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During the coronavirus disease 2019 (COVID-19) epidemic, many reports have indicated that children shed the virus longer than adults in stool, and that most of the children had mild or even asymptomatic infections, which increased the potential risk for feces to be a source of contamination and may play an important role in the spread of the virus. In this review, we collected relevant literature to summarize the duration of fecal viral shedding in children with COVID-19. We found that in about 60% of the cases, the fecal shedding time was between 28 and 42 days, which was much longer than that of adults. We further explored the possible reason for prolonged shedding and its the potential impact. The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the significant difference in expression of angiotensin-converting enzyme 2 (ACE2) in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children. Conclusion: Children with COVID-19 show prolonged fecal shedding compared to adults. Several mechanisms may be involved in the longer fecal viral shedding. Viral shedding in the stool could be contributing to a possible route of transmission. Therefore, we think that further preventive measures in children should be taken to reduce the spread of the disease. What is Known: • Children with COVID-19 are more likely to have asymptomatic infections and to experience mild symptoms. • Some patients continue to shed the virus in feces, despite respiratory samples testing negative. What is New: • Children with COVID-19 carried a longer-term fecal viral shedding than adults. • The poor hand hygiene practices of children, their tendency to swallow sputum and/or saliva, the difference in expression of ACE2 in intestine between children and adults, and the variance in immune status and intestinal microbiome could be considered as potential casual agents of longer fecal viral shedding duration of children.

Ibrutinib is a drug that inhibits the protein Burton’s tyrosine kinase and thereby the nuclear translocation of Nrf2, which played a key role in mediating the activation of antioxidants during stress conditions and ferroptosis resistance. This study aimed to identify the effect of Ibrutinib and ferroptosis inducer on colorectal cancer (CRC) treatment and its underlying mechanism. In our study, we found the upregulation of Nrf2 was correlated with CRC progression and antioxidant proteins. Ibrutinib sensitized CRC to ferroptosis inducers, suggested by further reduced CRC cell viability, proliferation and decreased antioxidant protein levels in CRC cells after combination treatment of Ibrutinib and RSL3 or Ibrutinib and Erastin both in vivo and in vitro. Knockout of Nrf2 diminished the regulatory effect of Ibrutinib on CRC sensitivity to ferroptosis inducers. Altogether, this study demonstrated that Ibrutinib increases the sensitivity of CRC cell to ferroptosis inducers by inhibiting Nrf2.

Objective Antipsychotics, in particular olanzapine, are first-line medications for schizophrenia. The prefrontal cortex (PFC) is an important region for antipsychotics' therapeutic effects. The PFC inflammatory and immune pathways are associated with schizophrenia pathogenesis. However, the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains unclear. We aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of rats. Since the inflammatory and immune pathways are related to endoplasmic reticulum (ER) stress, we further investigated whether or not olanzapine-induced inflammation and immune responses were related to ER stress. Methods Expression of pro-inflammatory markers including IkappaB kinase β (IKKβ), nuclear factor kappa B (NFκB), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and IL-1β, and immune-related proteins including inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2) and cluster of differentiation 14 (CD14) were examined by Western blotting. Results Olanzapine treatments for 1, 8 and 36 days significantly activated the inflammatory IKKβ/NFκB signaling, and increased the expression of TNF-α, IL-6, IL-1β and immune-related proteins such as iNOS, TLR4 and CD14. Olanzapine treatment for 1 day, 8 and 36 days also induced ER stress in the PFC. Co-treatment with an ER stress inhibitor, 4-phenylbutyrate, inhibited olanzapine-induced inflammation and the immune response in the PFC. Conclusion These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia subjects. Olanzapine induces PFC inflammation and immune response, possibly via activating ER stress signaling.

