[Establishment and validation of nomogram prediction model for complicated acute appendicitis].

Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 µmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.

[A novel nomogram for individualized preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma].

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.

Platelet safety range before splenectomy for hypersplenism: based on 244 cases of splenectomy in hepatolenticular degeneration patients.

Background and study aims: To investigate the safety and efficacy of splenectomy for hepatolenticular degeneration (HLD) patients with PLT less than 20 × 109/L. Patients and methods: A total of 244 HLD patients with hypersplenism underwent splenectomy. According to the preoperative PLT values, the patients were divided into three groups : group A of 53 patients with PLT < 20 × 109/L ; group B of 92 patients with 20 × 109/L ≤ PLT ≤ 30 × 109/L ; group C of 99 patients with PLT > 30 × 109/L. General information including : blood cell counts, liver function , coagulation function 1 day before sugery and 1, 7, 14 days after surgery ; intraoperative blood loss ; operation time ; vital signs at the beginning, at 60 minutes and the end of the operation. Pressure and blood oxygen ; postoperative drainage ; postoperative complications and mortality. Results: Blood cell counts, liver function, and coagulation function were improved after splenectomy in three groups (P<0.05) ; there was no significant difference in blood loss, operation time, vital signs during the operation, postoperative drainage, postoperative complications and mortality between three groups (P>0.05). Conclusion: For HLD patients with hypersplenism, it is safe and effective to conduct splenectomy under PLT < 20 × 109/L.

[Effect of icariin on the proteomic expression profile of bone microvascular endothelial cells of human femoral head against steroids-induced lesion].

OBJECTIVE: To explore the effect of icariin on the proteomic expression profile of bone microvascular endothelial cells of human femoral head against steroids-induced lesion using protein chip system in vitro. METHODS: Bone microvascular endothelial cells (BMECs) in cancellous bone of femoral head were isolated and harvested in vitro.The model of BMECs injury induced by glucocorticoid and icariin preconditioning was established. The apoptosis of BMECs were detected with terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)methods. The proteomic expression profile of BMECs in each group were detected by protein chip system. RESULTS: The apoptosis rates of hydrocortisone groups (46.9%±5.8%, 78.0%±8.5%) were significantly higher than that of normal group(4.8%±1.3%), meanwhile the apoptosis rate of icariin+ hydrocortisone groups(15.2%±7.7%, 44.6%±5.3%)significantly decreased compared with hydrocortisone group (P<0.001). The results of protein chip showed that the expression of granulocyte colony-stimulating factor (G-CSF) in the hydrocortisone group decreased compared with the control group, meanwhile the expression of IL-4 increased. The expression of G-CSF in the icariin+ hydrocortisone groups increased compared with the hydrocortisone group, meanwhile the expression of IL-4 decreased.No appreciable change was found in the expression of apoptotic factors. CONCLUSION: The therapy effect of icariin for steroid-induced necrosis of femoral head might be related with the protective action to BMECs and the moderating effect of promoting the proteins expression of pro-angiogenesis factor and inhibiting expression of inflammatory factor.

Post-trauma administration of the pifithrin-α oxygen analog improves histological and functional outcomes after experimental traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Programmed death of neuronal cells plays a crucial role in acute and chronic neurodegeneration following TBI. The tumor suppressor protein p53, a transcription factor, has been recognized as an important regulator of apoptotic neuronal death. The p53 inactivator pifithrin-α (PFT-α) has been shown to be neuroprotective against stroke. A previous cellular study indicated that PFT-α oxygen analog (PFT-α (O)) is more stable and active than PFT-α. We aimed to investigate whether inhibition of p53 using PFT-α or PFT-α (O) would be a potential neuroprotective strategy for TBI. To evaluate whether these drugs protect against excitotoxicity in vitro, primary rat cortical cultures were challenged with glutamate (50mM) in the presence or absence of various concentrations of the p53 inhibitors PFT-α or PFT-α (O). Cell viability was estimated by LDH assay. In vivo, adult Sprague Dawley rats were subjected to controlled cortical impact (CCI, with 4m/s velocity, 2mm deformation). Five hours after injury, PFT-α or PFT-α (O) (2mg/kg, i.v.) was administered to animals. Sensory and motor functions were evaluated by behavioral tests at 24h after TBI. The p53-positive neurons were identified by double staining with cell-specific markers. Levels of mRNA encoding for p53-regulated genes (BAX, PUMA, Bcl-2 and p21) were measured by reverse transcription followed by real time-PCR from TBI animals without or with PFT-α/PFT-α (O) treatment. We found that PFT-α(O) (10 µM) enhanced neuronal survival against glutamate-induced cytotoxicity in vitro more effectively than PFT-α (10 µM). In vivo PFT-α (O) treatment enhanced functional recovery and decreased contusion volume at 24h post-injury. Neuroprotection by PFT-α (O) treatment also reduced p53-positive neurons in the cortical contusion region. In addition, p53-regulated PUMA mRNA levels at 8h were significantly reduced by PFT-α (O) administration after TBI. PFT-α (O) treatment also decreased phospho-p53 positive neurons in the cortical contusion region. Our data suggest that PFT-α (O) provided a significant reduction of cortical cell death and protected neurons from glutamate-induced excitotoxicity in vitro, as well as improved neurological functional outcome and reduced brain injury in vivo via anti-apoptotic mechanisms. The inhibition of p53-induced apoptosis by PFT-α (O) provides a useful tool to evaluate reversible apoptotic mechanisms and may develop into a novel therapeutic strategy for TBI.

