Carbon-nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes.

Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon-nitrogen transmutation. The reaction features selective nitrogen insertion into the C-C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.

A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Miniaturized Laser Probe for Exosome-Based Cancer Liquid Biopsy.

Exosomes have been established as a valuable tool for clinical applications for the purpose of liquid biopsy and therapy. However, the clinical practice of exosomes as cancer biopsy markers is still to a very low extent. Active mode optical microcavity with microlaser emission has aroused as a versatile approach for chemical and biological sensing due to its benefits of larger photon population, increased effective Q-factor, decreased line width, and improved sensitivity. Herein, we report a label-free and precise quantification of exosome vesicles and surface protein profiling of breast cancer exosomes using functionalized active whispering gallery mode (WGM) microlaser probes. A detection limit of 40 exosomes per microresonator was achieved. The proposed system enabled a pilot assay of quantitative exosome analysis in cancer patients' blood with only a few microliters of sample consumption, holding good potential for large-scale cancer liquid biopsy. Multiplexed functionalization of the optical microresonator allowed us to profile cancer exosomal surface markers and distinct subclasses of breast cancer-associated exosomes and monitor drug treatment outcomes. Our findings speak volumes about the advantages of the WGM microlaser sensor, including very small sample consumption, low detection limit, high specificity, and ease of operation, offering a promising means for precious clinical sample analysis.

[Relationship between home literacy environment and emotional regulation in children: the mediating effect of the parent-child relationship]. / å®¶åº­é˜ è¯»çŽ¯å¢ƒä¸Žå„¿ç«¥æƒ ç»ªè°ƒèŠ‚èƒ½åŠ›çš„å ³ç³»ï¼šäº²å­å ³ç³»çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them. METHODS: A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method. RESULTS: The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (ß=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect. CONCLUSIONS: The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

Giant Enhancement of Raman Scattering by a Hollow-Core Microstructured Optical Fiber Allows Single Exosome Probing.

Microstructured optical fibers (MOFs) provide solutions for breaking through the bottlenecks in areas of high-power transmission and high-efficiency optical waveguides. Other than transporting light waves, MOFs can synergistically combine microfluidics and optics in a single fiber with an unprecedented light path length not readily achievable by planar optofluidic configurations. Here, we demonstrate that hollow-core anti-resonant optical fibers (HcARFs) can significantly enhance Raman scattering by over three orders of magnitude (EF ≈ 5000) compared with a planar setup, due to the joint mechanisms of strong light-matter interaction in the fiber core and the cumulative effect of the fiber. The giant enhancement enables us to develop the first optical fiber sensor to achieve single cancer exosome detection via a sandwich-structured strategy. This enables a multiplexed analysis of surface proteins of exosome samples, potentially allowing an accurate identification of the cellular origin of exosomes for cancer diagnosis. Our findings could expand the applications of HcARF in many exciting areas beyond the waveguide.

Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer.

Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured antiresonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs-dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.

Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity.

Single cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Förster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules.

Effect of Intravenous Paracetamol on Opioid Consumption in Multimodal Analgesia After Lumbar Disc Surgery: A Meta-Analysis of Randomized Controlled Trials.

Background: Intravenous paracetamol, as an adjunct to multimodal analgesia, has been shown to successfully reduce opioid consumption after joint arthroplasty, abdominal surgery, and caesarean delivery. However, there are limited data on the opioid-sparing effect of intravenous paracetamol on lumbar disc surgery. Objectives: The aim of this study was to investigate the effectiveness and safety of intravenous paracetamol for reducing opioid consumption in lumbar disc surgery. The primary outcome was cumulative opioid consumption within 24 h postoperatively. Method: We followed the PRISMA-P guidelines and used GRADE to assess the quality of evidence. The review was registered in PROSPERO under the registration number CRD42021288168. Two reviewers conducted electronic searches in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science (Clarivate Analytics). Randomized controlled trials (RCTs) that compared the postoperative opioid consumption of intravenous paracetamol with placebo in lumbar discectomy were included. Results: Five trials comprising a total of 271 patients were included. The overall opioid consumption within 24 h postoperatively was reduced [mean difference (MD), -10.61 (95% CI, -16.00 to -5.22) mg, p = 0.0001, I2 = 90%] in patients with intravenous paracetamol. Intravenous paracetamol significantly reduced the postoperative pain scores at 1 h [MD, -2.37 (95%CI, -3.81 to -0.94), p = 0.001, I2 = 82%], 2 h [MD, -3.17 (95%CI, -3.85 to -2.48), p < 0.00001, I2 = 38%], 6 h [MD, -1.75 (95%CI, -3.10 to -0.40), p = 0.01], 12 h [MD, -0.96 (95%CI, -1.77 to -0.15), p = 0.02], and 24 h [MD, -0.97 (95%CI, -1.67 to -0.27), p = 0.006] compared with the placebo. There were no differences in postoperative adverse effects. Conclusion: Intravenous paracetamol reduced postoperative opioid consumption and decreased postoperative pain scores without increasing adverse effects. The overall GRADE quality of the evidence was rated as low to moderate. Intravenous paracetamol appears to be an applicable option as an important part of multimodal analgesia for postoperative analgesia after lumbar disc surgery. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42021288168.

