Comparison of the effects of contrast-enhanced ultrasound and conventional ultrasound-guided radiofrequency ablation on benign thyroid nodules.

Objective: To compare the effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound-guided radiofrequency ablation (RFA) on benign thyroid nodules (BTNs). Methods: In this retrospective observational study, the data of 72 patients with BTNs who received RFA treatment in The Fourth Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to December 2021 were retrospectively reviewed and selected. The records showed that 34 patients received RFA under the guidance of conventional ultrasound (conventional ultrasound group) and 38 patients received RFA under the guidance of CEUS (CEUS group). The effect of treatment, complications and recurrence of the two groups were compared and analyzed. Results: There was a smaller volume of thyroid nodules in the two groups immediately post-operation. The incidence of complications was lower in the CEUS group (5.26%) compared to the conventional ultrasound group (23.53%) (P<0.05). The recurrence rate at 6-months (0.00% vs 11.76%) and 12- months (2.63% vs 20.59%) post-operation was lower in the CEUS group compared to the conventional ultrasound group (P<0.05). Conclusions: Compared with conventional ultrasound, CEUS-guided RFA is effective in treating BTNs, with smaller postoperative nodule volume, reduced occurrence of surgical complications, and reduced recurrence rate of thyroid nodules.

Quantitative Imaging of Lipid Synthesis and Lipolysis Dynamics in Caenorhabditis elegans by Stimulated Raman Scattering Microscopy.

Quantitative methods to precisely measure cellular states in vivo have become increasingly important and desirable in modern biology. Recently, stimulated Raman scattering (SRS) microscopy has emerged as a powerful tool to visualize small biological molecules tagged with alkyne (C≡C) or carbon-deuterium (C-D) bonds in the cell-silent region. In this study, we developed a technique based on SRS microscopy of vibrational tags for quantitative imaging of lipid synthesis and lipolysis in live animals. The technique aims to overcome the major limitations of conventional fluorescent staining and lipid extraction methods that do not provide the capability of in vivo quantitative analysis. Specifically, we used three bioorthogonal lipid molecules (the alkyne-tagged fatty acid 17-ODYA, deuterium-labeled saturated fatty acid PA-D31, and unsaturated fatty acid OA-D34) to investigate the metabolic dynamics of lipid droplets (LDs) in live Caenorhabditis elegans ( C. elegans). Using a hyperspectral SRS (hsSRS) microscope and subtraction method, the interfering non-Raman background was eliminated to improve the accuracy of lipid quantification. A linear relationship between SRS signals and fatty acid molar concentrations was accurately established. With this quantitative analysis tool, we imaged and determined the changes in concentration of the three fatty acids in LDs of fed or starved adult C. elegans. Using the hsSRS imaging mode, we also observed the desaturation of fatty acids in adult C. elegans via spectral analysis on the SRS signals from LDs. The results demonstrated the unique capability of hsSRS microscopy in quantitative analysis of lipid metabolism in vivo.

Mitochondrial Imaging with Combined Fluorescence and Stimulated Raman Scattering Microscopy Using a Probe of the Aggregation-Induced Emission Characteristic.

In vivo quantitative measurement of biodistribution plays a critical role in the drug/probe development and diagnosis/treatment process monitoring. In this work, we report a probe, named AIE-SRS-Mito, for imaging mitochondria in live cells via fluorescence (FL) and stimulated Raman scattering (SRS) imaging. The probe features an aggregation-induced emission (AIE) characteristic and possesses an enhanced alkyne Raman peak at 2223 cm-1. The dual-mode imaging of AIE-SRS-Mito for selective mitochondrion-targeting was examined on a homemade FL-SRS microscope system. The detection limit of the probe in the SRS imaging was estimated to be 8.5 µM. Due to the linear concentration dependence of SRS and inertness of the alkyne Raman signal to environmental changes, the intracellular distribution of the probe was studied, showing a local concentration of >2.0 mM in the mitochondria matrix, which was >100-fold higher than the incubation concentration. To the best of our knowledge, this is the first time that the local concentration of AIE molecules inside cells has been measured noninvasively and directly. Also, the nonquenching effect of such AIE molecules in cell imaging has been verified by the positive correlation of FL and SRS signals. Our work will encourage the utilization of SRS microscopy for quantitative characterization of FL probes or other nonfluorescent compounds in living biological systems and the development of FL-SRS dual-mode probes for specific biotargets.

