Dl-3-n-Butylphthalide (NBP) Mitigates Muscular Injury Induced by Limb Ischemia/Reperfusion in Mice through the HMGB1/TLR4/NF-κB Pathway.

Objective: Limb ischemia/reperfusion (I/R) injury is a clinical syndrome associated with severe damages to skeletal muscles and other fatal outcomes. Oxidative stress and inflammatory response play vital roles in the development of limb I/R injury. Existing evidence further indicates that Dl-3-n-butylphthalide (NBP) has anti-inflammatory and antioxidative properties. However, whether NBP can protect skeletal muscles from limb I/R injury and the mechanism in mediating the action of NBP treatment still remain to be investigated, which are the focuses of the current study. Methods: The model of limb I/R injury was established and H&E staining was adopted to assess the pathological changes in skeletal muscles following limb I/R injury. Additionally, the W/D ratio of muscle tissue was also measured. ELISA and biochemical tests were carried out to measure the levels of inflammatory cytokines and oxidative stress in mouse models of limb I/R injury. Moreover, the levels of the HMGB1/TLR4/NF-κB pathway-related proteins were also determined using immunohistochemistry and immunoblotting. Results: It was established that NBP treatment alleviated I/R-induced pathological changes in muscular tissue of mice, accompanied by lower W/D ratio of skeletal muscular tissue. Meanwhile, the limb I/R-induced inflammation and oxidative stress in skeletal muscles of mice were also inhibited by NBP. Mechanistic study indicated that the alleviatory effect of NBP was ascribed to inactivation of the HMGB1/TLR4/NF-κB pathway. Conclusions: Our findings highlighted the potential of NBP as a novel strategy for limb I/R-driven muscle tissue damages by suppressing inflammatory response and oxidative stress via the HMGB1/TLR4/NF-κB pathway.

Human activities have reduced plant diversity in eastern China over the last two millennia.

Understanding the history and regional singularities of human impact on vegetation is key to developing strategies for sustainable ecosystem management. In this study, fossil and modern pollen datasets from China are employed to investigate temporal changes in pollen composition, analogue quality, and pollen diversity during the Holocene. Anthropogenic disturbance and vegetation's responses are also assessed. Results reveal that pollen assemblages from non-forest communities fail to provide evidence of human impact for the western part of China (annual precipitation less than 400 mm and/or elevation more than 3000 m.a.s.l.), as inferred from the stable quality of modern analogues, principal components, and diversity of species and communities throughout the Holocene. For the eastern part of China, the proportion of fossil pollen spectra with good modern analogues increases from ca. 50% to ca. 80% during the last 2 millennia, indicating an enhanced intensity of anthropogenic disturbance on vegetation. This disturbance has caused the pollen spectra to become taxonomically less diverse over space (reduced abundances of arboreal taxa and increased abundances of herbaceous taxa), highlighting a reduced south-north differentiation and divergence from past vegetation between regions in the eastern part of China. We recommend that care is taken in eastern China when basing the development of ecosystem management strategies on vegetation changes in the region during the last 2000 years, since humans have significantly disturbed the vegetation during this period.

Ischemia-Reperfusion Injury in Peripheral Artery Disease and Traditional Chinese Medicine Treatment.

Peripheral artery disease (PAD) is a serious public health issue, characterized by circulation disorder of the lower extreme that reduces the physical activity of the lower extremity muscle. The artery narrowed by atherosclerotic lesions initiates limb ischemia. In the progression of treatment, reperfusion injury is still inevitable. Ischemia-reperfusion injury induced by PAD is responsible for hypoxia and nutrient deficiency. PAD triggers hindlimb ischemia and reperfusion (I/R) cycles through various mechanisms, mainly including mitochondrial dysfunction and inflammation. Alternatively, mitochondrial dysfunction plays a central role. The I/R injury may cause cells' injury and even death. However, the mechanism of I/R injury and the way of cell damage or death are still unclear. We review the pathophysiology of I/R injury, which is majorly about mitochondrial dysfunction. Then, we focus on the cell damage and death during I/R injury. Further comprehension of the progress of I/R will help identify biomarkers for diagnosis and therapeutic targets to PAD. In addition, traditional Chinese medicine has played an important role in the treatment of I/R injury, and we will make a brief introduction.

The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy.

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients' life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

Preparation and Characterization of a Novel Polysaccharide-Iron(III) Complex in Auricularia auricula Potentially Used as an Iron Supplement.

