Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

Midazolam suppresses ischemia/reperfusion-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway.

Myocardial ischemia/reperfusion (I/R) injury causes irreversible injury to the heart, thereby causing acute myocardial infarction. Midazolam is a benzodiazepine commonly utilized in anesthesia and intensive care. Research has indicated that midazolam plays a critical role in many diseases; however, the function of midazolam in myocardial injury induced by I/R still needs further investigation. The infarct size and damage to the heart tissues were examined through 2,3,5-triphenyl tetrazolium chloride (TTC) staining and hematoxylin and eosin staining. The creatine kinase-myocardial band isoenzyme, lactate dehydrogenase, and aspartate aminotransferase levels were tested using commercial kits. Cell apoptosis was determined through TUNEL staining or flow cytometry assays. Bax, Bcl-2, cleaved caspase-3, phospho-38 (p-p38), p38, p-JNK, JNK, extracellular signal-regulated kinases (ERK), and p-ERK expression was examined through Western blot. In our study, midazolam was shown to suppress the infarct size and heart tissue damage and reduce myocardial enzyme leakage in I/R rats. Additionally, midazolam was found to retard cardiomyocyte apoptosis in I/R rats. The JNK/p38 MAPK signaling pathway in I/R rats was inhibited by midazolam. Our findings demonstrated that in hypoxia/reoxygenation (H/R) - mediated H9C2 cells, anisomycin abolished the suppressive effects of midazolam on the JNK/p38 MAPK signaling pathway. Next, exploration discovered that anisomycin abolished the cytoprotective effects of midazolam on H/R-treated H9C2 cell apoptosis. In conclusion, this work demonstrated that midazolam retarded I/R-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway. These results may provide new insight into the treatment of myocardial I/R injury.

NIR-II-activated biocompatible hollow nanocarbons for cancer photothermal therapy.

Photothermal therapy has attracted extensive attentions in cancer treatment due to its precise spatial-temporal controllability, minimal invasiveness, and negligible side effects. However, two major deficiencies, unsatisfactory heat conversion efficiency and limited tissue penetration depth, hugely impeded its clinical application. In this work, hollow carbon nanosphere modified with polyethylene glycol-graft-polyethylenimine (HPP) was elaborately synthesized. The synthesized HPP owns outstanding physical properties as a photothermal agent, such as uniform core-shell structure, good biocompatibility and excellent heat conversion efficiency. Upon NIR-II laser irradiation, the intracellular HPP shows excellent photothermal activity towards cancer cell killing. In addition, depending on the large internal cavity of HPP, the extended biomedical application as drug carrier was also demonstrated. In general, the synthesized HPP holds a great potential in NIR-II laser-activated cancer photothermal therapy.

Exposure to heavy metals and trace elements among pregnant women with twins: levels and association with twin growth discordance.

Background: Twin growth discordance is one of the leading causes of perinatal mortality in twin pregnancies. Whether prenatal exposure to heavy metals and trace elements is associated with twin growth discordance has not been studied yet. Objective: To evaluate the prenatal level of heavy metals and trace elements in twin pregnancy and its relationship with twin growth discordance. Methods: This study involving 60 twin pairs and their mothers was conducted in Zhejiang Province, China, in 2020-2021. The concentration of heavy metals and trace elements in maternal blood, umbilical cord, and placenta were collected at delivery and measured by inductively coupled plasma tandem mass spectrometer. The association of prenatal level with twin growth discordance was evaluated using conditional logistic regression. Results: High levels of heavy metal elements (thallium in maternal blood and umbilical cord blood of larger twins, vanadium in the placenta of larger twins) and trace elements (iodine in the placenta of larger twins) during pregnancy, as well as low levels of heavy metal elements (strontium in the umbilical cord blood of larger twins, strontium and chromium in the umbilical cord blood of smaller twins, strontium in the placenta of larger twins, molybdenum and lead in the placenta of smaller twins and difference of molybdenum in the placenta of twins), are associated with intertwin birthweight discordance. Univariate regression analyses showed a significant effect of gestational age at delivery and eleven trace element data on intertwin birthweight discordance. Multivariable logistic regression analysis with transformed variables as dichotomous risk factors combined with baseline demographic characteristics showed Tl in maternal blood as an independent risk factor. The model constructed by combining Tl in maternal blood (OR = 54.833, 95% CI, 3.839-83.156) with the gestational week (OR = 0.618, 95% CI, 0.463-0.824) had good predictive power for intertwin birthweight discordance (AUC = 0.871). The sensitivity analysis results indicate that the effect of maternal blood thallium on intertwin birthweight discordance is stable and reliable. Conclusion: To our knowledge, ours is the first case-control study to investigate the association between elevated maternal thallium levels before delivery and twin growth discordance.

