Serum metabolomics analysis combined with network pharmacology reveals possible mechanisms of postoperative cognitive dysfunction in the treatment of Mongolian medicine Eerdun Wurile basic formula.

This study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague-Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite-disease-target" network; and performs protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K-Akt pathway, the HIF-1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD.

Study on the Mechanism of Eerdun Wurile's Effects on Post-operative Cognitive Dysfunction by the TLR4/NF-κB Pathway.

The object of our work was to observe whether the Mongolian medicine Eerdun Wurile (EW) improve postoperative cognitive dysfunction (POCD) by affecting the TLR4/NF-κB. Mice (6-8-week-old male C57BL/6 J) were selected to establish an animal model of POCD by combining intracerebroventricular injection of lipopolysaccharide and nephrectomy; EW formulation and EW basic formulation were administered intra-gastrically for 7 consecutive days. The cognitive performance was assessed by Morris water maze test. H&E staining was examined to detect alterations in hippocampal tissue. Immunohistochemical staining was performed to evaluate MyD88, NF-κB, TLR4, iNOS, and IBA-1 expressions; Western blotting and RT-qPCR were performed to evaluate MyD88, NF-κB, and TLR4. The expressions of IL-6, IL-1ß, and TNF-α were evaluated by ELISA. Intracerebroventricular injection of lipopolysaccharide combined with nephrectomy induced cognitive dysfunction in mice, stimulated TLR4/NF-κB and microglia, and promoted the secretion of murine TNF-α, IL-1ß, and IL-6. EW formulation and EW basic formulation treatment are able to suppress the TLR4/NF-κB pathway activation and microglia, and the serum cytokine secretions related to proinflammation, and restore the cognitive performance. EW formulation and EW basic formulation can improve POCD in mice, and TLR4/NF-κB pathway seems to be one of the important mechanisms in EW's improvement of POCD.

Mechanism of the Mongolian medicine Eerdun Wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mongolian medicine Eerdun Wurile is a commonly used Mongolian in folk medicine used to treat cerebral nervous system diseases such as cerebral hemorrhage, cerebral thrombosis, nerve injury and cognitive function, cardiovascular diseases such as hypertension and coronary heart disease. Eerdun wurile may effect anti-postoperative cognitive function. AIM OF THE STUDY: To investigate the molecular mechanism of the Mongolian medicine Eerdun Wurile Basic Formula (EWB) in improving postoperative cognitive dysfunction (POCD) based on Network pharmacology, and to confirm involvement of the SIRT1/p53 signal pathway, one of the key signal pathways, by using the POCD mouse model. MATERIAL AND METHODS: Obtain compounds and disease-related targets through TCMSP, TCMID, PubChem, PharmMapper platforms, GeneCards, and OMIM databases, and screen intersection genes; Use Cytoscape software to build a "drug-ingredient-disease-target" network, and the STRING platform for protein interaction analysis.; R software was used to analyze the function of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.; AutoDock Vina software for active components and core targets to Perform molecular docking. The POCD mouse model was prepared by intracerebroventricular injection of lipopolysaccharide (LPS), and the morphological changes of hippocampal tissue were observed by hematoxylin-eosin (HE) staining, Western blot, immunofluorescence and TUNEL were used to verify the results of network pharmacological enrichment analysis. RESULTS: There were 110 potential targets for improving POCD by EWB, 117 items were enriched by GO, and 113 pathways were enriched by KEGG, among which the SIRT1/p53 signaling pathway was related to the occurrence of POCD. Quercetin, kaempferol, vestitol, ß-sitosterol and 7-methoxy-2-methyl isoflavone in EWB can form stable conformations with low binding energy with core target proteins IL-6, CASP3, VEGFA, EGFR and ESR1. Animal experiments showed that compared with the POCD model group, the EWB group could significantly improve the apoptosis in the hippocampus of the mice, and significantly down-regulate the expression of Acetyl-p53 protein (P < 0.05). CONCLUSION: EWB can improve POCD with the characteristics of multi-component, multi-target, and multi-pathway synergistic effects. Studies have confirmed that EWB can improve the occurrence of POCD by regulating the expression of genes related to the SIRT1/p53 signal pathway, which provides a new target and basis for the treatment of POCD.

