Hesperidin promotes gastric motility in rats with functional dyspepsia by regulating Drp1-mediated ICC mitophagy.

Hesperidin is one of the main active ingredients of Citrus aurantium L. (Rutaceae) and tangerine peel, which have anti-inflammatory and antioxidant effects. In previous study, we found that gastric motility disorder in functional dyspepsia (FD) rats accompanied by excessive autophagy/mitochondrial swelling and even vacuolization in the interstitial cells of cajal (ICC), but the exact mechanism has not yet been investigated. Therefore, we used different doses of hesperidin (50 mg/kg, 100 mg/kg, and 200 mg/kg) to intervene in FD rats, and found that medium doses of hesperidin (100 mg/kg) significantly increased gastric motility in FD rats. Subsequently, FD rats were randomly divided into control group, model group, mdivi-1 group, mdivi-1+hesperidin group and hesperidin group, and mitochondrial division inhibitor (mdivi-1) was injected intraperitoneally to further investigate whether hesperidin could regulate dynamin-related protein 1 (Drp1)-mediated mitophagy in ICC to improve mitochondrial damage. The results showed that compared with the model group, the serum malondialdehyde (MDA) level decreased and the superoxide dismutase (SOD) level increased in the mdivi-1 and hesperidin groups (p < 0.001). Transmission electron microscopy (TEM) observed that the mitochondrial nuclear membrane was intact in gastric tissues with a clear internal cristae pattern, and autophagy lysosomes were rare. The co-localization expression of microtubule associated protein 1 light chain 3 (LC3) and voltage dependent anion channel 1 (VDAC1), Drp1 and translocase of the outer mitochondrial membrane 20 (Tom20) was significantly decreased (p < 0.001), the protein expression of mitochondrial Drp1, Beclin1 and LC3 were significantly decreased (p < 0.001), the protein expression of mitochondrial P62 and ckit in gastric tissue were significantly increased (p < 0.05, p < 0.001). The above situation was improved more significantly by the synergistic intervention of mdivi-1 and hesperidin. Therefore, hesperidin can improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp1-mediated ICC mitophagy.

A multimodal transformer to fuse images and metadata for skin disease classification.

Skin disease cases are rising in prevalence, and the diagnosis of skin diseases is always a challenging task in the clinic. Utilizing deep learning to diagnose skin diseases could help to meet these challenges. In this study, a novel neural network is proposed for the classification of skin diseases. Since the datasets for the research consist of skin disease images and clinical metadata, we propose a novel multimodal Transformer, which consists of two encoders for both images and metadata and one decoder to fuse the multimodal information. In the proposed network, a suitable Vision Transformer (ViT) model is utilized as the backbone to extract image deep features. As for metadata, they are regarded as labels and a new Soft Label Encoder (SLE) is designed to embed them. Furthermore, in the decoder part, a novel Mutual Attention (MA) block is proposed to better fuse image features and metadata features. To evaluate the model's effectiveness, extensive experiments have been conducted on the private skin disease dataset and the benchmark dataset ISIC 2018. Compared with state-of-the-art methods, the proposed model shows better performance and represents an advancement in skin disease diagnosis.

Mechanism of Elian granules in the treatment of precancerous lesions of gastric cancer in rats through the MAPK signalling pathway based on network pharmacology.

CONTEXT: Elian Granules have been applied in the treatment of precancerous lesions of gastric cancer (PLGC) and achieved good results. However, its exact mechanism remains unclear. OBJECTIVES: To explore the mechanism of Elian granules in treating PLGC through the mitogen-activated protein kinase (MAPK) signalling pathway based on network pharmacology. MATERIALS AND METHODS: Through network pharmacological methods, the targets of the active component of Elian granules against PLGC were obtained. Subsequently, Specific Pathogen Free (SPF) male Sprague Dawley (SD) rats were randomly divided into normal, model, and Elian granule groups. The N-methyl-N'-nitro-N-nitrosoguanidine comprehensive method was used to establish the PLGC rat model. The model and Elian granule groups were given normal saline and Elian granule aqueous solution (3.24 g/kg/d) intragastric administration, respectively, for 24 weeks. The pathological changes in gastric tissues were observed by hematoxylin-eosin staining. The protein expression of p-JNK and p-p38 was verified by western blotting. RESULTS: 394 and 4,395 targets were identified in Elian granules and PLGC, respectively. The 190 common targets were mainly enriched in MAPK signalling pathways. The gastric mucosal epithelium was still intact, the glands were arranged regularly, and no goblet cells or apparent inflammatory cell infiltration were observed in the Elian granule group. The expression of p-JNK and p-p38 protein of the Elian granule group (0.83 ± 0.08; 1.18 ± 0.40) was significantly higher than the model group (0.27 ± 0.14; 0.63 ± 0.14) (p < 0.01; p < 0.05). DISCUSSION AND CONCLUSIONS: Elian granules may play a critical role in the treatment of rat PLGC by up-regulating the expression of p-JNK and p-p38 proteins in the MAPK signalling pathway, thus providing a scientific basis for clinical application.

