Water Rewarming After Seawater Hypothermia Mitigates IL-1ß in Both Intestinal Tissue and Blood.

In this study, the rat models of severe hypothermia induced by seawater immersion were established in artificial seawater immersion at 15°C for 5 hours. With the rewarming measurement of 37°C water bath, the rewarming effects were evaluated by monitoring basic vital signs and dynamically detecting intestinal inflammation cytokines. Fifty Sprague-Dawley rats were randomly divided into five groups including the control group (group C), hypothermia group (group H), 2-hour rewarming group (group R2), 6-hour rewarming group (group R6), and 12-hour rewarming group (group R12), with 10 in each group. The basic vital signs of rats (i.e., core temperature, respiration, heart rate, and muscle tremor) were constantly recorded. The inflammatory factors were detected in the intestinal tissue via a protein chip GSR-CAA-67 of Innopsys, and the verification by reverse transcription-quantitative polymerase chain reaction. The levels of cytokines (interleukin IL-1ß, IL-6, and IL-10) were detected from blood samples collected at the end of the observation period via enzyme-linked immunosorbent assay. The expression landscape of IL-1ß in the intestinal tissue was validated by immunohistochemistry. Five hours of immersion in artificial seawater at 15°C successfully induced severe hypothermia of rats. After 2 hours of constant water bath rewarming at 37°C, the basic vital signs recovered to the normal level and maintained stably as well as the acute inflammatory reaction alleviated effectively, which indicated that 37°C of water immersion rewarming had the potential to be a suitable method for early treatment of water immersion hypothermia. After the process of hypothermia, several inflammatory cytokines of rats in rewarming groups changed distinctly with IL-1ß, showing the most significant variations compared with group C, which confirmed IL-1ß as a potential monitoring biomarker referring to the therapeutic effect of rewarming for severe hypothermia caused by seawater immersion.

Hypothermia-rewarming: A Double-edged sword?

Hypothermia is a condition in which the body's core temperature drops below 35.0 °C. Hypothermia is the opposite of hyperthermia, which the metabolism and body functions are abnormal. Severe hypothermia is a life-threatening problem that may cause atrial and ventricular dysrhythmias, coagulopathy, cardiac, and central nervous system depression. What is worse, it is fatal when untreated or treated improperly. Accidental deaths due to hypothermia resulting from immersion in cold water, especially involving naval fighters and maritime victims have occurred continually in the past years. Currently, the treatment of hypothermia has become a research focus. Rewarming is the only approach that should be considered for hypothermia treatment. However, the treatment is of low efficiency, and few active rewarming cases have been reported. It is well known that timely reperfusion is the best way to save the lives of patients with ischemia. Similarly, reoxygenation is effective for hypoxia. However, several studies have identified that improper reperfusion of ischemic tissues and reoxygenation of hypoxic tissues give rise to further injury. Analogically, this study attempts to propose the hypothesis that hypothermia-rewarming injury may also exist. When suffered from hypothermia, both the blood circulation and the oxygen supply in the body will be affected in a deficient state, an injury may also appear in the improper rewarming process. In a word, hypothermia-rewarming may be a double-edged sword.

Numerical simulation for treatment of hypothermia based on vascular interventional direct heating system.

The treatment of hypothermia suffered by naval fighters owing to seawater immersion has been a focus of research in recent years. Currently, the treatment of hypothermia in China is limited to external rewarming, which is of low efficiency and is not effective for patients suffering moderate to severe hypothermia. We thus proposed a vascular interventional heating method which directly heats the blood flow via a minimally invasive heating needle for rewarming. And a numerical simulation using a compartment model based on finite difference method was conducted. A set of whole body heating treatment simulation was also developed. Appropriate treatment parameters and procedures can be set and adjusted based on patient physical parameters. Here temperature response curves of different heating modes were obtained and analyzed. It was demonstrated that the desired thermal response can be achieved by adjusting the heating power and heating time, ensuring controllable accuracy in the treatment of patients with severe hypothermia. The proposed treatment for hypothermia is a new and effective alternative, and further progress is expected in clinical trials.