Research progress on the mechanism of chronic neuropathic pain.

Chronic neuropathic pain (CNP) refers to pain that lasts for more than three months due to a disease or an injury to the somatosensory nervous system. The incidence of CNP has been increasing in the world, causing it to become a global concern and patients often experience spontaneous pain, hyperalgesia, abnormal pain or even abnormal sensation as some of its main symptoms. In addition to serious pain and poor physical health, CNP also negatively affects patients' mental health, thus impacting the overall quality of their lives. The pathogenesis of CNP is not clear, but some studies have proved that central sensitization, peripheral sensitization, neuroinflammation, dysfunction in descending nociceptive modulatory systems, oxidative stress reaction, activation of glial cells and psychological factors play an important role in the occurrence and development of CNP. In this context, this article summarizes the current research progress on the mechanism of CNP to provide a basis for further research in preventing and treating the disease.

Complete Thoracoscopic Resection of Left Ventricular Myxoma - A Case Report.

Cardiac myxoma is a common cardiac tumor. Most are found in the left cardiac system, of which 75% of myxomas are located in the left atrium [Pinede 2001], and the origin of the left ventricle is relatively rare. Surgical resection is the most effective method for the treatment of myxoma, but because of the complex anatomy of the left ventricle, most of the reported cases are performed through the traditional median thoracotomy through the ascending aorta and vena cava to establish cardiopulmonary bypass. It is rare to establish cardiopulmonary bypass through the femoral artery and femoral vein to remove left ventricular myxoma under complete video-assisted thoracoscopy. This paper reports the surgical process and perioperative echocardiographic, magnetic resonance, radiological and pathological features of a completely thoracoscopic resection of left ventricular myxoma.

The Impact on 30-Day Mortality From a Brief Focused Ultrasound-Guided Management Protocol Immediately Before Emergency Noncardiac Surgery in Critically Ill Patients: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether brief ultrasound-guided treatment of hemodynamic shock and respiratory failure immediately before emergency noncardiac surgery reduced 30-day mortality. DESIGN: Parallel, nonblinded, randomized trial with 1:1 allocation to control and intervention groups. SETTING: Twenty-eight major hospitals within China. PARTICIPANTS: Six-hundred sixty patients ≥14 years of age, scheduled for emergency noncardiac surgery with evidence of shock (heart rate >120 beat/min, systolic blood pressure< 90 mmHg or requiring inotrope infusion), or respiratory failure (Pulse Oxygen Saturation <92%, respiratory rate >20 beat/min, or requiring mechanical ventilation). INTERVENTIONS: A brief (<15 minutes) focused ultrasound of ventricular filling and function, lung, and peritoneal spaces, with predefined treatment recommendation based on the ultrasound was performed before surgery or standard care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 30-day mortality. Secondary outcomes included changes in medical or surgical diagnosis and management due to ultrasound, intensive care unit, and hospital stay and cost, and Short Form-8 quality-of-life scores. Although there were frequent changes in diagnosis (82%) and management (49%) after the ultrasound, mortality at 30 days was not different between groups (50 [15.7%] v 53 [16.3%]; odds ratio 1.05, 0.69-1.6, p = 0.826). There were no differences in the secondary outcomes of the days spent in the hospital (mean 13.8 days, 95% confidence interval [CI] 12.1-15.6 v 14.4 d, 11.8-17.1, p = 0.718) or intensive care unit (mean 9.3 days, 95% CI 7.7-11.0 v 8.7 d, 7.2-10.2, p = 0.562), hospital cost (USD$14.5K, 12.2-16.7 v 13.7, 11.5-15.9, p = 0.611) or Short Form-8 scores at one year (mean 80.9, 95% CI 78.4-83.3 v 79.7, 76.9-82.5, p = 0.54) between participants allocated to the ultrasound and control groups. CONCLUSIONS: In critically ill patients with hemodynamic shock or respiratory failure, a focused ultrasound-guided management did not reduce 30-day mortality but led to frequent changes in diagnosis and patient management.

