradeca-manipulative reduction and percataneous Kirschner wire internal fixation,included 18 males and 14 females with an average age of (7.8 +/- 2.7) years old ranging from 5 to 11; in the control group 28 patients were treated with open reduction and Kirschner wire internal fixation,included 16 males and 12 females with an average age of (7.2 +/- 3.0) years old ranging from 4 to 12. The motion range of the elbow joint,the time of fracture clinical healing, and the effect after 6 months of Flynm clinical functional assessment standards were observed and compared., Results: The average fracture healing time of the control group (5.01 +/- 0.43) weeks was longer than that of the treatment group (4.29 +/- 0.29) weeks (t = 7.49, P = 0.00). At 6 months after treatment,the elbow motion range of the treatment group (146.02 +/- 2.28) was more than that of the control group (140.76 +/- 4.42) (t = -5.67, P = 0.00). At 6 months after treatment, according to Flynn evaluation, in the control group,there were 7 cases as excellent, 16 as good, 4 fair, 1 poor; in the treatment group, excellent in 21, good in 9, fair in 2 (U = 3.09, P = 0.002)., Conclusion: Manipulative reduction and Kirschner wire percataneous internal fixation for treatment of children's Gartland III humerus condyle fractures can shorten fracture clinical healing time and the clinical curative effect is better.

Objective: To evaluate the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of isolated mediastinal lesions., Methods: A retrospective study was conducted of 73 consecutive patients with isolated mediastinal lesions of unknown origin without parenchymal lung abnormalities, who underwent EBUS-TBNA from September 2009 to April 2011. The patients who were nondiagnostic with EBUS-TBNA subsequently underwent surgical biopsies and a minimum of 6 months'clinical and radiologic follow-up., Results: EBUS-TBNA achieved definitive diagnoses in 60 patients of the 73 patients (82.2%, 60/73). Malignancies were diagnosed in 23 patients and benignancies in 37. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing malignant mediastinal lesions were 95.8%(23/24), 100%(49/49) and 98.6%(72/73), respectively. EBUS was well tolerated by all of the patients with no complications., Conclusion: EBUS-TBNA of isolated mediastinal lesions is a minimally invasive and safe diagnostic technique with high yield.

Objective: To evaluate the clinical factors affecting the definite pathological diagnosis of solitary pulmonary nodules (SPN) with multivariate Logistic regression analysis, and to build the clinical prediction model to estimate the probability of malignancy., Methods: A retrospective cohort study in our institution included 371 patients (197 males and 174 females) with definite pathological diagnosis of solitary pulmonary nodules from Jan 2000 to Sep 2009 (group A). Clinical data included age, gender, course of disease, symptoms, history and quantity of smoking history, history of tumor, family history of tumor, site, diameter, calcification, speculation, border, lobulation, traction of pleural, vascular convergence sign, and cavity. The independent predictors of malignancy were estimated with multivariate analysis, then the clinical prediction model was built. Other 62 SPN patients (group B) with definite pathological diagnosis in our institute from Oct 2009 to Mar 2010, were used to validate value of this clinical prediction model., Results: 53.1% of the nodules were malignant, and 46.9% were benign in goup A. Logistic regression analysis showed that seven clinical characteristics [age of patient (OR: 1.073), diameter (OR: 1.966), border (OR: 0.245), calcification (OR: 0.199), spiculation (OR: 2.088) and the family history of tumor (OR: 3.550)] were independent predictors of malignancy in patients with SPN (P<0.05). The cut-off value was 0.463. The sensitivity in group B was 92.5%, specificity 81.8%, positive predictive value 90.2%, and negative predictive value 85.7%. The area under the ROC curve for our model was 0.888±0.054., Conclusion: Age of patient, diameter, border, calcification, spiculation and the family history of tumor are independent predictors of malignancy in patients with SPN. Our prediction model is accurate and sufficient to estimate the malignancy of patients with SPN.

