Risk factor for interstitial pregnancy following ipsilateral salpingectomy? A retrospective matched case control study.

BACKGROUND: Interstitial pregnancy may still happen even after ipsilateral salpingectomy, resulting in massive hemorrhage. Therefore, the purpose of the study is to identify risk factors associated with interstitial pregnancy following ipsilateral salpingectomy and discuss possible prevention. METHODS: We conducted a retrospective cohort study in a single, large, university-affiliated hospital. Data of 29 patients diagnosed with interstitial pregnancy following ipsilateral salpingectomy from January 2011 to November 2020 were assigned into the case group (IP group). Whereas there were 6151 patients with intrauterine pregnancy after unilateral salpingectomy in the same period. A sample size of 87 control patients was calculated to achieve statistical power (99.9%) and an α of 0.05. The age, BMI and previous salpingectomy side between the two group were adjusted with PSM at a ratio of 1:3. After PSM, 87 intrauterine pregnancy patients were successfully matched to 29 IP patients. RESULTS: After PSM, parous women were more common and intrauterine operation was more frequent in the IP group compared with control group (P<0.05). There was only one patient undergoing IVF-ET in the IP group as compared with 29 cases in the control group (3.4% vs. 33.3%, P<0.05). Salpingectomy was performed on 5 patients in the IP group and 4 patients in the control group due to hydrosalpinx (P<0.05). Logistic regression indicated that hydrosalpinx was the high risk factor of interstitial pregnancy following ipsilateral salpingectomy (OR = 8.175). CONCLUSIONS: Hydrosalpinx appears to be an independent factor contributing to interstitial pregnancy following ipsilateral salpingectomy in subsequent pregnancy.

Ceftazidime/avibactam-induced severe neutropenia: A case report.

Ceftazidime/avibactam is an important option for the treatment of infections caused by multidrug-resistant gram-negative bacteria. Haematological abnormalities are rare adverse events. We describe a case of a 63-year-old male who developed severe neutropenia following exposure to ceftazidime/avibactam in the intensive care unit for the treatment of abdominal infections. Six days after ceftazidime/avibactam was prescribed, the patient experienced a sheer drop in absolute neutrophil count, down to a minimum of 0.13 × 109 /L. A bone marrow examination showed neutrophilic maturation arrest. After careful screening of all drugs used by the patient and other potential causes of severe neutropenia, ceftazidime/avibactam was suspected to be the most likely culprit and was therefore replaced by cefoperazone/sulbactam, while a dose of colony-stimulating factor was given. The next day, neutrophils rose to 3.64 × 109 /L. To the best of our knowledge, this is the first case report of severe neutropenia associated with ceftazidime/avibactam. When neutropenia occurs during treatment, the clinician should keep this possibility in mind. Regular monitoring of neutrophil counts for timely recognition, immediate discontinuation of the drug and substitution of antibiotics are key steps in management.

Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids.

BACKGROUND: Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients. METHODS: Liver organoids (n = 51) were generated from liver/bile duct biopsies of CC (n = 7; type I) and hepatoblastoma (n = 5; HB: non-tumor & tumor) for RNA sequencing. Bioinformatics analysis was conducted to identify differentially expressed cancer-related genes in CC and controls. We compared CC with non-cancerous and cancerous controls, normal adjacent non-tumor region of hepatoblastoma (HB) liver as non-cancerous control and tumor region as non-CC cancer control (HB-tumor). Reverse transcription real-time quantitative PCR (RT-qPCR) verification and immunohistochemistry of selected genes was conducted in additional CC and HB liver biopsies. FINDINGS: HB non-tumor and HB tumor organoids displayed distinct gene expression profiles. Expression profiling separated CC organoids into two clusters, one overlapping with HB non-tumor and the other one with HB tumor organoids. Genes selected based on their log2FoldChange values for RT-qPCR verification in 31 CC and 11 HB non-tumor liver tissues revealed significantly elevated expression of FGFR2 in 7 and CEBPB in 2 CC liver tissues (CC vs HB: 4.082 vs. 0.7671, p<0.01; 2.506 vs. 1.210, p<0.01). Distinctive positive staining in bile ducts were seen in CC, HB tumor and non-tumor liver tissues for FGFR2 and CEBPB. Percentages of CEBPB-immuno-positive or FGFR2-immuno-positive bile duct cells in CC and HB-tumor liver were higher than that in HB non-tumor liver. INTERPRETATION: The study identified dysregulated genes related to cancer pathways in CC patients suggesting cancer risk. The findings suggest that the elevated expression of FGFR2 and CEBPB in liver may contribute to cancer development in CC patients.