Two new monoterpene esters, illigerates H and I (

Hemifacial spasm (HFS) and temporomandibular joint (TMJ) pain are common facial diseases which cause depression, anxiety, insomnia, and poor quality of life. However, currently there are still no effective therapies to treat HFS and TMJ. Electroacupuncture (EA) has advantages of safety, rapid work, easy operation and convenience. Here, we reported a case of a 50-year-old woman who presented with irregular spasm of eyelids and facial muscles on the left side, and TMJ pain on the right side. The patient had been treated with carbamazepine (20mg per day) and alternative therapies for a year, but still not much improvement in the symptoms. The scores of the Jankovic Rating Scale (JRS), global rating scale (GRS), and visual analog scale (VAS) were 7, 60, and 7 points, respectively. The EMG test showed that the spastic side had higher R1 amplitude, longer R2 duration, and larger R2 area than the non-spasmodic side, and the occurrence rate of the lateral spread responses (LSR) in the Orbicularis oris and the Orbicularis oculi muscle was 60% and 40%, respectively. We considered this patient had left HFS and right TMJ pain. EA was successfully undertaken for two periods over 30 weeks. After EA, JRS and VAS were reduced sharply, and the symptoms of HFS were stable without recurrence. However, the frequency of the lower eyelid increased gradually during the 6-month follow-up. These findings reveal that EA with the frequency of 2 Hz and intensity of ~ 1–2 mA may be a benefit for alleviating symptoms of HFS and TMJ pain without adverse reaction. The potential mechanisms of EA in HFS and TMJ pain co-morbidity involve brain stem mechanism and DNIC mechanism for distal acupuncture and segmental mechanism for local acupuncture analgesia.

From the perspective view of Chinese medicine, the Gan (Liver) meridian of Foot-Jueyin starts from the great toe, running upward along the medial side of the thigh to the perineal area, where it curves around the external genitalia and goes up to the lower abdomen. In clinical practice, acupoints in the feet of the Gan meridian of Foot-Jueyin are used to treat the genitourinary and external genitalia diseases. Studies have shown that reproductive system diseases have specific pathological reactions in the places (radial side of tibia and foot) where Gan meridian of Foot-Jueyin passes by. Why does this happen? In this article, we begin by briefly reviewing the evidences linking foot and genitalia. We then explore the potential mechanism of the relationship between genitals and the Gan meridian of Foot-Jueyin. The brain cerebral cortex is characterized by cortical interactions. Numerous studies show that different cerebral cortex function areas (especially the adjacent areas) are overlapping and interact with each other. Finally, we presume that there is a specific connection between the feet and the genitals. Physiologically in the cortical homunculus, the genital area lies adjacent or overlapped to the foot areas, the two areas may interact with each other. The functional reorganization between different areas of the cerebral cortex under pathological conditions may be the underlying mechanism of the relationship between the feet and the genitals.

CircFNDC3B induced TIMP3 to suppress angiogenesis to inhibit CRC cell proliferation, migration and invasion by negatively targeting miR‐937‐5p. Also, circFNDC3B exosomes could repress CRC angiogenesis by decreasing VEGFR expression., Circular RNA (circRNA) are single‐stranded RNA with covalently closed 3′ and 5′ ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back‐splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)‐937‐5p expression was high in CRC. MicroRNA‐937‐5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR‐937‐5p. CircFNDC3B and circFNDC3B‐enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR‐937‐5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B‐enriched exosomes or miR‐937‐5p knockdown. In conclusion, our work reports a tumor‐suppressing role for the circFNDC3B–miR‐97‐5p–TIMP3 pathway and suggests that circFNDC3B‐enriched exosomes can inhibit angiogenesis and CRC progression.

