[Treatment of patent ductus arteriosus in very preterm infants in China].

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

[Preliminary study on the effect of B7H3 interaction with fibronectin on apoptosis of human chronic myeloid leukemia cells].

Objective: To explore the effect of the interaction between B7H3 and fibronectin (FN) on the apoptosis of human chronic myeloid leukemia K562 cells. Methods: The expression of B7H3 molecules in K562 cells was detected using flow cytometry and B7H3 overexpressing cells were constructed. The interaction between B7H3 and FN was detected using the co-immunoprecipitation technology. After adding exogenous FN, cell experiments were performed to detect changes in adhesion and cell apoptosis. The changes in apoptosis-related proteins and PI3K/AKT signaling pathway were detected using Western blot. Results: The expression of B7H3 was low in K562, and the cell line K562 OE (overexpression) -B7H3 and the control cell line K562 NC (negative control) -B7H3 were obtained after lentivirus transfection. There is an interaction between B7H3 and FN (P=0.036) , and this interaction promoted cell adhesion (P<0.05) , inhibited cell apoptosis (P<0.05) , and activated the PI3K/AKT signaling pathway (P<0.05) . Conclusion: B7H3 interacts with FN to promote cell adhesion and may inhibit K562 cell apoptosis by activating the PI3K/AKT signaling pathway.

MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis.

OBJECTIVE: Recovery of blood flow after ischemic cardiomyopathy can lead to aggravation of myocardial injury. This is very detrimental to the patient's prognosis. The purpose of this study was to investigate the effects and mechanisms of microRNA-140-5p (miR-140-5p) on myocardial ischemia-reperfusion injury (IRI). MATERIALS AND METHODS: We made the myocardial IRI model in rats and detected the expression of miR-140-5p. Anta-miR-140-5p was administered intravenously in the tail of rats. Then, we used 2, 3, 5-triphenyl tetrazolium chloride staining, cardiac function test, and histological experiment to observe the changes in myocardial infarct size, cardiac function, and cardiomyocyte apoptosis in rats. In in vitro experiments, we induced the damage of H9c2 cells by hypoxia/reoxygenation (H/R) model and detected the effects of miR-140-5p on the proliferation ability and apoptosis level of H9c2 cells. TargetScan database was used to predict the binding target of miR-140-5p and we verified the effect of miR-140-5p on the target through Dual-Luciferase reporter assay. RESULTS: MiR-140-5p is highly expressed in myocardial tissue of IRI rats and anta-miR-140-5p can reduce myocardial infarct area, improve cardiac function, and reduce the rate of myocardial cells apoptosis in rats. The expression of miR-140-5p in H/R-induced H9c2 cells was higher than that in the control group. MiR-140-5p inhibitor was found to promote the proliferation and decrease the apoptosis level of H9c2 cells, while miR-140-5p mimic was the opposite. The TargetScan system predicts the presence of binding sites for miR-140-5p and B-cell lymphoma-2 like 1 (BCL2L1). The Dual-Luciferase reporter assay found that miR-140-5p can bind to BCL2L1 and promote its degradation. In addition, the inhibition of BCL2L1 was found to promote apoptosis in H9c2 cells. CONCLUSIONS: In myocardial IRI, miR-140-5p targets BCL2L1 and promotes its degradation, thereby inducing myocardial apoptosis.

[Value of serum alpha-fetoprotein for the prognostic evaluation of hepatitis B virus-related acute-on-chronic liver failure treated with artificial liver].