3D hierarchical rose-like Ni2P@rGO assembled from interconnected nanoflakes as anode for lithium ion batteries.

In recent years, anode materials of transition metal phosphates (TMPs) for lithium ion batteries (LIBs) have drawn a vast amount of attention from researchers, due to their high theoretical capacity and comparatively low intercalation potentials vs. Li/Li+. However, in practice, their application remains constrained by poor electrical conductivity, and dramatic volume expansion and severe agglomeration during the lithium process, which leads to questionable kinetic issues and a prompt decline in capacity during cycling. Herein, through an elaborate design, we developed a novel three-dimensional (3D) hierarchical rose-like architecture self-assembled from two-dimensional (2D) Ni2P nanoflakes immobilized on reduced graphene oxide (rGO) via a combination of a hydrothermal process and phosphating treatment. Such a design provides unique superiority for Ni2P-based anode materials for LIBs. Paraphrasing, the 3D hierarchical structure of Ni2P distributes the stress on the anode material while cycling and provides more lithium storage space. The rGO not only enhances the conductivity of materials, but also serves as a flexible framework which immobilizes Ni2P so that it prevents it from pulverization. Therefore, the synergistic effect between them guarantees the integrity of the material structure after a long-term cycling Li+ intercalation and deintercalation process. When it acted as anode material for LIBs, the as-obtained 3D rose-like Ni2P@rGO electrode exhibited a noticeable electrochemical performance, which delivers a discharge capacity of 330.5 mA h g-1 at a current density of 100 mA g-1 after 100 cycles and retains 200.5 mA h g-1 at 1000 mA g-1.

Skin Allografting Activates Anti-tumor Immunity and Suppresses Growth of Colon Cancer in Mice.

INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b) donors to BALB/c (H-2d) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation. RESULTS: The results showed that as compared to non-transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11c+MHC-classII+CD86+ DCs, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, as well as decreased percentage of CD4+CD25+Foxp3+ T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were significantly higher within the tumor in skin transplant groups than that in non-transplant group. CONCLUSIONS: Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment.

[Non-contacting photoacoustic tomography in biological samples].

In photoacoustic imaging the ultrasonic signals are usually detected by contacting transducers. For some applications, contact with the tissue should be avoided, e.g. in those of brain functional imaging. As alternatives to contacting transducers interferometric techniques can be used to acquire photoacoustic signals remotely. Here, a system for non-contact photoacoustic tomography imaging (NCPAT) has been established. This approach enables NCPAT not to exceed laser exposure safety limits. The stimulated source of NCPAT utilized a laser with center wavelength of 532 nm and output intensity of 17.5 mJ/cm 2, and a laser heterodyne interferometry was used to receive the photoacoustic signals. The NCPAT was used to implement on a rotational imaging geometry for photoacoustic tomography with a real-tissue phantom. The photoacoustic imaging was obtained by applying a reconstruction algorithm to the data acquired for NCPAT. Experiments results showed that the NCPAT system with detection 15 dB bandwidth of 2.25 MHz could resolve spherical optical inclusions with dimension of 500 µm and multi-layered structure with optical contrast in strongly scattering medium. The method could expand the scope of photoacoustic and ultrasonic technology to in-vivo biomedical applications where contact is impractical.

The current role and therapeutic targets of vitamin D in gastrointestinal inflammation and cancer.