Role of Vascular Endothelial Cells in Disseminated Intravascular Coagulation Induced by Seawater Immersion in a Rat Trauma Model.

Trauma complicated by seawater immersion is a complex pathophysiological process with higher mortality than trauma occurring on land. This study investigated the role of vascular endothelial cells (VECs) in trauma development in a seawater environment. An open abdominal injury rat model was used. The rat core temperatures in the seawater (SW, 22°C) group and normal sodium (NS, 22°C) group declined equivalently. No rats died within 12 hours in the control and NS groups. However, the median lethal time of the rats in the SW group was only 260 minutes. Among the 84 genes involved in rat VEC biology, the genes exhibiting the high expression changes (84.62%, 11/13) on a qPCR array were associated with thrombin activity. The plasma activated partial thromboplastin time and fibrinogen and vWF levels decreased, whereas the prothrombin time and TFPI levels increased, indicating intrinsic and extrinsic coagulation pathway activation and inhibition, respectively. The plasma plasminogen, FDP, and D-dimer levels were elevated after 2 hours, and those of uPA, tPA, and PAI-1 exhibited marked changes, indicating disseminated intravascular coagulation (DIC). Additionally, multiorgan haemorrhagia was observed. It indicated that seawater immersion during trauma may increase DIC, elevating mortality. VECs injury might play an essential role in this process.

Prognostic value of circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma.

OBJECTIVE: Circulating tumor cells (CTCs) of patients with malignant tumors can be used as a prognostic marker. However, there are few relevant reports to date on esophageal squamous cell carcinoma (ESCC). Our study assesses the clinical significance of CTCs in ESCC patients. PATIENTS AND METHODS: CTCs were detected in 103 peripheral blood (PB) samples from 59 ESCC patients. Correlation between CTCs and clinical parameters was analyzed using the χ2 test or Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier analysis and univariate and multivariate methods. RESULTS: The CTC detection rate was 79.7% (47/59) at baseline. The frequency of CTC-positive patients increased as the disease stage advanced (88.0% in stages III-IV, 58.9% in stages I-II). CTC counts ≥0/7.5 mL of PB were correlated with the degree of tumor differentiation, tumor infiltration, and lymph node and distant metastases. Overall, the OS and PFS of patients with CTC counts ≥3 or ≥5/7.5 mL of PB before surgery were significantly shorter than those of patients with CTC counts <3 or <5/7.5 mL. Multivariate analysis showed CTC counts ≥5/7.5 mL of PB to be a strong prognostic indicator of OS (hazard ratio [HR] 12.478; 95% confidence interval [CI], 8.2-34.3; P<0.05) and PFS (HR 6.524; 95% CI, 1.2-34.3; P<0.05) in ESCC patients. Patients in whom CTCs changed from positive at baseline to a negative value after surgery had an excellent prognosis. CONCLUSION: CTCs might serve as a reference indicator for the prognosis and monitoring of disease progression and treatment effects in ESCC.

PERCEPTION OF ACADEMIC PHARMACISTS TOWARDS THEIR ROLE IN HEALTHCARE SYSTEM OF A DEVELOPING COUNTRY, PAKISTAN: A QUANTITATIVE SIGHT.