Lilly's Technique for Delayed Hemorrhage After Choledochal Cyst Radical Surgery.

Background: Choledochal cysts (CCs) are characterized by dilations of the extra- and/or intrahepatic bile ducts. Surgery (cyst excision and Roux-en-Y hepaticojejunostomy) remains the gold standard for treatment. However, delayed hemorrhage can occur postoperatively, and although rare, it can be life-threatening. This study aimed to determine the risk factors and corresponding prevention of delayed hemorrhage after radical CC surgery, and to apply a technique to lower its incidence. Materials and Methods: This retrospective study enrolled 267 patients who received CC surgery between June 2016 and December 2020 at Shenzhen Children's Hospital. Univariate and multivariate logistic regression analyses were performed to identify risk factors for delayed hemorrhage. Results: Eleven (4.1%) patients had delayed hemorrhage after laparoscopic radical surgery. The most common hemorrhage site was the dissected surface between the cyst and adjacent structures with chronic severe adhesions, postoperatively. The occurrence of recurrent CC-associated complication and excessive total blood loss during surgery were risk factors for delayed hemorrhage after CC radical surgery. Length of disease course, operation when cholangitis/pancreatitis still existed, cyst diameter, and application of trypsin inhibitor after the surgery were not significantly different between the two groups. Conclusion: For patients without adhesions, complete cyst resection is the gold standard. However, for those with intensive adhesions, in cases of delayed hemorrhage on the dissection surface and malignancy transformation risk, the Lilly's technique with Roux-en-Y hepaticojejunostomy could be an alternative.

The correlation between serum Cyclophilin A level and severity, prognosis of craniocerebral injury.

Background: To investigate the value of serum Cyclophilin A(Cyp A) in evaluating the prognosis of patients with different severity of craniocerebral injury. Methods: The clinical data of patients with craniocerebral injury treated in the Department of Emergency from July 2014 to August 2017 were collected. The patients were divided into survival group and death group, good neurological function group and poor neurological function group with 28-day prognosis and were divided into mild (13-15) group, moderate (9-12) group, and severe (3-8) group with Glasgow Coma Scale (GCS) score. Clinical parameters such as Cyp A and mortality in groups and the relationship between Cyp A and GCS score were compared and its predictive value for prognosis was analyzed with Binary Logistics regression, Cox proportional hazards model and kaplan-meier survival curve. Results: In a single-center retrospective study, 503 patients were enrolled, including 365 males and 138 females; serum Cyp A in the survival group was significantly smaller than the death group [18.7 (10.1, 51.5) ng/mL vs. 149.8 (79.5, 194.4) ng/mL, P < 0.005]. There were significant differences in mortality and Cyp A levels between patients with different severity of craniocerebral injury (P < 0.001). Serum Cyp A levels were negatively correlated with GCS scores in all patients with craniocerebral injury, mild, moderate, or severe craniocerebral injury (r = -0.844, r = -0.256, r = -0.540, r = -0.531, P < 0.001). Predictive value of Serum Cyp A level for all patients with craniocerebral injury, mild, moderate, and severe craniocerebral injury is 0.890, 0.789, 0.806, and 0.833, respectively. Logistics regression analysis showed that lactate (OR = 1.260, 95%CI: 1.023-1.551) and Cyp A (OR = 1.021, 95%CI: 1.011-1.031) were positively correlated with death (P < 0.05), Lactic acid (HR 1.115; 95%CI:1.001-1.243; P = 0.048), GCS score (HR 0.888; 95% CI: 0.794-0.993; P = 0.038), Cyp A levels (HR 1.009; 95% CI: 1.004-1.013; P < 0.001) had a significant effect on short-term mortality. Similar results were seen when neurologic function was used as the outcome. Kaplan-meier survival curve analysis found survival rate of patients with Cyp A level below the cut-off value was significantly higher. Conclusion: Serum Cyp A has a certain predictive value for the prognosis of patients with different severity of craniocerebral injury. Among them, patients with severe craniocerebral injury have the highest predictive value and mild craniocerebral injury patients have the least.