Vitamin D, beyond its classical roles in the regulation of calcium and phosphorus homeostasis and bone metabolism, has been implicated in multiple pathological processes, including progression from inflammation to cancer development and also involvement in autoimmune diseases as well as cardiovascular disorders. In this review, we shall discuss the different roles of vitamin D and its therapeutic targets in different gastrointestinal diseases, focusing on colorectal cancer (CRC) and inflammatory bowel disease (IBD). To this end, vitamin D deficiency has been identified as a risk factor of CRC. On the other hand the active metabolite of vitamin D, 1, 25- dihydroxyvitamin D3 (1, 25(OH)2D3) has multiple anti-cancerous benefits including inhibition of proliferation, induction of apoptosis, promotion of differentiation and suppression of angiogenesis in tumors. In IBD, vitamin D is involved in the pathogenic process through the normalization of immune responses in the colon. With these experimental findings, well-designed and large-scale clinical trials are warranted to further define the therapeutic action of vitamin D in the prevention and/or treatment of IBD and further on CRC in humans.

Etiology and morphology of carditis: experiences from a single center in China.

OBJECTIVE: To investigate the type of cardiac mucosa and its relationship with age and gender of the participants and to determine the coincidence of endoscopic and pathological diagnosis of carditis as well as its etiology. METHODS: The data of 70 patients with carditis (the carditis group) and 30 individuals with endoscopically normal-appearing cardiac mucosa (the control group), including their baseline characteristics and histopathological findings, were reviewed. Their Helicobacter pylori (H. pylori) status was also reviewed. RESULTS: Three main types of cardiac mucosa: mucous, oxyntic and mixed types, were found in 45.0%, 40.0% and 15.0% of all the participants, respectively. The distribution of these types was related to the age of the participants but not to their gender. Moderate to severe mucosal inflammation was detected in 60.0% (18/30) of the control group. The etiologies of cardiac inflammation were H. pylori infection and gastroesophageal reflux disease (GERD). For antral H. pylori-negative participants, cardiac mucosal inflammation was correlated with esophageal mucosal inflammation (P < 0.05), while for those with antral H. pylori infection it was associated with antral mucosal inflammation (P < 0.01). CONCLUSIONS: The distribution of different cardiac mucosal types was related to the participants' age. Normal-appearing cardiac mucosa under endoscopy might present with histopathologically moderate to severe cardiac inflammation. The etiologies of cardiac inflammation were H. pylori infection and GERD. Different causes of carditis may result in the different histological performance of the cardia.

[A randomized single-blind controlled clinical trial of tacrolimus mouth rinse on erosive oral lichen planus].

PURPOSE: To evaluate the efficacy and safety of tacrolimus mouth rinse on the treatment of erosive and ulcerative oral lichen planus (OLP). METHODS: A randomized single-blind open trial of tacrolimus mouth rinse with dexamethasone as control was designed. The VAS and REU scoring system was utilized to compare the signs and symptoms. The scores and therapeutic effects were analyzed with SPSS 17.0 software package. RESULTS: There was no significant difference in effective rate between the treatment group and control group (X(2)=0.295,0.413, P>0.01) at 4-week and 12-week after treatment. There was significant difference in REU scores between the 2 groups (P<0.01) 4 weeks after treatment. CONCLUSIONS: Tacrolimus mouth rinse effects quickly and is worthy of application in the treatment of erosive and ulcerative OLP.

Comparison of intestinal metaplasia in gastric cardia and Barrett's esophagus.

OBJECTIVE: To evaluate and compare the pathological features and immunostaining pattern (cytokeratin 7 (CK-7), mucin core peptide 1 (Muc-1)) in Barrett's esophagus (BE) and cardiac intestinal metaplasia (CIM). METHODS: According to endoscopic diagnosis, patients with gastric cardiac inflammation and BE were selected from March 2008 to February 2009 in Renji Hospital, Shanghai Jiaotong University School of Medicine. Those patients who had histological findings of intestinal metaplasia (82 cases of CIM and 64 special type BE) were enrolled in our study. Hematoxylin-eosin, periodic acid-Schiff and Alcian blue staining and an immunohistochemical examination (CK-7, Muc-1) were undertaken in all of them. RESULTS: Squamous mucosa overlying the columnar crypts with intestinal metaplasia, also called buried metaplasia, was often found in the BE group (56.2%), mainly as an incomplete type (85.9%). Inflammation in the gastric antrum was more severe in the CIM group (45.1% vs 26.6%), in contrast, esophagitis was more severe in the BE group (53.1% vs 35.4%). CK-7 was highly expressed in the BE group (84.4%) in contrast to the CIM group (37.8%). There was no difference in the expression of Muc-1 in these two kinds of intestinal metaplasia (14.1% vs 19.5%). CONCLUSIONS: Buried intestinal metaplasia, mainly as an incomplete type, is the major predominant type of BE. The degree of inflammation in the gastric antrum and esophagus can differentiate BE from CIM to some extent. CK-7 immunohistochemical staining can help identify BE and CIM but Muc-1 cannot.