Objective: Previous studies have suggested that under hypoxic conditions hypoxia inducible factor-1 alpha (HIF-1 alpha) contributes to the progression of neonatal pulmonary hemorrhage (NPH) by increasing the expression of endothelin-1 (ET-1) gene. RNA interference (RNAi) refers to the process of sequence-specific post-transcriptional gene-silencing mediated by double-stranded RNA. This new gene-silencing technique has recently been shown to be a powerful approach for studying gene function. The aim of this study was to construct the small interfering RNA (siRNA) eukaryotic expression vectors specific to human HIF-1 alpha gene (pSIREN-Shuttle HIF-1 alpha siRNAin order to observe its silencing effect on HIF-1 alpha under hypoxic conditions., Methods: Six potential siRNA target sites (a-fspecific to human HIF-1 alpha gene were designed and synthesized to two complementary oligonucleotides (A-F) for each siRNA target site. Using a gene recombination technique, the recombinant expression vectors (A-F') were constructed by cloning the double strands oligonucleotide into RNAi-Ready pSIREN vector. The recombinant vectors were then transfected into the cultured human umbilical vein endothelial cells (HUVECs). After 48 hrs of culture, the cells were treated with CoCl2 (100 mu M) for 3 hrs. Expression of HIF-1 alpha mRNA and protein was detected using RT-PCR and Western blot. ET-1 level in cell culture supernates was detected using ELISA., Results: The recombinant HIF-1 alpha siRNA eukaryotic expression vectors A'-F'respectively aiming at sites (a-f) were constructed successfully. Compared to the non-transfection group, liposome-mediated gene transfection of pSIREN-Shuttle HIF-1 alpha siRNA expression vectors into HUVECs obviously down-regulated the mRNA and protein levels of HIF-1 alpha, and partly decreased the ET-1 level in the B' and D' transfection groups., Conclusions: The specific pSIREN-Shuttle HIF-1 alpha siRNA expression vectors B' and D' aiming at b and d sites can inhibit the expression of HIF-1 alpha, thus decreasing the level of its target gene ET-1. This may be helpful to study the relationship between HIF-1 alpha and neonatal pulmonary hemorrhage in vivo in future.

Octa-carboxylic phthalocyanine aluminium (AlPc(COOH)8) was used as fluorescent probe of infrared region. The interaction of octa-carboxylic phthalocyanine aluminium (AlPc(COOH)s) and bovine serum albumin(BSA) was studied by UV/ Vis and fluorescence spectra methods. The binding constant KA and n of phthalocyanine aluminium with BSA were determined. The results were K=5. 74 X 10(5) , n= 5. 7 and K= 3. 51 X 10(5) , for these two methods respectively. The same results by using two different analytical methods were obtained. Besides, hemin chloride(HE), ibuprofen(IB) and L-tryptophan(TRP) were used as probes, and the effects of these probes on the spectra of AlPc(COOH)8 )-BSA were studied by competitive binding method. The result indicated that, by adding HE into the AlPc(COOH)8)-BSA system, obvious spectral change of the system was observed, while adding TRP and IB caused no spectral changes. The binding site of octa-carboxylic phthalocyanine aluminium on the BSA was found to be at the I site by competitive binding method.