Anti-N-methyl-D-aspartate receptor(NMDAR) antibody encephalitis presents in atypical types and coexists with neuromyelitis optica spectrum disorder or neurosyphilis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a clinically heterogeneous disorder characterized by epileptic seizures, psychosis, dyskinesia, consciousness impairments, and autonomic instability. Symptoms are always various. Sometimes it presents in milder or incomplete forms. We report 4 cases of anti-NMDAR encephalitis with incomplete forms, 3 cases of which were accompanied by neuromyelitis optica spectrum disorder or neurosyphilis respectively. CASE PRESENTATION: A 33-year-old man presented with dysarthria, movement disorder and occasional seizures. He had 6 relapses in 28 years. When suffered from upper respiratory tract syndrome, he developed behavioral and consciousness impairment. Cranial MRI was normal. Viral PCR studies and oncologic work-up were negative. Anti-NMDAR antibody was detected in CSF and serum. A 21-year-old female manifested dizziness and diplopia ten months and six months before, respectively. Both responded to steroid therapy and improved completely. This time she presented with progressive left limb and facial anesthesia, walking and holding unsteadily. Spinal cord MRI follow-up showed abnormality of medulla oblongata and cervical cord(C1). Anti-AQP4 and anti-NMDAR were positive in CSF. Steroid-pulse therapy ameliorated her symptoms. A 37-year-old male experienced worsening vision. He was confirmed neurosyphilis since the CSF tests for syphilis were positive. Protein was elevated and the oligoclonal IgG bands(OB) and anti-NMDAR was positive in CSF. Anti-aquaporin 4(AQP4) antibodies and NMO-IgG were negative. Cranial MRI showed high FLAIR signal on frontal lobe and low T2 signal adjacent to the right cornu posterious ventriculi lateralis. Treatment for neurosyphlis was commenced with gradual improvement. A 39-year-old male, developed serious behavioral and psychiatric symptoms. Examination showed abnormal pupils and unsteady gait. He was confirmed neurosyphilis according to the CSF tests for syphilis. Anti-NMDAR was positive in CSF and serum. Cranial MRI showed lateral ventricles and the third ventricle enlargement and signal abnormality involving bilateral temporal lobe, corona radiate and centrum semiovale. PenicillinG, pulsed methylprednisolone and intravenous immunoglobulin was administered. He was stable. CONCLUSION: Anti-NMDAR encephalitis can present in atypical types. When relapsing, it may present with partial aspects or with isolated symptoms of the full-blown syndrome. Anti-NMDAR encephalitis may be related to neuromyelitis optica spectrum disorder or neurosyphilis.

Self-degradable photosensitizer exhibiting bacterial agglutination and membrane insertion toward safe photodynamic ablation.

Self-oxidative degradation photosensitizers capable of bacterial agglutination and membrane insertion were fabricated based on a simple co-assembly strategy, for efficiently killing P. aeruginosa and rapidly deactivating their function post-treatment.

Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET and 11C-Labeled Radioligands That Avoid Radiometabolite Contamination.