To investigate perception of academic pharmacists towards their role in healthcare system of a developing country, Pakistan, was the aim of this study. The study participants consisted of academic pharmacists from the government and private universities of Pakistan. Study was conducted for a period of three months, from January to March 2011, in Pakistan. Academic pharmacists were informed regarding the aim, objective and nature of the study. Verbal consent was given and execution of the study took place. Main sections of the questionnaire were comprised of series of statements pertaining to pharmacist perception and experience with the pharmacists. During the period, of January to April, the total number of questionnaires received from different government and private universities was 113. The response rate based on the 205 academic pharmacists working in universities during the study period was 63.9%. A majority (93.9%) of the respondents were satisfied working as academic pharmacist, 68.7% expressed that their interest in research is the reason to embark carrier as an academic pharmacist. Only half (55.7%) of the respondents agreed about pharmacy curriculum standard in Pakistan, and their satisfaction towards curriculum is less, as after the implementation of Pharm. D. (Doctor of Pharmacy). In the country, the curriculum is still focusing more towards theoretical knowledge rather than practical. In this case significant difference was noted with respect to university (p = 0.012). Academic pharmacists do have concern about the pharmacy profession in Pakistan. They ascertain the key issues facing the profession and its educators. Recommendations have been made to improve the current pharmacy curricula in order that future pharmacists in Pakistan practice effectively with the collaboration of other healthcare professionals.

Monitoring disease progression and treatment efficacy with circulating tumor cells in esophageal squamous cell carcinoma: A case report.

This study investigated whether changes in circulating tumor cell (CTC) numbers reflect tumor progression and treatment efficacy in esophageal squamous cell carcinoma (ESCC). A 47-year-old male patient with ESCC is presented in this case study. The patient was evaluated for a series of serum tumor markers and subjected to radiological examinations before and after surgery and during follow-up over the course of five years. In addition, the CTCs in 7.5 mL of peripheral blood were enriched by magnetic-activated cell sorting negative selection and identified by immunofluorescence staining. Serum tumor markers remained within normal ranges and were discordant with imaging scans during the follow-up. Initially, one CTC was detected in the peripheral blood sample, and 14 were observed seven days after the operation. After 12 wk, subcutaneous metastases and bone metastases occurred, and the number of CTCs increased to 84. After 48 wk, lung metastases were noted, and the CTC level was 21. At 104 wk, the number of CTCs was 14, and disease recurrence was detected by positron emission tomography-computed tomography. The CTC counts were in accord with the imaging studies at several time points. The additional information provided by CTC enumeration could thus facilitate monitoring of disease status and treatment efficacy and provide support for treatment decisions.

The expression and distributions of ANP32A in the developing brain.

Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has multiple functions involved in neuritogenesis, transcriptional regulation, and apoptosis. However, whether ANP32A has an effect on the mammalian developing brain is still in question. In this study, it was shown that brain was the organ that expressed the most abundant ANP32A by human multiple tissue expression (MTE) array. The distribution of ANP32A in the different adult brain areas was diverse dramatically, with high expression in cerebellum, temporal lobe, and cerebral cortex and with low expression in pons, medulla oblongata, and spinal cord. The expression of ANP32A was higher in the adult brain than in the fetal brain of not only humans but also mice in a time-dependent manner. ANP32A signals were dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in the granular layer of the cerebellum and the cerebral cortex when the mice were growing up, as well as in the Purkinje cells of the cerebellum. The variation of expression levels and distribution of ANP32A in the developing brain would imply that ANP32A may play an important role in mammalian brain development, especially in the differentiation and function of neurons in the cerebellum and the cerebral cortex.

Influence of Per3 genotypes on circadian rhythmicity in flight cadets after militarized management.

OBJECTIVE: The purpose of this study was to explore the effect of PERIOD3 (PER3) genotypes on circadian rhythmicity in flight cadets after militarized management. METHODS: We performed a preliminary study in 146 newly enrolled male flight cadets. Venous blood samples were collected, and genotyping of PER3 (4/5) was determined by using PCR. The morningness-eveningness questionnaire (MEQ) survey was given to flight cadets upon enrollment and after militarized management for 24 months respectively. Comparison of frequency distribution of PER3 genotypes between cases and controls (120 well-matched civilians) was performed using the X(2) test. We also compared the circadian rhythmicity upon enrollment and 24 months after enrollment in flight cadets, and analyzed the connection of changes in circadian clock with PER3 genotypes. RESULTS: The frequency distribution of PER3 genotypes in flight cadets was not significantly different from that in controls subjects. MEQ survey results showed chronotype within flight cadet group varied widely at the two time-points: the moderately morning type (50%) and the neither type (41.1%) upon enrollment; the neither type (76.7%) and the moderately morning type (21.2%) 24 months after enrollment. The circadian rhythm of individuals with the PER3 (5/5) genotype showed no significant difference before and after 24 months of militarized management, whereas notable changes were found in individuals with the PER3 (4/4) genotype (n=116, X(2) =37.26, P < 0.001). CONCLUSION: In conclusion, we provide some evidence that circadian rhythm of flight cadets with the PER3 (5) allele are less likely to be affected compared to those with the PER3 (4) allele.