Natural evolution and risk factors for adverse outcome in selective intrauterine growth restriction under expectant management: A retrospective observational study.

OBJECTIVE: To evaluate the natural evolution of and risk factors for the adverse outcome of monochorionic twins with selective intrauterine growth restriction (sIUGR) under expectant management. METHODS: Retrospective study conducted in a single tertiary referral center. The clinical characteristics and neonatal outcomes of 153 patients with sIUGR under expectant management were evaluated, and the risk factors leading to adverse outcomes were explored. RESULTS: Fifty-one patients (33.3%) showed a changed pattern in umbilical artery Doppler at the last examination, occurring in all types of sIUGR. Compared with type Ia, the gestational age of diagnosis was earlier, the estimated fetal body weight difference at diagnosis was greater, and the rate of severe neonatal complications in both fetuses was significantly higher in type Ib (P < 0.05). Univariate and multivariate logistic regression analyses showed that type II (odds ratio [OR] 5.41, 95% confidence interval [CI] 2.34-12.51; P < 0.001) and type III (OR 9.11, 95% CI 3.02-27.50; P < 0.001) were associated with adverse perinatal outcomes in sIUGR. CONCLUSION: Type II and III sIUGR are independent risk factors predicting adverse outcomes of sIUGR. Different types of sIUGR could convert to each other. The outcome of type Ib is poorer than that of type Ia.

Nomogram to predict postpartum hemorrhage in cesarean delivery for twin pregnancies: a retrospective cohort study in China.

Background: Postpartum hemorrhage (PPH) is the most common cause of maternal morbidity and mortality worldwide. A reliable risk assessment tool for PPH could optimize available interventions to reduce adverse maternal outcomes. Objective: The objective of this study was to explore a nomogram predicting the risk of postpartum hemorrhage after cesarean delivery for twin pregnancies. Methods: This single-center retrospective cohort study conducted twin pregnancies who underwent cesarean delivery between January 2014 and July 2021. Propensity score matching at baseline was used to match PPH (blood loss ≥1000 mL) and non-PPH group (blood loss <1000 mL). A nomogram was developed to predict the risk of PPH in cesarean delivery for twin pregnancies. The receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were, respectively, used to evaluate the discrimination, calibration, and clinical utility of the prediction models. Results: After propensity score matching, 186 twin pregnancies in the PPH group were matched with 186 controls in the non-PPH group. Seven independent prognostic variables, including antepartum albumin, assisted reproductive technology, hypertensive disorders of pregnancy, placenta previa, placenta accrete spectrum, intrapartum cesarean delivered, and estimated weights of twins, were used to build the nomogram. Based on the performance of the model, it appears that a good calibration (Hosmer-Lemeshow χ2 = 4.84, P > 0.05), an excellent predictive ability (area under the curve: 0.778, 95% CI: 0.732-0.825), and a good positive net benefit in the predictive model have been achieved. Conclusion: The nomogram was first generated to predict PPH in cesarean delivery for twin pregnancies, which could help clinicians to provide a reference for the preoperative surgical plan, choose optimal treatments, optimize healthcare resources, and thereby reduce the associated adverse maternal outcomes.

The risk factors for miscarriage of viable intrauterine pregnancies in patients with heterotopic pregnancy after surgical intervention.

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.

Predictive factors associated with disease recurrence in patients with severe intrahepatic cholestasis of pregnancy: a retrospective study of 118 cases.

PURPOSE: To compare the clinical characteristics of pregnant women and perinatal outcomes with or without recurrent severe intrahepatic cholestasis of pregnancy (sICP), and identify possible factors associated with disease recurrence. METHODS: A retrospective study of 164,603 deliveries was performed to identify pregnant women diagnosed with sICP in the previous pregnancy from January 2012 to December 2020. Eligible patients were divided into two subgroups according to the status of disease recurrence in the second pregnancy: recurrent severe ICP (r-sICP) and non-recurrent severe ICP (nr-sICP). Demographics, clinical characteristics, maternal and perinatal outcomes, and potential factors linked to disease recurrence were analyzed. RESULTS: Totally 118 patients were enrolled and respectively classified into the r-sICP group (n = 63) and the nr-sICP group (n = 55). The proportion of hepatitis B virus (HBV) infection (HBsAg+, HBeAg+, HBcAb+) and early-onset ICP (<28 weeks) in the r-sICP group in the previous pregnancy were higher than those in the nr-sICP group. In the second delivery, neonatal outcomes in the r-sICP group were worse than those in the nr-sICP group. Logistic regression analysis of predictive factors for disease recurrence in the second delivery revealed that the combination of HBV infection and early-onset ICP in the previous delivery had the steepest receiver-operating characteristic (ROC) curve value 0.720 (95%CI: 0.629-0.812). CONCLUSION: Patients with sICP displayed a higher recurrence rate in the second pregnancy. Being <28 weeks at the time of ICP diagnosis and having HBV infection in the previous delivery appear to be independent predictive factors for disease recurrence of sICP.