Radiolabeling and Preliminary Evaluation of 99mTc-Labeled DNA Cube Nanoparticles as Potential Tracers for SPECT Imaging.

PURPOSE: DNA nanostructures, with the advantages of structural designability and spatial addressability, have shown a great potential in the field of drug delivery and bio-medicine. Herein, we aimed to prepare technetium-99m radiolabeled DNA cube nanoparticles (99mTc-DCN) and expect to build a DCN-based drug carrier and nuclear medicine imaging platform. METHODS: DCN could be readily assembled with 6 designed DNA oligonucleotides at an equal mole ratio in a single annealing procedure. 99mTc-MAG3-ssDNA (A20) was obtained by labeling MAG3-ssDNA (A20) with technetium-99m by using a stannous chloride reduction method. 99mTc-DCN was prepared by hybridize DCN with side chains (T20-DCN) with 99mTc-MAG3-ssDNA (A20). The biodistribution study and SPECT/CT imaging were conducted on KM mice. RESULTS: DCN was successfully assembled, and as-prepared DCN was characterized by native polyacrylamide gel electrophoresis, atomic force microscope and fluorescence resonance energy transfer. The size of DCN was about 5 nm. The radiolabeling yield of 99mTc-MAG3-ssDNA (A20) was approximately 90% by radio thin-layer chromatography. T20-DCN mixed with 99mTc-MAG3-ssDNA (A20) in PBS could generate 99mTc-DCN upon hybridization. The retention time (RT) of 99mTc-MAG3-ssDNA (A20) was at ~22 min, and the RT of as-prepared 99mTc-DCN was at ~12 min by radio-HPLC. The results from biodistribution study and SPECT/CT imaging showed that a significant proportion of DCNs were metabolized through the liver and kidney. Intestine exhibited a relatively indicative signal as well, which might be explained by the enterohepatic circulation of DCN via the liver and gallbladder. CONCLUSION: We have successfully prepared 99mTc-DCN as a SPECT/CT imaging probe via the side-chain hybridization strategy. The probe was metabolized mainly by the liver and excreted primarily to the bladder. Due to the superior properties of DNA cube nanoparticles, we believe DCN may potentially be translated into a preclinical setting for diagnosis and treatment of cancer-related diseases.

Mechanism of Mongolian Medicine Eerdun Wurile in Improving Postoperative Cognitive Dysfunction Through Activation of the PI3K Signaling Pathway.

OBJECTIVE: To study the effect of Eerdun Wurile (EW), a traditional Mongolian medicine, on the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway in an animal model of postoperative cognitive dysfunction (POCD). METHODS: Fifty clean-grade adults Sprague Dawley (SD) male rats were assigned to one of five groups: (1) a control group with no anesthesia (Group C), (2) a POCD model group with anesthesia only (Group P), (3) POCD group with low-dose EW treated (Group L), (4) a POCD group with high-dose EW treated (Group H), and (5) a POCD model group with dexmedetomidine treated (Group D) for positive control. The study started 7 days after all rats had acclimated to housing. Rats were trained in the Morris Water Maze navigation 5 days before surgery. All rats underwent the same maze for navigation and spatial exploration experiments on the preoperative day 1 and postoperative days 1, 3, 5, and their learning and memory abilities were assessed. At the end of the water maze experiment, rats were sacrificed to obtain hippocampal tissue. The mRNA levels of IRS-2, PI3K, AKT, and GLUT4 were measured in the hippocampus by real-time PCR, and the expression of IRS-2, PI3K, AKT, and GLUT4 protein in the hippocampus was determined by Western blotting to investigate the potential mechanisms at the molecular level. RESULTS: Compared to control Group C, Group P, L, H, and D showed prolonged escape latency (P < 0.05) and decreased number of times to cross the platform (P < 0.05) at 1, 3 and 5 days after surgery. Compared to Group P, Group L, H, and D showed a decrease in escape latency with an increased number of crossing the platform at all-time points after surgery (P < 0.05). Within individual P, L, H, and D groups, escape latencies decreased (P < 0.05) and the number of times that the platform was crossed increased (P < 0.05) between postoperative days 3 and 5 compared to postoperative 1 day. Compared to Group C, the mRNA expression of IRS-2, PI3K, AKT and GLUT4 in the hippocampus of P, L, H, and D groups were decreased (P < 0.05). Compared to Group P, IRS-2, PI3K, AKT, and GLUT4 in the hippocampus of L, H, and D groups were increased (P < 0.05). Compared with Group D, the expression levels of IRS-2 and AKT in both L and H groups were higher. The expression level of PI3K in Group L was also higher (P < 0.05) vs Group D. The expression of AKT mRNA in Group H was higher than in Group L (P < 0.05). Compared to Group C, the p-IRS-2/IRS-2 ratio in the hippocampus of Group P was higher than that of Group C (P < 0.05). Compared to Group P, the ratios of p-IRS-2/IRS-2 in Group L, Group H, and Group D were lower, and the ratios of the p-PI3K/PI3K, p-AKT/AKT, and p-GLUT4/GLUT4 were higher (P < 0.05). CONCLUSION: Administration of EW showed the effect on the signaling pathway in rats with POCD. The therapeutic effect was better in the low-dose group. This could be related to the insulin downstream signal molecule PI3K and the IRS-PI3K-AKT-GLUT4 signaling pathway.

