Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Pure Severe Aortic Regurgitation.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups. In this study, patients with PSAR who underwent TAVR at Zhongshan Hospital, Fudan University, China, during the inclusion period were included and categorized into 3 groups based on STS scores. The baseline data, imaging results, and follow-up data of the patients were documented. Therefore, of 75 TAVR patients, 38 (50.7%) were categorized as low risk (STS <4), and 37 (49.3%) patients were categorized as intermediate and high risk (STS ≥4). Compared with patients at intermediate and high risk, those in the low-risk group were younger, had a lower body mass index, had a lower prevalence of hypertension, chronic obstructive pulmonary disease, and previous percutaneous coronary intervention, and had better cardiac function (p all <0.05). In the hospital and at the 1-month follow-up, the degree of aortic regurgitation and cardiac function were significantly improved. No significant difference was found between the 2 groups in the hospital or during the 30-day follow-up. In conclusion, TAVR for PSAR in low-STS-risk patients is safe and efficient during 30 days of follow-up compared with intermediate- and high-STS-risk groups. TAVR for PSAR should not be limited to inoperable or STS-defined high-risk patients. Long-term follow-up is needed for further investigation.

Advances in wastewater analysis revealing the co-circulating viral trends of noroviruses and Omicron subvariants.

Co-presence of enveloped and non-enveloped viruses is common both in community circulation and in wastewater. Community surveillance of infections requires robust methods enabling simultaneous quantification of multiple viruses in wastewater. Using enveloped SARS-CoV-2 Omicron subvariants and non-enveloped norovirus (NoV) as examples, this study reports a robust method that integrates electronegative membrane (EM) concentration, viral inactivation, and RNA preservation (VIP) with efficient capture and enrichment of the viral RNA on magnetic (Mag) beads, and direct detection of RNA on the beads. This method provided improved viral recoveries of 80 ± 4 % for SARS-CoV-2 and 72 ± 5 % for Murine NoV. Duplex reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays with newly designed degenerate primer-probe sets offered high PCR efficiencies (90-91 %) for NoV (GI and GII) targets and were able to detect as few as 15 copies of the viral RNA per PCR reaction. This technique, combined with duplex detection of NoV and multiplex detection of Omicron, successfully quantified NoV (GI and GII) and Omicron variants in the same sets of 94 influent wastewater samples collected from two large wastewater systems between July 2022 and June 2023. The wastewater viral RNA results showed temporal changes of both NoV and Omicron variants in the same wastewater systems and revealed an inverse relationship of their emergence. This study demonstrated the importance of a robust analytical platform for simultaneous surveillance of enveloped and non-enveloped viruses in wastewater. The ability to sensitively determine multiple viral pathogens in wastewater will advance applications of wastewater surveillance as a complementary public health tool.

ChloroDBPFinder: Machine Learning-Guided Recognition of Chlorinated Disinfection Byproducts from Nontargeted LC-HRMS Analysis.

High-resolution mass spectrometry (HRMS) is a prominent analytical tool that characterizes chlorinated disinfection byproducts (Cl-DBPs) in an unbiased manner. Due to the diversity of chemicals, complex background signals, and the inherent analytical fluctuations of HRMS, conventional isotopic pattern (37Cl/35Cl), mass defect, and direct molecular formula (MF) prediction are insufficient for accurate recognition of the diverse Cl-DBPs in real environmental samples. This work proposes a novel strategy to recognize Cl-containing chemicals based on machine learning. Our hierarchical machine learning framework has two random forest-based models: the first layer is a binary classifier to recognize Cl-containing chemicals, and the second layer is a multiclass classifier to annotate the number of Cl present. This model was trained using ∼1.4 million distinctive MFs from PubChem. Evaluated on over 14,000 unique MFs from NIST20, this machine learning model achieved 93.3% accuracy in recognizing Cl-containing MFs (Cl-MFs) and 92.9% accuracy in annotating the number of Cl for Cl-MFs. Furthermore, the trained model was integrated into ChloroDBPFinder, a standalone R package for the streamlined processing of LC-HRMS data and annotating both known and unknown Cl-containing compounds. Tested on existing Cl-DBP data sets related to aspartame chlorination in tap water, our ChloroDBPFinder efficiently extracted 159 Cl-containing DBP features and tentatively annotated the structures of 10 Cl-DBPs via molecular networking. In another application of a chlorinated humic substance, ChloroDBPFinder extracted 79 high-quality Cl-DBPs and tentatively annotated six compounds. In summary, our proposed machine learning strategy and the developed ChloroDBPFinder provide an advanced solution to identifying Cl-containing compounds in nontargeted analysis of water samples. It is freely available on GitHub (https://github.com/HuanLab/ChloroDBPFinder).