Objective: To investigate the value of alpha-fetoprotein (AFP) level on survived hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver. Methods: Clinical indicators of HBV-ACLF patients who were previously treated with plasma exchange-based artificial liver at our department were retrospectively collected. The difference of serum AFP level between the survival and the death group was compared at 30, 90 and 180 days after artificial liver treatment. The ROC curves of the subjects were plotted, and the sensitivity and specificity of AFP for the survival prediction of the patients at 30, 90 and 180 days after artificial liver surgery were calculated. AFP was divided into a high AFP group and a low AFP group using median value. AFP and postoperative survival predictive value at 30, 90, and 180 days were analyzed. Results: A total of 93 cases were included in this study. The AFP of the survival group at 30, 90, and 180 days was (231.0 ± 286.2) ng / ml, (237.69 ± 297) ng / ml, (229.44 ± 286.46) ng/ml, and the death group was (76.4 ± 104.7) ng/ml, (103.13 ± 116.99) ng / ml, (136.34 ± 2.9.29) ng/ml, respectively. AFP of the death group was significantly lower than the corresponding survival group (P < 0.05). Receiver operating characteristic (ROC) curve analyses indicated that the area under the curve (AUC) and its 95% confidence interval at 30, 90, and 180 days after artificial liver surgery were 0.739 (0.611 ~ 0.867), 0.675 (0.550 ~ 0.80), 0.653 (0.524 ~ 0.781), respectively. The median serum AFP value was 110 ng/ml, and the survival analysis showed that the survival time of the high AFP group was significantly higher than the low AFP group at 30 d (P = 0.01), 90 d (P = 0.04) and 180 d (P = 0.03) after artificial liver surgery. Conclusion: Serum AFP can be used as a predictor of survival for HBV-ACLF patients after artificial liver therapy and its clinical value needs to be further verified by the larger sample size.

MiR-885-5p promotes gastric cancer proliferation and invasion through regulating YPEL1.

OBJECTIVE: Dysregulation of microRNAs (miRNAs) was found to play crucial roles in the carcinogenesis of multiple human cancers. This study was aimed to investigate the biological function of miR-885-5p and associated mechanisms in gastric cancer (GC). MATERIALS AND METHODS: Reverse Transcription-quantitative Polymerase Chain Reaction was used to measure miR-885-5p level in GC cell lines and normal cell line. The effects of miR-885-5p expression on cell proliferation, colony formation, and invasion were investigated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell invasion assay, respectively. Furthermore, Luciferase activity reporter assay and Western blot were conducted to validate Yippee-like-1 (YPEL1) as a direct target of miR-885-5p. RESULTS: We found that miR-885-5p expression level was elevated in GC cell lines compared with normal cell line. Additionally, the knockdown of miR-885-5p inhibits GC cell proliferation, colony formation, and cell invasion in vitro. Notably, rescue experiments demonstrated that the knockdown of YPEL1 partially reversed the effects of miR-885-5p on GC cell growth and invasion. CONCLUSIONS: The present study suggested that miR-885-5p regulates GC proliferation, colony formation, and invasion via targeting YPEL1.

[Tolerance and pharmacodynamics phase â clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma].

Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n=3; 375 mg/m(2), n=3; 500 mg/m(2), n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19(+), CD20(+) B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m(2) group, 14 events of AE in 375 mg/m(2) group and 20 events of AE in 500 mg/m(2) group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20(+) and CD19(+) B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration: Chinadrugtrials, CTR20140762.

[A case report of tracheotomy complicated by hemorrhage after radical operation of tongue].

A 55-year old middle-aged male presented swelling lymph nodes in neck and mass in left tongue for three mouths. Physical examination shows a size 5 cm×5 cm mass in tongue and went over the midline. The mandibular lymph nodes were touched with moderate tenderness and little mobility in bilateral. The laboratory results, function of the kidney and heart liver, nasopharyngeal fiber area were basically normal. The result of CT and MRI shows the mass reached the lingual muscle layer and several suspected metastatic lymph nodes in neck. Pathological examination shows much atypical squamous cell reached muscle layer, diagnosed as highly differentiated squamous cell carcinoma. We determined to treat the patient with removal of primary lesion and bilateral neck dissection. We performed tracheotomy after the operation. During the surgeon's blunt dissection of the trachea surrounding tissue, the hemorrhage occurred. After staunching the blood, we transferred sternocleidomastoid muscle flap to fill the soft gas space and finished the surgery.

[Chronic neutrophilic leukemia complicated with multiple myeloma: two cases report and literature review].

OBJECTIVE: To explored the diagnosis and treatment of chronic neutrophilic leukemia (CNL) complicated with multiple myeloma (MM). METHODS: The clinical features and molecular biological characteristics of 2 patients with CNL complicated with MM were summarized, and the diagnosis and treatment of the patients were retrospectively reviewed. RESULTS: The diagnosis of CNL complicated with MM was established in 2 cases. Case 1 had CSF3R mutation (P733T), but CSF3R-exon 14 mutation and SETBP1 mutation were all negative. The neutrophil count returned to normal when MM was successfully treated in case 1. When the patient relapsed, neutrophil count increased again. CONCLUSION: Coexistence of CNL and MM is rare. CSF3R is a very important molecular marker for CNL. To the best of our knowledge, it's the first time to report the coexistence of CNL and MM carried CSF3R mutation (P733T). Chemotherapy regimens for MM may be effective in the treatment of CNL complicated with MM.