[Reduced expression of miR-218 and its significance in gastric cancer].

OBJECTIVE: To investigate the expression and function of miR-218 in gastric cancer. METHODS: miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion. RESULTS: Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control. CONCLUSION: miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.

Expression of polycomb protein EZH2 in multi-stage tissues of gastric carcinogenesis.

OBJECTIVE: To study the role and significance of the polycomb group (PcG) protein EZH2 (enhancer of zeste homolog 2) in the multi-step process of intestinal-type gastric carcinogenesis. METHODS: Gastric specimens were obtained from 142 patients with gastric disease, including 34 with chronic non-atrophic gastritis (NCAG), 33 chronic atrophic gastritis (CAG) with intestinal metaplasia (IM), 40 CAG with dysplasia (DYS) and 35 with intestinal-type gastric carcinomas (GC), and 32 Helicobacter pylori-negative controls. The EZH2 protein was stained by the immunohistochemical method and was expressed as the intensity and percentage of the total number of epithelial cells. The chronic gastritis and the grading of dysplasia were classified according to Chinese National Consensus on chronic gastritis and the Padova international classification. RESULTS: The EZH2 protein levels in the specimens of normal gastric tissue, NCAG, CAG with IM, DYS and intestinal-type GC were gradually increased (P < 0.05), but statistical significance was not found between the groups of DYS and GC. CONCLUSION: PcG protein EZH2 plays an important role in the multi-step process of intestinal-type gastric carcinogenesis.

[Content of somatostatin and cholecystokinin-8 in hypothalamus and colons in a rat model of spleen-deficiency syndrome].

OBJECTIVE: To investigate the changes of neuropeptides content in a rat model of spleen-deficiency syndrome. METHODS: Rats were randomly divided into three groups: normal group, untreated group and treatment group. There were ten rats in each group. Spleen-deficiency syndrome was induced by intragastrically administration of rhubarb concentrate in rats of the untreated and treatment group. The rats in the treatment group were intragastrically administered with Sijunzi decoction, a traditional Chinese compound herbal medicine for strengthening spleen and supporting qi. Normal saline was intragastrically administered to the rats in the normal and untreated groups. The somatostatin (SS) and cholecystokinin-8 (CCK-8) content in hypothalamus and colons was detected by the method of radioimmunoassay and the D-xylose content in urine was also detected. RESULTS: The CCK-8 content in hypothalamus of the untreated group was higher than that of the normal group (P<0.05). SS and CCK-8 content in colons of the untreated group was higher than that of the normal group (P<0.05). The CCK-8 content in colons of the untreated group was lower than that of the treatment group (P<0.05). The excretion rate of D-xylose in the untreated group was lower than that of the normal group (P<0.05). CONCLUSION: The disorder of neuroendocrine regulation in rats with spleen-deficiency syndrome may be chiefly responsible for "spleen-deficency and dysfunction of spleen" in traditional Chinese medicine.

[Clinical study of chronic renal failure with syndrome of dampness-heat due to spleen deficiency treated with Jianpi Qinghua Recipe].

OBJECTIVE: To evaluate the effects of Jianpi Qinghua Recipe (JPQHR) on chronic renal failure with syndrome of dampness-heat due to spleen deficiency and its mechanism. METHODS: One hundred and six patients were randomly divided into two groups: control group (53 patients treated with routine therapy) and JPQHR-treated group (53 patients treated with routine therapy and JPQHR). RESULTS: Routine therapy combined with JPQHR could improve symptoms. The serum creatinine, blood urea nitrogen, triglyceride and low density lipoprotein decreased significantly in the JPQHR-treated group as compared with those in the control group (P<0.05), while the number of erythrocyte rosette-forming cells increased significantly in the JPQHR-treated group as compared with those in the control group (P<0.05). CONCLUSION: Routine therapy combined with JPQHR can significantly decrease blood lipid level and strengthen cellular immune system, so it can lower the urine protein in the early and middle stages of chronic renal failure and improve renal function.

