Limonitum Ameliorates Castor Oil-Induced Diarrhoea in Mice by Modulating Gut Microbiota.

Diarrhoea is a common clinical condition; its pathogenesis is strongly associated with gut microbiota dysbiosis. Limonitum is a well-known traditional Chinese medicine that exerts appreciable benefits regarding the amelioration of diarrhoea. However, the mechanism through which Limonitum ameliorates diarrhoea remains unclear. Here, the efficacy and underlying mechanism of Limonitum decoction (LD) regarding diarrhoea were explored from the aspect of gut microbiota. Castor oil (CO) was used to induce diarrhoea in mice, which were then used to evaluate the effects of LD regarding the timing of the first defecation, diarrhoea stool rate, degree of diarrhoea, diarrhoea score, intestinal propulsive rate, and weight of intestinal contents. The concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric and valeric acids, were analysed by gas chromatography-mass spectrometry (GC-MS). The 16S rRNA high-throughput sequencing technology was applied to evaluate changes in the gut microbiota under exposure to LD. LD was found to effectively ameliorate the symptoms of diarrhoea, and the diversity and relative abundance of gut microbiota were restored to normal levels following LD treatment. Additionally, LD significantly restored the observed reductions in SCFAs. These results provide strong evidence that LD can sufficiently ameliorate diarrhoea in mice by regulating their gut microbiota. The findings presented here highlight that Limonitum may constitute a prospective remedy for diarrhoea.

[COVID-19 epidemic and its characteristics in Heilongjiang province].

Objective: To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province. Methods: The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software's of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases. Results: On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant (P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions: The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

Ionization-induced adiabatic soliton compression in gas-filled hollow-core photonic crystal fibers.

We investigate in the experiments the ionization-induced adiabatic soliton compression process in a short length of He-filled single-ring photonic crystal fiber. We observe that the plasma-driven blueshifting solitons show little residual light near the pump wavelength in a certain pulse energy region, leading to a high-efficiency frequency upconversion process. In contrast, at high pulse energy levels, we observe that the quality of the frequency upshifting process is impaired due to the existence of a dynamical loss channel induced by the coupling of the soliton to linear modes near the pump wavelength. In addition, through adjusting the input pulse energy, the central wavelength of blueshifting solitons can be continuously tuned over 300 nm. These experimental results, confirmed by numerical simulations, not only offer a deep insight into ionization-induced soliton-plasma dynamics in gas-filled hollow-core photonic crystal fibers, but also develop highly tunable ultrafast light sources at visible wavelengths, which may have many applications in ultrafast spectroscopy.

Effect of gene polymorphims on the warfarin treatment at initial stage.

The adverse reactions of warfarin that were found mainly occurred in the first month. This study was carried out to observe the effect of gene polymorphisms on the warfarin therapy at the initial stage. Four-hundred and sixty Chinese patients began warfarin treatment with daily 2.5 mg after heart valve replacement operations were enrolled. The daily international normalized ratio (INR) for anticoagulation were recorded till the seventh day. Blood samples were collected and used to detect genotypes for VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650. INR and their changes were compared among genotypes. INR was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 polymorphisms from the third, fourth and sixth day on, respectively. VKORC1 rs7294 and CYP4F2 rs2108622 carriers responded lower than the wild genotype, whereas CYP2C9 rs1057910 and ORM1 rs17650 carriers responded higher, respectively. Fifty percent of AA/*1*3/CC/*S*S patients and 16% of AA/*1*1/CC/*S*S patients were over anticoagulation treated with INR >4.0 at the third day. Ninety percent of VKORC1 rs7294 carrier patients have INR <1.63, a mark of the 25% of lower responders of the wild genotype. Our study provided another kind of evidence that VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 affected the action of warfarin in different styles. Patients with AA/*1*1/CC/*S*S, AA/*1*3/CC/*S*S should use a less initial dosage to avoid over anticoagulation, and patients with VKORC1 rs7294 should use larger initial dose to proof an effective therapy.