Phosphodiesterase-4D (PDE4D) has emerged as a significant target for treating neuropsychiatric disorders, but no PET radioligand currently exists for robustly quantifying human brain PDE4D to assist biomedical research and drug discovery. A prior candidate PDE4D PET radioligand, namely [11C]T1650, failed in humans because of poor time stability of brain PDE4D-specific signal (indexed by total volume of distribution), likely due to radiometabolites accumulating in brain. Its nitro group was considered to be a source of the brain radiometabolites. Methods: We selected 5 high-affinity and selective PDE4D inhibitors, absent of a nitro group, from our prior structure-activity relationship study for evaluation as PET radioligands. Results: All 5 radioligands were labeled with 11C (half-time, 20.4 min) in useful yields and with high molar activity. All displayed sizable PDE4D-specific signals in rhesus monkey brain. Notably, [11C]JMJ-81 and [11C]JMJ-129 exhibited excellent time stability of signal (total volume of distribution). Furthermore, as an example, [11C]JMJ-81 was found to be free of radiometabolites in ex vivo monkey brain, affirming that this radioligand can provide robust quantification of brain PDE4D with PET. Conclusion: Given their high similarity in structures and metabolic profiles, both [11C]JMJ-81 and [11C]JMJ-129 warrant further evaluation in human subjects. [11C]JMJ-129 shows a higher PDE4D specific-to-nonspecific binding ratio and will be the first to be evaluated.

An Empirical Quantitative Structure-Activity Relationship Equation Assists the Discovery of High-Affinity Phosphodiesterase 4D Inhibitors as Leads to PET Radioligands.

A positron emission tomography (PET) radioligand for imaging phosphodiesterase 4D (PDE4D) would benefit drug discovery and the investigation of neuropsychiatric disorders. The most promising radioligand to date, namely, [11C]T1650, has shown unstable quantification in humans. Structural elaboration of [11C]T1650 was therefore deemed necessary. High target affinity in the low nM range is usually required for successful PET radioligands. In our PDE4D PET radioligand development, we formulated and optimized an empirical equation (log[IC50 (nM)] = P1 + P2 + P3 + P4) that well described the relationship between binding affinity and empirically derived values (P1-P4) for the individual fragments in four subregions commonly composing each inhibitor (R2 = 0.988, n = 62). This equation was used to predict compounds that would have high inhibitory potency. Fourteen new compounds were obtained with IC50 of 0.3-10 nM. Finally, eight compounds were judged to be worthy of future radiolabeling and evaluation as PDE4D PET radioligands.

Combination of ultra-micro angiography and sound touch elastography for diagnosis of primary Sjögren's syndrome: a diagnostic test.

Background: Primary Sjogren's syndrome (PSS) is a prevalent systemic autoimmune disease. However, the current gold standard diagnostic method is invasive, increasing the difficulty of patient acceptance and then delaying treatment. Therefore, a non-invasive, convenient, and effective diagnostic method is required. Although salivary gland ultrasonography (SGUS) is a good choice, previous studies have not found suitable parameters to diagnose PSS. Salivary gland involvement in patients with PSS leads to changes in gland stiffness and vascularization, so we combined sound touch elastography (STE) and ultra-microangiography (UMA) to demonstrate the diagnostic effectiveness of ultrasonography in PSS. Methods: This prospective study included 27 patients with PSS and 20 healthy controls, with all participants forming a random series. Major salivary glands were examined with UMA and STE. Color pixel percentage (CPP), shear wave velocity (SWV), and Young's modulus values were investigated, and the combination of these parameters was evaluated by logistic regression analysis. Results: For Young's modulus and SWV in the elasticity index, combined evaluation of both parotid glands and submandibular glands yielded an area under the receiver operating characteristic (ROC) curve (AUC) and confidence interval (CI) of 0.819, 0.699-0.938 and 0.801, 0.677-0.925, respectively. The levels of CPP in the parotid glands were significantly elevated (P<0.003) among patients compared to those in the control group, whereas the CPP values in the submandibular glands were not statistically different (P>0.086). We evaluated the elasticity values of the total 4 glands and the CPP of parotid glands together by logistic regression modeling. The ROC curve yielded an AUC of 0.954 (95% CI: specificity 0.849-0.994) which showed the best accuracy, with 92.6% sensitivity and 85.0% specificity. Conclusions: The use of STE and UMA to examine the salivary glands may aid in the diagnosis of PSS, and their combination may be a promising method. This is good news for patients with PSS who are not suitable or unwilling to undergo labial gland biopsy.

