New horizons for the role of RNA N6-methyladenosine modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy, presenting a formidable challenge to the medical community owing to its intricate pathogenic mechanisms. Although current prevention, surveillance, early detection, diagnosis, and treatment have achieved some success in preventing HCC and controlling overall disease mortality, the imperative to explore novel treatment modalities for HCC remains increasingly urgent. Epigenetic modification has emerged as pivotal factors in the etiology of cancer. Among these, RNA N6-methyladenosine (m6A) modification stands out as one of the most prevalent, abundant, and evolutionarily conserved post-transcriptional alterations in eukaryotes. The literature underscores that the dynamic and reversible nature of m6A modifications orchestrates the intricate regulation of gene expression, thereby exerting a profound influence on cell destinies. Increasing evidence has substantiated conspicuous fluctuations in m6A modification levels throughout the progression of HCC. The deliberate modulation of m6A modification levels through molecular biology and pharmacological interventions has been demonstrated to exert a discernible impact on the pathogenesis of HCC. In this review, we elucidate the multifaceted biological functions of m6A modifications in HCC, and concurrently advancing novel therapeutic strategies for the management of this malignancy.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy: Two case reports.

BACKGROUND: The pathological complete response (ypCR) rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol. Immunotherapy has achieved breakthrough progress. CASE SUMMARY: We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0. Detection of mismatch repair protein showed mismatch repair function defect, and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR. Surprisingly, the patients underwent clinical observation after surgery but developed different degrees of metastasis at ~6 mo after surgery. CONCLUSION: PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

Lipopolysaccharide-induced endotoxaemia during adolescence promotes stress vulnerability in adult mice via deregulation of nuclear factor erythroid 2-related factor 2 in the medial prefrontal cortex.

RATIONALE: Sepsis is a severe inflammatory response to infection that leads to long-lasting cognitive impairment and depression after resolution. The lipopolysaccharide (LPS)-induced endotoxaemia model is a well-established model of gram-negative bacterial infection and recapitulates the clinical characteristics of sepsis. However, whether LPS-induced endotoxaemia during adolescence can modulate depressive and anxiety-like behaviours in adulthood remains unclear. OBJECTIVES: To determine whether LPS-induced endotoxaemia in adolescence can modulate the stress vulnerability to depressive and anxiety-like behaviours in adulthood and explore the underlying molecular mechanisms. METHODS: Quantitative real-time PCR was used to measure inflammatory cytokine expression in the brain. A stress vulnerability model was established by exposure to subthreshold social defeat stress (SSDS), and depressive- and anxiety-like behaviours were evaluated by the social interaction test (SIT), sucrose preference test (SPT), tail suspension test (TST), force swimming test (FST), elevated plus-maze (EPM) test, and open field test (OFT). Western blotting was used to measure Nrf2 and BDNF expression levels in the brain. RESULTS: Our results showed that inflammation occurred in the brain 24 h after the induction of LPS-induced endotoxaemia at P21 but resolved in adulthood. Furthermore, LPS-induced endotoxaemia during adolescence promoted the inflammatory response and the stress vulnerability after SSDS during adulthood. Notably, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and BDNF in the mPFC were decreased after SSDS exposure in mice treated with LPS during adolescence. Activation of the Nrf2-BDNF signalling pathway by sulforaphane (SFN), an Nrf2 activator, ameliorated the effect of LPS-induced endotoxaemia during adolescence on stress vulnerability after SSDS during adulthood. CONCLUSIONS: Our study identified adolescence as a critical period during which LPS-induced endotoxaemia can promote stress vulnerability during adulthood and showed that this effect is mediated by impairment of Nrf2-BDNF signalling in the mPFC.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Characterization of the remediation of chromium ion contamination with bentonite by terahertz time-domain spectroscopy.