Improvements in neuroelectrophysiological and rear limb functions in rats with spinal cord injury after Schwann cell transplantation in combination with a C5a receptor antagonist.

We measured the effect of Schwann cell transplantation and complement factor 5a (C5a) receptor antagonist on nerve function recovery in rats with spinal cord injury. Experimental spinal cord injury was induced in eighty Wistar rats and these were randomly divided into four treatment groups: culture medium and saline injection (control group), Schwann cell injection (cell transplantation group), C5a receptor antagonist injection (C5a receptor antagonist group), and both Schwann cell and C5a receptor antagonist injections (combination group). Rear limb functional recovery was assessed 1, 2, 4, 6, and 8 weeks after the spinal cord injury with the tilt table test and the Basso, Beattie, Bresnahan scale. Sex-determining region Y (SRY) gene expression was measured at week 4 and horseradish peroxidase (HRP) labeling was used at week 8 to further assess the recovery of neuroelectrophysiological functions. The rear limb functional assessment showed that the combination group had better outcomes than the cell transplantation and C5a receptor antagonist groups. All treatment groups had better outcomes than control. Only the cell transplantation and combination groups showed SRY expression. The number of HRP-positive nerve fibers in the different groups ranked as follows: combination group > cell transplantation and C5a receptor antagonist > control. The refractory period and amplitude of the induced potential in the combination group were significantly greater than in the other three groups. These results suggest that the combination of Schwann cell transplantation and the C5a receptor antagonist enhances the regeneration of injured synapses and improves limb function and electrophysiology.

Chemical correlation between Gegen Qinlian dispensing granule and its four raw herbs by LC fingerprint.

Gegen Qinlian dispensing granule, a favorite composite formula, is a combination of Radix Puerariae Lobatae, Radix Scutellariae, Rhizoma Coptidis and Radix et Rhizoma Glycyrrhizae Praeparata cum Melle. To develop a method to overall evaluate correlation between the formula and its four raw herbs, LC fingerprints of the formula and its raw herbs were developed and LC-DAD-MS was employed to identify the components in the formula fingerprint. According to the characteristic fragmentation behavior of known flavonoids, alkaloids and saponins isolated from the four raw herbs as well as retention time, UV and MS data of detected compounds, a total of 23 constituents in the formula fingerprint were structurally characterized. Chemical correlation between the formula and the four crude herbs was evaluated qualitatively and quantitatively by the developed LC fingerprints. The results showed that 8 components in the formula fingerprint were addressed to Radix Puerariae Lobatae, 11 to Radix Scutellariae, 7 to Rhizoma Coptidis, 3 to Radix et Rhizoma Glycyrrhizae Praeparata cum Melle, and that the relative area ratios of the common peaks in the formula vary slightly in comparison with corresponding ratios in its crude herbs, demonstrating the chemical constituents in the formula have patterns similar to those in its crude herbs.

Prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis according to baseline MRI findings: comparison of revised McDonald criteria and Swanton modified criteria.

BACKGROUND: The International Panel on the Diagnosis of Multiple Sclerosis first incorporated abnormalities demonstrated by brain and spinal cord MRI into the diagnostic criteria (McDonald criteria) for multiple sclerosis (MS), which were later revised in 2005. In 2006, Swanton and colleagues modified the MRI criteria to simplify and speed the diagnosis. OBJECTIVE: The purpose of this study was to compare the ability of two sets of criteria (the revised McDonald MRI criteria and Swanton's modified criteria) to predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) from baseline MRI findings. METHODS: Sixty-four patients presenting with CIS suggestive of multiple sclerosis were recruited from 2001 to 2006 and followed up for at least 2 years. Their baseline brain and spinal cord MRI studies were retrospectively evaluated. The patients who developed CDMS during follow-up were treated as positive cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the two MRI dissemination-in-space criteria were calculated. RESULTS: Thirty patients (46.9%) converted to CDMS. The sensitivity specificity, PPV, NPV and accuracy (%) of the revised McDonald criteria were 53, 100, 100, 71 and 78, respectively, while those for Swanton's modified criteria were 60, 100, 100, 74 and 81. CONCLUSIONS: In conclusion, Swanton's modified criteria are more sensitive and accurate (but not significantly so). However, Swanton's criteria are simpler to use and have equally high specificity and PPV.

Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29.

Tight junctions in the cochlear duct are thought to compartmentalize endolymph and provide structural support for the auditory neuroepithelium. The claudin family of genes is known to express protein components of tight junctions in other tissues. The essential function of one of these claudins in the inner ear was established by identifying mutations in CLDN14 that cause nonsyndromic recessive deafness DFNB29 in two large consanguineous Pakistani families. In situ hybridization and immunofluorescence studies demonstrated mouse claudin-14 expression in the sensory epithelium of the organ of Corti.

Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome.

Following the positional cloning of PDS, the gene mutated in the deafness/goitre disorder Pendred syndrome (PS), numerous studies have focused on defining the role of PDS in deafness and PS as well as elucidating the function of the PDS-encoded protein (pendrin). To facilitate these efforts and to provide a system for more detailed study of the inner-ear defects that occur in the absence of pendrin, we have generated a Pds-knockout mouse. Pds(-/-) mice are completely deaf and also display signs of vestibular dysfunction. The inner ears of these mice appear to develop normally until embryonic day 15, after which time severe endolymphatic dilatation occurs, reminiscent of that seen radiologically in deaf individuals with PDS mutations. Additionally, in the second postnatal week, severe degeneration of sensory cells and malformation of otoconia and otoconial membranes occur, as revealed by scanning electron and fluorescence confocal microscopy. The ultrastructural defects seen in the Pds(-/-) mice provide important clues about the mechanisms responsible for the inner-ear pathology associated with PDS mutations.

External beam radiation therapy for inoperable hepatocellular carcinoma with portal vein thrombosis.

Portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has a poor impact on prognosis. Many of these tumors may cause intrahepatic and extrahepatic metastases. From January 1991 to December 1996, 41 unresectable HCC patients with PVT underwent transcatheter arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) to the portion of PVT. The irradiated field, with a mean equivalent field size of 6.6 x 7.1 cm2, was localized and simulated by abdominal sonography, angiography and computed tomography. Radiation dose ranged from 36 to 66 Gy (mean dose: 51.4 Gy), in a daily fraction of 1.8 to 2 Gy. The response of EBRT was evaluated by abdominal sonography within 3 months of completion of EBRT. The response rates of the PVT after treatment were 39% for complete response (CR), 41% for partial response (PR), and 19% for no response (NR), respectively. The median overall survival time from start of radiotherapy was 10 months for all patients, 17 months for CR patients, 8 months for PR patients and 4 months for NR patients. By multivariate analysis, response of PVT resulted in a significant improvement in survival. (P = 0.001) There was no occurrence of severe complication of radiation-induced liver disease. The results obtained with combined treatment modality of EBRT and TACE in the treatment of HCC patients with PVT are encouraging.

Patterning of the mammalian cochlea.

The mammalian cochlea is sophisticated in its function and highly organized in its structure. Although the anatomy of this sense organ has been well documented, the molecular mechanisms underlying its development have remained elusive. Information generated from mutant and knockout mice in recent years has increased our understanding of cochlear development and physiology. This article discusses factors important for the development of the inner ear and summarizes cochlear phenotypes of mutant and knockout mice, particularly Otx and Otx2. We also present data on gross development of the mouse cochlea.

Sensory organ generation in the chicken inner ear: contributions of bone morphogenetic protein 4, serrate1, and lunatic fringe.