Effect of positive end-expiratory pressure ventilation on plasma nitric oxide, endothelin-1 and vascular celladhesion molecule-1 levels in patients undergoing uvulopalatopharyngoplasty.

BACKGROUND: During uvulopalatopharyngoplasty (UPPP), cardiovascular adverse events may occur which can be harmful to patients. OBJECTIVE: To evaluate the effect of the protective ventilation strategy on the function of vascular endothelial cells. METHODS: Forty obstructive apnea syndrome (OSA) patients who underwent uvulopalatopharyngoplasty (UPPP) were enrolled. Patients were randomly divided into the control group (group C, PEEP = 0 cm H2O) and PEEP group (group P, PEEP = 5 cm H2O). Each group (n= 20) received intermittent volume controlled ventilation (VCV) with tidal volume 6 ml/kg of the predicted body weight, I:E 1:2, rate titrated for ETCO2 35-45, FiO2 0.7. Blood from the radial artery was sampled for blood gas analysis at four time points: the fifth minute of inhaling pure oxygen (T0), after tracheal intubation (T1), at the end of the operation (T2), and 20 minutes after extubation (T3). Three ml of arterial blood was retained, preserved at -20∘C after serum isolation, and plasma nitric oxide (NO), endothelin-1 (ET-1) and vascular celladhesion molecule-1 (VCAM-1) levels were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with group C, plasma ET-1 at T3 decreased in group P, and plasma NO levels at T2 and T3 increased (P< 0.05). Compared with samples collected at T0, plasma VCAM-1 levels at T1, T2 and T3 increased in group C, while plasma VCAM-1 levels at T2 and T3 decreased in group P (P< 0.05). Compared with group C, plasma VCAM-1 levels T2 and T3 decreased in group P (P< 0.05). CONCLUSIONS: Positive end-expiratory pressure (PEEP) ventilation has a protective effect on vascular endothelial cell function in patients during UPPP.

The mechanism of lipopolysaccharide administration-induced cognitive function impairment caused by glucose metabolism disorder in adult rats.

