[Assessment of MS-Score and HScore in timeliness of diagnosis of macrophage activation syndrome associated with adult-onset Still's disease].

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [M (Q1,Q3)] earlier than by HLH-2004 criteria, and 13.5 (0.5, 21.5) days earlier than by HScore (both P<0.05). The difference was not statistically significant between the time of diagnosis of AOSD-associated MAS by Hscore and by HLH-2004 criteria (P>0.05). There was significant difference among the three criteria (P<0.001). MS-Score can be used to diagnose AOSD-associated MAS earlier than HLH-2004 criteria, while the timeliness of HScore is not certain.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

HPV genotype analysis for women in Shaanxi Province of China.

The aim of this study was to examine the subtype distribution of human papilloma virus (HPV) in women in the Shaanxi Province of China. A DNA chip, along with polymerase chain reaction amplification and reverse dot blot technology, was adopted to analyze the HPV genotypes of 22,937 cases of cervical cell specimens. The HPV infection rate was 18.70%, wherein high-risk, low-risk, and high- and low-risk multiple infection rates were 15.75, 2.96 and 1.91%, respectively. High-risk infections accounted for 84.20% of total infections. The rate of HPV infection in women with rural residence, high school education or less, a low income, or age over 40 years was significantly higher than that in the control group (negative HPV infection women). Of the 18 detected high-risk HPV subtypes, the most common in single infections were, in the order of prevalence, HPV16, 58, 18, 52, 33, and 56. For multiple high-risk infections, the most common subtypes in the order of prevalence were HPV16, 52, 58, 18, 56, and 33. Age was a factor in the rate of infection, as the 41-50-year age group had a significantly higher risk of infection than the other groups (P < 0.05). In multiple infections, double infections were common, accounting for 77.10% of multiple infections, and triple or more infections were more common in women aged 51-60 years. In Shaanxi Province, high-risk HPV infection in women was mainly attributed to rural residence, age over 40 years, low income, and low education level.

Prevalence of human papillomavirus genotypes among women with cervical lesions in the Shaanxi Province of China.

This study aimed to investigate human papilloma virus (HPV) genotypes among women with cervical lesions in Shaanxi Province, China, to obtain information regarding cervical lesion prevention and treatment. The study included 4508 HPV-positive subjects; cervical swab specimens were collected and tested for HPV infection status and HPV genotypes using polymerase chain reaction and reverse dot-blot hybridization. Women positive for HPV with cervical lesions, including chronic cervicitis, cervical intraepithelial neoplasia, and cervical squamous cell carcinoma (SCC), were examined; HPV-positive women with no cervical lesions were controls. Data were pooled and weighted estimates have been presented. For women with no cervical lesions and positive for one HPV genotype, HPV 52, 16, 58, 81, 33, and 56 were the most common; for multiple-HPV genotype infection, HPV 16, 52, 6, 18, 58, and 66 were the most common. Collectively, HPV 16, 58, 52, 18, 33, and 81 were the most common in women with cervical lesions. HPV 16 comprised 26.71% of single-genotype and 15.64% of multiple-genotype infections. The proportion of HPV-16-positive cases was 29.15%, which was the highest among all HPV genotypes (P < 0.01). Single-HPV genotype infection was the most common in cervical HPV infection (77.48%); infection with two HPV genotypes comprised 72.22% of multiple-genotype infections. The proportion of single-low-risk HPV genotype infections decreased with increase in cervical lesion severity; there were no single- or multiple-low-risk genotype HPV infections in cervical SCC patients. The proportion of multiple-genotype HPV infections with at least one high-risk genotype increased with cervical lesion severity.

Dihydromyricetin induces cell apoptosis via a p53-related pathway in AGS human gastric cancer cells.

The aim of the present study was to determine the anti-proliferative and pro-apoptotic effects of dihydromyricetin (DHM) on the AGS human gastric cancer cells and their underlying mechanisms. The effects of DHM on AGS cells were evaluated by using 3-(4, 5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, and Annexin V/propidium iodide (PI) double-staining assays. The underlying mechanisms were determined by using quantitative real-time polymerase chain reaction. The results demonstrated that DHM significantly (P < 0.05) inhibited AGS cell proliferation and induced cell cytotoxicity in a dose- and time-dependent manner. Additionally, Annexin V/PI double-staining assay showed that DHM promoted cell apoptosis in both, early and late stages. Furthermore, DHM also regulated the expression of apoptotic genes such as p53 and B-cell lymphoma-2 (bcl-2) in a dose- and time-dependent manner. In conclusion, this is the first report demonstrating the anticancer and pro-apoptosis effects of DHM on AGS human gastric cancer cells. The results strongly suggest that DHM may be a potential therapeutic candidate for the treatment of gastric cancer.