Heavy metal pollution of agricultural and urban soils limits economic progress in the rapidly developing society. Terahertz technology is applied to detect heavy metal pollutants under existence of multiple pathways of their dissemination. In this study, terahertz time-domain spectroscopy (THz-TDS) is employed as an advanced probing technique in combination with traditional detecting methods to measure the adsorption ability of trivalent chromium ions on bentonite. The concentration of chromium ions and the weight of bentonite are known to influence on the adsorption capacity of the latter. It is tested here by both qualitative and quantitative measurements of two mentioned parameters. The adsorption process of chromium ions by bentonite is monitored using THz-TDS. The adsorptions signal from samples at 0.5 THz gradually increases with the increase of bentonite weight or chromium ion concentration. It would appear to indicate that terahertz could be used for quantitative detection of metal ions. Secondly, the ratios of results obtained by inductively coupled plasma mass spectrometry (ICP-MS) and the THz-TDS ones are stabilized at 0.105  ±  0.014 as the bentonite weight or chromium ion concentration increase. Such finding confirms that terahertz technology can be used for the quantitative detection of metal ions. Using the relationship between the ICP-MS test results and the THz-TDS ones, the amplitude value of bentonite is obtained to be 13.925 at the concentration of chromium ions of 0.05 mol/L, the mass of bentonite sample involved in adsorption of 1.5 g, and the detection frequency in THz-TDS measurements of 0.5 THz. The adsorption coefficient of bentonite is calculated to be 1.44%. Increase of the chromium ion concentration to 0.2 mol/L, and the mass of bentonite involved in adsorption to 3 g leads to the increase of the amplitude corresponding to adsorbed chromium ions to about 19.463, and the adsorption coefficient to about 2.1%. Obtained results demonstrate that terahertz technology is promising to meet the ever-increasing requirements in mineral analyses for rapid detection of chemical contaminants and measurement of the adsorption efficiencies of materials.

The value of dynamic contrast-enhanced magnetic resonance imaging combined with apparent diffusion coefficient in the differentiation of benign and malignant diseases of the breast.

BACKGROUND: The value of combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) histogram analysis for the diagnosis of breast cancer has not been evaluated in previous studies. PURPOSE: To investigate the diagnostic value of DCE-MRI combined with ADC in benign and malignant breast lesions. MATERIAL AND METHODS: The clinicopathological imaging data included 168 patients (177 lesions) with breast lesions who underwent convention breast MRI, DCE-MRI, and diffusion-weighted imaging (DWI); they were divided into the benign lesion group (n = 39) and malignant lesion group (n = 129) based on pathology. RESULTS: Using the type III outflow curve as a diagnostic criterion for malignant breast lesions, the diagnostic sensitivity was 76.9%, the specificity was 80%, the correct rate was 72.2%, and its area under the curve (AUC) was 0.823. Using an enhancement ratio > 100% as a diagnostic criterion for malignant breast lesions, the sensitivity was 61.5%, specificity was 80%, and AUC was 0.723. Using > 3 ipsilateral vessels as a diagnostic criterion for malignant lesions in the breast resulted in a diagnostic sensitivity of 81.6%, a specificity of 80.8%, and an AUC of 0.805. CONCLUSION: The type of time intensity curve DCE-MRI, the early enhancement rate in the first phase, the number of ipsilateral vessels, and the ADC full volume histogram of the blood supply score and DWI are valuable in the diagnosis of benign and malignant breast lesions.

Endoplasmic reticulum stress and protein degradation in chronic liver disease.

Endoplasmic reticulum (ER) stress is easily observed in chronic liver disease, which often causes accumulation of unfolded or misfolded proteins in the ER, leading to unfolded protein response (UPR). Regulating protein degradation is an integral part of UPR to relieve ER stress. The major protein degradation system includes the ubiquitin-proteasome system (UPS) and autophagy. All three arms of UPR triggered in response to ER stress can regulate UPS and autophagy. Accumulated misfolded proteins could activate these arms, and then generate various transcription factors to regulate the expression of UPS-related and autophagy-related genes. The protein degradation process regulated by UPR has great significance in many chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, liver fibrosis, and hepatocellular carcinoma(HCC). In most instances, the degradation of excessive proteins protects cells with ER stress survival from apoptosis. According to the specific functions of protein degradation in chronic liver disease, choosing to promote or inhibit this process is promising as a potential method for treating chronic liver disease.