The diagnostic value of novel ultrasound attenuation analysis in detecting liver steatosis identified by the controlled attenuation parameter: a diagnostic accuracy study.

Background: Ultrasound attenuation analysis (USAT) is a type of novel ultrasound attenuation imaging that can be used to detect hepatic steatosis based on the attenuation coefficient. We sought to evaluate the diagnostic accuracy for assessing the severity of liver steatosis by USAT using the controlled attenuation parameter (CAP) as a reference in patients with non-alcoholic fatty liver diseases (NAFLD) and chronic hepatitis B (CHB) infections. Methods: In total, 326 consecutive subjects with or without chronic liver diseases were enrolled in this study who underwent CAP examination and USAT to evaluate hepatic steatosis from October 2022 to November 2022 at The Fourth Affiliated Hospital of Zhejiang University School of Medicine. Hepatic steatosis stage (S) was determined by CAP according to the following cut-off values recommended by the manufacturer: S ≥ S1 (≥11%, mild): 238 dB/m; S ≥ S2 (≥34%, moderate): 259 dB/m; and S ≥ S3 (≥67%, severe): 292 dB/m, and thus the optimal cut-off values for the USAT were acquired. The area under the receiver operating characteristic curves (AUROCs) for the categories of steatosis were used to measure the diagnostic accuracy of USAT. Results: A total of 296 patients were recruited, including 101 (34.1%) patients with NAFLD, 172 (58.1%) with CHB and the remainder were healthy control subjects (7.8%). We used the CAP as the reference standard and found that the USAT increased gradually as the stage of steatosis increased (P<0.001). A strong positive correlation was found between USAT and CAP (r=0.787, P<0.001). In the whole population, the AUROCs of the USAT for S ≥ S1, S ≥ S2 and S ≥ 3 were 0.89, 0.90, and 0.90, respectively, and the cut-off values according to the Youden index for S ≥ S1, S ≥ S2, and S ≥ 3 were 0.62, 0.66, and 0.72 dB/cm/MHz, respectively. Our study showed that the USAT had a good ability to detect hepatic steatosis in NAFLD and CHB patients. Conclusions: USAT had a strong association with CAP and a good diagnostic capability in the detection of hepatic steatosis, which appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis.

Diagnostic accuracy of contrast-enhanced ultrasound synchronized with shear wave elastography in the differential diagnosis of benign and malignant breast lesions: a diagnostic test.

Background: Breast cancer (BC) is one of the most common malignancies affecting women. Timely and accurate diagnosis is crucial for treatment and prognosis. Some studies have found that elastography combined with microperfusion characteristics, which are mostly described by contrast-enhanced ultrasound (CEUS), could help in the diagnosis of breast lesions. This study aimed to assess the diagnostic performance of CEUS synchronized with shear wave elastography (SWE) in discriminating between benign and malignant breast lesions by using real-time contrast elastography images to analyze shell elasticity and contrast intensity. Methods: A total of 26 pathologically confirmed breast lesions in 26 patients were retrospectively reviewed. Each patient underwent conventional B-mode ultrasound, CEUS, and then SWE data was obtained from a frame of image that was almost identical to the B-mode and CEUS images when acquiring time to peak (TTP). Breast lesions were evaluated based on the Breast Imaging Reporting and Data System (BI-RADS) and quantitative characteristics that describe the stiffness and intensity of contrast of the 1.0-3.0 mm shell region. Quantitative aspects of the inner lesions and shell on the elastogram included the maximum (Emax), mean (Emean), and minimum (Emin) Young's moduli. Quantitative enhanced features included maximum (Imax) and mean (Imean) intensity. We took postoperative pathological results as the gold standard. Receiver operating characteristic (ROC) curves were used to compare the diagnostic efficacy of the 2 examination modalities, either alone or in combination. Results: The age of the patients ranged from 23 to 76 years, with a 42.5-year average age. In all breast lesions, 19 were benign and 7 were malignant. SWE synchronized with CEUS can effectively improve the diagnostic performance of breast lesions, and Emean + Imean and Emax + Emean + Imean of shell at 1.0 mm both had the highest area under the curve (AUC) of 0.86 [95% confidence interval (CI): 0.67, 0.96], with the sensitivity and specificity of 71.43% and 89.47%, respectively. Conclusions: The combination of CEUS and SWE has a better diagnostic value in differentiating benign and malignant breast lesions compared to separate techniques.

