The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.

[Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology].

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Eudesmane-type sesquiterpenes from the rhizomes of Atractylodes macrocephala and their bioactivities.

Fifteen undescribed eudesmane-type sesquiterpenes, named atramacronoids D-R, along with fourteen known analogues were isolated from the rhizomes of Atractylodes macrocephala. The structures of atramacronoids D-R were elucidated based on extensive spectroscopic data analysis, Snatzke's rule, electronic circular dichroism (ECD) calculations, and X-ray crystallographic analysis. Notably, of the undescribed isolates, atramacronoids D and E are the first example of eudesmanolactam-phenol and eudesmanolactam-ethyl hybrids obtained from plants, respectively. A pair of enantiomers, (+)- and (-)-atramacronoids F, were successfully resolved by chiral-phase HPLC. Atramacronoid D exhibited weak cytotoxicity against SGC-7901 cells. Atramacronoid E significantly promoted the proliferation of LPS-induced IEC-6 cells.

Ultrasonographic manifestations and misdiagnosis analysis of ovarian leiomyoma.

Objectives: Ovarian leiomyomas (OLs) are rare and account for only 0.5 to 1% of benign ovarian tumors. This study investigated the ultrasonographic manifestations of OL and the potential reasons for misdiagnosis. Methods: Between July 2018 and July 2023, 7 patients diagnosed with OL by surgical pathology and immunohistochemistry were enrolled in this retrospective analysis. Ultrasound (US) examinations were performed before surgery. Clinical characteristics, pathological findings, ultrasonographic manifestations, and treatment were reviewed. Results: The mean age of the 7 patients was 39.0 ± 11.57 years, with a disease course of 0.1 to 24 months. All ovarian leiomyomas were unilateral. Four cases occurred in the right ovary, and three cases occurred in the left ovary. All lesions presented as hypoechogenic, well-circumscribed, round or oval in shape, and regular in morphology. No significant blood flow signal was detected peripheral to or inside the mass in 3 cases (42.8%), and a minimal flow signal was detected peripheral to or inside the mass in 4 cases (58.2%). A total of 7 ultrasonographic images of OL were misdiagnosed: 1 patient was misdiagnosed with subserosal uterine leiomyoma, and 6 patients were misdiagnosed with a tumor in the ovarian thecoma-fibroma group. Conclusion: The imaging manifestation of OL lacks specificity; thus, preoperatively distinguishing OL from other ovarian tumors and subserosal uterine leiomyomas is difficult. Immunohistochemistry may be helpful for the definitive diagnosis of OL. The possibility of ovarian leiomyoma should be considered in patients with uterine leiomyomas coexisting with an adnexal ovarian solid mass.

The value of colorectal filling contrast ultrasonography in diagnosing pediatric juvenile polyps.

OBJECTIVES: To describe a facilitated procedure of colorectal filling contrast ultrasonography (CFCUS) and explore its value in the diagnosis of pediatric juvenile polyps. METHODS: One hundred and eleven children with clinical signs of colorectal polyps admitted to our hospital between May 2018 and May 2021 were retrospectively reviewed. All children underwent conventional transabdominal ultrasonography (CTUS) and CFCUS prior to undergoing colonoscopy. Pathologic findings were used as the gold standard. Chi-squared tests and Mann-Whitney U tests were used for the statistical analysis. RESULTS: Forty-five children with fifty-two colorectal polyps were confirmed via pathological examination. The sensitivity, specificity, positive predictive value, and negative predictive value of CFCUS vs. CTUS were 92.3% versus 80.7%, 100% versus 100%, 100% versus 100%, and 93.3% versus 84.8%, respectively. The missed polyps were significantly smaller than the polyps detected in diameter (7.50 ± 2.12 mm vs. 19.62 ± 7.89 mm, p < 0.0001) by CTUS. A significant difference between CTUS and CFCUS was observed in the detection rate of polyps with a diameter < 1 cm (p = 0.031) and pedicles (p < 0.001). The kappa values for the assessment of Yamada's classification between CTUS and colonoscopy and CFCUS and colonoscopy were 0.51 and 0.84, respectively. Moreover, CFCUS incidentally revealed a punctate hyperechoic area on the surface of colonic polyps in six cases, which may be suggestive of a correlation with erosion and bleeding findings. CONCLUSION: CFCUS can increase the detection rate of polyps and pedicles, especially polyps with diameters <1 cm, and accurately evaluate Yamada's classification, providing useful preoperative information for colonoscopy.