Quantification and Differentiation of SARS-CoV-2 Variants in Wastewater for Surveillance.

Wastewater surveillance plays an important role in the monitoring of infections of SARS-CoV-2 at the community level. We report here the determination of SARS-CoV-2 and differentiation of its variants of concern in 294 wastewater samples collected from two major Canadian cities from May 2021 to March 2023. The overall method of analysis involved extraction of the virus and viral components using electronegative membranes, in situ stabilization and concentration of the viral RNA onto magnetic beads, and direct analysis of the viral RNA on the magnetic beads. Multiplex reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays, targeting specific and naturally selected mutations in SARS-CoV-2, enabled detection and differentiation of the Alpha, Beta, Gamma, Delta, and Omicron variants. An Omicron triplex RT-qPCR assay targeting three mutations, HV 69-70 deletion, K417N, and L452R, was able to detect and differentiate the Omicron BA.1/BA.3, BA.2/XBB, and BA.4/5. This assay had efficiencies of 90-104% for all three mutation targets and a limit of detection of 28 RNA copies per reaction. Analyses of 294 wastewater samples collected over a two-year span showed the concentrations and trends of Alpha, Beta, Gamma, Delta, and Omicron variants as they emerge in two major Canadian cities participating in the wastewater surveillance program. The trends of specific variants were consistent with clinical reports for the same period. At the beginning of each wave, the corresponding variants were detectable in wastewater. For example, RNA concentrations of the BA.2 variant were as high as 104 copies per 100 mL of wastewater collected in January 2022, when approximately only 50-60 clinical cases of BA.2 infection were reported in Canada. These results show that the strategy and highly sensitive assays for the variants of concern in wastewater are potentially useful for the detection of newly emerging SARS-CoV-2 variants and other viruses for future community biomonitoring.

Predictive factors and clinical efficacy of Chinese medicine Shengji ointment in the treatment of diabetic foot ulcers in the elderly: a prospective study.