Effects of comfort nursing on pain and quality of life in children undergoing tonsillectomy.

OBJECTIVE: To observe the effect of comfort nursing on pain, quality of life, and nutritional status in children undergoing tonsillectomy. METHODS: In this retrospective study, a total of 114 children who underwent tonsillectomy in Chun'an Hospital of Traditional Chinese Medicine were divided into a research group and a control group according to the nursing methods, with 57 cases in each group. The control group received routine nursing care, and the research group received additional comfort nursing. We compared the pain level (assessed by visual analogue scale (VAS) scale), quality of life (assessed by Generic Quality of Life Inventory-74 (GQOLI-74)), relevant clinical indicators (postoperative swallowing recovery time, wake-up time, and hospital stay), nutrition indicators (total blood protein and albumin), sleep quality (assessed by Pittsburgh Sleep Quality Index (PAQI)), nursing satisfaction, and postoperative complications between the two groups. RESULTS: After postoperative nursing, the VAS scores and PSQI scores were significantly decreased (both P<0.05), and the GQOLI-74 scores were significantly increased (P<0.05) in both groups. The postoperative swallowing recovery time, wake-up time, and hospital stay in the research group were significantly shorter than those in the control group (all P<0.05). The levels of total serum protein and albumin in the research group were significantly higher than those in the control group (both P<0.05). The research group showed a significantly higher satisfaction rate and lower incidence of complications as compared with the control group (both P<0.05). The results of the logistic regression analysis showed that postoperative upper respiratory infection and the degree of tonsillar embedment were independent risk factors for hemorrhage after tonsillectomy (P<0.05). CONCLUSION: In children undergoing tonsillectomy, providing comfort nursing can significantly reduce pain and improve their quality of life.

Supramolecular coordination complexes as diagnostic and therapeutic agents.

The metal-based drugs represented by cisplatin, carboplatin, and oxaliplatin, prevail in cancer treatment, whereas new therapeutics are extremely slow to step into the clinic. Poor pharmacokinetics, multidrug resistance, and severe side effects greatly limit the development of metal-based anticancer drugs. The robustness and modular composition of supramolecular coordination complexes allow for the incorporation of novel diagnostic and therapeutic modalities, showing promising potentials for precise cancer theranostics. In this mini review, we highlight the recent advances in the development of supramolecular coordination complexes as diagnostic and therapeutic agents. The key focuses of these reports lie in searching sophisticated coordination ligands and nanoformulations that can potentially solve the issues faced by current metal-based drugs including imaging, resistance, toxicity, and pharmacological deficiencies.

Vision redemption: Self-reporting AIEgens for combined treatment of bacterial keratitis.

Bacterial keratitis (BK) is one of the most commonly leading causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Herein, we report a cationic diphenyl luminogen with aggregation-induced emission called IQ-Cm containing isoquinolinium and coumarin units for theranostic study of BK. IQ-Cm has no obvious cytotoxicity to mammalian cells below a certain concentration, and could preferentially bind to bacteria over mammalian cells. IQ-Cm can be used as a sensitive self-reporting probe to rapidly discriminate live and dead bacteria by the visual emission colors. The intrinsic dark toxicity to bacteria and generation of reactive oxygen species under light irradiation endow IQ-Cm with excellent antibacterial activity in vitro and in BK rabbit models infected with S. aureus. The present study provides a sensitive and efficient theranostic strategy for rapid discrimination of various bacterial states and the combined treatment of BK based on the intrinsic dark antibacterial activity and photodynamic therapy effect.

Mitochondria-Specific Aggregation-Induced Emission Luminogens for Selective Photodynamic Killing of Fungi and Efficacious Treatment of Keratitis.