A review on antidiabetic activity of Citrullus colocynthis Schrad.

Current studies have elaborated diabetes mellitus as one of the most prevalent endocrine disorder throughout the world. Citrullus colocynthis (C. colocynthis) is one of the most common traditional plants used as remedy against diabetes mellitus. It is well recognized by its hypoglycemic effect, which is substantiated in current phytotherapy. Its undesired effects include the disturbance of gastrointestinal and urinary tracts. This review article encompasses various blood glucose lowering studies that have been carried out till date. Various parts of plants used in extract preparation were roots, fruits, seeds, rinds and leaves. The nature of these extracts was ethnolic, methanolic, or aqueous and their doses varied from 10 to 500 mg/kg body weight/day. All these published articles elaborate C. colocynthis as a potential antiglycemic medicinal plant.

Systematic review of randomized controlled trials of traditional Chinese medicine treatment of non-acute bronchial asthma complicated by gastroesophageal reflux.

OBJECTIVE: To assess the effectiveness and safety of Traditional Chinese Medicine (TCM) treatment of non-acute bronchial asthma complicated by gastroesophageal reflux. METHODS: We searched databases from MEDLINE, Cochrane Library, CNKI, VIP, CBM, Wanfang Data, and TCM Database Systems. All randomized, controlled trials (RTCs) of TCM treatment of non-acute asthma complicated by gastroesophageal reflux were included. Data were independently collected by two reviewers. The standards for assessing quality described in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate articles. Meta-analyses were conducted using Rev- Man 5.0.17 software. Heterogeneity was assessed, and a corresponding effects model was used to merge and analyze results. Indexes used to evaluate curative effects were: clinical efficacy, symptom scores, pulmonary function values, and adverse incidents. Effectiveness was indicated using risk ratio (RR) or mean difference (MD), and 95% confidence intervals (CIs) were calculated. RESULTS: Six RCTs were included, involving 304 patients with non-acute asthma complicated by gastroesophageal reflux. The treatment groups received Chinese drugs alone or TCM combined with standard Western medical treatment, and the control groups received standard Western medical treatment alone. Standard Western medical treatment included anti-inflammatory drugs and bronchodilators for asthma, and drugs to promote gastric peristalsis and inhibit gastric acid production for gastroesophageal reflux. Methodological quality was low in all six RCTs. Two RCTs showed that clinical efficacy was higher in the treatment group than in the control group (RR: 1.43, 95%CI: 1.10 to 1.87 vs RR: 1.51, 95% CI: 1.09 to 2.08). One RCT showed that the asthma score was lowered more effectively in the treatment group than in the control group (MD:-1.10, 95% CI:-2.04 to-0.16). Two RCTs showed that the gastroesophageal reflux score was reduced more effectively in the treatment group than in the control group (RR:-3.70, 95% CI:-4.30 to 3.10 vs RR:-5.30, 95% CI:-6.32 to -4.28). One RCT showed that some pulmonary function values were improved more effectively in the treatment group than in the control group (P < 0.05). No differences were seen in the various indexes between groups in the other RCTs. No adverse reactions, dropout rates, or follow-up rates were reported in any of the RCTs. CONCLUSIONS: The clinical symptoms of non-acute asthma complicated by gastroesophageal reflux can be improved by some Chinese drugs. Curative effects can be increased by combining the use of TCM with Western medicine. Because of the small quantity and low quality of research reported to date, it is necessary to conduct further RCTs to confirm these results. The results of this systematic review indicate that the quality of future clinical trials should be improved by including larger patient numbers, correctly randomizing patients into study groups, using blinding methods to measure and assess outcomes, and using accepted indexes to evaluate curative effects.