Hsa-miR-4730 as a new and potential diagnostic and prognostic indicators for pancreatic cancer.

OBJECTIVE: Pancreatic cancer is a gastrointestinal tumor with the highest malignancy and few diagnostic and prognostic markers. Patients with disease have a 5-year survival rate that is not more than 10%. As a research hotspot in recent years, miRs (microRNAs) are differentially expressed in various tumors, so they can be used as the potential diagnostic and prognostic markers. In this study, differentially expressed miRs in patients with pancreatic cancer were screened out through the GEO chip, to provide potential markers for clinical practice. This study aimed to explore the expression and potential value of miR-4730 in pancreatic cancer. PATIENTS AND METHODS: Differentially expressed miRs in pancreatic cancer were analyzed through logging in GEO DataSets to download GSE112264. Fifty patients with pancreatic cancer who were treated in our hospital from May 2012 to January 2014 (Group A), 50 patients with benign pancreatic lesions during the same period (Group B), and 50 healthy individuals undergoing physical examinations (Group C) were enrolled in this study. The expression of miR-4730 in the serum and the cancer tissue was detected by qRT-PCR. The correlation of miR-4730 with pathological data, and the diagnostic values of differential indicators in the data were analyzed. The patients were followed up for 5 years to observe the relationship between miR-4730 and their survival. RESULTS: The analysis of the GEO chip showed 305 differentially expressed miRs, among which 225 were highly expressed and 80 were lowly expressed, with miR-4730 differentially expressed most. The expression of serum miR-4730 in Group A was significantly lower than that in Groups B and C (p<0.05), so miR-4730 had a diagnostic value. The expression of miR-4730 in the cancer tissue was significantly lower than that in the adjacent tissue. The correlation analysis showed that the expression of miR-4730 in the cancer tissue was positively correlated with that in the serum. Patients with low miR-4730 expression had poorly differentiated pancreatic cancer, and patients with stages III+IV of pancreatic cancer had higher incidences of lymphatic invasion and distal metastasis (p<0.05), so miR-4730 had a diagnostic value. The 3- and 5-year survival rates in the high miR-4730 expression group were higher than those in the low expression group (both p<0.05). TNM staging, lymphatic invasion, distal metastasis, and miR-4730 were independent prognostic factors for the 3- and 5-year survival of patients with pancreatic cancer. CONCLUSIONS: For patients with pancreatic cancer, those with low miR-4730 expression have poor survival and prognoses, so miR-4730 can be used as a potential observational index for the prognosis and diagnosis of the disease.

[Experience of diagnosis and treatment of lingual thyroglossal duct cyst].

Objective: To explore and analyse the imaging examinations, clinical presentation, operative methods complication and the surgical outcomes of lingual thyroglossal duct cyst (LTGDC) . Methods: The clinical data of 30 patients with LTGDC were analyzed retrospectively from January 2015 to October 2018 at the First Affiliated Hospital of Zhengzhou University. Results: 30 cases were treated with endoscopic coblation cauterization firstly. Follow-up for 7.5-45.0(25.4) months showed that 25 cases had no recurrence, 2 cases had no connection, 2 cases had recurrence once, and 1 cases had recurrence twice,the recurrence rate was 10.7%(3/28).Two patients recurred once, and the last operation was performed with endoscopic coblation cauterization, and no recurrence was found in the follow-up of 1 year; one patient recurred twice underwent the last operation with Sistrunk operation, and no recurrence was found in the follow-up of 1 year. There was no pharyngeal fistula and hoarseness in 28 patients. Conclusions: For LTGDC,especially, those of the first-episode children, endoscopic coblation cauterization is the first choice. Recurrent LTGDC can be treated by endoscopic coblation cauterization, so that patients with multiple recurrences can be considered the Sistrunk operation.