Objective: To study the effect of NADPH oxidase on hypoxia-inducible factor (HIF)-1alpha and endothelin (ET)-1 expression in human umbilical endothelia cells (HUVECs) and its possible mechanism., Methods: Twenty-five bottles of HUVECs culture fluid were randomly assigned into five groups: group A (normoxic control), group B (hypoxic), group C (NADPH oxidase inhibitor apocynin + normoxic), group D (H2O2 which can degrade HIF-1alpha rapidly+hypoxic) and group E (H2O2+apocynin+normoxic), with five bottles in each group. The culture supernates were collected and the total protein was extracted 3 hrs after treatment. Western Blot and ELISA were used to detect the HIF-1alpha protein expression in HUVECs and the ET-1 level in the culture supernates respectively., Results: There was a lower expression of HIF-1alpha protein (0.336 +/- 0.012) and lower ET-1 levels (5.87 +/- 2.22 pg/mL) in group A. The HIF-1alpha protein expression in groups B and C (0.773 +/- 0.018 and 0.888 +/- 0.022) and ET-1 levels (95.38 +/- 8.06 and 33.67 +/- 4.21 pg/mL) were noticeably higher than in group A (P < 0.05). The groups D and E had the HIF-1alpha protein expression levels similar to group A, but the ET-1 levels in group D (108.43 +/- 8.38 pg/mL) and group E (109.66 +/- 5.80 pg/mL) were significantly higher than in group A (P < 0.05)., Conclusions: Hypoxia or apocynin can increase the HIF-1alpha and ET-1 expression in HUVECs. H2O2 can inhibit the HIF-1alpha expression but increase the ET-1levels. It is speculated that NADPH oxidase as an oxygen sensor regulates the HIF-1alpha expression by changing the intracellular redox reaction and that except HIF-1, H2O2 might contribute to ET-1 synthesis and release.

Objective: To probe into the mechanisms of thread implantation at Zusanli(ST 36) and Chinese herbs in treatment of chronic renal failure(CRF)., Methods: CRF rat model was made by Platt subtotal nephrectomy. They were divided into 5 groups, sham operation group, model group, Chinese herbs group, thread implantation group and thread implantation plus Chinese herbs group. After treatment of 8 weeks, serum parathyroid hormone (PHT), transforming growth factor beta1 (TGF-beta1) expression in residual renal cells, malondialdehyde(MDA) content in the residual renal tissue, serum urea nitrogen(BUN) and creatinine(Scr), protein in urine and pathological changes were investigated., Results: The above indexes after treatment by thread implantation at acupoint, Chinese herbs, and acupoint thread implantation plus Chinese herbs showed begin reversion, especially, the most obviously improvement in the acupoint thread implantation plus Chinese herbs treatment group., Conclusion: The mechanism of acupoint thread implantation and Chinese herbs in improvement of CRF is related with decrease of PTH, inhibition of TGF-beta1 expression, decrease of MDA content and resisting lesion of renal fibrosis.

Reform thought was the mainstream of thoughts among the modern Wenzhou intellectual communities. It exerted great and profound influences on medical learning and activities, with medical education as the chief reform practice of Wenzhou intellectual communities in the late Qing Dynasty. Liji Hospital and Liji Medical School were the symbols of the reform. Chen Qiu was a thinker and doctor; Xu Dingchao was an officer and doctor; Chen Baoshan was a professionally educated physician; and Xu Yunzhi was a folk doctor inherited the experiences handed down from his family. The four representatives of Wenzhou medicine, though with different social backgrounds, and their purpose of studying medicine and experience of being a doctor different alike, their medical thoughts are naturally different, reflected the overall condition of Wenzhou medicine in the late Qing Dynasty.