BACKGROUND: During pulmonary arterial hypertension (PAH)- targeted therapies for patients with idiopathic pulmonary arterial hypertension (IPAH), regular follow up to evaluate treatment efficacy is essential. Serum biomarkers can reflect various pathobiological processes in IPAH and have the advantages of being non-invasive, simple to carry out and low cost. The aim of our study was to evaluate whether serum biomarkers could serve as non-invasive markers to reflect haemodynamic changes after PAH-targeted therapies in patients with IPAH. METHODS: A total of 31 eligible patients aged 38.1 ± 12.1 years (25 were female) were included in this study. Changes in haemodynamic parameters and several serum biomarkers (cardiac markers, serum uric acid, high-sensitivity C-reactive protein, hepatic and kidney function markers) were compared before and after at least six months of PAH-targeted therapies. The time interval between the blood assays and right heart catheterisation was within five days. RESULTS: After at least six months of PAH-targeted therapies, the N-terminal pro-brain natriuretic peptide (NT-proBNP) level decreased from 579 (191–905) to 135 pg/ml (60–395) (p < 0.01), high-sensitivity cardiac troponin T (hsTnT) level decreased from 0.009 (0.006–0.012) to 0.007 ng/ml (0.005– 0.01) (p < 0.01), and serum uric acid level decreased from 381.5 ± 131.4 to 327.2 ± 110.0 μmol/l (p = 0.011). The change in NT-proBNP level was positively correlated with changes in pulmonary vascular resistance (r = 0.538, p < 0.01) and mean pulmonary arterial pressure (r = 0.440, p = 0.013). The change in hsTnT level was positively correlated with the change in mean right atrium pressure (r = 0.504, p < 0.01). The change in serum uric acid level was negatively correlated with that of cardiac index (r = –0.471, p < 0.01). CONCLUSION: NT-proBNP, hsTnT and serum uric acid levels can be used as non-invasive tools for evaluating the efficacy of PAH-targeted medications for IPAH patients. The role of these biomarkers in the follow up should be emphasised.

Background: It was designed to investigate whether umbilical cord matrix stem cells (CVMSC) could affect the functionality of trophoblasts to prevent preeclampsia. Methods: In this study, CVMSC-derived exosomes were isolated; its effect on trophoblasts was investigated based on the CCK8 assay, migration assay, and apoptosis detection. And the underlying mechanism of this effect was investigated using mRNA sequencing, western blot, co-immunoprecipitation, luciferase report assay, and ubiquitination assay. Findings: The results showed that CVMSC-derived exosomes promoted migration and proliferation of trophoblasts, and also reduced cell apoptosis. mRNA sequencing confirmed that after treatment of CVMSC-derived exosomes, TRIM72 expression was upregulated and P53 expression was downregulated, both significantly in trophoblasts. Subsequent study confirmed that TRM72 could directly interact with P53 and promoted P53 ubiquitination and proteasomal degradation, reducing apoptosis rate and elevating proliferation and migration in trophoblasts. Interpretation: Our study confirmed that CVMSC-derived exosomes promoted trophoblast migration and proliferation by upregulating TRIM72 expression, and subsequently advanced P53 ubiquitination and proteasomal degradation. Funding Statement: This study received no specific grant from public funding agencies, commercial, or not-for-profit sectors. Declaration of Interests: All authors declare there is no competing interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University.

ObjectivesAbnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown. The aim of this study was to explore the role of STX2 on trophoblast biology and unravel the molecular mechanisms that contribute to the development and progression of PE.Materials and MethodsWe first compared the expression of STX2 in placental tissues from women with PE and women with normal pregnancies. Then, we investigated the role of STX2 on trophoblast proliferation, migration and invasion in HTR-8/SVneo and primary human trophoblast cells by loss or gain of function experiments. In addition, co-immunoprecipitation, pulldown and immunofluorescence assays were performed to investigate the co-localization of STX2 with other proteins, and to help clarify the mechanisms underlying STX2-mediated functions on trophoblasts.ResultsWe demonstrated that STX2 expression was downregulated in placental tissues of women with PE compared with those from normal pregnancies. Loss and gain of function experiments further confirmed a role for STX2 in cell proliferation, migration and invasion in trophoblasts. By co-immunoprecipitation, pulldown and immunofluorescence co-localization assays, we revealed that STX2 selectively interacted with p85, a subunit of PI3K, and directly recruited p85 to the cytomembrane, thereby activating the AKT signaling pathway. We further demonstrated that the AKT activation was abolished by the use of a PI3K inhibitor (LY294002), which negatively affected STX2-mediated functions on trophoblasts.ConclusionAll together, our findings point to a crucial role for STX2 in PE progression. Our new insights also suggest that STX2 may be a potential diagnostic tool and a novel therapeutic target for treating PE.