[Single-segment lumbar microdiscectomy:drainage or not].

OBJECTIVE: To evaluate the safety and feasibility of single-segment lumbar microdiscectomy without drainage. METHODS: The clinical data of 135 patients with single-segment lumbar disc herniation treated by microdiscectomy surgery from January 2018 to August 2019 were retrospectively analyzed. There were 95 males and 40 females, aged from 18 to 40 years old, with a mean of (28.3±5.4) years. They were divided into drainage group (78 cases) and non-drainage group (57 cases) according to whether the drainage tube was placed during operation. The general conditions of patients were recorded such as age, gender, operation segment, body mass index(BMI), symptom duration, follow-up time, operation time, intraoperative blood loss, out-of-bed time, hospital stay, postoperative drainage removal time and drainage volume of drainage group, postoperative body temperature. VAS of incisional pain in supine resting state on the 1 and 3 days after operation, the VAS of low back pain and lower extremity radiating pain during ground exercise before operation, 3 days, 1 month and 3 months after operation were compared. Oswestry Disability Index (ODI) was collected before operation, 1 month and 3 months after operation. The ratio of complications was calculated such as symptomatic incision hematoma, poor incision healing, incision infection, exacerbation and progressive aggravation of neurological dysfunction, and unplanned secondary surgery. RESULTS: There were no significant differences in age, gender, operation segment, BMI, symptom duration, follow-up time, operation time, intraoperative blood loss, and postoperative body temperature between two groups. The average hospital stay and out-of-bed time in non-drainage group were shorter than in drainage group(P=0.0000). VAS of incision pain in non-drainage group was lower than that in control group at 1 and 3 days after surgery (P<0.05). Postoperative low back pain VAS and ODI of all patients were significantly reduced compared with those before surgery. No symptomatic hematoma occurred in two groups. Postoperative neurological dysfunction immediately aggravated each one patient in two groups, and no progressive aggravation of neurological function was found in two groups. Incision infection occurred in one case in each of the two groups, and both were cured by drug treatment; poor incision healing occurred in one case in each of the two groups, and both were healed after repeated dressing changes. There was one case of unplanned second operation in drainage group, the patient received a second operation due to disc protrusion recurrence within 1 month. CONCLUSION: Single-segment lumbar microdiscectomy without drainage can shorten the average hospital stay and promote early exercise out of bed, and reduce the trauma and stress reaction of drainage. No drainage may be an option for patients with enhanced recovery after lumbar microdiscectomy.

[Value of Elastography Strain Ratio Combined with Breast Ultrasound Imaging Reporting and Data System in the Diagnosis of Breast Nodules].

Objective To explore the value of elastography strain ratio(SR)combined with breast ultrasound imaging reporting and data system(BI-RADS-US)in the differential diagnosis of breast nodules.Methods A total of 471 breast nodules(from 471 patients)were reclassified by SR combined with BI-RADS-US.With the pathology results as gold standard,the area under the receiver operating characteristic(ROC)curve(AUC)was employed to evaluate the diagnostic performance,and the sensitivity,specificity,and accuracy were compared between the combined method and BI-RADS-US.Results Among the 471 breast nodules,180 nodules were benign and 291 were malignant.The AUC of the combined method was statistically significantly higher than that of BI-RADS-US(0.798 vs. 0.730;Z= 2.583, P= 0.010).SR,BI-RADS-US,and the combined method for diagnosing breast nodules had the sensitivity of 86.6%,99.0%,and 96.6%,the specificity of 67.2%,47.2%,and 63.3%,and the accuracy of 79.2%,79.2%,and 83.9%,respectively.The combined method increased the specificity from 47.2%(BI-RADS-US)to 63.3%(χ 2=14.25,P < 0.001),and downgraded 57.5%(42/73)benign nodules of BI-RADS category 4A to category 3.Conclusions SR combined with BI-RADS-US can improve the diagnostic performance for breast nodules.Especially,it can improve the specificity,avoiding unnecessary biopsy of breast nodules.