LncRNA-H19 induces hepatic stellate cell activation via upregulating alcohol dehydrogenase III-mediated retinoic acid signals.

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.

Ectopic liver tissue in the esophagus: A case report.

INTRODUCTION: Ectopic liver (EL) is a rare entity, which is reported to develop at various sites, such as the abdominal cavity, the retroperitoneal cavity, the pleural cavity, and the mediastinum. PATIENT CONCERNS: A 27-year-old previously healthy Chinese man suffered from a discontinuous abdominal pain in the upper abdomen for 2 months. DIAGNOSIS: The upper gastrointestinal endoscopy revealed there was a polypoid mucosal uplift on the distal region of the esophagus near the cardia. INTERVENTIONS: Endoscopic polypectomy was performed. OUTCOMES: Pathology examination showed the liver tissue. CONCLUSION: EL should be excised as it may possibly lead to the development of a malignancy. Endoscopic resection was found to be safe and reliable in this case.

Circulating Neutrophil Counts Decrease in Response to Mitigated Air Quality in Stable COPD Patients.

This three-year study, based on the Guangzhou Institute of Respiratory Disease (GRID), chronic obstructive pulmonary disease (COPD) Biobank, was conducted in 36 COPD patients to estimate whether changes in levels of leukocytes, erythrocytes, hemoglobin, and platelets were related to changes in air pollutant concentration. Daily NO2 levels exhibited significant differences between baseline years and the 2010 Asian Game period. We observed significant reductions in leukocyte and neutrophils counts levels, by 15.51% and 23.01%, from pre-Asian Games to during-Asian Games, respectively. In the post-Asian Game period, most pollutants approximated pre-Asian Game period levels, and similar effects were demonstrated in leukocyte and neutrophil counts. For both items, we identified significant increases resulting from elevated NO2 at lag days 0-2/5-6. We concluded that reductions in pollutants during the intervention period were associated with inactivation of hematological events in COPD.

Hollow Porous VOx/C Nanoscrolls as High-Performance Anodes for Lithium-Ion Batteries.

Novel hollow porous VOx/C nanoscrolls are synthesized by an annealing process with the VOx/octadecylamine (ODA) nanoscrolls as both vanadium and carbon sources. In the preparation, the VOx/ODA nanoscrolls are first achieved by a two-phase solvothermal method using ammonium metavanadat as the precursor. Upon subsequent heating, the intercalated amines between the vanadate layers in the VOx/ODA nanoscrolls decompose into gases, which escape from inside the nanoscrolls and leave sufficient pores in the walls. As the anodes of lithium-ion batteries (LIBs), such hollow porous VOx/C nanoscrolls possess exceedingly high capacity and rate capability (904 mAh g-1 at 1 A g-1) and long cyclic stability (872 mAh g-1 after 210 cycles at 1 A g-1). The good performance is derived from the unique structural features of the hollow hierarchical porous nanoscrolls with low crystallinity, which could significantly suppress irreversible Li+ trapping as well as improve Li+ diffusion kinetics. This universal method of annealing amine-intercalated oxide could be widely applied to the fabrication of a variety of porous electrode materials for high-performance LIBs and supercapacitors.

Synthesis of Mesoporous Single Crystal Co(OH)2 Nanoplate and Its Topotactic Conversion to Dual-Pore Mesoporous Single Crystal Co3O4.

A new class of mesoporous single crystalline (MSC) material, Co(OH)2 nanoplates, is synthesized by a soft template method, and it is topotactically converted to dual-pore MSC Co3O4. Most mesoporous materials derived from the soft template method are reported to be amorphous or polycrystallined; however, in our synthesis, Co(OH)2 seeds grow to form single crystals, with amphiphilic block copolymer F127 colloids as the pore producer. The single-crystalline nature of material can be kept during the conversion from Co(OH)2 to Co3O4, and special dual-pore MSC Co3O4 nanoplates can be obtained. As the anode of lithium-ion batteries, such dual-pore MSC Co3O4 nanoplates possess exceedingly high capacity as well as long cyclic performance (730 mAh g(-1) at 1 A g(-1) after the 350th cycle). The superior performance is because of the unique hierarchical mesoporous structure, which could significantly improve Li(+) diffusion kinetics, and the exposed highly active (111) crystal planes are in favor of the conversion reaction in the charge/discharge cycles.