The development of effective antifungal agents remains a big challenge in view of the close evolutionary relationship between mammalian cells and fungi. Moreover, rapid mutations of fungal receptors at the molecular level result in the emergence of drug resistance. Here, with low tendency to develop drug-resistance, the subcellular organelle mitochondrion is exploited as an alternative target for efficient fungal killing by photodynamic therapy (PDT) of mitochondrial-targeting luminogens with aggregation-induced emission characteristics (AIEgens). With cationic isoquinolinium (IQ) moiety and proper hydrophobicity, three AIEgens, namely, IQ-TPE-2O, IQ-Cm, and IQ-TPA, can preferentially accumulate at the mitochondria of fungi over the mammalian cells. Upon white light irradiation, these AIEgens efficiently generate reactive 1O2, which causes irreversible damage to fungal mitochondria and further triggers the fungal death. Among them, IQ-TPA shows the highest PDT efficiency against fungi and negligible toxicity to mammalian cells, achieving the selective and highly efficient killing of fungi. Furthermore, we tested the clinical utility of this PDT strategy by treating fungal keratitis on a fungus-infected rabbit model. It was demonstrated that IQ-TPA presents obviously better therapeutic effects as compared with the clinically used rose bengal, suggesting the success of this PDT strategy and its great potential for clinical treatment of fungal infections.

Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease.

The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1ß, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) α; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients (p < 0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients (p = 0.024 and p < 0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

Objective: To explore cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and neurofilament light proteins (NFL) in patients with neurosyphilis (NS). Methods: We enrolled 71 NS patients (41 early-NS and 30 late-NS patients) and 20 syphilis but non-NS patients whose CSF samples were collected. The CSF levels of the microglial activation biomarker sTREM2 and neuronal injury biomarker NFL were measured using ELISA. Results: CSF sTREM2 levels were significantly higher in NS patients compared to those in syphilis/non-NS patients (p < 0.001). In a subgroup analysis, the CSF sTREM2 levels elevated significantly in late-NS patients than those in early-NS patients (p < 0.001). The CSF sTREM2 levels in early-NS group were also significantly higher than those in syphilis/non-NS group (p = 0.024). Like CSF sTREM2, similar differences between groups were also found in CSF NFL. There was a moderate correlation between CSF sTREM2 and CSF NFL (r = 0.406, p < 0.001) in NS group. Conclusions: CSF sTREM2 levels elevated in NS and peaked at the late stage, suggesting that CSF sTREM2 may be a useful marker to quantify microglia activation in NS and may play a role in the progression of NS. The positive correlation between CSF sTREM2 and CSF NFL indicates a linkage between microglial activation and neuronal injury in NS.

One stone, three birds: one AIEgen with three colors for fast differentiation of three pathogens.

Visually identifying pathogens favors rapid diagnosis at the point-of-care testing level. Here, we developed a microenvironment-sensitive aggregation-induced emission luminogen (AIEgen), namely IQ-Cm, for achieving fast discrimination of Gram-negative bacteria, Gram-positive bacteria and fungi by the naked-eye. With a twisted donor-acceptor and multi-rotor structure, IQ-Cm shows twisted intramolecular charge transfer (TICT) and AIE properties with sensitive fluorescence color response to the microenvironment of pathogens. Driven by the intrinsic structural differences of pathogens, IQ-Cm with a cationic isoquinolinium moiety and a membrane-active coumarin unit as the targeting and interacting groups selectively locates in different sites of three pathogens and gives three naked-eye discernible emission colors. Gram-negative bacteria are weak pink, Gram-positive bacteria are orange-red and fungi are bright yellow. Therefore, based on their distinctive fluorescence response, IQ-Cm can directly discriminate the three pathogens at the cell level under a fluorescence microscope. Furthermore, we demonstrated the feasibility of IQ-Cm as a visual probe for fast diagnosis of urinary tract infections, timely monitoring of hospital-acquired infection processes and fast detection of molds in the food field. This simple visualization strategy based on one single AIEgen provides a promising platform for rapid pathogen detection and point-of-care diagnosis.