[Values of the Quantitative Parameters of Contrast-enhanced Ultrasound in the Diagnosis of Thyroid Benign and Malignant Nodules].

Objective To investigate the value of contrast-enhanced ultrasound(CEUS)quantitative parameters in the diagnosis of thyroid benign and malignant nodules. Methods The CEUS features of 85 histopathologically confirmed thyroid nodules were quantitatively analyzed using five parameters including rising time(RT),time to peak(TTP),area under the curve(AUC),maximum intensity(Imax),and mean transit time(mTT).The dynamic vascular pattern(DVP)curves were also drawn. Results The Imax(Z=-7.08,P=0.01)and AUC(Z=-2.03,P=0.04)of thyroid malignant nodules were significantly smaller than those of thyroid tissue,and the Imax(Z=-1.35,P=0.02)and AUC(Z=-0.21,P=0.02)of thyroid benign nodules were significantly larger than those of thyroid tissue.There were significant differences between thyroid benign and malignant nodules in Imax(Z=-4.16,P=0.00),AUC(Z=-3.01,P=0.01),and DVP curve types(P=0.00).RT(Z=-0.28,P=0.62),TTP(Z=-0.10,P=0.89),and mTT(Z=-0.79,P=0.05)were not significantly different between thyroid benign and malignant nodules. Conclusion The quantitative parameters of CEUS,especially Imax and AUC parameters,are valuable in the diagnosis of benign and malignant thyroid nodules.

Integration of black phosphorus and hollow-core anti-resonant fiber enables two-order magnitude enhancement of sensitivity for bisphenol A detection.

Hollow core anti-resonant fiber (HARF) has found a handful applications in optical communications, nonlinear optics and high power delivery. The intrinsic property of the fiber also renders it an ideal candidate for biosensing, which has not been explored intensively. Herein, we demonstrate an optical fiber sensing platform, taking advantages of the state-of-the-art HARF technology and superior physicochemical properties of 2D material black phosphorus, for ultra-sensitive detection of bisphenol A (BPA) in blood and environmental samples. The specially designed HARF can not only achieve broadband transmission of light, but also confine light in the low refractive-index liquid core, ensuring maximum overlap of light and liquid core. Modification of the inner surface of HARF with 2D black phosphorus nanoflakes functionalized with fluorescently labeled BPA-specific aptamer provides a smart sensing interface enabling highly selective detection of BPA via measuring the fluorescence. The limit of detection is 1.69pM, which is more than two orders of magnitude enhancement compared to the conventional plate assay. The proposed assay is not interfered with the BPA analogues BPB and BPS. The long optical path with tight optical confinement greatly enhances the analyte-light interaction and improves the sensitivity of the sensing platform. The proposed sensing platform can be further developed for versatile applications.

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature.

BACKGROUND: Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma (MNT) and micronodular thymic carcinoma with lymphoid hyperplasia (MNC), whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells. This type of tumor is rare; therefore, the corresponding clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. CASE SUMMARY: This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods. Morphologically, this tumor type is a series of benign to malignant pedigrees. We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma: (1) Tumor cells with moderate-to-severe dysplasia; (2) Tumor cell mitotic figures > 2/10 high-power fields; (3) Appearance of neoplastic necrosis; (4) No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor; (5) Tumor cells with a Ki-67 index ≥ 10%; and (6) Tumor cells express CD5. Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT. It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above. CONCLUSION: Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis, which offers a practical reference for oncologists and pathologists.

Antimonene Nanoflakes: Extraordinary Photoacoustic Performance for High-Contrast Imaging of Small Volume Tumors.

Photoacoustic imaging (PAI) has evolved to a stage that high-performance exogeneous contrast agents are urgently needed for imminent biomedical and clinical applications. Given that a material meets the basic criteria of efficient photoacoustic conversion, high biocompatibility, and fast excretion, great effort has been devoted to evaluating various materials for developing advantageous contrast agents to explore the full potentials of PAI. One focus is through modification of the current agents to boost their PA performance; whilst the other focus is to develop novel agents. Antimonene (AM) has emerged as a promising candidate for next generation of electronics among 2D materials due to its outstanding properties. Herein, it is reported that liquid-phase exfoliated antimonene exhibits extraordinary photoacoustic performance, which is not only more advantageous than other 2D materials, such as black phosphorus, graphene oxide, and transition metal dichalcogenides, but also superior to the commonly used PA contrast agents, such as ICG and gold nanorods. An insight analysis reveals that the unique thermal property of AM, including intrinsic low thermal conductivity and the morphology-related high interfacial thermal conductivity, might interpret the high photothermal conversion efficiency, and thus the excellent photoacoustic performance. The prodigious performance allows sensitive monitoring of intracellular events and high-quality in vivo tumor imaging.

Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation.

BACKGROUND: Unconjugated bilirubin (UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved. AIM: To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis. METHODS: Acute colitis was induced by 3% (w/v) dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d. Concurrently, mice with colitis were administered 0.2 mL UCB (400 µmol/L) by intra-gastric gavage for 7 d. Disease activity index (DAI) was monitored daily. Mice were sacrificed at the end of the experiment. The length of the colon and weight of the spleen were recorded. Serum level of D-lactate, intestinal digestive proteases activity, and changes to the gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins. RESULTS: Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight (colon length: 4.92 ± 0.09 cm vs 3.9 ± 0.15 cm; spleen weight: 0.33 ± 0.04 vs 0.74 ± 0.04, P < 0.001). UCB administration inactivated digestive proteases (chymotrypsin: 18.70 ± 0.69 U/g vs 44.81 ± 8.60 U/g; trypsin: 1.52 ± 0.23 U/g vs 9.05 ± 1.77 U/g, P < 0.01), increased expression of tight junction (0.99 ± 0.05 vs 0.57 ± 0.03, P < 0.001), decreased serum level of D-lactate (31.76 ± 3.37 µmol/L vs 54.25 ± 1.45 µmol/L, P < 0.001), and lowered histopathological score (4 ± 0.57 vs 7 ± 0.57, P < 0.001) and activity of myeloperoxidase (46.79 ± 2.57 U/g vs 110.32 ± 19.19 U/g, P < 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor (TNF) α and interleukin 1ß (TNF-α: 52.61 ± 7.81 pg/mg vs 105.04 ± 11.92 pg/mg, interleukin 1ß: 13.43 ± 1.68 vs 32.41 ± 4.62 pg/mg, P < 0.001), decreased expression of Toll-like receptor 4 (0.61 ± 0.09 vs 1.07 ± 0.03, P < 0.001) and myeloid differentiation primary response gene 88 (0.73 ± 0.08 vs 1.01 ± 0.07, P < 0.05), and increased expression of TNF-receptor-associated factor 6 (0.79 ± 0.02 vs 0.43 ± 0.09 P < 0.05) and inhibitor of kappa B α (0.93 ± 0.07 vs 0.72 ± 0.07, P < 0.05) in the colon. CONCLUSION: UCB can protect intestinal barrier function, regulate normal intestinal homeostasis, and suppress inflammation via the Toll-like receptor 4/ nuclear factor-κB signaling pathway.

Comprehensive preoperative regime of selective gut decontamination in combination with probiotics, and smectite for reducing endotoxemia and cytokine activation during cardiopulmonary bypass: A pilot randomized, controlled trial.

BACKGROUND: Both selective digestive decontamination (SDD) and probiotics have been reported to reduce endotoxemia. However, the available results are conflicting and few studies have investigated the combined effect of SDD and probiotics. This study aimed to examine the effectiveness of a comprehensive preoperative regimen of SDD in combination with probiotics and smectite on perioperative endotoxemia and cytokine activation in patients who underwent elective cardiac surgery with cardiopulmonary bypass (CPB) in a pilot, prospective, randomized, controlled trial. METHODS: Patients who underwent elective Aortic Valve Replacement or Mitral Valve Replacement surgery from July 2010 to March 2015 were included. In total, 30 eligible patients were randomly assigned to receive either the comprehensive preoperative regimen (n = 15) (a combination of preoperative SDD, probiotics, and smectite) or the control group (n = 15) who did not receive this treatment. The levels of endotoxin, IL-6, and procalcitonin were measured at the time before anesthesia induction, immediately after cardiopulmonary bypass (CPB), 24 hours after CPB, and 48 hours after CPB. The primary outcomes were changes in endotoxin, IL-6, and procalcitonin concentrations after CPB. RESULTS: The mean levels of change in endotoxin levels after CPB in patients receiving the comprehensive preoperative regimen was marginally significantly lower than those in control group (F = 4.0, P = .0552) but was not significantly different for procalcitonin (F = .14, P = .7134). An interaction between group and time for IL-6 was identified (F = 4.35, P = .0231). The increase in IL-6 concentration immediately after CPB in the comprehensive preoperative group was significantly lower than that in the control group (P = .0112). The changes in IL-6 concentration at 24 hours and 48 hours after CPB were not significant between the comprehensive preoperative group and control group. CONCLUSION: The present pilot, prospective, randomized, controlled study in patients undergoing cardiac surgery with CPB demonstrated that 3 days of a comprehensive preoperative regime of SDD in combination with probiotics and smectite may reduce the endotoxin and IL-6 levels after CPB compared with the control group.