Objective: This study aims to investigate the predictive factors and efficacy of traditional Chinese medicine Shengji Ointment in the treatment of diabetic foot ulcers in the elderly population, with the intent of formulating an effective predictive model for deep diabetic foot ulcer healing. The importance of this research lies in its provision of new perspectives and tools for addressing the severe health impact of diabetic foot ulcers in the elderly population, considering the complexity and diversity of its treatment methods. Methods: The study includes 180 elderly patients with Wagner grade 3-4 diabetic foot ulcers that involve the tendon or fascia. The dependent variable is the initiation time of granulation tissue development. Independent variables encompass demographic information, a treatment strategy including Shengji Ointment, pre-treatment trauma assessment data, routine blood count, and biochemical index test results. Lasso regression is employed for variable selection, and Cox regression is utilized for the construction of a prediction model. A nomogram is generated to authenticate the model. Results: The Chinese Medicine treatment approach, ulcer location, creatinine levels, BMI, and haemoglobin levels are identified as independent predictors of granulation tissue development in diabetic foot ulcers. The combined treatment of Chinese herbal Shengji ointment and bromelain positively influenced granulation tissue development. The location of plantar ulcers, impaired renal functionality, obesity, and anaemia are established as independent risk factors that might influence the speed and probability of ulcer healing. The area under the time-dependent ROC curve fluctuates between 0.7 and 0.8, demonstrating substantial discrimination and calibration of the model. Conclusion: The study ascertains that a combined treatment strategy incorporating Shengji Ointment demonstrates greater effectiveness than the use of cleansing gel debridement alone in facilitating the healing of Wagner grade 3 or higher diabetic foot ulcers. Furthermore, the predictive model developed in this research serves as a valuable tool in evaluating the efficacy of Chinese Medicine treatments like Shengji Ointment for diabetic foot ulcers in the elderly. It aids clinicians in effectively assessing and adjusting treatment strategies, thereby proving its significant application value in clinical practice. Clinical Trial Registration: (https://www.chictr.org.cn/hvshowproject.html?id=73862&v=1.5&u_atoken=b403af53-d3b9-41ae-a7e2-db5498609b0c&u_asession=01tNh69p235bMUO4CmHIXcv8Hxirl5-557Duue9QB5lGfl3mf8IvPlcs2kN2zC30voX0KNBwm7Lovlpxjd_P_q4JsKWYrT3W_NKPr8w6oU7K_AyPrQhedMUWBMR2-ZDL_KO0uwDPR9XlF566xraDvT9mBkFo3NEHBv0PZUm6pbxQU&u_asig=05Kd_Q8fjv-24MVbZpOS9ef3xuCCN-tSVH5eUoJKgNLM7E0-n0zMpW6xLq9gh9aUhkKEEA15rdDoCydncF99APBwVSaTPgEG_V_B1iT4wimdCTxV_4ZVbTlDewxyQtE4YgU4-Oza7KPi94RJ64Utel0yZfqg3Tlm-bVxFNOY-zXFP9JS7q8ZD7Xtz2Ly-b0kmuyAKRFSVJkkdwVUnyHAIJzSYJ6SfhFl0WMTCCasZ7zV2I2qfyrp5m-SELPVeREKgX_6yRmLu26qT8kGfcS-Yaeu3h9VXwMyh6PgyDIVSG1W-7D_Sko5YQtpDbs3uvezYkZcUUY4o9-zDPaoYelmMDs8u7I4TPvtCXaPp44YUJcQ9bHr-_RmKA5V8nji3daArhmWspDxyAEEo4kbsryBKb9Q&u_aref=NNH1nHSUCE6pNvCilV%2F1MD0aERs%3D), identifier (ChiCTR2000039327).

Amino Acids as Potential Precursors to Odorous Compounds in Tap Water during Spring Runoff Events.

The onset of spring runoff in northern climates and tap water odor events are difficult to predict because common water quality parameters cannot fully explain the intermittent odor events that occurred over past decades. Studies have shown that small polar water-soluble compounds, such as amino acids (AAs), leach first from ice/snowmelt. AAs are known to produce odorous compounds, such as aldehydes and chloroaldimines, upon chlorination. Therefore, we proposed that AAs may serve as markers for small and soluble organics that contribute to the odor of chlorinated tap water. Here, we studied the occurrence of AAs in source water collected at two water treatment plants and the odor profiles of tap water at >300 homes during the 2021 and 2022 spring runoff events. AA concentrations were at baseline levels (<100 ng/L) during the 2021 runoff but much higher (up to 5500 ng/L) in 2022 and associated with an escalation in odor complaints. AA concentrations peaked at the onset of the 2022 spring runoff and corresponded with the strongest reported odor intensities in tap water. We obtained high resolution MS and MS/MS spectra of chloroaldimines and confirmed the formation of chloroaldimines under chlorination of the six AAs detected in source water. The results indicate that AAs signal the onset of spring runoff and represent small polar water-soluble compounds that may contribute to tap water odor problems.

Multiplex Assays Enable Simultaneous Detection and Identification of SARS-CoV-2 Variants of Concern in Clinical and Wastewater Samples.

