This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

Background Aluminum can cause synaptic plasticity damage in the hippocampus, probably due to blocked interneuronal signal transmission. MicroRNA-29a (miR-29a) can target phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and participate in the generation of neuronal networks, and may be involved in the effect of aluminum on the electrical activity of neuronal networks. Objective To study the role and mechanism of miR-29a-targeted PTEN in aluminum-induced neuronal network injury in primary hippocampal neurons of ICR mice treated with maltol aluminum [Al(mal)₃] in vitro. Methods Primary hippocampal neurons of ICR mice born within 24 h were cultured in vitro. The purity of neurons was determined by labeling neuron-specific microtubule-associated protein 2 (MAP2) by immunofluorescence staining on day six of the culture; neurons were treated with different concentrations of Al(mal)₃, and divided into a control group, and 10, 20, and 40 μmol·L⁻¹ Al(mal)₃ groups, and neuronal cell viability was detected by CCK-8 method. Al(mal)₃ at 20 μmol·L⁻¹ was selected for subsequent experiments to establish a neuronal network injury model for intervention. The lentivirus infection method was used to transfect miR-29a into neurons, which were divided into mNG, mNG+20 μmol·L⁻¹ Al(mal)₃, miR-29a, and miR-29a+20 μmol·L⁻¹ Al(mal)₃ groups, and micro-electrode array (MEA) was used to analyze the firing of neuronal network. The expressions of miR-29a and PTEN mRNA in each group were detected by real-time PCR (RT-PCR), and the expression of PTEN protein in each group was detected by Western blotting. Results The purity of primary mouse hippocampal neurons was greater than 90%, and the viability of the neurons was above 80% in all groups. At 48 h of the designed Al(mal)₃ treatments, the changes in spike frequency, burst frequency, network burst frequency, and synchrony index of neurons cultivated on MEA plates in the control group were 207.56%±38.70%, 73.19%±46.43%, 75.42%±33.04%, and 117.13%±15.54%, respectively; the Al(mal)₃ groups’ neuronal network electrical activity showed a decreasing trend. Compared with the control group, the spike frequency, burst frequency, network burst frequency, and synchrony index of the 20 and 40 μmol·L⁻¹ Al(mal)₃ groups significantly decreased (The changes were 171.70%±28.08%, 49.20%±23.23%, 50.20%±18.18%, and 85.45%±20.30%; 150.68%±26.15%, 43.43%±15.54%, 52.05%±26.31%, and 26.80%±8.29%, respectively, P < 0.05). Compared with the control group (1.00), the miR-29a relative expression levels were significantly decreased in the 20 μmol·L⁻¹ Al(mal)₃ group (0.74±0.09) and the 40 μmol·L⁻¹ Al(mal)₃ group (0.62±0.12) (P < 0.05); the relative expression levels of PTEN mRNA were significantly increased in the 20 μmol·L⁻¹ Al(mal)₃ group (1.32±0.12) and the 40 μmol·L⁻¹ Al(mal)₃ group (1.48±0.11) (P < 0.05); the PTEN protein relative expression levels (1.29±0.12 and 1.82±0.10, respectively) were also significantly increased (P < 0.05). By overexpressing miR-29a in mouse primary hippocampal neurons, the spike frequency, burst frequency, and network burst frequency were significantly higher in the miR-29a group compared with the mNG group (The changes were 252.80%±62.03%, 171.65%±56.30%, and 197.75%±27.12%, respectively, P<0.05). The mNG+20 μmol·L⁻¹ Al(mal)₃ group showed a significant decrease in all indicators of neuronal network electrical activity (The changes were 123.28%±47.31%, 66.62%±31.53%, 70.60%±12.48%, and 52.86%±20.26%, respectively, P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the electrical activity indicators of neuronal network were significantly higher in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (The changes were 161.41%±42.13%, 101.16%±30.63%, 127.02%±29.58%, and 109.73%±15.61%, respectively, P < 0.05). Compared with the mNG group (1.00), the neuronal PTEN mRNA relative expression (0.67±0.11) and the PTEN protein expression (0.75±0.08) were decreased in the miR-29a group (P < 0.05); the PTEN mRNA relative expression (1.32±0.12) and the PTEN protein relative expression (1.46±0.15) in the mNG+20 μmol·L⁻¹ Al(mal)₃ group were increased (P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the PTEN mRNA relative expression (0.93±0.06) and the PTEN protein relative expression (0.92±0.09) were decreased in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (P < 0.05). Conclusion Aluminum significantly inhibits the electrical activity of hippocampal neuronal networks, and miRNA-29a may be involved in the aluminum-induced impairment of hippocampal neuronal network electrical activity by regulating PTEN expression.