Electroluminescence of ordered ZnO nanorod array/p-GaN light-emitting diodes with graphene current spreading layer.

Ordered ZnO nanorod array/p-GaN heterojunction light-emitting diodes (LEDs) have been fabricated by introducing graphene as the current spreading layer, which exhibit improved electroluminescence performance by comparison to the LED using a conventional structure (indium-tin-oxide as the current spreading layer). In addition, by adjusting the diameter of ZnO nanorod array in use, the light emission of the ZnO nanorod array/p-GaN heterojunction LEDs was enhanced further. This work has great potential applications in solid-state lighting, high performance optoelectronic devices, and so on. PACS: 78.60.Fi; 85.60.Jb; 78.67.Lt; 81.10.Dn.

Controllable synthesis of ZnO nanostructures on the Si substrate by a hydrothermal route.

In this paper, controllable synthesis of various ZnO nanostructures was achieved via a simple and cost-effective hydrothermal process on the Si substrate. The morphology evolution of the ZnO nanostructures was well monitored by tuning hydrothermal growth parameters, such as the seed layer, solution concentration, reaction temperature, and surfactant. X-ray diffraction and photoluminescence measurements reveal that crystal quality and optical properties crucially depend on the morphology of the ZnO nanostructures. The ease of synthesis and convenience to tune morphology and optical properties bring this approach great potential for nanoscale applications.

Tetramethylpyrazine induces G0/G1 cell cycle arrest and stimulates mitochondrial-mediated and caspase-dependent apoptosis through modulating ERK/p53 signaling in hepatic stellate cells in vitro.

Activation of hepatic stellate cells (HSCs) is a pivotal event in the pathogenesis of liver fibrosis. Pharmacological induction of HSC apoptosis could be a promising strategy for fibrosis regression. Natural product tetramethylpyrazine (TMP) exhibits potent antifibrotic activities in vivo. However, the molecular mechanisms remain to be defined. The present study aimed at investigating the anti-proliferative and pro-apoptotic effects of TMP on HSCs and elucidating the underlying mechanisms. Our results demonstrated that TMP had no apparent cytotoxic effects on hepatocytes, but significantly inhibited HSC proliferation and induced cell cycle arrest at the G0/G1 checkpoint. These effects were associated with TMP regulation of cyclin D1, p21, p27 and p53. Furthermore, we found that TMP disrupted mitochondrial functions and led to activation of caspase cascades in HSCs. Mechanistic investigations revealed that TMP selectively blocked the extracellular signal-regulated kinase (ERK) signaling and activated p53, which was required for TMP induction of caspase-dependent mitochondrial apoptosis in HSCs. Autodock simulations predicted that TMP could directly bind to ERK2 with two hydrogen bonds and low energy score, indicating that ERK2 could be a direct target molecule for TMP within HSCs. Moreover, TMP altered expression of some marker proteins relevant to HSC activation. These data collectively revealed that TMP modulation of ERK/p53 signaling led to mitochondrial-mediated and caspase-dependent apoptosis in HSCs in vitro. These studies provided mechanistic insights into the antifibrotic properties of TMP that may be exploited as a potential option for hepatic fibrosis.

Acupuncture combined with curcumin disrupts platelet-derived growth factor ß receptor/extracellular signal-regulated kinase signalling and stimulates extracellular matrix degradation in carbon tetrachloride-induced hepatic fibrosis in rats.