Study on the drug selection law for treatment of chronic gastritis with spleen deficiency and stomach dryness by complex system entropy cluster.

OBJECTIVE: To study on Prof. GAO Zhong-ying's drug selection law for treatment of chronic gastritis with data mining technique. METHODS: The 407 medical records of chronic gastritis treated by Prof. GAO Zhong-ying were collected and the study on these drugs in the recipes was carried out with data mining method. Among them, the recipe composed of one drug was studied with frequency statistical method, correlativity between drug pairs with improved mutual information, correlativity among multi-drugs with complex system entropy cluster technique. RESULTS: In treatment of chronic gastritis by Prof. GAO Zhong-ying there were 30 drugs with a higher use frequency of over 38 times, 94 commonly-used drug pairs with correlation coefficient of over 0.05, 11 commonly-used drug core combinations. CONCLUSION: The results attained with data mining technique for studying experience of famous and old TCM physicians conform to the clinical practice and the method is of an important significance for summarization of famous and old TCM physicians' experiences.

Gene damages of mitochondrial DNA encoding cytochrome oxidase of intestinal epithelial cells in hemorrhagic shock rats.

OBJECTIVE: To investigate the detrimental effects of hemorrhagic shock on the structure and function of mitochondria DNA (mtDNA) encoding cytochrome oxidase genes in intestinal epithelial cells. METHODS: Wistar rats were used and divided into two groups: hemorrhagic shock group and control group. Hemorrhagic shock model of rats was utilized in this experiment. The mtDNA was extracted from the intestinal epithelial cells and amplified by polymerase chain reaction (PCR) with different primers of cytochrome oxidase (COX I, COX II and COX III). The products of PCR were directly sequenced. RESULTS: Hemorrhagic shock could result in the point mutagenesis in mitochondrial genome encoding cytochrome oxidase (COX I and COX II). There were 4, 4, 22, 16, 35 point mutations in COX I from 5545 to 6838 bp in 5 shocked rats. There were five point mutations in COX II from 7191 to 7542 bp at the site of t7191c, t7212c, a7386g, a7483g, c7542g in 1 shocked rat. There was no mutation found in COX III. CONCLUSIONS: Hemorrhagic shock could significantly induce the damage of the gene of cytochrome oxidase encoded by mtDNA.

Effects of seawater immersion on the functions of mitochondria of myocardium and hepatocyte in hemorrhagic shock rats.

OBJECTIVE: To investigate the effects of seawater immersion on the function of myocardium and hepatocyte mitochondria in experimental hemorrhagic shock rats. METHODS: Twenty-four male Wistar rats were divided into three groups (n=8 in each group): control group, HSL group (hemorrhagic shock group on land) and HSS group (hemorrhagic shock group in seawater). The hemodynamic parameters, activities of H(+)-ATPase (adenosinetriphosphatase), succinate dehydrogenase (SDH) and Ca(2+)-Mg(2+)-ATPase, the calcium contents in myocardium and hepatocyte mitochondria were measured and the changes of proton translocation across the inner mitochondrial membrane were analyzed. RESULTS: The hemodynamic indexes and the activities of H+-ATPase, SDH, Ca(2+)-Mg(2+)-ATPase in HSS group were significantly lower than those in control group and HSL group (P<0.05). In HSS group the calcium levels in tissue and mitochondria of myocardium and hepatocyte were elevated significantly compared with control group and HSL group (P<0.05). There was no significant difference in proton translocation among three groups. CONCLUSIONS: This investigation demonstrates that seawater immersion can aggravate the conditions of hemorrhagic shock rats.