Circular RNA-ABCB10 suppresses hepatocellular carcinoma progression through upregulating NRP1/ABL2 via sponging miR-340-5p/miR-452-5p.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common liver malignancies worldwide with a high rate of recurrence and mortality. Circular RNA-ABCB10 (circ-ABCB10), 724 nucleotides in length, plays a pro-oncogenic role in tumor progression. However, the role of circ-ABCB10 in HCC is still unknown. Therefore, the objective of this study was to determine the role of circ-ABCB10 in HCC progression in vitro and in vivo and to elucidate the underlying mechanism. PATIENTS AND METHODS: Tumor tissues from patients with HCC and multiple HCC cell lines were used for in vitro experiments and a mouse xenograft model was used for in vivo experiments. Quantitative Real Time-PCR, Western blots, lentivirus transfection, cell proliferation assays, cloning formation, migration, and invasion assays, flow cytometry, Luciferase reporter assays, and biotin-coupled probe pull-down assays were performed to investigate the mechanism underlying the effect of circ-ABCB10 on HCC. RESULTS: The results revealed that the expression of circ-ABCB10 was downregulated in both HCC tissues and cell lines and was positively correlated with histological grade and tumor size. The overexpression of circ-ABCB10 exerted inhibitory effects on HCC cell proliferation, invasion, and migration. Mechanistic and functional evidence together showed that circ-ABCB10 elevated expressions of neuropilin-1 (NRP1) and ABL related gene (ABL2) by sponging miR-340-5p and miR-452-5p, which inhibited the progression of HCC. Furthermore, the in vivo study suggests that circ-ABCB10 inhibited tumor growth in nude mice. CONCLUSIONS: In brief, the results demonstrate that circ-ABCB10 exerts anti-tumor roles via miR-340-5p/miR-452-5p-NRP1/ABL2 signaling axis, providing a promising biomarker and therapeutic target for HCC.

[Experience of diagnosis and treatment for congenital pyriform sinus fistula].

Objective: To evaluate the imaging features, clinical presentation, operative methods complication and the surgical outcomes of the congenital pyriform sinus fistula(CPSF). Methods: The clinical data of 185 patients with CPSF treated from January 2013 to October 2017 at the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. Results: The lesions were predominantly on the left side(170/185). Among 185 cases, 146 cases received endoscopic coblation cauterization, 27 cases had traditional open surgery, 8 cases underwent endoscopic coblation cauterization plus traditional open surgery, 2 cases for endoscopic chemocauterization, and 2 cases for endoscopic electrosection. Twenty-eight cases recurred, with a recurrence rate of 15.1%. Postoperative hoarseness occurred in 22 cases, disappeared within 0.5-6.0 months later. Conclusions: Patients with a history of recurrent cervical abscess should be highly suspect the existence of CPSF. Endoscopic coblation cauterization is a kind of surgical method with minimal injury, with low recurrence rate and low operative risk.

Sequential therapy with "vacuum sealing drainage-artificial dermis implantation-thin partial thickness skin grafting" for deep and infected wound surfaces in children.

OBJECTIVE: To evaluate the efficacy of a "vacuum sealing drainage (VSD) - artificial dermis implantation (ADI) - thin partial thickness skin grafting (TSG)" sequential therapy for deep and infected wounds in children. MATERIALS AND METHODS: Fifty-three pediatric patients with deep and infected wounds were treated with sequential VSD-ADI-TSG therapy. The efficacy of this treatment was compared with that of the surgical debridement-change dressings-thin partial thickness skin grafting previously performed on 20 patients. Survival of tissue grafts, color and flexibility, subcutaneous fullness and scar formation of the graft site were examined and compared. RESULTS: The sequential therapy combined the advantages of the VSD treatment, in reducing tissue necrosis and infection on the wound surfaces and promoting the growth of granulation tissue, with the enhancement of grafting by artificial dermis. Compared with the 20 controls, skin grafted on the artificial dermis was more smooth and glossy, while the textures of the region were more elastic, and the scars were significantly lighter in Vancouver scale. CONCLUSION: The sequential VSD-ADI-TSG therapy is a simple and effective treatment for children with deep and infected wounds. LEVEL OF EVIDENCE: IV.

Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma.