BACKGROUND: Acupuncture treatment has been increasingly used to treat chronic liver diseases. We previously reported that acupuncture combined with curcumin, a natural antifibrotic compound, could remarkably attenuate liver fibrosis in chemically intoxicated rats, but the underlying molecular mechanisms are poorly understood. The present study was aimed at investigating the effects of acupuncture combined with curcumin on platelet-derived growth factor (PDGF) signalling and extracellular matrix (ECM) regulation in the fibrotic liver. METHODS: A total of 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination treatment groups. During the establishment of fibrosis using carbon tetrachloride (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, serum PDGF levels were measured. Protein and mRNA expression of key effectors in PDGF pathway and fibrinolysis in the liver was determined. RESULTS: Acupuncture combined with curcumin potently reduced serum PDGF levels and selectively disrupted the PDGF-ßR/extracellular signal-regulated kinase (ERK) cascade. Combination treatment also significantly repressed expression of connective tissue growth factor and upregulated expression of matrix metalloproteinase-9, promoting fibrinolysis in the fibrotic liver. CONCLUSIONS: The beneficial effects of acupuncture and its combination with curcumin could be attributed to the disruption of PDGF-ßR/ERK pathway and stimulated ECM degradation in the fibrotic liver. Acupuncture treatment significantly enhanced curcumin effects at the molecular level. These findings may provide molecular insights into the potential of acupuncture combined with curcumin for prevention of hepatic fibrosis.

[Clinical significance of D-dimer activity in thrombosis of patients with return of spontaneous circulation after cardiopulmonary resuscitation].

OBJECTIVE: To investigate the clinical significance of D-dimer contents in peripheral blood for monitoring the efficacy of thrombolytic therapy in patients with return of spontaneous circulation (ROSC) of cardiopulmonary resuscitation (CPR) cardiopulmonary resuscitation after cardiac arrest. METHODS: Forty-seven patients with sudden cardiac arrest received CPR according to 2005 American Heart Association (AHA) guidelines for CPR and emergency cardiovascular care (ECC). At the early stage of ROSC, those patients underwent head and breast CT scan if they were in a state of unconsciousness and had unstable vital signs. If intracranial hemorrhage, dissection of aorta and pneumothorax were rule out, and those patients who maintained blood circulation for over 24 hours were included. The expression of D-dimer contents in peripheral blood was determined at 0, 1, 2, 4, 8, 12 h after CPR in all patients. And the patients were randomly divided into control and experiment groups. Prior to thrombolysis, the patients whose D-dimer more than 512 µg/L were classified as Group A (n = 17); those whose D-dimer below 512 µg/L Group B (n = 14); and the remaining control group whose family members refused thrombolytic therapy Group C (n = 16). The general data, Glasgow coma scale, survival rate and the change of D-dimer in peripheral blood were analyzed. RESULTS: In Group A, D-dimer level began to increase significantly at CPR 1 hour. It peaked at CPR 2 hours then decreased gradually. The final survival rate was 67%. The survival rate and GCS were higher than those of Groups B and C. In Group B, the D-dimer concentrations began to increase gradually at CPR1 hour, peaked at CPR 12 hours and then decreased. The survival rate and GCS was lower than those of Group A and similar to those of Group C. Group C was control group with no thrombolysis. CONCLUSION: For those ROSC patients with D-dimer concentrations significantly higher than usual, the pathogenesis of cardiac arrest may be concerned with thromboembolism, thrombosis in circulatory system and hyperviscosity. After an initiation of thrombolytic therapy, blocked blood vessels are recanalized, blood circulation improves and the cause of cardiac arrest is removed. Thus their survival rate becomes better. For those with D-dimer concentrations no higher than usual, the cause of cardiac arrest is not concerned with thromboembolism, thrombolytic therapy can not improve the patient outcome. And the final survival rate remains unchanged. The significance of thrombolytic therapy is none.

[Effect of acupuncture on the activity of the peripheral blood T lymphocyte subsets and NK cells in patients with colorectal cancer liver metastasis].