Helicobacter pylori infection and normal colorectal mucosa-adenomatous polyp-adenocarcinoma sequence: a meta-analysis of 27 case-control studies.

AIM: The study aimed to determine whether Helicobacter pylori infection is associated with colorectal adenocarcinoma and to quantify the extent of the risk. METHOD: A literature search was performed to identify studies published between 1995 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for colorectal adenocarcinoma and adenomatous polyp. RESULTS: Twenty-seven case-controlled studies involving 3450 adenocarcinoma patients, 1304 adenomatous polyp patients and more than 4000 controls were included. Helicobacter pylori was associated with an increased risk of colorectal adenocarcinoma and adenomatous polyp [odds ratio (OR) 1.24, 95% CI 1.12-1.37, P = 0.66; OR 1.87, 95% CI 1.53-2.28, P = 0.81]. There was a significant association between the CagA-positive strain and adenocarcinoma risk (OR 1.22, 95% CI 1.08-1.37, P = 0.05). In addition, there was an increased risk of tubular adenoma and villous adenoma formation (OR 3.06, 95% CI 1.98-4.73, P = 0.14; OR 2.05, 95% CI 0.84-4.97, P = 0.86). CONCLUSION: The meta-analysis suggests a promoting effect of Helicobacter pylori on the risk of adenocarcinoma. It also suggests that Helicobacter infection might have its influence at the start of the adenomatous polyp disease sequence.

Association of DNMT1 and DNMT3B polymorphisms with breast cancer risk in Han Chinese women from South China.

Patterns of DNA methylation are established and maintained by a family of DNA methyltransferases (DNMTs). Aberrant promoter DNA methylation of tumor suppressor genes is found in breast cancer. Association studies between DNMT gene polymorphisms and breast cancer in various populations have reported inconsistent results. This study assessed the associations of single nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2 with breast cancer among Han Chinese women from South China. Sixteen SNPs (rs2114724, rs2228611, rs2228612, rs8101866, and rs16999593 in DNMT1; rs13420827, rs11887120, rs13428812, rs1550117, rs11695471, and rs6733301 in DNMT3A; rs2424908, rs2424913, and rs6087990 in DNMT3B; rs113593938 in DNMT3L, and rs11254413 in DNMT2) in 408 women with breast cancer and 469 controls were genotyped using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Two SNPs, rs16999593 in DNMT1 and rs2424908 in DNMT3B, were significantly associated with breast cancer risk. The heterozygous genotype CT of rs16999593 was associated with increased breast cancer risk [odds ratio (OR) = 1.60; 95% confidence interval (95%CI) = 1.20-2.14; P = 0.0052], whereas rs2424908 was associated with decreased risk (OR = 0.62; 95%CI = 0.46-0.84; P = 0.0061). Other DNMT polymorphisms showed no significant associations with breast cancer risk in the study population. Haplotype CGTC of rs2114724, rs2228611, rs8101866, and rs16999593 in DNMT1 differed significantly as a risk factor between the case and control groups (OR = 1.51; 95%CI = 1.18-1.93; P = 0.0012). The heterozygous genotypes of rs16999593 in DNMT1 and rs2424908 in DNMT3B were strongly associated with breast cancer risk.

Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell.

BACKGROUND: Overexpression of melanoma cell adhesion molecule (MCAM or CD146), a novel member of the immunoglobulin gene superfamily, promotes invasion, metastasis, growth and survival of malignant cells. MATERIALS AND METHODS: Here, we used a human U6 promoter-driven DNA template approach to induce short hairpin RNA (shRNA)-triggered RNA interference to block CD146 gene expression in the human high-metastatic adenoid cystic carcinoma (ACC) cell line ACC-M. reverse transcription-polymerase chain reaction, Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, flow cytometry analysis and in vitro perineural invasion (PNI) assay were used to investigate the effects of CD146 on cell growth, cell cycle distribution and cell PNI activity in ACC-M cells. RESULTS: We have demonstrated that different shRNAs can specifically knockdown the transcription of CD146, resulting in the inhibition of cell proliferation, and G(0)/G(1) to S phase arrest in ACC-M cells. Knockdown of CD146 by shRNA resulted in decrease of the ACC-M PNI activity in vitro. CONCLUSION: These findings suggested that CD146 was an ACC-related gene and CD146 may play an important role in the carcinogenesis, progression and PNI activity of ACC.