AIMS: Several studies have shown the presence of helicobacter species in the human biliary tract and in the intestinal tract of animals. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and hepatocellular carcinoma (HCC). This study investigated whether helicobacter species could be detected in the liver of patients with HCC. METHODS: Liver samples from 20 patients with primary liver carcinoma diagnosed by histopathology and 16 controls without primary liver carcinoma were studied. Histology with standard and immunohistochemical stains, culture, and polymerase chain reaction (PCR) amplification using helicobacter genus specific 16S rRNA primers were used to detect the presence of bacteria. Amplified products were identified by Southern hybridisation and sequencing. A search for other genes specific for Helicobacter pylori was also performed. RESULTS: Helicobacter species 16S rDNA was found in eight of 20 samples of primary liver carcinoma, whereas none of the controls harboured this rDNA. Six helicobacter specific PCR amplicons were sequenced and were found to have 98.5-99.0% similarity to the 16S rDNA of H pylori. Of the eight positive samples, seven were positive in PCR using 26 kDa protein primers and six showed morphological and immunohistochemical evidence of H pylori. The cagA and glmM genes were detected in only two samples. The vacA and rps4 genes were not detected. CONCLUSIONS: Helicobacter can be present in the liver of patients with primary liver carcinoma and is probably linked to the carcinogenic process in the liver.

Novel microbial hydroxylation of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one.

The microbial transformation of the dl and the d-enantiomer of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) were investigated. Poor yields and poor resolutions were usually obtained for the hydroxylation reactions. Transformation of 1 by Cunninghamella blakesleeana gave 6 beta-, 7 beta-, 10 beta-, 15 alpha-hydroxy derivatives 4, 5, 6, 7, and 6 beta,10 beta-dihydroxy derivative 8; transformation of 1 by Cunninghamella echinulata afforded 5, 6, and 8. Biotransformation of dl-1 by Cunninghamella species usually gave 10 beta-hydroxy product with the low enanitomeric excess or as the racemic form. However, C. echinulata was able to efficiently differentiate the two enantiomers of 1 in the course of 6 beta,10 beta-dihydroxylation reactions. The d-enantiomer of the dl-1 was the better substrate for this type hydroxylation. The 7 beta and 15 alpha-hydroxylations of 1 by microbial cultures was unusual for 19-nor type steroids, and these hydroxylation reactions were presumably due to the presence of 17 alpha-ethynyl group.

Microbial hydroxylation of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one.

The microbial transformation of the racemic mixture of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) was investigated. Rhizopus nigricans (AS 3.2050), R. arrhizus (AS 3.4523), Aspergillus niger (AS 3.2744), A. ochraceus (AS 3.1408), and Curvularia lunata (NRRL 4381) transformed 1 into its 10 beta-hydroxy derivative (2) as a major metabolite. Biotransformation of 1 by Aspergillus ochraceus AS 3.1408 afforded 7 beta-hydroxy derivative (3) as the only product.

Accelerated healing by composites containing herb epimedium for osteoinductive regeneration.

Porous composites composed of hydroxyapatite (HA), herb epimedium (EP), and chitosan (CS) were used to improve the repair of rabbit bone defects. The in vivo implantation of the HA/CS-EP showed that homogeneous bone formation occurred after 12 weeks' implantation and possessed good osteogenesis. The osteogenic process of the HA/CS-EP group was different from that of the HA/CS group. Direct bone formation of osteoblasts with HA/CS-EP as the matrix could be observed. Compared with the group filled with HA/CS, the group filled with HA/CS-EP showed significant increases in the number of osteoblasts and the bone formation area, and the areas of new bone formation in the HA/CS-EP group after 4 or 12 weeks' implantation reached 33% and 87%, respectively. The novel repair system of HA/CS-EP can induce bone formation, increase osteoblast quantity and improve osteogenesis, for EP can significantly promote the proliferation and activity of osteoblasts in the early stage and accelerate bone remodeling in the later stage. Composites containing EP could be a promising material with multifunctions of osteoinduction, osteoconduction and medication for bone repair, and herb medicine EP could be used as an osteoinduction material for bone tissue engineering.

The pathological effect of Helicobacter pylori infection on liver tissues in mice.