The targeted screening and sequencing approaches for COVID-19 surveillance need to be adjusted to fit the evolving surveillance objectives which necessarily change over time. We present the development of variant screening assays that can be applied to new targets in a timely manner and enable multiplexing of targets for efficient implementation in the laboratory. By targeting the HV69/70 deletion for Alpha, K417N for Beta, K417T for Gamma, and HV69/70 deletion plus K417N for sub-variants BA.1, BA.3, BA.4, and BA.5 of Omicron, we achieved simultaneous detection and differentiation of Alpha, Beta, Gamma, and Omicron in a single assay. Targeting both T478K and P681R mutations enabled specific detection of the Delta variant. The multiplex assays used in combination, targeting K417N and T478K, specifically detected the Omicron sub-variant BA.2. The limits of detection for the five variants of concern were 4-16 copies of the viral RNA per reaction. Both assays achieved 100% clinical sensitivity and 100% specificity. Analyses of 377 clinical samples and 24 wastewater samples revealed the Delta variant in 100 clinical samples (nasopharyngeal and throat swab) collected in November 2021. Omicron BA.1 was detected in 79 nasopharyngeal swab samples collected in January 2022. Alpha, Beta, and Gamma variants were detected in 24 wastewater samples collected in May-June 2021 from two major cities of Alberta (Canada), and the results were consistent with the clinical cases of multiple variants reported in the community.

Simultaneously metastatic cholangiocarcinoma and small intestine cancer from breast cancer misdiagnosed as primary cholangiocarcinoma: A case report.

BACKGROUND: Cholangiocarcinoma and small intestine cancer are common clinical malignancies, but metastatic cholangiocarcinoma and small intestine cancer are rare, especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer. Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor, it may lead to misdiagnosis preoperatively. CASE SUMMARY: A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice. Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct, considering a high possibility of primary bile duct tumor. Therefore, we performed a radical bile duct cancer surgery and cholecystectomy, and multiple tumors in the small intestine were found and removed during the surgery process. Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts. The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago. Combining with the immunohistochemical results, the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer. Postoperatively, the patient received four cycles of chemotherapy and targeted therapy with docetaxel, capecitabine and trastuzumab. Unfortunately, the patient eventually died from tumor progression, thoracoabdominal infection, and sepsis 5 mo after surgery. CONCLUSION: Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor. Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment. Treatment should be aimed at relieving biliary obstruction and abdominal pain, and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient's life.

Recent advances in RNA sample preparation techniques for the detection of SARS-CoV-2 in saliva and gargle.

Molecular detection of SARS-CoV-2 in gargle and saliva complements the standard analysis of nasopharyngeal swabs (NPS) specimens. Although gargle and saliva specimens can be readily obtained non-invasively, appropriate collection and processing of gargle and saliva specimens are critical to the accuracy and sensitivity of the overall analytical method. This review highlights challenges and recent advances in the treatment of gargle and saliva samples for subsequent analysis using reverse transcription polymerase chain reaction (RT-PCR) and isothermal amplification techniques. Important considerations include appropriate collection of gargle and saliva samples, on-site inactivation of viruses in the sample, preservation of viral RNA, extraction and concentration of viral RNA, removal of substances that inhibit nucleic acid amplification reactions, and the compatibility of sample treatment protocols with the subsequent nucleic acid amplification and detection techniques. The principles and approaches discussed in this review are applicable to molecular detection of other microbial pathogens.

Successful treatment of breast metastasis from primary transverse colon cancer: A case report.

BACKGROUND: The incidence of colon cancer is increasing worldwide. Treatments for colon cancer include surgery and surgery combined with chemotherapy and radiotherapy, but the median survival rate is still poor. Colon cancer most commonly metastasizes to the lymph nodes, lungs, liver, peritoneum, and brain, but breast metastasis is rare. There is no agreement on its treatment. CASE SUMMARY: A 23-year-old woman was admitted to our hospital for further treatment with a history of acute abdominal pain, nausea, and vomiting. Her physical examination and computed tomography scan revealed an abdominal tumor. Transverse colectomy was successfully performed. Histopathological examination revealed that the tumor was a mucosecretory adenocarcinoma with signet ring cells. The patient inadvertently found a mass in the outer upper quadrant of the right breast after four cycles of XELOX chemotherapy [oxaliplatin 130 mg/m2, d1, intravenous (iv) drip for 2 h; capecitabine 1000 mg/m2, po, bid, d1-d14]. After discussion with the patient, we performed a lumpectomy and frozen biopsy. The latter revealed that the breast tumor was intestinal metastasis. Genetic testing showed wild-type RAS and BRAF. So we replaced the original chemotherapy with FOLFIRI [irinotecan 180 mg/m2, d1, iv drip for 3-90 min; leucovorin 400 mg/m2, d1, iv drip for 2 h; 5-fluorouracil (5-FU) 400 mg/m2, d1 and 5-FU 1200 mg/(m2 d) × 2 d, continuous iv drip for 46-48 h] + cetuximab (500 mg/m2, d1, iv drip for 2 h). Serum levels of tumor markers returned to normal after several treatment cycles, and there was no evidence of tumor recurrence or metastasis. CONCLUSION: Breast metastasis from colon cancer is rare. Radical breast surgery should be avoided unless needed for palliation. Chemotherapy combined with targeted therapy should be the first choice.