Objective: To observe the phenomenon of pulmonary hemorrhage (PH) induced by exogenous endothelin-1 (exET-1) and the antagonizing effect of exogenous calcitonin gene-related peptide (exCGRP) in newborn rats., Methods: (1) To study the exET-1 induced PH: 100 newborn Wistar rats were randomly assigned into control group (group A, n = 10) and experiment groups (20 rats in each of groups B, C, D and E and 10 in group F). Thirty microl of normal saline and different concentrations of exET-1 in saline (ranged from 2 x 10(-6) mol/L to 10 x 10(-6) mol/L) were dripped into the rats' trachea through intubation for control group and the experiment groups, respectively. (2) To study the antagonizing effect of calcitonin gene-related peptide against endothelin: 50 rats were randomly assigned into control group (group D(1), n = 10) and experiment groups D(2), D(3), D(4) and D(5) (10 rats in each group), and were treated with 30 microl of normal saline as control and 4 x 10(-6) mol/L exET-1 via tracheal dripping. Twenty microl of exCGRP (concentrations ranged from 6.7 x 10(-8) mol/L to 6.7 x 10(-6) mol/L) were given by dripping to rats in groups D(3) to D(5) 30 minutes after the administration of exET-1. (3) The rats were sacrificed 3 hours after the first tracheal dripping and the gross anatomical and histological (HE staining) changes in lungs were observed., Results: (1) Following the treatment with exET-1, the rats showed cyanosis and dyspnea rapidly. The severity of respiratory symptoms varied in a dose dependent fashion with the concentrations of exET-1. The symptoms were relieved in the survived rats in about 30 minutes. The rats of all exET-1 treated groups presented with different degree of PH and group D (treated with 4 x 10(-6) mol/L of exET-1) had the highest incidence (diffuse PH 30%, focal PH 25%, spotty PH 25% and 80% in total), with a mortality of 20%. Rats in group E and F had lower incidence of PH (50% and 20%) but higher mortality (35% and 60%). (2) After the administration of different concentrations of exCGRP, the skin of the exET-1 treated rats turned ruddy rapidly with a significantly decreased incidence of PH and all the rats survived. The best protective effect was observed with the concentration of 6.7 x 10(-6) mol/L, and the incidence of PH was reduced to 20% (focal PH 10%, spotty PH 10%)., Conclusion: A significant increase of the endogenous ET-1 in hemorrhagic lung tissue caused by rewarming and reoxygenation following hypothermia and hypoxia had been confirmed. Administration of intratracheal exET-1 could induce pulmonary hemorrhage. This suggests that a significant increase of endogenous ET-1 in lung tissue may be one of the mechanisms in pathogenesis of PH caused by rewarming and reoxygenation following hypothermia and hypoxia. Endotracheal administration of exCGRP showed protective antagonizing effect against PH induced by exET-1. The authors speculate that the exCGRP has the potential to treat or even prevent PH caused by a significant increase of the endogenous ET-1.

The relationship between brain function and syndrome-types of TCM in 51 patients with non-insulin dependent diabetes mellitus (NIDDM) was observed. The syndromes were divided into three types. (1) Yin Deficiency with internal excessive Heat (YDIEH), 15 cases; (2) Qi-Yin Deficiency (QYD), 21 cases; (3) Deficiency of both Yin and Yang (DYY), 15 cases. The control group consisted of 30 healthy subjects matched in age, sex and educational level. The brain function were tested by neurobehavioral and neuroelectrophysiological tests. The former included short-term memory, thinking, eye-hand coordination and emotion tests; the latter consisted of brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP) and somatosensory evoked potentials (SEP). The results showed that the brain function in YDIEH group approached normal controls, and the brain function in QYD and QYY groups were significantly deteriorated. The results suggested that the brain function were correlated with the syndrome-types of patients with NIDDM. This would be valuable for diagnosis and treatment of NIDDM in TCM.

In order to make a systematic study of the effect of Coptis chinensis on free radicals, the authors used the method that the drug and the brain homogenate of rat were mixed and incubated to investigate the effect of Coptis on lipid peroxidation. The result showed that the malondialdehyde (MDA) product of rat brain homogenate inhibited by 5% Coptis was significantly different from control (P < 0.001). On the basis of the above-mentioned results, the effect of Coptis on lipid peroxidation and diabetes of rats induced by alloxan was investigated. The result showed: (1) The MDA product of both pancreas and liver homogenate in Coptis group was significantly less than that in control and alloxan group (P < 0.01, P < 0.05). (2) Superoxide dismutases (SODs) in erythrocytes activity was the same for all groups (P > 0.50). (3) The blood catalase (CAT) activity in alloxan group markedly decreased compared with control group (P < 0.05), but no significant change between Coptis and alloxan group (P > 0.05). (4) The value of serum glucose in alloxan group was significantly increased in comparing with control group (P < 0.05). There was a trend to decrease the value of serum glucose in Coptis group compared with alloxan group, but no significant difference between two groups (P > 0.05). The experiment indicated that there was very strong inhibitory effect of Coptis to the lipid peroxidation in vitro and in vivo. Coptis could protect rat from diabetes inducing by alloxan and that probably was due to the fact that Coptis was able to inhibit alloxan inducing free radicals.