The role of Schwann cell differentiation in perineural invasion of adenoid cystic and mucoepidermoid carcinoma of the salivary glands.

Twenty cases of adenoid cystic carcinoma (ACC) and 18 cases of mucoepidermoid carcinoma (MEC), were examined for expression of the Schwann cell markers S100 protein and glial fibrillary acidic protein (GFAP) by immunohistochemical staining. The relationship between expression of S100 and GFAP and the occurrence of perineural invasion was assessed. Ultrastructural localization of S100 and GFAP was examined by immunoelectron microscopy, and the co-expression of S100 and muscle actin by double fluorescence immunostain. Perineural invasion was found in 11 ACCs (55%) and 0 MECs (0%). S100 and GFAP were expressed in most of the ACCs but none of the MECs; the difference in the rate of perineural invasion and expression of S100 and GFAP was significant between ACC and MEC (P<0.001). There was a correlation between the expression of S100 and GFAP and perineural invasion in salivary malignancy (P<0.001). The ultrastructures of S100- and GFAP-positive cells were consistent with the characteristics of myoepithelial cells. Double fluorescence immunostain also showed that S100 and muscle actin were expressed in the same type of ACC cells. These results indicate that Schwann cell differentiation correlates with perineural invasion in salivary malignancy, and occurs in modified myoepithelial cells of ACC.

An inhibitor of type-1 cyclo-oxygenase in tissues from human pregnancy.

BACKGROUND: Previous work has shown that first trimester human decidua contains a protein which directly inhibits the activity of type-1 cyclo-oxygenase (COX-1). METHODS: Activity assays for cyclo-oxygenase types I and II were developed. Cell cytosol was prepared from a number of different sources: human placenta and decidua (first and third trimester), two placental cell-lines (BeWo and TCL-1), an endometrial stromal cell-line and K562 erythroleukemia cells. The effects of all cytosols on activity of type I cyclo-oxygenase, and of cytosols from BeWo choriocarcinoma and decidual cells on type II enzyme, were tested. RESULTS: Cytosols from first trimester human placenta, two placental cell-lines, an endometrial stromal cell-line and K562 erythroleukemia cells all inhibited the type I enzyme. The inhibitor protein could not be detected in third trimester human decidual cells after labor, and was present only at very low levels in third trimester decidua prior to the onset of labor. Cytosols from BeWo and decidual cells had no effect on the activity of the type-2 cyclo-oxygenase enzyme. CONCLUSIONS: The inhibitor of type I cyclo-oxygenase was not specific to pregnancy-related tissues, and may be a general regulator of this enzyme. Lower levels of inhibitor were present at term, but the physiological significance of this is unclear. The cytosolic inhibitor appears to be specific to the type I enzyme.

Effects of interleukin-6 and tumor necrosis factor-alpha on prostaglandin production by cultured human fetal membranes.

In this study we investigated the effects of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin production by cultured human fetal membranes. These cytokines stimulate prostaglandin synthesis by isolated components of human fetal membranes, but their effects on the intact tissue comprising amnion, chorion and decidua were not known. TNF-alpha added to the maternal side of the membrane activated decidual production of PGF2 alpha but had no effects on synthesis of PGE2 or PGE2 metabolites. Addition of TNF-alpha to the fetal side of the membrane increased production of PGE2 by amnion and PGE2 metabolites from chorion. The addition of IL-6 to the fetal or the maternal side of the membrane increased production of PGE2 from amnion and PGE2m from chorion, suggesting that IL-6 might pass through the fetal membrane. IL-6 had no effect on decidual PGF2 alpha production. These results suggest that TNF-alpha may be involved in labor by increasing decidual prostaglandin synthesis, whereas IL-6 is less likely to have a role.