An efficient method to enhance recovery and detection of SARS-CoV-2 RNA in wastewater.

Wastewater surveillance (WS) of SARS-CoV-2 currently requires multiple steps and suffers low recoveries and poor sensitivity. Here, we report an improved analytical method with high sensitivity and recovery to quantify SARS-CoV-2 RNA in wastewater. To improve the recovery, we concentrated SARS-CoV-2 viral particles and RNA from both the solid and aqueous phases of wastewater using an electronegative membrane (EM). The captured viral particles and RNA on the EM were incubated in our newly developed viral inactivation and RNA preservation (VIP) buffer. Subsequently, the RNA was concentrated on magnetic beads and inhibitors removed by washing. Without eluting, the RNA on the magnetic beads was directly detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Analysis of SARS-CoV-2 pseudovirus (SARS-CoV-2 RNA in a noninfectious viral coat) spiked to wastewater samples showed an improved recovery of 80%. Analysis of 120 wastewater samples collected twice weekly between May 2021 and February 2022 from two wastewater treatment plants showed 100% positive detection, which agreed with the results independently obtained by a provincial public health laboratory. The concentrations of SARS-CoV-2 RNA in these wastewater samples ranged from 2.4×102 to 2.9×106 copies per 100 mL of wastewater. Our method's capability of detecting trace and diverse concentrations of SARS-CoV-2 in complex wastewater samples is attributed to the enhanced recovery of SARS-CoV-2 RNA and efficient removal of PCR inhibitors. The improved method for the recovery and detection of viral RNA in wastewater is important for wastewater surveillance, complementing clinical diagnostic tests for public health protection.

UVA causes specific mutagenic DNA damage through ROS production, rather than CPD formation, in Drosophila larvae.

Evidence is accumulating that ultraviolet A (UVA) plays an important role in photo-carcinogenesis. However, the types of DNA damage involved in the resulting mutations remain unclear. Previously, using Drosophila, we found that UVA from light-emitting diode (LED-UVA) induces double-strand breaks in DNA through oxidative damage in an oxidative damage-sensitive (urate-null) strain. Recently, it was proposed that cyclobutane pyrimidine dimers (CPDs), which also are induced by UVA irradiation, might play a significant role in the induction of mutations. In the present study, we investigated whether reactive oxygen species (ROS) and CPDs are produced in larval bodies following LED-UVA irradiation. In addition, we assessed the somatic cell mutation rate in urate-null Drosophila induced by monochromatic UVA irradiation. The production of ROS through LED-UVA irradiation was markedly higher in the urate-null strain than in the wild-type Drosophila. CPDs were detected in the DNA of both of UVA- and UVB-irradiated larvae. The level of CPDs was unexpectedly higher in the wild-type strain than in urate-null flies following UVA irradiation, whereas this parameter was expectedly similar between the urate-null and wild-type Drosophila following UVB irradiation. The somatic cell mutation rate induced by UVA irradiation was higher in the urate-null strain than in the wild-type strain. These results suggest that mutations induced by UVA-specific pathways occur through ROS production, rather than via CPD formation.

Comprehensive analysis of transcriptome-wide expression patterns and a circRNA/lncRNA-miRNA-mRNA network in the pathogenesis of cerebral ischemia in Rattus norvegicus.