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)₃] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)₃. The stage I experimental groups were blank control group, maltol group, 10 µmol·L⁻¹ Al group, 20 µmol·L⁻¹ Al group, and 40 µmol·L⁻¹ Al group. Then 20 µmol·L⁻¹ Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L⁻¹) group, SB (GSK-3β inhibitor, 1 µmol·L⁻¹), and SB (1 µmol·L⁻¹)+Al (20 µmol·L⁻¹) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L⁻¹ Al groups were decreased after 48h of Al(mal)₃ treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

Objective:To explore the predictive value of a radiomics model based on preoperative contrast enhanced MRI in the assessment of the isocitrate dedydrogenase 1 (IDH 1) genotype in high-grade glioma.Methods:A retrospective analysis was performed on a dataset including 182 patients with high-grade glioma confirmed by surgical pathology between December 2012 and January 2018 in the Affiliated Hospital of Qingdao University. There were 79 patients with IDH1-mutant glioma (45 cases with WHO grade Ⅲ, 34 with WHO grade Ⅳ) and 103 with IDH 1 wild-type glioma (33 cases with WHO grade Ⅲ, 70 cases with WHO grade Ⅳ). All patients had complete preoperative brain contrast enhanced MRI.The cases were divided into a training dataset and a validation dataset at a ratio of 7∶3 using stratified random sampling. Radiomic features were initially extracted using A.K (Analysis Kit, GE healthcare) software, and were selected and excluded using Kruskal-Wallis and Spearman analyses. Using R softwear " GLM" function, the Lasso-logistic model was finally conducted to obtain the optimized subset of the feature to build the radiomics model, and the model was then tested with cross-validation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of the model in differentiating IDH1-mutant type and wild-type gliomas.Results:The radiomics model showed good performance in IDH genotype differentiation in both the training dataset (AUC 0.870, 95% CI: 0.754 to 0.855, accuracy rate 79.8%, sensitivity 85.5%, specificity 75.4%, positive predictive value 0.734, negative predictive value 0.867) and the validation dataset (AUC 0.860, 95% CI: 0.690 to 0.913, accuracy rate 78.9%, sensitivity 91.3%, specificity 69.0%, positive predictive value 0.700, negative predictive value 0.909).Conclusion:The radiomics model based on the preoperative enhanced MR can provide a way to predict the IDH1 genotype in high-grade gliomas.

OBJECTIVETo investigate the clinicopathological features and prognosis of colorectal synchronous multiple primary cancer(SMPC).

METHODSFrom January 2008 to June 2011, 51 patients diagnosed with colorectal SMPC underwent surgery at Department of General Surgery of Peking University First Hospital. Their clinicopathological features, diagnosis, treatment and prognosis were summarized and analyzed. SMPC was diagnosed according to the following criteria: each tumor must have a definite pathologic picture of malignancy; metastasis or recurrence from another colorectal cancer was excluded; tumors must be distinctly separated by at least 5 cm of all intact bowel wall from each other; SMPC has abnormal cells between tumor and normal mucosa and abnormal gland of transitional zone; each cancer is infiltrating carcinoma except the carcinoma in situ; all the cancers are detected at the same time or within 6 months. Multiple primary colorectal cancer originated from familial colonic polyposis or ulcerative colitis was excluded.

RESULTSThese 51 colorectal SMPC patients accounted for 3.5% of 1 452 colorectal cancer patients in the same period at our hospital, with 32 males and 19 females, and mean age of (63±13)(29 to 82) years. Of 51 cases, 46(90.2%) had 2 original carcinoma, 3(5.9%) had 3 original carcinoma and 2(3.9%) had 4 carcinoma; 23(45.1%) complicated with colon polyps, 4(7.8%) complicated with malignancy outside the colorectum. In TNM staging, 7(13.7%), 15(29.4%), 24(47.1%) and 5(9.8%) patients were stage I(, II(, III( and IIII( respectively. Among 51 patients undergoing surgery by different procedures, 16 were subtotal colon resection, 8 were extended right colon resection, 5 were extended left hemicolon resection, 8 were right hemicolon resection plus Dixon procedure, 10 were Dixon, and 4 were right hemicolon resection plus sigmoid colon resection. Adjuvant chemotherapy and support treatment were given according to the condition after operation. A total of 105 tumors were found, including 25(23.8%) tumors in sigmoid colon, 24(22.9%) in rectum, 22(21.0%) in ascending colon and 4 in organs outside the colorectum. Tubular adenocarcinoma (86/105, 81.9%) was the main pathological type in these colorectal SMPC patients. During the follow-up of median 43.5 months, 10 cases presented local recurrence and 6 cases had liver metastasis. Multivariable analysis showed that ≤65 years old (OR=22.757, 95%CI: 1.562-331.543, P=0.002),undifferentiated carcinoma or mucous adenocarcinoma (OR=27.174, 95%CI: 2.834-260.512, P=0.004), stage III(-IIII( (OR=29.626, 95%CI: 3.216-272.884, P=0.003) were independent risk factors of postoperative 5-year recurrence and metastasis, but the number of SMPC lesions and the surgical method were not associated with postoperative 5-year recurrence and metastasis (P=0.564, P=0.513). The 3-year and 5-year survival rates of colorectal SMPC patients were 76.5% and 64.7%.

CONCLUSIONTwo-original carcinoma is the most common in colorectal SMPC patients, which mainly distributes in sigmoid colon and rectum. Postoperative monitoring should be strengthened for those patients with younger age, poor pathological types and advanced staging to prevent recurrence and metastasis.