Iron deficiency anemia has been a widespread disease. As an effective and stable iron supplement, the physiochemical properties of the polysaccharide iron complex have been widely studied. In this study, we characterized a novel polysaccharide-iron(III) complex extracted in an edible fungal species Auricularia auricular (AAPS-iron(III)). The highest iron content (28.40%) in the AAPS-iron(III) complex was obtained under the optimized preparation conditions including an AAPS to FeCl3∙ 6H2O ratio of 2:3 (w/w), a pH value of 8.0 in solution, a reaction temperature of 50°C, and a reaction time of 3 h. The physical and chemical properties of the AAPS-iron(III) complex were characterized by qualitative and quantitative analyses using scanning electron microscope, particle size distribution, thermogravimetric analyzer, Fourier transform infrared spectroscopy, circular dichroism, and 1H nuclear magnetic resonance. Result showed that, although the iron was bound to the polysaccharide, it was released under artificial gastrointestinal conditions. The AAPS-iron(III) complex exhibited high stability (under 50-256°C) and water solubility. The AAPS-iron(III) complex also showed high antioxidant activity in vitro, demonstrating an additional health benefit over other typical nonantioxidant iron nutritional supplements. Furthermore, the AAPS-iron(III) complex showed high efficiency on the treatment of the iron deficiency anemia in the model rats. Therefore, the AAPS-iron(III) complex can be used as a nutritional fortifier to supply iron in industrial processing and to assist the treatment of iron deficiency anemia.

Testing Different Combinations of Acoustic Pressure and Doses of Quinolinic Acid for Induction of Focal Neuron Loss in Mice Using Transcranial Low-Intensity Focused Ultrasound.

The goal of this study was to test different combinations of acoustic pressure and doses of quinolinic acid (QA) for producing a focal neuronal lesion in the murine hippocampus without causing unwanted damage to adjacent brain structures. Sixty male CD-1 mice were divided into 12 groups that underwent magnetic resonance-guided focused ultrasound at high (0.67 MPa), medium (0.5 MPa) and low (0.33 MPa) acoustic peak negative pressures and received QA at high (0.012 mmol), medium (0.006 mmol) and low (0.003 mmol) dosages. Neuronal loss occurred only when magnetic resonance-guided focused ultrasound with adequate acoustic power (0.67 or 0.5 MPa) was combined with QA. The animals subjected to the highest acoustic power had larger lesions than those treated with medium acoustic power, but two mice had evidence of bleeding. When the intermediate acoustic power was used, medium and high dosages of QA produced lesions larger than those produced by the low dosage.

Laser-induced interstitial thermotherapy via a single-needle delivery system: Optimal conditions of ablation, pathological and ultrasonic changes.

This study aimed to examine the optimal conditions of laser-induced interstitial thermotherapy (LITT) via a single-needle delivery system, and the ablation-related pathological and ultrasonic changes. Ultrasound (US)-guided LITT (EchoLaser system) was performed at the output power of 2-4 Wattage (W) for 1-10 min in ex vivo bovine liver. Based on the results of the ex vivo study, the output power of 3 and 4 W with different durations was applied to in vivo rabbit livers (n=24), and VX2 tumors implanted in the hind limbs of rabbits (n=24). The ablation area was histologically determined by hematoxylin-eosin (HE) staining. Traditional US and contrast enhanced ultrasound (CEUS) were used to evaluate the treatment outcomes. The results showed: (1) In the bovine liver, ablation disruption was grossly seen, including a strip-like ablation crater, a carbonization zone anteriorly along the fiber tip, and a surrounding gray-white coagulation zone. The coagulation area, 1.2 cm in length and 1.0 cm in width, was formed in the bovine liver subjected to the ablation at 3 W for 5 min and 4 W for 4 min, and it extended slightly with the ablation time. (2) In the rabbit liver, after LITT at 3 W for 3 min and more, the coagulation area with length greater than or equal to 1.2 cm, and width greater than or equal to 1.0 cm, was found. Similar coagulation area was seen in the implanted VX2 carcinoma at 3 W for 5 min. (3) Gross examination of the liver and carcinoma showed three distinct regions: ablation crater/carbonization, coagulation and congestion distributed from the center outwards. (4) Microscopy revealed four zones after LITT, including ablation crater/carbonization, coagulation, edema and congestion from the center outwards. A large area with coagulative necrosis was observed around a vessel in the peripheral area with edema and hyperemia. (5) The size of coagulation was consistent well to the CEUS findings. It was concluded that EchoLaser system at low power can produce a coagulation area larger than 1.0 cm×1.0 cm during a short time period. The real-time US imaging can be used to effectively guide and assess the treatment.

[The development of chemical narcotic and related anesthetic techniques in modern times].