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Some reports also suggest that it causes extragastric disease, including hepatitis. In this study, the pathological changes in the liver and gall bladder in H. pylori-colonized C57BL/6 mice were investigated. Twenty mice were inoculated orally with H. pylori strain SS1, and ten controls were injected with phosphate-buffered saline. Gastric colonization with H. pylori was assessed at 2 months after inoculation. Mice were examined at 8 months by histopathology, culture for H. pylori, and PCR for specific H. pylori genes. All C57BL/6 mice infected with H. pylori for 8 months developed severe gastric mucosal inflammation. Three mice showed mild-to-moderate multifocal hepatitis. The gall bladder mucosa of one H. pylori-infected mouse showed thickening of the mucous membrane with mild submucosal lymphocytic infiltration. H. pylori was observed morphologically in four liver specimens and six gall bladders from infected mice by immunohistochemistry. Specific H. pylori genes were also detected in six liver samples from infected mice, six samples of bile, and two blood samples by nested PCR. Thus, H. pylori inoculated orally may reach the hepatobiliary system and cause inflammation as an independent aetiological factor. The pathway to the liver may be via the blood or the biliary system.

Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems.

The objective of this study was to compare the osteogenic potential of human embryonic stem cells (hESCs) within two- and three-dimensional (2D and 3D) culture systems. hESCs of the H1 line (Wicell Inc., Madison, Wisc., USA) were induced to form embryoid bodies (EBs) through 5 days of suspension culture within non-adherent culture dishes. Following enzymatic dissociation, the EB-derived single cells were seeded on either novel 3D porous PLGA scaffolds or 2D culture dishes with the same total cell number. Osteogenic differentiation was induced through culture media supplemented with dexamethasone, L-ascorbic acid and beta-glycerophosphate. After 3 weeks of in vitro culture, quantitative and qualitative assays of osteogenic differentiation were conducted. Osteocalcin secretion and alkaline phosphatase (AP) activities were detected at significantly higher levels within 3D culture compared with the 2D system. Subsequently, the cell-scaffold constructs were implanted in iliac crest defects of immunosuppressed rabbits. After 4 weeks, the constructs were subsequently explanted and characterized by histology and X-ray analysis. Formation of new bone was detected within and around the implanted scaffolds. The results demonstrate that the osteogenic differentiation of human embryonic stem cells is enhanced in a 3D culture system compared to a 2D culture environment. Upon implantation in situ, the differentiating human embryonic stem cells can contribute positively to the repair and regeneration of bone defects.

Conditioned medium from activated microglia promotes cholinergic differentiation in the basal forebrain in vitro.

In earlier studies we found that treatment with interferon-gamma (IFN-gamma) produced an 8- to 11-fold increase in choline acetyltransferase (ChAT) in cultured cells taken from Embryonic Day 16 (E16) septal nuclei with adjacent basal forebrain (SN/BF). Since younger cultures responded even more profoundly to IFN treatment, we have tested the possibility that the action of IFN (or its intermediate; see below) is to prompt the cholinergic differentiation of neuronal precursors. SN/BF cultures of various ages were labeled with a retrovirus engineered to express beta-galactosidase (Lac-Z), and ChAT-positive descendants of the retrovirally labeled precursors were counted. IFN-gamma treatment of cultures caused as much as an 8.8-fold increase in the proportion of ChAT-positive cells present in Lac-Z-positive clones, suggesting that IFN promoted cholinergic differentiation in precursor populations. By contrast, bFGF increased clone size but did not change the proportion of ChAT-positive cells. NGF affected neither. Only ameboid microglia present in the cultures responded to IFN with characteristic nuclear translocation of the signal transducing molecule p91, suggesting that a microglial-derived molecule may mediate the action of IFN. Consistent with this hypothesis, conditioned media from cultures of enriched, activated microglia also increased ChAT activity in a dose-dependent fashion. Conditioned media from an unstimulated macrophage/monocyte cell line (RAW 264.7) also proved extremely efficacious in raising ChAT activity. In addition, conditioned media from both activated microglia and RAW 264.7 cells increased the proportion of ChAT-positive cells in retrovirally labeled clones to the same extent as IFN itself, suggesting the possibility that they contain the molecule(s) that mediates the action of IFN. Preliminary characterization of this molecule suggests that it is a very stable and large protein. Together these data suggest that a molecule promoting cholinergic differentiation is produced by activated microglia and other macrophage-like cells. The identity of this molecule and its precise role in normal development await its further purification.