BACKGROUND: Although ischemic stroke exhibits a high prevalence in the elderly population, the involved genes and pathways are poorly understood. In this study, we proposed to identify differentially expressed genes (DEGs) and constructed a circular RAN (circRNA)/long noncoding RNA (lncRNA)/microRNA (miRNA)-mRNA network associated with the pathogenesis of ischemic stroke by using bioinformatics analysis. METHODS: We constructed a rat model of middle cerebral artery occlusion (MCAO) and conducted total RNA and microRNA sequencing in brain specimens from MCAO and normal rats. Transcriptome-wide expression patterns were analyzed and DEGs were defined by applying Ballgown and a cut of log2-transformed fold-change (log2FC) ≥ 1 (or ≤ -1) with a P value < 0.05. We exploited Pearson correlation analysis to determine the association between the circRNA/lncRNA/mRNA network and miRNAs (P < 0.05 and corr ≤ -0.6), and the competing endogenous RNAs (ceRNA) interaction network was visualized with Cytoscape software and separated into subnetworks using the Molecular Complex Detection (MCODE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented for the pathway analysis of DEGs. RESULTS: Upregulated DEGs were significantly enhanced in positive regulation of cell migration, response to wounding, blood vessel morphogenesis, inflammatory response, and cell activation; Downregulated DEGs were associated with control of the modulation of chemical synaptic transmission, synapse organization, regulation of membrane potential, and regulation of ion transport. KEGG-pathway analysis showed that DEG-enhanced pathways were associated with the pathways of TNF signaling pathway, Fluid shear stress and atherosclerosis, NF-kappa B signaling pathway, Lipid and atherosclerosis, Human cytomegalovirus infection, Osteoclast differentiation, Chemokine signaling pathway, IL-17 signaling pathway, Viral protein interaction with cytokine and cytokine receptor, and Cytokine-cytokine receptor interaction. We uncovered several novel lncRNAs (lnc_00231, lnc_002239, lnc_004172; and a novel_circ0001704), five miRNAs (miR-200b-3p, miR-223-3p, miR-200c-3p, miR-3084a-3p, and miR-664-2-5p), and the top-10 mRNAs (upregulated mRNAs were Pdgfa, Il1b, Gdf15, Fosl1, and Cxcl2; downregulated mRNAs were Prkar2b, Olfm3, Lrrc73, Tmem38a, and Dlgap3) that were involved in ischemic stroke. CONCLUSIONS: Through bioinformatic network analysis, we identified the underlying molecular mechanisms and key central genes that may contribute to an inflammatory response after cerebral infarction.

Aspartame-Sweetened Tap Water: Transformation Products and 2,6-Dichloro-1,4-Benzoquinone Formation.

Aspartame (APM), a dipeptide of aspartic acid (ASP) and phenylalanine (PHE), is a widely used artificial sweetener in beverages. It is unclear whether residual chlorine in tap water can react with APM to form disinfection byproducts (DBPs). Therefore, we investigated the formation of DBPs from the reaction of APM with residual chlorine in authentic tap water. APM and a commercial sweetener (CS) packet containing APM were studied under authentic and simulated tap water conditions. Eight chlorinated products of APM were detected using solid-phase extraction (SPE) and high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS). These new chloro-products were tentatively identified based on accurate masses, isotopic patterns of 35,37Cl, and MS/MS spectra. Furthermore, we identified APM as a precursor to 2,6-dichloro-1,4-benzoquinone (DCBQ). DCBQ significantly increased to 2.3-12 ng/L with the addition of APM or CS in tap waters collected from different locations compared to 1.4-1.8 ng/L in the same tap water samples without sweetener. DCBQ and two of the chlorinated transformation products were identified in cold prepared tea containing APM. DCBQ formation was eliminated when the residual chlorine in tap water was reduced by ascorbic acid or boiling prior to the addition of APM or CS. This study found that eight new DBPs and DCBQ were produced by the reactions of residual chlorine with APM and CS. These findings show an unintended exposure source of emerging DBPs via APM sweetened beverages.

Mobile APP-assisted family physician program for improving blood pressure outcome in hypertensive patients.