OBJECTIVE: To study the effect of acupuncture on the immune function of patients with colorectal cancer liver metastasis. METHODS: Sixty cases with colorectal cancer liver metastasis confirmed by pathology and mageology diagnosis were treated with acupuncture. Zusanli (ST 36), Sanyinjiao (SP 6), Neiguan (PC 6), Shangjuxu (ST 37), Hegu (LI 4), Taixi (KI 3), Taichong (LR 3) ,Yinlingquan (SP 9), Yanglingquan (GB 34), etc. were selected for acupuncture, and Shenque (CV 8), Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36) were selected for moxibustion. The changes of CD(3) , CD(4) , CD(8) T cells and NK cells in value were examined with flow cytometry before and after treatment. RESULTS: The value of T lymphocyte subsets such as CD(3) , CD(4), and CD(8) , as well as NK cells were obviously increased after treatment, and there were significant differences between them before and after treatment. CONCLUSION: Acupuncture can improve the immune function of patients with colorectal cancer liver metastasis.

[Identification and diagnosis of myocardial damage and acute myocardial infarction during cardiopulmonary resuscitation].

OBJECTIVE: To observe the change in contents of creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI) in peripheral blood, the elevation of ST in electrocardiogram, and the result of coronary arteriography, to identify myocardial damage and acute myocardial infarction during cardiopulmonary resuscitation (CPR). METHODS: Twenty-six patients with sudden cardiac arrest received CPR, and those patients who had blood circulation maintained for over 24 hours were included. The expression of CK-MB and cTnI activation in peripheral blood were determined at 0, 4, 8, 12, 16 and 20 hours after CPR in all patients. Electrocardiogram was checked every 2 hours in all patients. If CK-MB, cTnI and ST segment of electrocardiogram was higher than usual, or myocardial infarct with suspicious elevation of ST (STEMI), coronary arteriography and interventional therapy were carried out immediately. Patients were divided into three groups. The patients who were not found to have coronary artery block were classified as group A (15 cases), those who were found to have coronary artery block were group B (6 cases), and the remaining patients in whom ST segment of electrocardiogram did not elevate, and coronary arteriography and interventional therapy were not consider were classified as group C (5 cases). Control group consisted of 15 healthy people (group D). The change in CK-MB and cTnI in peripheral blood and the elevation of electrocardiogram ST segment were analyzed. RESULTS: In group A, CK-MB level began to elevate at CPR 4 hours, and it peaked at CPR 12 hours. cTnI began to raise at CPR 4 hours, peaking at CPR 16 hours, then decreased gradually. Elevation of ST was seen in more than two leads in electrocardiogram at the beginning of restoration of spontaneous circulation (ROSC), then lowered quickly, and the decrease exceeded 50% of the elevation at ROSC 2 hours. In group B, the levels of CK-MB and cTnI began to increase at CPR 4 hours, and remained elevated at CPR 20 hours. ST segment was elevated in more than two leads in electrocardiogram at the beginning of ROSC, and remained elevated after ROSC 2 hours. In group C, the CK-MB and cTnI concentrations were increased 4 hours after successful CPR, and reached peak at CPR 12, 16 hours respectively, then they decreased. ST segment of electrocardiogram was not elevated. In group D, the CK-MB and cTnI concentration was in the normal range. ST segment of electrocardiogram was not elevated. CONCLUSION: All patients manifested myocardial damage after CPR. Some patients showed STEMI after CPR. CK-MB and cTnI concentrations increased gradually after successful CPR without specificity for earlier identification of myocardial damage and STEMI. It is necessary to find a new reliable marker to check for myocardial damage. Relatively speaking, elevation of the ST segment in electrocardiogram has more predictive value. A decrease exceeds 50% of the elevation of ST segment in electrocardiogram at ROSC 2 hours, or the peak of contents of CK-MB and cTnI appear at CPR 12 hours or 16 hours indicates myocardial damage. If the elevation of ST segment does not descend after ROSC 2 hours, or the levels of CK-MB and cTnI remain elevated at CPR 20 hours, STEMI should be suspected, and it is necessary to undertake interventional therapy or thrombolysis therapy.

Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1.

Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.