Ectopic pregnancy in China during 2011-2020: a single-centre retrospective study of 9499 cases.

BACKGROUND: Previous studies have shown that the incidence of ectopic pregnancy (EP) is increasing in China. It is unclear, however, whether the incidence of EP has changed after the implementation of the universal two-child policy in the context of China's aging population and declining fertility rate. METHODS: Data concerning EP from January 2011 to December 2020 were collected from the hospital's electronic medical records, which included the annual number of delivery, caesarean section rate, ectopic pregnancies, treatment of tubal pregnancy, and average costs and length of hospitalization. Trends of the EP incidence were analysed and annual percentage change (APC) was calculated using connected point regression analyses. RESULTS: A total of 9499 cases of EP were collected, among which caesarean scar pregnancy (CSP) accounts for the second highest (6.73%). The EP per 100 deliveries revealed a downward trend, from 7.60% in 2011 to 4.28% in 2020 with an APC of -1.87 (P < 0.05). The maternal age was increased, especially after the implementation of the universal two-child policy. The constituent ratio for the advanced maternal age (≥ 35) and the caesarean section rate, but not the CSP, were also increased. Laparoscopic salpingectomy was the main surgical method, whereas the adoption of laparotomy and laparoscopic salpingostomy was decreasing year by year. CONCLUSIONS: Although no obvious effect of the two-child policy on EP has been observed under the conditions of this study, the change in EP especially in advanced-age women after the policy implementation needs further evaluation. A decreased caesarean section rate, in primipara is beneficial to reducing the CSP.

Interaction between human leukocyte antigen (HLA-C) and killer cell Ig-like receptors (KIR2DL) inhibits the cytotoxicity of natural killer cells in patients with hepatoblastoma.

Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.

Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia.

Background: Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aß) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aß levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown. Method: Plasma samples of 11 BA and 24 controls were collected for liver function test, Aß40 and Aß42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann-Whitney U test was performed to assess differences between groups. Correlation between Aß42/Aß40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of Aß42/Aß40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aß42/Aß40 combined with other hepatic function parameters. Results: Plasma Aß42/Aß40 was elevated in BA patients. Aß42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson's correlation = 0.349), while there was no correlation for Aß40 with hepatic functions. Aß42/Aß40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson's correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson's correlation = 0.337). Aß42/Aß40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552-0.941), p < 0.05]. Diagnostic powers of Aß42/Aß40 together with hepatic function parameters for cholestasis were markedly improved compared to any indicator alone. Neither Aß42/Aß40 nor hepatic function parameters displayed sufficient power in discriminating BA from choledochal cysts (CC); however, combinations of Aß42/Aß40 + GGT along with any other hepatic function parameters could differentiate BA from CC-cholestasis (AUC = 1.000, p < 0.05) with a cut-off value as 0.02371, -0.28387, -0.34583, 0.06224, 0.01040, 0.06808, and 0.05898, respectively. Conclusion: Aß42/Aß40 is a good indicator for cholestasis, but alone is insufficient for a distinction of BA from non-BA. However, Aß42/Aß40 combined with GGT and one other hepatic function parameter displayed a high predictive power as a screening test for jaundiced neonates who are more likely to be BA, enabling them to early intraoperative cholangiography for BA confirmation and KPE to improve surgical outcomes. However, a multi-centers validation is needed before introduction into daily clinical practice.

mRNA and lncRNA expression profiles of liver tissues in children with biliary atresia.