This essay aims to make investigation on the mechanism of glucose metabolism disorder and Lipopolysaccharide administration-induced cognitive function impairment in adult rats with surgery. METHODS: Divide the objects, 40 male Sprague-Dawley rats at the age of 9 months, into 4 groups. Provide unilateral nephrectomy surgery and/or lipopolysaccharide intraperitoneal injection. Postoperative cognitive function evaluation would be tested by the Morris water maze. Rats with Postoperative Cognitive Dysfunction (POCD) were scanned to analyze the brain glucose metabolism by means of 18F-FDG PET/CT. Phosphatidylinositol 3-Kinase (PI3K), Protein Kinase ß (AKT), Insulin Substrates Receptor-2 (IRS-2) and Glucose Transporter 4 (GLUT4) were detected as well. Data will be captured through gene expression in POCD rats via Quantitative Real-Time PCR (QRT-PCR). On the other side, Western Blot was used to measure the expression levels of IRS-2, p-IRS-2, p-PI3K, PI3K, p-AKT, AKT, GLUT4, and p-GLUT4. RESULTS: During the Morris water maze test, the staging time (latency) of rats in each group was becoming short gradually as the training progressed. The incubation time of Day 5 of each group was shorter than that of Day 1 (P < 0.05). On the Day 3 after the surgery, the average target quadrant residence time of Group S+L (100 µg/Kg) was shorter, compared with Group C, L and S. Of which, the average number of perforation was reduced greater than that of Group C (P < 0.05). The average swimming speed of the groups is of no distinct difference (P > 0.05). After the operation, there was no great difference shown among the subjects (P > 0.05) in the average residence time of the target quadrant, the mean number of passages, and the mean swimming speed. On Day 3, the average latency of Group S+L (100 µg/Kg) was longer than Group C (P < 0.05) in the working memory test after the operation. The average latency of rats in Group L and S was showed longer than that in Group C, with tiny difference (P > 0.05). In the 7-Day working memory test, the average latency of the rats in Group L, S and S+L (100 µg/Kg) was obviously longer than that in Group C. Comparing to preoperative rats, POCD rats of Group S+L (100 µg/Kg) were scanned by 18F-FDG PET/CT three days later after the operation. Its SUVmax of the frontal and temporal lobe areas were decreased significantly (P < 0.05). However, difference degree was not significantly shown in the SUVmax between Group C and the preoperative rats (P > 0.05). In comparison with the gene expression of of Group C, the PI3K, IRS-2, AKT and GLUT4 mRNA genes are the key genes in the insulin signaling pathways of the hippocampus of the POCD rats. The expression level was reduced. The expression level of all protein of PI3K, IRS-2, GLUT4 and AKT in the POCD rats was of no great contrast with that in Group C. But for IRS-2 protein, the phosphorylation level has increased, and meanwhile decreased for AKT, PI3K and GLUT4 proteins (P < 0.05). CONCLUSIONS: Adult SD rats cognitive dysfunction model treated with unilateral nephrectomy combined and 100 µg/kg LPS intraperitoneal injection were led to abnormal both brain glucose metabolism and insulin expression. The proved phenomenal results signal pathway-related proteins PI3K, IRS-2, AKT and GLUT4. It reached the conclusion that surgical trauma, rather than anesthesia, leads to impaired cognitive function. PI3K, IRS-2, AKT, and GLUT4pathway of brain can be partial explanations of the pathogenesis of POCD.

Comparison in anesthetic effects of propofol among patients with different ABO blood groups.

Our study was aimed to investigate anesthetic effects of propofol in patients with different blood groups.A total of 72 participants were enrolled from patients arranged for surgeries of cholecystectomy, tonsillectomy, and spinal operation. Each blood group (A, B, AB, and O) contained 18 participants. Mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were assayed with Philips monitor. These indexes were observed before propofol anesthesia (T0), and then were recorded when concentration of propofol was 1 µg/mL (T1), 2 µg/mL (T2), 3 µg/mL (T3), and 4 µg/mL (T4). The differences in MAP, HR, and BIS at T0 among groups were compared with the χ test. Multiple comparisons were adopted to calculate the differences in MAP, HR, and BIS between groups at T1, T2, T3, and T4.No significant differences in age, sex, and weight of all groups were found (P > .05). Before propofol anesthesia (T0), all the participants exhibited no differences in MAP, HR, and BIS (P > .05). Subsequently, we found obvious differences in ΔMAP, ΔHR, and ΔBIS between groups. The patients in the B blood group showed highest ΔMAP and ΔHR at each time point (P < .05 for both). As for ΔBIS, patients in A blood group exhibited highest value at T3 and T4 (P < .05).The blood group remarkably affects the anesthetic effects of propofol.

Intravenous acid fibroblast growth factor protects intestinal mucosal cells against ischemia-reperfusion injury via regulating Bcl-2/Bax expression.