Background There are discrepancies in the understanding of the structure of the capsuloligamentous complex of the first metatarsophalangeal joint (MTPJ); this study aims to investigate the differences with previous anatomical reports of high-resolution 3T magnetic resonance imaging (MRI) and histological analysis in illustrating the structure of the capsuloligamentous complex of the first MTPJ. Methods Nine fresh frozen cadaveric feet specimens (from two women and three men; aged 32 to 58 years) were used in this study. All specimens underwent MR examination with T1-weighted imaging and T2-weighted spectral attenuated inversion recovery in three planes. Subsequently, all cadaveric feet specimens were sliced into 2-mm-thick sections. The MRI features of the capsuloligamentous complex of the first MTPJ were analyzed in these specimens. Hematoxylin–eosin and Masson’s trichrome staining methods were used to explore the histologic features of the capsuloligamentous complex of the first MTPJ. Results Different from most previous studies, our results showed that the plantar plate could be divided into four portions including the central portion of the plantar plate, the intersesamoid, the sesamoid phalangeal and the metatarsosesamoid ligaments. The normal central portion of the plantar plate could be clearly visualized in the sagittal and coronal plane MR images. The intersesamoid ligament is a continuation of the central portion of the plantar plate on the sagittal plane on the gross specimen, the MR imaging, and the histological examination. On the coronal plane of the gross specimen and MR imaging, the sesamoid phalangeal ligaments and the central portion of the plantar plate can be seen as separate ligaments, but they appeared interwoven with the same continuous collagenous fibers on the histological analysis. Conclusion High-resolution 3T MRI allows accurate demonstration of the different anatomical details of the capsuloligamentous complex of the first MTPJ from previous anatomical reports. The histological analysis provides further understanding of the structures of the capsuloligamentous complex of the first MTPJ from previous studies.

The molecular characteristics and antimicrobial susceptibility of Staphylococcus aureus (S. aureus) in general pediatric wards and county-level hospitals were rarely reported in China. Staphylococcus aureus was isolated from children hospitalized with respiratory tract infection (RTI) in Zhongjiang and Youyang counties in 2015. All isolates were typed by multilocus sequence, staphylococcal protein A, accessory gene regulator (agr), and staphylococcal cassette chromosome mec [SCCmec, for methicillin-resistant S. aureus (MRSA) only]. Polymerase chain reaction was used to screen 21 super-antigen (SAg) genes and panton–valentine leukocidin (pvl). Antimicrobial susceptibility testing was performed by E test. A total of 2136 children were enrolled. Overall, 125 (5.9%) children carried S. aureus, among which MRSA accounted for 42.4%. ST59-SCCmec type IV-t437-agr group I (58.5%) was the most prevalent genotype in MRSA, and ST188-t189-agr group I (22.2%) was the top genotype in methicillin-sensitive S. aureus (MSSA). The pvl carriage rate in MRSA and MSSA was 15.1% and 9.7%, respectively (P = 0.4112). About 96.8% of S. aureus isolates were positive for at least one SAg gene. The most common SAg gene profile in the dominant ST59 clone was seb–sek–seq (42.8%). All S. aureus isolates were resistant to penicillin and erythromycin (minimum inhibitory concentration 90 was > 32 and 256 mg/L to penicillin and erythromycin, respectively), but usually susceptible to other tested non-β-lactam antimicrobials. Staphylococcus aureus and MRSA were detected with a high frequency in children with RTI in county-level hospitals of China. ST59-SCCmec type IV-t437-agr group I was the dominant MRSA clone. The S. aureus isolates exhibited high resistance to penicillin and erythromycin.

Background/Aims Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. Methods TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. Results Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. Conclusions Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.

Under investigation in this work is a nonlinear shallow water equation, Camassa–Holm equation, which is very important in fluid dynamics, nonlinear dynamics and physical application. The new equivariant moving frames method is implemented to obtain a finite generating set of differential invariants, recurrence relations, and syzygies among the generating differential invariants, for Lie symmetry group of Camassa–Holm equation. This method is very efficient, only using the infinitesimal determining equations and choice of cross-section normalization. The results are useful support for describing the invariant properties and trend of physical, oceanic or atmospheric motion.