Progressive liver fibrosis is the most common phenotype in biliary atresia (BA). A number of pathways contribute to the fibrosis process so comprehensive understanding the mechanisms of liver fibrosis in BA will pave the way to improve patient's outcome after operation. In this study, the differentially expressed profiles of mRNAs and long non-coding RNAs from BA and choledochal cyst (CC) liver tissues were investigated and analyzed, which may provide potential clues to clarify hepatofibrosis mechanism in BA. A total of two BA and two CC liver tissue specimens were collected, the expression level of mRNAs and lncRNAs was detected by RNA sequencing. Differentially expressed mRNAs (DEmRNAs) were functionally annotated and protein-protein interaction networks (PPI) was established to predict the biological roles and interactive relationships. Differentially expressed lncRNAs (DElncRNAs) nearby targeted DEmRNA network and DElncRNA-DEmRNA co-expression network were constructed to further explore the roles of DElncRNAs in BA pathogenesis. The expression profiles of significant DEmRNAs were validated in Gene Expression Omnibus database. A total of 2,086 DEmRNAs and 184 DElncRNAs between BA and CC liver tissues were obtained. DEmRNAs were enriched in 521 Gene Ontology terms and 71 Kyoto Encyclopedia of Genes and Genomes terms which were mainly biological processes and metabolic pathways related to immune response and inflammatory response. A total of five hub proteins (TYRO protein tyrosine kinase binding protein, C-X-C motif chemokine ligand 8, pleckstrin, Toll-like receptor 8 and C-C motif chemokine receptor 5) were found in the PPI networks. A total of 31 DElncRNA-nearby-targeted DEmRNA pairs and 2,337 DElncRNA-DEmRNA co-expression pairs were obtained. The expression of DEmRNAs obtained from RNA sequencing were verified in GSE46960 dataset, generally. The present study identified key genes and lncRNAs participated in BA associated liver fibrosis, which may present a new avenue for understanding the patho-mechanism for hepatic fibrosis in BA.

Neural Dysconnectivity in the Hippocampus Correlates With White Matter Lesions and Cognitive Measures in Patients With Coronary Artery Disease.

Purpose: Recent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures. Methods: Thirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE). Results: Our data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R. Conclusion: These findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.

Establishment of centromere identity is dependent on nuclear spatial organization.

The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-ACnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-ACnp1 overexpression bypasses heterochromatin dependency, suggesting that heterochromatin ensures exposure to conditions or locations permissive for CENP-ACnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-ACnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-ACnp1 chromatin assembly occurs when central domain DNA is placed near, but not far from, endogenous centromeres or neocentromeres. Moreover, direct tethering of central domain DNA at SPBs permits CENP-ACnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation because target sequences are exposed to high levels of CENP-ACnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.

Successful treatment of pulmonary injury due to nitrogen oxide exposure with extracorporeal membrane oxygenation: a report of two cases and literature review.

Background: Severe nitrogen oxide poisoning can lead to life-threatening pulmonary injury.Methods: we report two cases of severe nitrogen-oxide-induced hypoxia treated with veno-venous extracorporeal membrane oxygenation (ECMO). After exposure, the conditions of both patients continued to deteriorate despite maximal mechanical ventilation with a fraction of inspired oxygen of 100%; therefore, we started veno-venous ECMO. The times from presentation to the initiation of ECMO in the two patients were 1 and 2 days. The hypoxemia and respiratory failure improved quickly after ECMO support.Results: The patients were discharged without complications. The durations of ECMO for the two patients were 5 and 6 days. Conclusion: This report describes how early ECMO support was used to treat potentially fatal pulmonary injury after exposure to nitrogen oxide. The duration of the ECMO run is a critical determinant of patient survival.

Role of long non-coding RNA-adducin 3 antisense RNA1 in liver fibrosis of biliary atresia.

Biliary atresia (BA) is a devastating liver disease in neonates. Liver fibrosis is regarded as a universal and prominent feature of BA. Studies have revealed that long non-coding RNAs (lncRNAs) regulate cellular processes during the development of liver fibrosis in BA. Long non-coding RNA-adducin 3 antisense RNA1 (lnc-ADD3-AS1) has been shown to increase susceptibility to BA. However, the role of lnc-ADD3-AS1 in liver fibrosis in BA remains unclear. Here, we investigated the role of lnc-ADD3-AS1 in the proliferation, migration, and apoptosis of the immortalized human hepatic stellate cell (HSC) line, LX-2. We successfully overexpressed and silenced lnc-ADD3-AS1 in LX-2 cells using adenovirus vectors and evaluated the proliferation of transfected cells using the Cell Counting Kit-8 (CCK8) assay. Cell apoptosis was detected using annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining and flow cytometry. We then analyzed cell migration by performing wound-scratch and transwell migration assays. Our results show that lnc-ADD3-AS1 significantly promoted LX-2 cell proliferation and attenuated apoptosis. More importantly, lncRNA-ADD3-AS1 significantly accelerated the migration of LX-2 cells. Our data indicated that lncRNA-ADD3-AS1 plays a role in the pathogenesis of liver fibrosis in patients with BA and may serve as a potential diagnostic marker for monitoring liver fibrosis in BA or as a therapeutic target for the disease.