The chicken inner ear is a remarkably complex structure consisting of eight morphologically distinct sensory organs. Unraveling how these sensory organs are specified during development is key to understanding how such a complex structure is generated. Previously, we have shown that each sensory organ in the chicken inner ear arises independently in the rudimentary otocyst based on Bone morphogenetic protein 4 (Bmp4) expression. Here, we compare the expression of Bmp4 with two other putative sensory organ markers, Lunatic Fringe (L-fng) and chicken Serrate1 (Ser1), both of which are components of the Notch signaling pathway. L-fng and Ser1 expression domains were asymmetrically distributed in the otic cup. At this early stage, expression of L-fng is similar to Delta1 (Dl1), in an anteroventral domain apparently corresponding to the neurogenic region, while Ser1 is expressed at both the anterior and posterior poles. By the otocyst stage, the expression of both L-fng and Ser1 largely coincided in the medial region. All presumptive sensory organs, as identified by Bmp4 expression, arose within the broad L-fng- and Ser1-positive domain, indicating the existence of a sensory-competent region in the rudimentary otocyst. In addition, there is a qualitative difference in the levels of expression between L-fng and Ser1 such that L-fng expression was stronger in the ventral anterior, whereas Ser1 was stronger in the dorsal posterior region of this broad domain. This early difference in expression may presage the differences among sensory organs as they arise from this sensory competent zone.

Ectopic noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear.

Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development.

Characterization and expression of sema4g, a novel member of the semaphorin gene family.

Semaphorins constitute a large and growing gene family, several members of which are axon guidance molecules. We report the characterization of sema4g, a novel class IV member of the semaphorin gene family, located on mouse chromosome 19. sema4g is expressed early in development in the brain, spinal cord, and several sensory organs as well as specific populations of projection neurons, compatible with the well-established function of semaphorins as axon guidance molecules.

Expression pattern of the mouse ortholog of the Pendred's syndrome gene (Pds) suggests a key role for pendrin in the inner ear.

Pendred's syndrome is an autosomal-recessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred's syndrome (PDS), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin). Toward that end, we isolated the corresponding mouse ortholog (Pds) and performed RNA in situ hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of Pds in the developing auditory and vestibular systems. Pds expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea. This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic fluid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter. These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred's syndrome.

Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.

The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.

Imaging features of simultaneous occurrence of renal and pancreatic foreign body granuloma due to chronically retained gauze: a case report.

Herein we are reporting a case of simultaneous occurrence of renal and pancreatic foreign body granuloma due to retained gauze. The different imaging features of the two lesions make correct preoperative diagnosis difficult. Foreign body granulomas due to retained surgical gauze or sponges should be considered in patients who have previous histories of operations and who also have a mass in the surgical bed. Simultaneous occurrence of foreign body granuloma away from primary surgical field is also possible.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

The differential sensitivities of inner ear structures to retinoic acid during development.

In order to examine the mechanisms that underlie development of the inner ear, the normal processes were perturbed using all-trans-retinoic acid (RA). By implanting a resin exchange bead saturated with RA into stage 16 (Hamburger and Hamilton, 1951, J. Morphol. 88, 49-92) embryonic day 2.5 chick ears, it was possible to analyze its in vivo effects on inner ear development. There is a temporal window during which the developing chick inner ear is particularly susceptible to the effects of RA (stages 16-19). This RA period of sensitivity precedes evidence of gross morphologic or histologic differentiation by at least 24 h, suggesting that mechanisms controlling formation of key inner ear structures are already in progress. There is a dose dependence on RA, with increasing doses of RA generating increasingly severe phenotypic abnormalities. Data indicate that these effects are due to differential sensitivities of the various inner ear structures to RA during their formation. In general, the vestibular structures were more susceptible to RA effects than the cochlear duct. Furthermore, nonsensory structures such as semicircular canals seemed to display a greater susceptibility to RA than their associated sensory structures (i.e., cristae). Among the three semicircular canals, the superior canal was the most susceptible to RA treatment, whereas the common crus was particularly resistant, suggesting that the molecular mechanisms for each structure's formation are different. The defect in semicircular canal formation is due to problems in the initial outgrowth of the canal plate which in turn is related to a down-regulation of early otocyst cell proliferation. This perturbation model provides valuable insight into the processes involved in producing the intricate patterning of the inner ear.