Although several researches have reported potential gender differences in adaptations during microgravity, the musculoskeletal alterations of different genders are still under debate. Besides, there were few researches which involved recovery phase after reloading. In the present study, we investigated the musculoskeletal alterations of rats hindlimb via tail-suspension in both genders, and analyzed the serum sex hormone at the same time. Thirty-two Sprague Dawley rats were equally divided by gender into four groups randomly: control of male (CONM), tail-suspension of male (TSM), control of female (CONF) and tail-suspension of female (TSF). The experiment consisted two phases, which were 21 days of tail suspension phase and 21 days’ reloading phase, and parameters of bone, muscle and serum were tested at the end point of each phase. The results indicated that during tail suspension phase, male rats showed a greater and earlier bone loss and microstructure deterioration compared with females, but they could maintain muscle strength much better. In addition, during reloading phase, male rats showed a slower bone recovery and some parameters could not recover until the end, while loss in muscle mass and strength in both genders could recover to control level.

The transmission loss of photons during quantum key distribution (QKD) process leads to the linear key rate bound for practical QKD systems without quantum repeaters. Phase matching quantum key distribution (PM-QKD) protocol, an novel QKD protocol, can overcome the constraint with a measurement-device-independent structure, while it still requires the light source to be ideal. This assumption is not guaranteed in practice, leading to practical secure issues. In this paper, we propose a modified PM-QKD protocol with a light source monitoring, named PM-QKD-LSM protocol, which can guarantee the security of the system under the non-ideal source condition. The results show that our proposed protocol performs almost the same as the ideal PM-QKD protocol even considering the imperfect factors in practical systems. PM-QKD-LSM protocol has a better performance with source fluctuation, and it is robust in symmetric or asymmetric cases.

This research aims to develop a hand gesture recognition (HGR) by combining the OpenPose and Spatial Temporal Graph Convolution Network (ST-GCN) to classify the operator’s assembly motion. By defining the hand gestures with five types of therbligs, the network model was trained to recognize the human hand gesture. Although the accuracy of recognition is 78.3% with room for improvement based on preliminary experiment results, the structure of the proposed network establishes a foundation for further improvement in future work.

Background Psychological stress is an important factor for the development and recurrence of irritable bowel syndrome (IBS). The mechanisms underlying stress-induced visceral hypersensitivity (VH), a key pathophysiological component in IBS, are still incompletely understood. We aimed to test whether transient receptor potential melastatin 8 (TRPM8) participates in acute stress-induced VH. Methods Rats were subjected to 1-hour water avoidance stress (WAS). Visceral sensitivity was measured with visceromotor response to colorectal distension. Western blot and immunofluorescence were applied to evaluate the expression of GR and TRPM8 and activation of PKA, Akt, and PKC pathways. Results WAS-caused VH depended on glucocorticoid receptors (GRs) and TRPM8 channels. In a dorsal root ganglion (DRG)-derived cell line, corticosterone rapidly (within 30 minutes) induced membrane expression of TRPM8. This effect was inhibited by GR antagonism and was mimicked by membrane-impermeable corticosterone. PKA, PI3K/Akt, and PKC pathways, which lied downstream of GR and acted in parallel to promote membrane expression of TRPM8, contributed to WAS-induced VH. The non-receptor tyrosine kinase Pyk2, which may serve as a convergence point for PKA, PI3K/Akt, and PKC pathways, facilitated membrane insertion of TRPM8 via tyrosine-phosphorylating TRPM8 in L6-S2 DRGs and participated in WAS-induced VH. Conclusions Collectively, acute stress-induced VH could involve membrane-bound GR-dependent enhancement of TRPM8 function in nociceptive DRG neurons. Mechanistically, Pyk2 could act as a key mediator that coordinates multiple protein kinase signaling and triggers phosphorylation and membrane insertion of TRPM8.

From the perspective view of Chinese medicine, the Gan (Liver) meridian of Foot-Jueyin starts from the great toe, running upward along the medial side of the thigh to the perineal area, where it curves around the external genitalia and goes up to the lower abdomen. In clinical practice, acupoints in the feet of the Gan meridian of Foot-Jueyin are used to treat the genitourinary and external genitalia diseases. Studies have shown that reproductive system diseases have specific pathological reactions in the places (radial side of tibia and foot) where Gan meridian of Foot-Jueyin passes by. Why does this happen? In this article, we begin by briefly reviewing the evidences linking foot and genitalia. We then explore the potential mechanism of the relationship between genitals and the Gan meridian of Foot-Jueyin. The brain cerebral cortex is characterized by cortical interactions. Numerous studies show that different cerebral cortex function areas (especially the adjacent areas) are overlapping and interact with each other. Finally, we presume that there is a specific connection between the feet and the genitals. Physiologically in the cortical homunculus, the genital area lies adjacent or overlapped to the foot areas, the two areas may interact with each other. The functional reorganization between different areas of the cerebral cortex under pathological conditions may be the underlying mechanism of the relationship between the feet and the genitals.