Before the 19(th) century, ether and nitrous oxide were synthesized. However, they were just used as a kind of enjoyable things at night gatherings for their hypnotic and analgesic effect. In the 19(th) century, ether and nitrous oxide came into use in clinical anesthesia. Thereafter, more and more chemical narcotics were synthesized and applied to clinical anesthesia. In 1872, chloroform was injected into man's vein for anesthesia. In the 20(th) century, along with many kinds of barbiturates being synthesized, intravenous anesthesia got much development and application. At the same time, related techniques of anesthesia also improved. In the early 19(th) century, open inhalation anesthesia was often used. In 1900, there came a new anesthesia method by blowing into the windpipe through the cut of throat. Later on, the technique of endotracheal anesthesia and artificial respiration anesthesia (1908), the anesthetic instrument of endotracheal intubation and laryngeal mask and laryngoscope were invented. In the mid 19(th) century, the appearance of injection syringe and cocaine made local anesthesia possible. In 1880, local anesthesia also became successful. Thereafter, a variety of local anesthetic drugs were synthesized and applied, companying with various techniques of local anesthesia such as subarachnoid anesthesia (1900), sacral anesthesia (1901), epidural block (1903), plexus block (1902) and so on. In order to control the depth of anesthesia and respiration effectively, people attempted a lot so that anesthesia machine (1910), improved endotracheal anesthesia (1921), cryogenic technique (1902), controlled hypotension (1940s) and artificial hibernation (1950) came into being.

[Nursing in America during the Civil War].

Before the Civil War, nursing was performed by untrained nurses and female religious groups. After the outbreak of the Civil war, more women went out of the family and engaged in nursing service in military hospitals. Nursing in America transferred from religious charity activities and sporadic simple work into an indispensable profession and was developed. In the Civil War, excellent nurses saved soldiers' lives, reduced casualties and were gradually recognized by soldiers, doctors and the society. On the other hand, untrained nurses' lack of ability was exposed. The contradiction made nurses controversial and people began to consider what nursing was. Thus professional training for nurses was necessary, which caused the development of nursing education. This promoted the development of nursing education and professionalization of nursing.

[A revolution led by ideas: the analysis of the Flexner medical educational revolution in America].

The medical education of America gradually became one of the models of the advanced medical education throughout the world in the beginning of 20th century. The medical educational revolution in America led by the report of Flexner was an important foundation for the successful development of medical education in America. The occurrence of the Flexner Revolution was closely connected with the transformation of medical concepts and educational ideas which were led by the revolution in various social factors. So we can say that the Flexner Revolution was led by ideas.

[The establishment of Medical College in Philadelphia, the first medical college of North America].

Modern medical education system of America was established in the 20th century. However, the beginning of American medical education was far early in the colonial times when the Medical College in Philadelphia was set up. The historical review on the establishment of the first medical college, Medical College in Philadelphia, is helpful to the understanding of the history of American medical education, the characteristics of modern medical education in the U. S., even to get some historical experience from the development of American medical education.

Potential anticancer activity of litchi fruit pericarp extract against hepatocellular carcinoma in vitro and in vivo.

Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds, and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract against hepatocellular carcinoma in vitro and in vivo, and to elucidate the mechanism of its activity. Human hepatocellular carcinoma cell line was tested in vitro for cytotoxicity, colony formation inhibition, and cell cycle distribution through flow cytometry after treatment with water-soluble crude ethanolic extract (CEE) from LFP. Murine hepatoma bearing-mice were fed doses of 0.15, 0.3, and 0.6g/kg/day of water-soluble CEE in DH(2)O p.o. for 10 days, respectively, to test the anticancer activity and BrdU incorporation of cancer cells in vivo. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cancer cell growth; IC(50) was 80microg/ml, and significantly inhibited colony formation in vitro, tumor growth and BrdU incorporation into cancer cells in vivo. The tumor inhibitory rates at doses of 0.15, 0.3, and 0.6g/kg/day were 17.31% (P>0.05), 30.77% (P<0.05), and 44.23% (P<0.01), respectively. BrdU labeled tumor cells of treated animals were 11.80+/-2.79%, and were significantly lower than that in untreated controls (23.00+/-5.42%, P<0.05). Our findings showed that LFP extract exhibited potential anticancer activity against hepatocellular carcinoma in vitro and in vivo through proliferating inhibition and apoptosis induction of cancer cells.

[Influence of World War II on high medical school education in the US].

Modern medical education was gradually established in the US since Flexner's report was published in 1910. Medical education had developed rapidly before World War II. The outbreak of World War II had become an important factor influencing the development of medical education in history. By analyzing the influence of World War II in medical education and analyzing and summarizing the American medical education before and after this War, we hope that it can offer some useful experiences to the development of medical education in our country.

[A review of the transformation of American higher medical education in the early 20th century].

This paper has a review of the transformation of American higher medical education in the early 20th century, which is signalized by the publication of Flexner report in 1910. At the same time, the author also has an analysis on the whole event. The experience of its success or failure is summarized in order to give references to the reform of Chinese higher medical education.