Quality markers of Baizhu dispensing granules based on multi-component qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The dispensing granules of traditional Chinese medicines (TCMs) is an innovative form of medicinal material for TCMs decoction, which is gradually recognized in the clinic due to being suitable for production on a large scale and convenient to take for patients. However, the quality control of TCMs dispensing granules is being challenged, because they contain too many unrevealed hydrophilic components. AIM OF THE STUDY: Here, the dispensing granules produced from the rhizome of Atractylodes macrocephala (Baizhu dispensing granules), were explored as a case to explore the quality markers correlated to the clinical efficacy of TCMs dispensing granules by a comprehensive strategy of integrating chemical profiling, network pharmacology, and chemometric analysis. MATERIALS AND METHODS: First, the chemical profiling of Baizhu dispensing granules was characterized by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Subsequently, the potential active components responsible for the efficacy of Baizhu dispensing granules were screened via network pharmacology, and the ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was developed for quantitative analysis of the potential active components in 26 batches of Baizhu dispensing granules. Finally, the quality markers of Baizhu dispensing granules were deciphered based on content variations of potential active components and chemometric analysis. RESULTS: A total of 69 components were identified from Baizhu dispensing granules. Network pharmacology analysis further revealed that eight of them including five caffeoylquinic acids (31, 32, 36, 42, 44) and three sesquiterpenoids (63, 67, 76) were intimately connected to the core targets of dyspepsia, enteritis, gastritis and immunity. The contents of eight components differed greatly among 26 batches of Baizhu dispensing granules. Chlorogenic acid (31), cryptochlorogenic acid (32) and atractylenolide III (63) have higher concentrations and make great contributions to distinguish different batches of the Baizhu dispensing granules based on principal component analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA), and could be used as the quality markers of Baizhu dispensing granules. CONCLUSIONS: Our study defined the quality markers of Baizhu dispensing granules, which will benefit further investigation on the quality evaluation of TCMs dispensing granules containing Baizhu. The strategy used in this study will be helpful for discovering the quality markers of other TCMs dispensing granules.

Gut microbiota and gut tissue metabolites involved in development and prevention of depression.

Depression is a prevalent, life-threatening, and highly recurrent psychiatric illness. Several studies have shown that depression is associated with endogenous metabolites and the gut microbiota. However, it is unclear whether metabolites in different gut tissues play a role in the pathogenesis of depression and whether the gut microbiota has an impact on depression. Here, we investigated the metabolic signatures in the jejunum, ileum, and colorectum using metabolomics and explored the influence of the gut microbiota on both the development of chronic variable stress (CVS)-induced depression rat model and variations in gut tissue metabolites using a gnotobiotic rat model. The results showed that CVS induced disturbances in gut metabolites (29 differential metabolites) and had different effects on the different segments. When CVS rats were treated with antibiotics, depression-like ethological disorders disappeared, and the decreased catecholamine levels almost normalized. The depression recovery was attributed to the influence of antibiotics on the gut microbiota, especially inhibiting Clostridiaceae (F1), Candidatus arthromitus (G2), Lactobacillus (G6), and elevating Pseudomonadaceae (F6). Moreover, 16 of 29 varied metabolites in CVS rats were reversed with antibiotic treatment. Among them, 12 increased metabolites were decreased, suggesting a trigger for depression. However, four decreased metabolites were increased, indicating a potential therapeutic effect on depression. Based on the Pearson's correlation analysis, hypoxanthine, 3-hydroxypristanic acid, threonic acid, and L-carnitine were strongly associated with F6, F1, G2, and G6, which are involved in the development and prevention of depression. These findings provide a possibility for further exploration of the pathogenesis and prevention of depression.

Imaging appearance of ovarian mature teratoma with gliomatosis peritonei.

Gliomatosis peritonei (GP), almost exclusively linked to mature or immature ovarian teratoma, is a very rare disease. To the best of our knowledge, reports on the complete clinical course and imaging features of ovarian mature teratoma with GP are extremely rare. We present a case of ovarian mature teratoma with GP in a 9-year-old girl admitted to the emergency department for a 2-month history of a large abdominal mass found accidentally. Carcinoembryonic antigen and cancer antigen 125 levels were elevated. CT scans suggested a large mass with mild enhancement, and an immature teratoma derived from the left ovary with ascites was diagnosed by ultrasound. Subsequently, left ovarian tumor resection and omentectomy were performed, and a solid cystic mass accompanied by massive ascites and numerous white to grayish nodules was identified on the left ovary. The pathology results revealed a mature teratoma with GP. The patient had good postoperative recovery, and her serum tumor marker levels decreased to normal at the 3-month follow-up.