The Novel Cucurbitaceae miRNA ClmiR86 Is Involved in Grafting-Enhanced Phosphate Utilization and Phosphate Starvation Tolerance in Watermelon.

Watermelon (Citrullus lanatus) is a globally important Cucurbitaceae crop in which grafting is commonly used to improve stress tolerance and enhance nutrient utilization. However, the mechanism underlying grafting-enhanced nutrient assimilation remains unclear. Here, we demonstrate the possible involvement of a novel Cucurbitaceae miRNA, ClmiR86, in grafting-enhanced phosphate-starvation tolerance via CALCINEURIN B-LIKE INTERACTING PROTEIN KINASE 5 (ClCIPK5) suppression in watermelon. Transcript analyses revealed that the induction of ClmiR86 expression was correlated with the downregulation of ClCIPK5 in squash-grafted watermelon under phosphate starvation. In addition, the differential expression of ClmiR86 in various watermelon genotypes was consistent with their phosphate utilization efficiency. Furthermore, ClmiR86 overexpression in Arabidopsis enhanced root growth and phosphate uptake under phosphate starvation and promoted inflorescence elongation under normal conditions. These results suggest that the ClmiR86-ClCIPK5 axis is involved in phosphate starvation response as well as grafting-enhanced growth vigor and phosphate assimilation. The present study provides valuable insights for investigating long-distance signaling and nutrient utilization in plants.

Efficient preparation of c-di-AMP at gram-scale using an immobilized Vibrio cholerae dinucleotide cyclase DncV.

Cyclic di-AMP is a bacterial nucleotide second messenger and evaluated as a potential vaccine adjuvant candidate. Here, we report a practical and economical enzymatic method for gram-scale preparation of c-di-AMP using an immobilized Vibrio cholerae dinucleotide cyclase DncV. The method mainly includes four steps: preparation of DncV-immobilized resin, enzymatic synthesis of c-di-AMP, purification using macroporous absorption resin SP207, and desiccation using rotary evaporation and lyophilization. Enzymatic synthesis is the most critical step, and almost all substrate ATP was converted to c-di-AMP under an optimum condition in which 300 mL of 300 mM NH4Ac/NH3 pH 9.5 buffer supplemented with 20 mM MnCl2, 10 mM ATP and 4 mL of DncV-immobilized resin containing ∼19 mg DncV were incubated at 30 °C overnight. After purification, up to 1 g of the diammonium salt of c-di-AMP with weight purity of ≥98% was obtained as white powder, which corresponds to an overall yield of ∼80% based on the ATP input into the reaction. The method is easily performed in laboratory to prepare c-di-AMP on a gram scale and could be used in industry on a large scale.

MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity.

Macrophage-stimulating protein (MSP), a soluble protein mainly synthesized by the liver, is the only known ligand for recepteur d'origine nantais (RON), which is a member of the MET proto-oncogene family. Recent studies show that the MSP-RON signaling pathway not only was important in tumor behavior but also participates in the occurrence or development of many immune system diseases. Activation of RON in macrophages results in the inhibition of nitric oxide synthesis as well as lipopolysaccharide (LPS)-induced inflammatory response. MSP-RON is also associated with chronic inflammatory responses, especially chronic liver inflammation, and might serve as a novel regulator of inflammation, which may affect the metabolism in the body. Another study provided evidence of the relationship between MSP-RON and autoimmune diseases, suggesting a potential role for MSP-RON in the development of drugs for autoimmune diseases. Moreover, MSP-RON plays an important role in maintaining the stability of the tissue microenvironment and contributes to immune escape in the tumor immune microenvironment. Here, we summarize the role of MSP-RON in immunity, based on recent findings, and lay the foundation for further research.