Long non­coding RNA LOC284454 promotes hepatocellular carcinoma cell invasion and migration by inhibiting E­cadherin expression.

Numerous studies have elucidated the impact of long non­coding (lnc)RNAs in carcinogenesis; however, the role and the mechanism of the lncRNA LOC284454 in hepatocellular carcinoma (HCC) remain unknown. In the present study, reverse transcription­quantitative PCR assay, χ2 analysis and Kaplan­Meier analysis were performed to assess the role of LOC284454 in HCC. Furthermore, MTT and Transwell assays were performed to measure the function of LOC284454 on HCC cell proliferation, invasion and migration. RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull­down, fluorescence in situ hybridization and luciferase reporter assays were performed to explore the mechanism of LOC284454. The results revealed that LOC284454 expression was aberrantly elevated in HCC and increased LOC284454 expression was markedly associated with aggressive clinicopathological factors and shorter survival time in patients with HCC, suggesting that LOC284454 behaved as an oncogenic factor in HCC. Mechanistically, LOC284454 could bind with the enhancer of zeste homolog 2 (EZH2) mRNA and subsequently inhibit E­cadherin expression by binding to its promoter region. The rescue assay demonstrated that E­cadherin was essential for the oncogenic function of LOC284454 in HCC cells. The present results suggested that the LOC284454/EZH2/E­cadherin axis may be an alternative therapeutic target for patients with HCC.

Micro-/Nano-Structures on Biodegradable Magnesium@PLGA and Their Cytotoxicity, Photothermal, and Anti-Tumor Effects.

The size and structural control of particulate carriers for imaging agents and therapeutics are constant themes in designing smart delivery systems. This is motivated by the causal relationship between geometric parameters and functionalities of delivery vehicles. Here, both in vitro and in vivo, the controlling factors for cytotoxicity, photothermal, and anti-tumor effects of biodegradable magnesium@poly(lactic-co-glycolic acid (Mg@PLGA) particulate carriers with different sizes and shell thicknesses are investigated. Mg@PLGA microspheres fabricated by microfluidic emulsification are shown to have higher Mg encapsulation efficiency, 87%, than nanospheres by ultrasonic homogenization, 50%. The photothermal and anti-tumor effects of Mg@PLGA spheres are found to be dictated by their Mg content, irrelevant to size and structural features, as demonstrated in both in vitro cell assays and in vivo mice models. These results also provide important implications for designing and fabricating stimuli-responsive drug delivery vehicles.

Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration.

The design of orthopedic biomaterials has gradually shifted from "immune-friendly" to "immunomodulatory," in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg2+) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg2+-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-ß1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The in vivo results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.

Stabilization/solidification of lead in MSWI fly ash with mercapto functionalized dendrimer Chelator.

This work compares the performance of stabilizing Pb by Sodium sulfide (Na2S), Sodium phosphate (Na3PO4), thiourea (H2NCSNH2), and mercapto functionalized dendrimer (TEPA-SNa) in MSWI fly ash, including leaching toxicity analysis and leaching behavior analysis, as a function of pH. The leaching toxicity in fly ash indicated that leaching value of Pb stabilized by Na2S, Na3PO4, and H2NCSNH2 has remained higher than the limit value (0.25mg/L) with a dosage of 10%. However, the leaching value associated with TEPA-SNa approaches zero at a dosage of 3%. The effective leaching test results showed the leaching amount of Pb stabilized by TEPA-SNa with a dosage of 3% to be 3.58 mg/kg less than the maximum allowable amount of leaching (5mg/kg), but the amount of Pb leached by Na2S, Na3PO4, and H2NCSNH2 was much higher than 5mg/kg. The leaching behavior of Pb as a function of pH showed that the leaching concentration of Pb stabilized by TEPA-SNa can approach zero at a dosage of 5% no matter how the pH changes. In summary, TEPA-SNa can interact with Pb(2+) in the acid-base environment and effectively immobilize Pb(2+) in fly ash in the long term.