Molecular cloning and characterization of the glyceraldehyde-3-phosphate dehydrogenase gene from Penicillium expansum PE-12.

Penicillium expansum produces large amounts of lipase, which is widely used in laundry detergent and leather industry. We isolated the glyceraldehyde-3-phosphate dehydrogenase gene (PeGPD) from P. expansum PE-12 through reverse transcriptase PCR and 5'-3' rapid amplification of cDNA ends (RACE-PCR). The gene is 1266 bp long, including an ORF of 1014 bp, encoding a polypeptide chain of 337 amino acids. A phylogenetic tree based on GPD proteins showed that P. expansum is close to Aspergillus species, but comparatively distant from P. marneffei. Southern blot results revealed a single copy of PeGPD, and expression analysis gave evidence of high expression levels. PeGPD genes have potential for genetic engineering of P. expansum for industrial lipase production.

Bacterial inactivation using a low-temperature atmospheric plasma brush sustained with argon gas.

This study investigated the bacterial inactivation/sterilization effects of a new atmospheric plasma source, which is a brush-shaped argon glow discharge created under 1 atm pressure. Such an atmospheric plasma brush requires extremely low power of less than 20 W to operate; and therefore is essentially a low-temperature discharge as confirmed by gas-phase temperature measurements. Two bacteria, Escherichia coli (E. coli) and Micrococcus luteus (M. luteus), seeded in various media were subjected to plasma treatment and their survivability was examined. It was found that such argon atmospheric plasma brush is very effective in destruction of the bacteria cells. With nutrient broth and standard methods agar as supporting media, a cell reduction in a level of 6 orders of magnitude was observed for E. coli within 3-4 min plasma treatment. A similar level of cell reduction was also observed for M. luteus in the two media with 2 or 3 min plasma treatment. The plasma treatment effects on the bacteria cell structures were also examined using scanning electron microscopy and the cell structure damages due to the plasma exposure were observed on both bacteria. The possible sterilization mechanism of the argon plasmas is also discussed in this article.

Prediction of human intestinal absorption using an artificial neural network.

An artificial neural network model is developed to predict percent human intestinal absorption (%FA) of compounds from their molecular structural parameters. These parameters are the polar molecular surface area (PSA), the fraction of polar molecular surface area (FPSA, polar molecular surface area/ molecular surface area), the sum of the net atomic charges of oxygen atoms (Q(O)), the sum of the net atomic charges of nitrogen atoms with net negative atomic charges (Q(N)), the sum of the net atomic charges of hydrogen atoms attached to oxygen or nitrogen atoms (Q(H)), and the number of carboxyls (nCOOH). For a training set of 85 compounds anda test set of 10 compounds, root mean squared errors (RMSE) between experimental %FA valuesand calculated/predicted %FA values are 8.86% and 14.1%, respectively.

Phenserine regulates translation of beta -amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development.

The reduction in levels of the potentially toxic amyloid-beta peptide (Abeta) has emerged as one of the most important therapeutic goals in Alzheimer's disease. Key targets for this goal are factors that affect the expression and processing of the Abeta precursor protein (betaAPP). Earlier reports from our laboratory have shown that a novel cholinesterase inhibitor, phenserine, reduces betaAPP levels in vivo. Herein, we studied the mechanism of phenserine's actions to define the regulatory elements in betaAPP processing. Phenserine treatment resulted in decreased secretion of soluble betaAPP and Abeta into the conditioned media of human neuroblastoma cells without cellular toxicity. The regulation of betaAPP protein expression by phenserine was posttranscriptional as it suppressed betaAPP protein expression without altering betaAPP mRNA levels. However, phenserine's action was neither mediated through classical receptor signaling pathways, involving extracellular signal-regulated kinase or phosphatidylinositol 3-kinase activation, nor was it associated with the anticholinesterase activity of the drug. Furthermore, phenserine reduced expression of a chloramphenicol acetyltransferase reporter fused to the 5'-mRNA leader sequence of betaAPP without altering expression of a control chloramphenicol acetyltransferase reporter. These studies suggest that phenserine reduces Abeta levels by regulating betaAPP translation via the recently described iron regulatory element in the 5'-untranslated region of betaAPP mRNA, which has been shown previously to be up-regulated in the presence of interleukin-1. This study identifies an approach for the regulation of betaAPP expression that can result in a substantial reduction in the level of Abeta.