AIM: To detect the effect of acid fibroblast growth factor (aFGF) on apoptosis and gene expression of bax and bcl-2 gene in rat intestine after ischemia/reperfusion (I/R) injury, and to explore the protective mechanisms of aFGF. METHODS: One hundred and eight Wistar rats were randomly divided into sham-operated control group (C) (n = 6), intestinal ischemia group (I) (n = 6), aFGF treatment group (A) (n = 48) and intestinal ischemia-reperfusion group (R) (n = 48). In group I, the animals were killed after 45 min of superior mesenteric artery (SMA) occlusion, while in groups R and A, the rats sustained 45 min of SMA occlusion and were then treated with normal saline and aFGF, respectively, sustained 15 min, 30 min, 1, 2, 6, 12, 24, or 48 h of reperfusion, respectively. In group C, SMA was separated, but without occlusion. Apoptosis in intestinal villus was determined with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken not only for detection of bax and bcl-2 gene expression by RT-PCR, but also for detection of bax and bcl-2 protein expression and distribution by immunohistochemical analysis. RESULTS: The rat survival rates in aFGF treated group were higher than group R (P<0.05) and the improvement of intestinal histological structures was observed at 2, 6, and 12 h after the reperfusion in group A compared with group R. The apoptotic rates were (41.17+/-3.49)%, (42.83+/-5.23)% and (53.33+/-6.92)% at 2, 6 and 12 h after reperfusion, respectively in group A, apparently less than those of group R at matched time points (50.67+/-6.95, 54.17+/-7.86, 64.33+/-6.47, respectively) (P<0.05). The bax gene transcription and translation were significantly decreased in group A vs group R, while mRNA and protein contents of Bcl-2 in group A were obviously higher than those in group R during 2-12 h period after reperfusion. CONCLUSION: The changes in histological structure and the increment of apoptotic rate indicated that the intestinal barrier was damaged after intestinal I/R injury, whilst intravenous aFGF could alleviate apoptosis induced by ischemia and reperfusion in rat intestinal tissues, in which genes of bax and bcl-2 might play important roles.

[The proapoptotic effect of the homogenate of the tissue of different parts of pig's full thickness dermal wounds on cultured fibroblasts].

OBJECTIVE: To observe the proapoptotic effect of the homogenate of different parts of pig's full thickness dermal wounds on cultured fibroblasts. METHODS: The tissues were dissected from the wound center and sub-neoepithelium separately 15 days after homogenization and sterilization, the specimens stored at -70 degrees C. The forth passage of the fibroblasts were cultured for 16 hours in different culture solutions and were grouped into 7 groups: DMEM containing 5% fetal bovine serum as Group I, DMEM containing 5% homogenate of tissue from wound center as Group II, DMEM containing 5% homogenate of tissue from sub-neoepithelium as Group III, the culture solution of Group I mixed with 10 microg/ml GM6001 in Group IV, with the culturing medium of Group III plus 10 microg/ml GM6001 as Group V, the culture solution of Group II mixed with 10 ng/ml aFGF as Group VII, and the culture solution of Group III mixed with 10 ng/ml aFGF as Group VII. In all groups except Group I, the fibroblasts of the 6 pigs were treated with the homogenate derived from the same animal respectively. After being incubated in Annexin V-FITC and PI, cells were analyzed by Flow Cytometry and the rate of apoptotic cells was acquired. The data were analyzed by SPSS 11.0 using Least-significant Difference test (LSD). RESULTS: The apoptotic rate of the 7 groups were as follows: 4.39% +/- 0.41% in Group I, 10.98% +/- 1.42% in Group II, 13.47% +/- 1.44% in Group III, 7.2% +/- 0.46% in Group IV, 12.1% +/- 0.85% in Group V, 3.9% +/- 0.63% in Group VI, 9.8% +/- 0.50% in Group VII; there were significant differences between every two groups except Group I and Group VI. CONCLUSION: Homogenate of the tissue derived from the sub-neoepithelium has greater proapoptotic effect than that from the wound center; the proapoptotic effect of homogenate of the tissue both under neoepithelium and in wound center can be significantly alleviated by acid fibroblast growth factor, partly because of MMPs.