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO−), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.

Background: Hand injuries are very common in sports, such as skiing and ball sports. One of the major reasons causing hand and finger deformity is due to ligament and tendon injury. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) can demonstrate the complex anatomy of the fingers and thumb, especially the tendons and ligaments, and provide the accurate diagnosis of clinically important fingers and thumbs deformity due to ligamentous and tendinous injuries during sport activities. Methods: Sixteen fresh un-embalmed cadaveric hands were harvested from eight cadavers. A total of 20 healthy volunteers' hands and 44 patients with fingers or thumb deformity due to sports-related injuries were included in this study. All subjects had MR examination with T1-weighted images and proton density-weighted imaging with fat suppression (PD FS) in axial, coronal, and sagittal plane, respectively. Subsequently, all 16 cadaveric hands were sliced into 2-mm thick slab with a band saw (six in coronal plane, six in sagittal plane, and four in axial plane). The correlation of anatomic sections and the MRI characteristics of tendons of fingers and the ulnar collateral ligament (UCL) at the metacarpal phalangeal joint (MCPJ) of thumb between 20 healthy volunteers and 44 patients (confirmed by surgery) were analyzed. Results: The normal ligaments and tendons in 16 cadaveric hands and 20 volunteers' hands showed uniform low-signal intensity on all the sequences of the MRI. Among 44 patients with tendinous and ligamentous injuries in the fingers or thumb, 12 cases with UCL injury at MCPJ of the thumb (Stener lesion = 8 and non-Stener lesion = 4), 6 cases with the central slip injury, 12 cases with terminal tendon injury, and 14 cases with flexor digitorum profundus injury. The ligaments and tendons disruption manifested as increased signal intensity and poor definition, discontinuity, and heterogeneous signal intensity of the involved ligaments and tendons. Conclusions: Sports injury-related fingers and thumb deformity are relatively common. MRI is an accurate method for evaluation of the anatomy and pathologic conditions of the fingers and thumb. It is a useful tool for accurate diagnosis of the sports-related ligaments and tendons injuries in hand.

One new alkaloid, named as acremolin C (1), was isolated from static culture of Antarctic fungus, Aspergillus sydowii SP-1, in an investigation of the antimicrobial constituents of this Antarctic microorganism, and its structure was determined by spectroscopic methods. Additionally, four known compounds, cyclo-(L-Trp-L-Phe) (2), 4-hydroxyphenylacetic acid (3), (7S)-(+)-hydroxysydonic acid (4) and (7S, 11S)-(+)-12-hydroxysydonic acid (5), were isolated and identified. Biological studies disclosed that compounds 2, 4 and 5 showed moderate inhibitions against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) as comparing to tigecycline, while compound 1 displayed weak inhibition activities against MRSA and MRSE.

Background: The injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar-sided wrist pain. The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging (MRI) could demonstrate the detailed complex anatomy of TFCC in Chinese. Methods: Fourteen Chinese cadaveric wrists (from four men and three women; age range at death from 30 to 60 years; mean age at 46 years) and forty healthy Chinese wrists (from 20 healthy volunteers, male/female: 10/10; age range from 21 to 53 years with a mean age of 32 years) in Beijing Jishuitan Hospital from March 2014 to March 2016 were included in this study. All cadavers and volunteers had magnetic resonance (MR) examination of the wrist with coronal T1-weighted and proton density-weighted imaging with fat suppression in three planes, respectively. MR arthrography (MRAr) was performed on one of the cadaveric wrists. Subsequently, all 14 cadaveric wrists were sliced into 2 mm thick slab with band saw (six in coronal plane, four in sagittal plane, and four in axial plane). The MRI features of normal TFCC were analyzed in these specimens and forty healthy wrists. Results: Triangular fibrocartilage, the ulnar collateral ligament, and the meniscal homolog could be best observed on images in coronal plane. The palmar and dorsal radioulnar ligaments were best evaluated in transverse plane. The ulnotriquetral and ulnolunate ligaments were best visualized in sagittal plane. The latter two structures and the volar and dorsal capsules were better demonstrated on MRAr. Conclusion: High-resolution 3T MRI is capable to show the detailed complex anatomy of the TFCC and can provide valuable information for the clinical diagnosis in Chinese.