[Observation on intestinal flora in patients of irritable bowel syndrome after treatment of Chinese integrative medicine].

OBJECTIVE: To observe the clinical efficacy of the combination of traditional Chinese medicine and western medicine in treating irritable bowel syndrome (IBS) and the result of intestinal flora regulation. METHODS: Sixty IBS patients, 36 males and 24 females, were divided into two groups, with 30 patients in each group. Herbal formula of TongxieYaofang and clostridium butyricum (Cb) were used in the first group for four weeks, while only Cb was used for four weeks in the second group. We observed the changes of coliform group, enterococcus, lactobacillus, bifidobacterium after treatment. RESULTS: The effective rate of the Tongxie Yaofang and Cb treated group was significantly higher than that of the Cb treated group (P < 0.05). The numbers of bifidobacterium and lactobacillus increased, while the numbers of coliform group and enterococcus decreased after the treatment, and the changes of intestinal flora in the integrative medicine treated group were significantly greater than those in the Cb treated group. CONCLUSION: After treatment with the combination of traditional Chinese medicine and western medicine, the intestinal flora can be regulated to equilibrium state.

[Randomized controlled clinical study on effect of Chinese compound changjitai in treating diarrheic irritable bowel syndrome].

OBJECTIVE: To verify the clinical efficacy and safety of the proven Chinese Compound Changjitai (CJT), in treating the diarrheic irritable bowel syndrome (DIBS). METHODS: Randomized controlled open clinical trial design was adopted, 45 patients were randomly divided into two groups, CJT and pinaverium bromide (PVB) were given as treated and control agent respectively. IBS scoring system (BSS), defecation state questionnaire (DSQ) were used to record the changes of the patients' main symptoms before and after treatment. RESULTS: The total effective rate of CJT group was 83.3%, while that of PVB was 73.3%. CJT was superior in efficacy to that of PVB in improving stool quality, reducing defecation episodes of diarrheic patients, alleviating tenesmus symptoms, decreasing bellyache days and ameliorating abdominal distention. Any drug-related adverse reaction was not seen. CONCLUSION: The efficacy of CJT in treating DIBS is definite and without any toxic and adverse effects.

A comparison between Zhishi Xiaopiwan and cisapride in treatment of functional dyspepsia.

AIM:To compare the therapeutic effect of the herbal medicine Zhishi Xiaopi with that of Cisapride in the treatment of functional dyspepsia (FD).METHODS:Fifty-one FD patients were randomized into Herbal group (n =27) and Cisapride group (n =24). Two two groups were given a four-week treatment of Zhishi Xiaopi 100ml, tid, a.c. and Cisapride 5mg, tid, a.c. respectively. Patients' symptoms were assessed and 39 patients'(22 of Herbal group and 17 of Cisapride group) gastric liquid emptying times were measured with ultrasonography before and after the treatment.RESULTS:The therapeutic effective rates of Herbal group and Cisapride group were 81.49% and 87.50% (P> 0.05). The half gastric emptying time (GET50) and gastric emptying time (GET) of healthy controls and FD patients were 36.12min ± 10.22min vs 52.95min ± 13.49min and 87.07min ± 21.11min vs 120.74min ± 23.08min (P < 0.001).The GET(50) and GET of Herbal group before and after the treatment were 51.63min ± 13.15min vs 45.62min ± 10.82min and 117.34min ± 23.29min vs 103.26min ± 22.19min (P < 0.01). The results of Cisapride group were 54.66min ± 14.14min vs 40.95min ± 11.29min and 125.12min ± 24.47minvs 95.49min ± 22.31min (P < 0.01). The differences in values (median) of GET(50) and GET for Herbal group and Cisapride group before and after treatment were 5.75min vs 17.18min and 13.22min vs 33.54min (P < 0.05). CONCLUSION:Delayed gastric emptying is one of the pathogenesis of FD. Both Zhishi Xiaopi pills and Cisapride can effectively alleviate the symptoms of FD and accelerate gastric liquid emptying.The effect of Zhishi Xiaopiwan on enhancing gastric motility is comparable with but less than that of Cisapride.