Sonographic imaging of appendiceal orifice polyps in children.

Although gastrointestinal polyps are a common disease, appendiceal orifice polyps are rare and usually found incidentally during autopsy or surgery. Data on the sonographic features of appendiceal orifice polyps in children are limited. We describe the sonographic features of appendiceal orifice polyps in two children.

Mechanisms for Improving Hepatic Glucolipid Metabolism by Cinnamic Acid and Cinnamic Aldehyde: An Insight Provided by Multi-Omics.

Cinnamic acid (AC) and cinnamic aldehyde (AL) are two chemicals enriched in cinnamon and have been previously proved to improve glucolipid metabolism, thus ameliorating metabolic disorders. In this study, we employed transcriptomes and proteomes on AC and AL treated db/db mice in order to explore the underlying mechanisms for their effects. Db/db mice were divided into three groups: the control group, AC group and AL group. Gender- and age-matched wt/wt mice were used as a normal group. After 4 weeks of treatments, mice were sacrificed, and liver tissues were used for further analyses. Functional enrichment of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. DEPs were further verified by parallel reaction monitoring (PRM). The results suggested that AC and AL share similar mechanisms, and they may improve glucolipid metabolism by improving mitochondrial functions, decreasing serotonin contents and upregulating autophagy mediated lipid clearance. This study provides an insight into the molecular mechanisms of AC and AL on hepatic transcriptomes and proteomes in disrupted metabolic situations and lays a foundation for future experiments.

Sonography of pediatric gastrointestinal venous malformations.

Gastrointestinal (GI) venous malformations are extremely rare. Such malformations present in the pediatric age group and can occur anywhere in the digestive tract (esophagus, stomach, small or large intestine, anus, and mesentery). We present the sonographic findings of three cases of pediatric GI venous malformation. Sonography is an important diagnostic method in pediatric GI venous malformations.

Herbal formula LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis in Zucker diabetic fatty rats.

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.

Two new sesquiterpenes produced by the endophytic fungus Aspergillus fumigatus from Ligusticum wallichii.

Two previously undescribed sesquiterpenes along with nine known compounds were isolated from the fermentation broth of Aspergillus fumigatus, an endophyte of Ligusticum wallichii. Their structures were elucidated through extensive spectroscopic analysis combined with quantum chemical ECD calculations. Two new compounds exhibited moderate growth inhibition against MV4-11 and MDA-MB-231 cell lines.

Association of PTTG1 polymorphism rs1895320, rs2910200 and rs6882742 with non-functioning pituitary adenomas in Chinese Han population: a case-control study.

Due to absence of clinical manifestations of hormonal hyper secretion, the treatment of Nonfunctioning pituitary adenoma (NFPA) was always delayed. PTTG1 was reported to be overexpressed in most of pituitary tumors, however, the polymorphism of PTTG1 rs1895320, rs2910200 and rs6882742 with NFPA were still not fully elucidated in NFPA. Thus, a hospital based case control study which included 79 patients and 142 healthy control participants were conducted. DNA was extracted from peripheral blood samples and genotyped by Mass Array methods. In addition, a meta-analysis of rs2910200 was also employed to further testify the conclusion. Significant difference were observed between patients and healthy controls under rs2910200 locus between allelic genotype (p = 0.0219). However, no other significant difference was observed in rs1895329 and rs6882742. In addition, a logistic regression analysis showed that the dominant model of rs2910200 were closely correlated with the NFPA susceptibility (OR = 1.951, 95% CI:1.075-3.542, p = 0.028). While no significant difference was observed in the rs1895320 and rs6882742 under dominant model, recessive model and additive model The meta-analysis results showed that the dominant model and heterozygote model can significantly increase the risk of PA (p = 0.007, OR = 1.57, 95% CI:1.14-2.18; p = 0.009, OR = 1.57, 95% CI:1.12-2.19). Whereas no significant difference were observed under the homozygous model and recessive model. In conclusion, the polymorphism of PTTG1 rs2910200 dominant model and T allelic might increase the risk of NFPA.

Isochromanes from Aspergillus fumigatus, an endophytic fungus from Cordyceps sinensis.