Reactive Oxygen Species Activatable Heterodimeric Prodrug as Tumor-Selective Nanotheranostics.

Nanotheranostics based on tumor-selective small molecular prodrugs could be more advantageous in clinical translation for cancer treatment, given its defined chemical structure, high drug loading efficiency, controlled drug release, and reduced side effects. To this end, we have designed and synthesized a reactive oxygen species (ROS)-activatable heterodimeric prodrug, namely, HRC, and nanoformulated it for tumor-selective imaging and synergistic chemo- and photodynamic therapy. The prodrug consists of the chemodrug camptothecin (CPT), the photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), and a thioketal linker. Compared to CPT- or HPPH-loaded polymeric nanoparticles (NPs), HRC-loaded NPs possess higher drug loading capacity, better colloidal stability, and less premature drug leakage. Interestingly, HRC NPs were almost nonfluorescent due to the strong π-π stacking and could be effectively activated by endogenous ROS once entering cells. Thanks to the higher ROS levels in cancer cells than normal cells, HRC NPs could selectively light up the cancer cells and exhibit much more potent cytotoxicity to cancer cells. Moreover, HRC NPs demonstrated highly effective tumor accumulation and synergistic tumor inhibition with reduced side effects on mice.

Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases.

A retrospective study was performed to compare the differences in clinical and laboratory features of asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS). A total of 264 HIV-negative inpatients with neurosyphilis were enrolled from Beijing Ditan Hospital and Beijing Tiantan Hospital between January 2014 and May 2018, including 110 SNS and 154 ANS. The SNS group had more patients in males, older median age and without antisyphilis treatment than ANS group (P<0.001, P<0.001, and P<0.001, respectively). The laboratory findings showed that the SNS group had higher pretreatment serum rapid plasma regain (RPR) titer, current serum RPR titer, cerebrospinal fluid (CSF) white blood cell (WBC) counts, CSF protein concentrations, and higher positive CSF RPR rate than those in the ANS group (P=0.011, P<0.001, P<0.001, P<0.001, and P<0.001, respectively). The multivariate logistic regression analysis revealed that male (OR=2.833, P=0.009), age≥45 years (OR=3.611, P=0.001), without antisyphilis treatment (OR=0.247, P<0.001), higher current serum RPR titer (OR=1.373, P=0.022), positive CSF RPR (OR=4.616, P<0.001), and higher CSF protein concentration (OR=1.017, P=0.026) were independent risk predictors for SNS. Therefore, clinical and laboratory features between SNS and ANS are quietly different. Male gender, age≥45 years, and lack of antisyphilis treatment are risk factors for SNS. The elevated level of serum RPR titer, CSF protein concentration, and CSF RPR titer may indicate the development of neurosyphilis and the aggravation of neurological symptoms.

miR-145-5p inhibits the proliferation and migration of bladder cancer cells by targeting TAGLN2.

MicroRNA-145-5p (miR-145-5p) is found to be involved in tumor development and progression. However, there are few studies on the effects of miR-145-5p on bladder cancer (BC). The role of miR-145-5p in BC was predicted by analysis of cell proliferation and migration in this study. The miR-145-5p and transgelin-2 (TAGLN2) expressions were evaluated via reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The MTT and Transwell assay assessed cell proliferation and migration. TAGLN2 targeted to miR-145-5p was determined using luciferase assays. The results showed that the miR-145-5p downregulation was found in BC. miR-145-5p overexpression inhibited cell proliferation and migration in BC. Moreover, miR-145-5p directly targeted TAGLN2, and TAGLN2 expression was increased in BC. In addition, the high expression of TAGLN2 promoted cell proliferation and migration in BC. miR-145-5p appeared to regulate TAGLN2 in BC, and it also inhibited the cell proliferation and migration. The novel miR-145-5p/TAGLN2 axis may provide new therapeutic implications for BC.