Characteristics and surgical invervention of ovarian torsion in pregnant compared with nonpregnant women.

The aim of our study was to compare the clinical and surgical characteristics of pregnant and nonpregnant women with surgically verified ovarian torsion, as well as the differences among 3 trimesters during pregnancy.We conducted a retrospective study of patients diagnosed with surgically proven ovarian torsion in our hospital from January 2012 to June 2018. The clinical characteristics, surgical procedure, pathologic outcomes, and trimesters of pregnancy were analyzed.Thirty-three pregnant and 72 nonpregnant patients diagnosed with surgically proven ovarian torsion were assessed during the study period. The most common presenting symptom in both groups was abdominal pain (90.2% and 99.0%, respectively). The median time from admission to surgery was shorter in pregnant patients than nonpregnant patients (5.3 compared with 47.7 hours, P < .001). Pregnant patients had a higher number of twists than nonpregnant patients (median of 2 compared with 1, P < .01). Benign cyst was the most common cyst causing ovarian torsion in both groups, and luteum cyst was more common in the pregnant group. The mean size of ovarian cyst in pregnant patients was much smaller in the third trimester than the first and the second trimesters (6.6 ±â€Š2.0, 8.4 ±â€Š2.1and 8.1 ±â€Š1.5 cm, respectively; P = .097). Cystectomy performed in the third trimester was more frequent compared with the other 2 trimesters (77.8%, 26.7%, and 22.2%, respectively; P = .021).Abdominal pain is the most common feature of ovarian torsion. Clinical presentation of ovarian torsion is relatively similar between pregnant and nonpregnant women, and among different trimesters. The tumor size was smaller in the third trimester of pregnancy than the other 2 trimesters of pregnancy. Cystectomy performed in pregnant patients is more during the third trimester compared with the other 2 trimesters.

RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I.

The macrophage stimulating protein (MSP)-Recepteur d'origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic dendritic cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.

The outcome of two pregnancies in a patient with Gitelman syndrome: case report and review of the literature.

We report a case of a 30-year-old woman who was first found to have a persistently low serum potassium level at 26 years of age during her first pregnancy. Genetic test of SLC12A3 confirmed Gitelman syndrome. The patient remained asymptomatic and had two deliveries following spontaneous labor. The first neonate died of heart failure due to cardiac abnormalities. The obstetric and neonatal outcome of the second pregnancy was good.

Effect of ropivacaine on peripheral neuropathy in streptozocin diabetes-induced rats through TRPV1-CGRP pathway.

Objective To determine the effect of ropivacaine on peripheral neuropathy in diabetic rats and its possible mechanism. Methods Forty-eight Sprague-Dawley rats were randomly divided into six groups: nondiabetic control group, nondiabetic group A (0.25% ropivacaine), nondiabetic group B (0.75% ropivacaine), diabetic control group (diabetic peripheral neuropathy (DPN) +artificial cerebrospinal fluid), diabetic group A (DPN+0.25% ropivacaine), and diabetic group B (DPN + 0.75% ropivacaine), with eight rats in each group. Within an hour of the last administration, the sciatic motor nerve conduction velocity (MNCV) of each group was measured, and the morphological changes of rat sciatic nerve were observed by HE, Weil's staining and electron microscopy. The expression of transient receptor potential vanilloid (TRPV1) in the spinal cord dorsal horn of rats was analyzed by immunohistochemistry, and the expression of Calcitonin gene-related peptide (CGRP) protein in the spinal cord was analyzed by Western blot. Results Compared with the nondiabetic control group, elevated blood glucose, decreased weight and reduced average mechanical withdrawal threshold (MWT), additionally, the sciatic nerves showed significantly slowed conduction velocity (both P<0.001) and damaged pathological structure, the expression of TRPV1 and CGRP were decreased (both P<0.001) in the diabetic groups. Compared with the diabetic control group, down-regulation of TRPV1 and CGRP in spinal cord was significant for the diabetic groups A and B treated with 0.25 and 0.75% ropivacaine, the higher concentration of ropivacaine correlated with a greater change. Conclusion Ropivacaine can significantly block sciatic nerve conduction velocity in DPN rats in a concentration-dependent manner, which may be related to the expression of the TRPV1-CGRP pathway.