Four previously undescribed isochromanes were isolated from the fermentation broth of an endophytic fungus Aspergillus fumigatus, which was obtained from the fruiting body of Cordyceps sinensis. Their structures were elucidated through extensive spectroscopic analyses. One racemic isochromane was further purified by chiral HPLC to yield a pair of enantiomers and their absolute configurations were determined by quantum chemical ECD calculations. These isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-ME-231) and the result showed that compounds 1a and 2 exhibited moderate growth inhibition against MV4-11 cell line.

Hypomagnetic fields cause anxiety in adult male mice.

Hypomagnetic fields (HMF), that is, the elimination of the geomagnetic field (GMF), are a risk factor to the health of astronauts in outer space. It has been established that continuous HMF exposure affects cytoskeleton assembly, cell proliferation, embryonic development, and even learning and memory. In addition, although there were some previous studies that focused on the effects of long-term HMF-exposure, so far very limited investigations have been conducted to examine the short-term HMF effect in animals. In this study, we exposed adult male C57BL/6 mice to a 3-axis Helmholtz-coil HMF-simulation system for 72 h and found that short-term HMF-exposure induced a significant increase in anxiety-related behaviors. And our findings provide important information for both psychological intervention and the health care of astronauts. Bioelectromagnetics. 40:27-32, 2019. © 2018 Wiley Periodicals, Inc.

Aryl-tetralin-type lignan isolated from Sanguisorba officinalis.

Three aryl-tetralin-type lignans, including 2 previously undescribed compounds, were isolated from the root of Sanguisorba officinalis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analyses and mass spectrometry. Experimental and calculated ECD were used to determine the absolute configurations. The isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-MB-231) and compound 1 exhibited moderate growth inhibition against MDA-MB-231 cell line with IC50 value of 15.76 µM.

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common, and the incidence increases with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular (IM) vitamin B12. Doctors may not be prescribing oral vitamin B12 formulations because they may be unaware of this option or have concerns regarding its effectiveness. OBJECTIVES: To assess the effects of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and LILACS, as well as the WHO ICTRP and ClinicalTrials.gov. The latest search date was 17 July 2017. We applied no language restrictions. We also contacted authors of relevant trials to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of oral versus IM vitamin B12 for vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were serum vitamin B12 levels, clinical signs and symptoms of vitamin B12 deficiency, and adverse events. Secondary outcomes were health-related quality of life, acceptability to patients, haemoglobin and mean corpuscular volume, total homocysteine and serum methylmalonic acid levels, and socioeconomic effects. We used GRADE to assess the quality of the evidence for important outcomes. We did not perform meta-analyses due to the small number of included trials and substantial clinical heterogeneity. MAIN RESULTS: Three RCTs met our inclusion criteria. The trials randomised 153 participants (74 participants to oral vitamin B12 and 79 participants to IM vitamin B12). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 38.6 to 72 years. The treatment frequency and daily dose of vitamin B12 in the oral and IM groups varied among trials. Only one trial had low or unclear risk of bias across all domains and outcome measures. Two trials reported data for serum vitamin B12 levels. The overall quality of evidence for this outcome was low due to serious imprecision (low number of trials and participants). In two trials employing 1000 µg/day oral vitamin B12, there was no clinically relevant difference in vitamin B12 levels when compared with IM vitamin B12. One trial used 2000 µg/day vitamin B12 and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B12. Two trials reported data on adverse events (very low-quality evidence due to risk of performance bias, detection bias, and serious imprecision). One trial stated that no treatment-related adverse events were seen in both the oral and IM vitamin B12 groups. One trial reported that 2 of 30 participants (6.7%) in the oral vitamin B12 group left the trial early due to adverse events. Orally taken vitamin B12 showed lower treatment-associated costs than IM vitamin B12 in one trial (low-quality evidence due to serious imprecision). No trial reported on clinical signs and symptoms of vitamin B12 deficiency, health-related quality of life, or acceptability of the treatment scheme. AUTHORS' CONCLUSIONS: Low quality evidence shows oral and IM vitamin B12 having similar effects in terms of normalising serum vitamin B12 levels, but oral treatment costs less. We found very low-quality evidence that oral vitamin B12 appears as safe as IM vitamin B12. Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B12 deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting.

A case of retroperitoneal para-aortic ectopic pregnancy detected by sonography.

Retroperitoneal ectopic pregnancy is extremely rare. We present a case of a retroperitoneal ectopic pregnancy with a gestational sac located to the left of the abdominal aorta and of the left renal vessels at 9 weeks of gestation. Careful transabdominal sonographic examination is suggested when an ectopic pregnancy is suspected and the examination of the pelvis is negative.