A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide.

The tumor suppressor protein p53 is essential for neuronal death in several experimental settings and may participate in human neurodegenerative disorders. Based upon recent studies characterizing chemical inhibitors of p53 in preclinical studies in the cancer therapy field, we synthesized the compound pifithrin-alpha and evaluated its potential neuroprotective properties in experimental models relevant to the pathogenesis of stroke and neurodegenerative disorders. Pifithrin-alpha protected neurons against apoptosis induced by DNA-damaging agents, amyloid beta-peptide and glutamate. Protection by pifithrin-alpha was correlated with decreased p53 DNA-binding activity, decreased expression of the p53 target gene BAX and suppression of mitochondrial dysfunction and caspase activation. Mice given pifithrin-alpha exhibited increased resistance of cortical and striatal neurons to focal ischemic injury and of hippocampal neurons to excitotoxic damage. These preclinical studies demonstrate the efficacy of a p53 inhibitor in models of stroke and neurodegenerative disorders, and suggest that drugs that inhibit p53 may reduce the extent of brain damage in related human neurodegenerative conditions.

Comparison of numerical and experimental methods for determination of SAR and radiation patterns of handheld wireless telephones.

Some recent developments in both the numerical and experimental methods for determination of SARs and radiation patterns of handheld wireless telephones are described, with emphasis on comparison of results using the two methods. For numerical calculations, it was possible to use the Pro-Engineer CAD Files of cellular telephones for a realistic description of the device. Also, we used the expanding grid formulation of the finite-difference time-domain (FDTD) method for finer-resolution representation of the coupled region, including the antenna, and an increasingly coarser representation of the more-distant, less-coupled region. Together with the truncation of the model of the head, this procedure led to a saving of computer memory needed for SAR calculations by a factor of over 20. Automated SAR and radiation pattern measurement systems were used to validate both the calculated 1-g SARs and radiation patterns for several telephones, including some research test samples, using a variety of antennas. Even though widely different peak 1-g SARs were obtained, ranging from 0.13 to 5.41 W/kg, agreement between the calculated and the measured data for these telephones, five each at 835 and 1900 MHz, was excellent and generally within +/-20% (+/-1 dB). An important observation was that for a maximum radiated power of 600 mW at 800/900 MHz, which may be used for telephones using AMPS technology, the peak 1-g SARs can be higher than 1.6 W/kg unless antennas are carefully designed and placed further away from the head.

Platelet aggregation in head and neck tumors in China.

We measured the maximum aggregation rate (MAR) of platelets in 770 patients with malignant head and neck tumors, 55 patients with benign tumors of the head and neck, and 164 healthy people as a control group. The results were as follows: 1. the mean MAR value of patients with malignant tumors was significantly higher than the control group mean value; 2. prior to treatment, the mean MAR value increased with advancing tumor stage; 3. both MAR values of relapsed or metastasized patients and of nonsurvivors in stage III and IV increased significantly compared with survivors or patients recovering from malignant tumors. The results of the present study suggest that MAR values of patients with malignant tumors of the head and neck may serve as indicators in evaluating therapeutic procedures and prognosis.

[Clinical study on early use of Chinese medicinal herbs and chemotherapy after operation of gastric cancer].

In order to study the efficacy of early chemotherapy after operation of gastric cancer, 84 cases of gastric cancer were divided randomly into two groups. The treated group received both Chinese medicinal herbs and chemotherapy on the first postoperational day and the control group were treated routinely in the same way two weeks later. The results showed that complications of incision and anastomoses of the treated group did not rise and all kinds of blood cells reduce in comparison with those of control group (P > 0.05). Meanwhile, nutritious condition of the treated group was improved significantly as compared with that of control group (P < 0.05) because of use of Chinese medicinal herbs and nutrition support. This study suggested that chemotherapy could be used early after operation of gastric cancer in combination with Chinese medicinal herbs.

Structure of an ether dimer of deoxydihydroqinghaosu, a potential metabolite of the antimalarial arteether.

C30H49O7, Mr = 518.69, triclinic, P1, a = 9.013 (2), b = 10.520 (2), c = 15.187 (3) A, alpha = 93.3 (2), beta = 93.73 (1), gamma = 95.88 (2) degrees, V = 1426.2 (5) A3, Z = 2, Dx = 1.21 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 0.65 mm-1, F(000) = 564, T = 295 K, final R = 0.043, wR = 0.042 for 3842 observed reflections. The dimer is formed such that the deoxyarteether moieties are cis to one another. Attempts to determine the absolute configuration of the molecule were inconclusive so the conformation corresponding to that found for qinghaosu was used for the refinement. Both halves of the dimer have the same chirality with five of the seven asymmetric carbons having an S conformation and two (C5 and C6) having an R conformation.