BACKGROUND: This study was aimed to examine the effectiveness of App-assisted self-care in a Beijing community based on intelligent family physician-optimised collaborative model (IFOCM) program.  METHODS: We conducted a survey of 12,050 hypertensive patients between Jan 2014 and Dec 2021. Generalized linear model was used to analyze the covariates that associated with blood pressure (BP) control. Decision tree and random forest algorithm was used to extract the important factors of BP outcome. RESULTS: The study included 5937 patients, mean age 66.2 ± 10.8, with hypertension in the baseline; 3108(52.4) were female. The community management resulted in mean systolic BP and diastolic BP reductions of 4.6 mmHg and 3.8 mmHg at follow-up. There were 3661 (61.6%) hypertension patients with BP control, increasing from 55.0% in 2014 to 75.0% in 2021. After adjusted for covariates, antihypertensive medication adherence, diabetes, and APP-assisted self-care were common predictors associated with BP control in GLM model and machine learning algorithm. CONCLUSION: Community management based on IFOCM program significantly improved BP control in hypertensive patients. APP-assisted self-care would be beneficial for the management of chronic disease.

Epidemiological characteristics of measles cases with immunization history of MCV in Liaoning in 2014-2021 / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of measles cases with immunization history of measles-containing vaccine (MCV), and to provide a basis for improving measles prevention and control measures. Methods Data were collected through the measles surveillance system and the immunization program information management system. Data were analyzed by descriptive epidemiological methods. Results A total of 9 164 cases of measles were reported in Liaoning Province during 2014-2021, of which the cases of measles with immunization history of 1 dose MCV accounted for 5.64%, and ≥ 2 doses accounted for 3.60%. There was a statistically significant difference in the immunization proportion among different years (χ2=184.534, P2=109.448, P2=4.147, P<0.05). The onset time of most cases was over 2 weeks after the last dose of MCV vaccination, accounting for 82.06%. The incidence rates of fever, cough, catarrh symptoms, conjunctivitis, lymph node enlargement and articular pain were all significantly lower in the cases with immunization history than those in the patients without a history of MCV immunization (P<0.05). Conclusion The cases with immunization history account for a certain proportion in measles cases, mainly secondary vaccination failure. The incidence rate of fever, cough, catarrhal symptoms, conjunctivitis, Koch's patches, lymphadenopathy, joint pain, and other clinical symptoms in measles patients with a history of MCV immunization is lower than that in patients without immunization history. Inoculation of MCV is of great significance in relieving clinical symptoms. It is necessary to inoculate two doses of MCV in time for measles prevention and control.

Rapid prediction of G protein-coupled receptor structures using nanoluciferase assay / 药学学报

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.

Emerging Disinfection Byproduct 2,6-Dichlorobenzoquinone-Induced Cardiovascular Developmental Toxicity of Embryonic Zebrafish and Larvae: Imaging and Transcriptome Analysis.

Epidemiological studies have observed the potential association of water disinfection byproduct (DBP) exposure with cardiac defects. Aromatic DBPs represent a significant portion of total DBPs, but their effects on cardiovascular development are unclear. In this study, we examined the effects of an aromatic DBP, 2,6-dichlorobenzoquinone (DCBQ), on the cardiovascular development of zebrafish embryos. After exposure to 2, 4, and 8 µM DCBQ, morphological images of growing zebrafish embryos clearly showed cardiovascular malformation. Fluorescent images of transgenic zebrafish strains with fluorescently labeled heart and blood vessels show that DCBQ exposure resulted in deformed atrium-ventricle looping, degenerated abdomen and trunk vessels, pericardial edema, and decreased blood flow. Furthermore, the expression of the marker gene myl7 (essential for the differentiation and motility of cardiomyocytes) was inhibited in a dose-dependent manner by DCBQ exposure. Finally, transcriptome analysis found that in the 4 µM DCBQ exposure group, the numbers of differentially expressed genes (DEGs) were 113 (50 upregulated and 63 downregulated) at 24 hpf, 2123 (762 upregulated and 1361 downregulated) at 48 hpf, and 61 (11 upregulated and 50 downregulated) at 120 hpf; in the 8 µM DCBQ exposure group, the number of DEGs was 1407 (647 upregulated and 760 downregulated) at 120 hpf. The FoxO signaling pathway was significantly altered. The in vivo results demonstrate the effects of 2,6-DCBQ (0-8 µM) on cardiovascular development, contributing to the understanding of the developmental toxicity of aromatic DBP halobenzoquinones (HBQs).