Adaptive optics via self-interference digital holography for non-scanning three-dimensional imaging in biological samples.

Three-dimensional imaging in biological samples usually suffers from performance degradation caused by optical inhomogeneities. Here we proposed an approach to adaptive optics in fluorescence microscopy where the aberrations are measured by self-interference holographic recording and then corrected by a post-processing optimization procedure. In our approach, only one complex-value hologram is sufficient to measure and then correct the aberrations, which results in fast acquisition speed, lower exposure time, and the ability to image in three-dimensions without the need to scan the sample or any other element in the system. We show proof-of-principle experiments on a tissue phantom containing fluorescence particles. Furthermore, we present three-dimensional reconstructions of actin-labeled MCF7 breast cancer cells, showing improved resolution after the correction of aberrations. Both experiments demonstrate the validity of our method and show the great potential of non-scanning adaptive three-dimensional microscopy in imaging biological samples with improved resolution and signal-to-noise ratio.

Precise and label-free tumour cell recognition based on a black phosphorus nanoquenching platform.

Breast cancer is a type of heterogeneous disease, which manifests as different molecular subtypes due to the complex nature of tumour initiation, progression, and metastasis. Accurate identification of a breast cancer subtype plays crucial roles in breast cancer management. Herein, taking advantage of the efficient quenching properties of black phosphorus nanosheets (BPNSs), in combination with the high specificity of ssDNA (or RNA) aptamer, a fluorometric duplexed assay that is capable of the simultaneous detection of two tumour markers within one run is developed. When mixed with BPNSs, the fluorescence of both FAM and Cy3 labelled aptamers was quenched. The presence of different subtypes of breast cancer cells restored the FAM and Cy3 fluorescence in distinct patterns according to their intrinsic features. The proposed assay can precisely recognise label-free breast cancer subtypes, providing an efficient method for cell type identification and guidance for subsequent breast cancer treatment. The significance of the proposed study is two-fold. First, we provide a simple method for sensitive and specific tumour cell detection; secondly, and more importantly, the proposed dual assay allows precise recognition of tumour cells and thus opens a door for rapid characterization and sorting of a wide range of tumours without using expensive instruments.

Distribution of human papillomavirus genotypes in cervical lesions.

The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical examination should be conducted, including colposcopy and biopsy.

Rituxan nanoconjugation prolongs drug/cell interaction and enables simultaneous depletion and enhanced Raman detection of lymphoma cells.

Antibody therapy is a type of immunotherapy that uses monoclonal antibodies (mAbs) to specifically bind to target cells to fight cancer. These mAbs have been conjugated with a number of nanocarriers to realize the targeted delivery of chemotherapeutics. Previous data indicate that the conjugation of a mAb to a nanocarrier promoted the faster internalization (endocytosis) of the nanoconjugates. In this study, we report that the crosslinking of Rituxan, an anti-lymphoma mAb, with silver nanoparticles prevented Rituxan from entering cells and prolonged drug/cell interaction. This finding was confirmed by both imaging flow cytometric and laser scanning confocal microscopic analyses of the fluorescently labeled nanoconjugates and cells. Furthermore, nanoconjugated Rituxan resulted in the enhanced capping of CD20 molecules on the cell membrane. We were able to show that the prolonged drug/cell interaction and enhanced capping directly contributed towards improved therapeutic efficiency. This represents a significant finding indicating that the nanocarrier served not only as a simple platform for targeted delivery, but also markedly altered the antibody performance at the molecular level and mediated key biological functions. The nanoconjugates also served as a Raman probe to specifically detect single live lymphoma cells with high sensitivity via surface-enhanced Raman scattering (SERS). Via integrating the single-cell level detection sensitivity of SERS with targeted and enhanced depletion ability, this nanoconjugate can be applied as a promising tool in lymphoma theranostics.