// Pei-Hua Lu 1, 2, * , Min-Bin Chen 3, * , Yuan-Yuan Liu 3, * , Mian-Hua Wu 2 , Wen-Ting Li 2 , Mu-Xin Wei 4 , Chao-Ying Liu 1 , Shu-Kui Qin 5 1 Department of Medical Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China 2 Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor of Nanjing University of Chinese Medicine, Nanjing, China 3 Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China 4 Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China 5 People’s Liberation Army Cancer Center, 81st Hospital of People’s Liberation Army, Nanjing, China * Co-first authors Correspondence to: Shu-Kui Qin, email: drqinshukuinj@126.com Min-Bin Chen, email: cmb1981@163.com Keywords: hepatocellular carcinoma (HCC), icaritin, sphingosine kinase 1 (SphK1), ceramide Received: September 20, 2016 Accepted: November 08, 2016 Published: February 09, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm. We aim to explore the anti-HCC activity by a natural prenylflavonoid icaritin. Icaritin was cytotoxic and pro-apoptotic when added to established (HepG2, KYN-2 and Huh-7 lines) and primary human HCC cells. At the signaling level, icaritin inhibited sphingosine kinase 1 (SphK1) activity in HCC cells, which led to pro-apoptotic ceramide production and JNK1 activation. SphK1 inhibition or silence (by shRNA/microRNA) mimicked icaritin-mediated cytotoxicity, and almost nullified icaritin’s activity in HepG2 cells. Reversely, exogenous over-expression of SphK1 sensitized icaritin-induced HepG2 cell apoptosis. In vivo , oral administration of icaritin dramatically inhibited HepG2 xenograft growth in SCID mice. Further, SphK1 activity in icaritin-treated tumors was largely inhibited. In summary, icaritin exerts potent anti-HCC activity in vitro and in vivo . SphK1 inhibition could be the primary mechanism of its actions in HCC cells.

Despite the fast development of manned space flight, the mechanism and countermeasures of weightlessness osteoporosis in astronauts are still within research. It is accepted that unloading has been considered as primary factor, but the precise mechanism is still unclear. Since bone’s interstitial fluid flow (IFF) is believed to be significant to nutrient supply and waste metabolism of bone tissue, it may influence bone quality as well. We investigated IFF’s variation in different parts of body (included parietal bone, ulna, lumbar, tibia and tailbone) of rats using a tail-suspended (TS) system. Ten female Sprague-Dawley (SD) rats were divided into two groups: control (CON) and tail-suspension (TS) group. And after 21 days’ experiment, the rats were injected reactive red to observe lacuna’s condition under a confocal laser scanning microscope. The variations of IFF were analyzed by the number and area of lacuna. Volumetric bone mineral density (vBMD) and microarchitecture of bones were evaluated by micro-CT. The correlation coefficients between lacuna’s number/area and vBMD were also analyzed. According to our experimental results, a 21 days’ tail-suspension could cause a decrease of IFF in lumbar, tibia and tailbone and an increase of IFF in ulna. But in parietal bone, it showed no significant change. The vBMD and microarchitecture parameters also decreased in lumbar and tibia and increased in ulna. But in parietal bone and tailbone, it showed no significant change. And correlation analysis showed significant correlation between vBMD and lacuna’s number in lumbar, tibia and ulna. Therefore, IFF decrease may be partly contribute to bone loss in tail-suspended rats, and it should be further investigated.

Background Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity. Methods HE rats were induced by the administration of thioacetamide (TAA, 300 mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100 mg/kg/day in vivo or added at 50 or 100 μM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na + K + -ATPase were measured to indicate the dysfunction of glutamate signaling. Results Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na + K + -ATPase activity. In contrast, ART, especially at 100 μM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro. Conclusion This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions.