The diabetes mellitus multimorbidity network in hospitalized patients over 50 years of age in China: data mining of medical records.

OBJECTIVE: Many diabetes mellitus (DM) patients suffer from multimorbidity. Understanding the DM multimorbidity network should be given priority. The purpose of this study is characterize the DM multimorbidity network in people over 50 years. METHODS: Data on 75 non-communicable diseases (NCDs) were extracted from electronic medical records of 309,843 hospitalized patients older than 50 years who had at least one NCD. The association rules analysis was used as a novel classification method and combined with the Chi-square tests to identify associations between NCDs and DM. RESULT: A total of 12 NCDs were closely related to DM, {cholelithiasis, DM} was an unexpected combination. {dyslipidemia, DM} and {gout, DM} had the largest lift in the male and female groups, respectively. The negative related group included 7 NCDs. There were 9 NCDs included in the strong association rules. Most combinations were different by age and sex. In males, the strongest rule was {peripheral vascular disease (PVD), dyslipidemia, DM}, while {hypertension, dyslipidemia, chronic liver disease (CLD), DM} was the strongest in females. In patients younger than 70 years, hypertension, CLD, and dyslipidemia were the most dominant NCDs in the DM multimorbidity network. In patients 70 years or older, chronic kidney disease (CKD), CVD, CHD, and heart disease (HD) frequently co-occurred with DM. CONCLUSION: Future primary healthcare policies for DM should be formulated based on age and sex. In patients younger than 70 years, more attention to hypertension, CLD, and dyslipidemia is required, while attention to CKD, CVD, CHD and HD is needed in patients older than 70 years.

Total Syntheses of the Structures Assigned to Denigrins A, B, C, F, and G, 3,4-Diaryl-Pyrrole and -Pyrrolidinone Alkaloids, and the Conversion of Congener B into the Co-metabolite Spirodactylone.

The title marine natural products have been prepared by total synthesis and in the case of congeners 3, 6, and 7 for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (2). The structure, 3, assigned to denigrin C is shown to be incorrect. Reaction of compound 2 with DDQ has led, in high yield, to the related natural product spirodactylone (16), while treating the corresponding permethyl ether 15 with PIFA/BF3·Et2O provides compound 20, embodying an isomeric framework.

Crystal structure and Hirshfeld surface analysis of a salt of antineoplastic kinase inhibitor vandetanib.

A salt of vandetanib, namely, 4-({4-[(4-bromo-2-fluorophenyl)amino]-6-methoxyquinazolin-7-yl}methoxy)-1-methylpiperazin-1-ium 2-(butylamino)-4-phenoxy-6-sulfamoylbenzoate acetonitrile monosolvate, C22H25BrFN4O2+·C17H19N2O5S-·C2H3N, composed of kinase inhibitor vandetanib and sulfamyl diuretic bumetanide in a 1:1 molar ratio, is reported. There is proton transfer between the piperidine ring of vandetanib and the carboxyl group of bumetanide to form the salt. In the vandetanib cation, the arene and pyrimidine rings are not coplanar, their planes subtending a dihedral angle of 60.47 (14)°. The roles of the intermolecular interactions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (40.5%), O...H/H...C (20.7%), C...H/ H...C (18.8%) and N...C/C...N (9.0%) contacts.

First detection of cutavirus DNA in stools of patients with rheumatic diseases in Guangzhou, China.

Cutavirus (CuV) is a novel protoparvovirus possibly associated with diarrhea and cutaneous T-cell lymphomas. Patients with rheumatic disease are immunosuppressed and may be more vulnerable to pathogenic viruses. A descriptive study was conducted among hospitalized patients with rheumatic diseases and individuals undergoing medical health check-ups between June 2019 and June 2022 in Guangzhou, China. Stool samples of subjects were tested for CuV DNA. Demographic and fecal examination data of patients were obtained from electronic medical records. A total of 505 patients with rheumatic diseases and 244 individuals who underwent medical health check-ups were included in the study. Of the patients with rheumatic disease, 5.74% [95% confidence interval (CI): 4.03%-8.12%] were positive for CuV DNA, while no individual in the medical health check-up group was positive, indicating a close correlation between CuV and rheumatic disease. Men and patients with rheumatoid arthritis or ankylosing spondylitis, according to the disease classification, were more susceptible to being infected with CuV (P â€‹< â€‹0.01). After adjustments, being male remained the only significant factor, with an adjusted odd ratio (OR) of 4.4 (95% CI: 1.7-11.4, P â€‹= â€‹0.002). Phylogenetic analysis of the CuV VP2 sequences showed three diverse clades, one of which was segregated to be a single branching independent of previously known sequences, which is possible a new genotype.

Identification and genetic characteristics of tusavirus in fecal samples of patients with chronic diseases in Guangzhou, China.

Purpose: The Tunisian stool-associated parvovirus [Tusavirus (TuV)] is a novel member of the genus Protoparvovirus, which may be linked to diarrhea. Herein, we investigated the prevalence of TuV in different populations and analyzed its genetic and bioinformatic characteristics. Methods: This study was conducted in a tertiary hospital in Guangzhou (China) from February 2018 to July 2022. Demographic and clinical information and stool samples were collected from individuals who visited the hospital. ProtScale, SwissModel, Datamonkey, and other tools were used to analyze and predict the physicochemical parameters, tertiary structure, selection pressure, and B-cell epitopes of capsid viral protein 2 of TuV (VP2-TuV). Results: A total of 3,837 participants were enrolled, among which two stool samples from patients with chronic illnesses were tested positive for TuV DNA. However, no positive sample was detected among patients with diarrhea. Two near-complete genome sequences were amplified. The genetic analysis revealed the presence of diversity among TuVs isolated from distinct host species. Bioinformatics analysis revealed that VP2-TuV exhibited hydrophilic properties and lacked transmembrane domains and signal peptides. The secondary structure of VP2-TuV was composed mainly of random coils and ß-strands. Selective-pressure analysis of the VP2 region suggested that TuV primarily underwent negative selection during evolution. Negatively selected codon sites coincided with residues comprising of B-cell epitopes, suggesting minimal changes in the immunogenicity of TuV over time. Conclusion: TuV was detected in patients with chronic diseases but not in patients with diarrhea. The putative roles of TuV in the pathogenicity of human diseases and zoonotic viruses must be determined by additional studies.

Heterogeneous expression of mismatch repair proteins and interpretation of immunohistochemical results in colorectal cancer and endometrial cancer.

To investigate the heterogeneous expression patterns of four mismatch repair (MMR) proteins in colorectal cancer (CRC) and endometrial cancer (EC), and their effects on the interpretation of immunohistochemical (IHC) results. A total of 1636 CRC and EC specimens were collected from two hospitals. Seventy-eight cases had heterogeneous expression of MMR proteins, including 49 CRC and 29 EC cases. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was then performed to detect the microsatellite instability (MSI) status, and 44 cases were further verified by targeted next-generation sequencing (NGS). Heterogeneous expression of MMR proteins was observed in 66 cases (66/78, 84.6%) of proficient MMR (pMMR) and 12 cases (12/78, 15.4%) of deficient MMR (dMMR). The proportion of heterogeneous MMR protein expression in EC (12.0%) was higher than that in CRC (3.5%). The heterogeneous expression patterns were divided into focal clonal heterogeneity (6/78, 7.7%) and glandular mosaic heterogeneity (72/78, 92.3%). Surprisingly, three pMMR CRC cases showed isolated small focal clonal heterogeneity of mutS homologue 6 (MSH6), with < 15% positive tumour cells, which was validated as high MSI (MSI-H) with PCR-CE and NGS. However, the other three EC pMMR cases with > 50% focal clonal heterogeneity of MMR proteins were verified as microsatellite stable (MSS) or low MSI (MSI-L). Fifteen EC cases with glandular mosaic heterogeneous expression of MMR proteins included two MSI-H cases, which were validated using PCR-CE and NGS. Among the dMMR cases, only two EC cases with mutL homologue 1 (MLH1)/PMS1 homologue 2, mismatch repair system component (PMS2) loss and MSH2/MSH6 mosaic heterogeneous expression were confirmed as MSS using PCR-CE and NGS, which may be related to the mechanism of MLH1 promoter methylation. Thus, in CRC, only cases with small focal clonal heterogeneous expression of MSH6 have a high likelihood of MSI-H, and further PCR-CE or NGS testing is recommended. The possibility of MSI-H cannot be ruled out in EC cases with glandular mosaic heterogeneous expression of MMR proteins; PCR-CE or NGS detection is therefore necessary.

Early and Sensitive Detection of Pathogens for Public Health and Biosafety: An Example of Surveillance and Genotyping of SARS-CoV-2 in Sewage Water by Cas12a-Facilitated Portable Plasmonic Biosensor.

Infectious diseases severely threaten public health and global biosafety. In addition to transmission through the air, pathogenic microorganisms have also been detected in environmental liquid samples, such as sewage water. Conventional biochemical detection methodologies are time-consuming and cost-ineffective, and their detection limits hinder early diagnosis. In the present study, ultrafine plasmonic fiber probes with a diameter of 125 µm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface, causing a sharp reduction in the surface plasmon resonance (SPR) wavelength. The proposed fiber probe is virus-specific with the limit of detection of ~2,300 copies/ml, and genomic copy numbers can be reflected as shifts in wavelengths. A total of 21 sewage water samples have been examined, and the data obtained are consistent with those of quantitative polymerase chain reaction (qPCR). In addition, the Omicron variant and its mutation sites have been fast detected using S gene-specific Cas12a. This study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.

Factors associated with influenza vaccination coverage and willingness in the elderly with chronic diseases in Shenzhen, China.

Elderly individuals with chronic illnesses are more prone to get influenza. We aimed to investigate the factors associated with influenza coverage and willingness in chronic disease patients aged ≥60 years in Longhua district, Shenzhen City of southern China. Data collected in October 2020 were used in this work. The immunization status of older persons with chronic conditions and their willingness to receive the vaccine were assessed. Multivariable logistic regression was employed to determine the respective independent factors related to vaccination coverage and willingness for influenza. Only 4.8% of 5045 people were immunized against influenza, whereas 92.7% of the individuals agreed to receive the vaccine. Individuals between the ages of 70 and 79 (adjusted OR [aOR] 1.47, P = .012), those with higher education levels (aOR 1.53, P = .005 for high school; aOR 2.44, P < .001 for college or above), those who use of a family doctor (aOR 2.91, P < .001), those who frequently have physical examinations once a year (aOR 2.52, P < .001), and those who have never smoked (aOR 1.62, P = .018) were positively associated with the influenza vaccination. Meanwhile, older age was adversely linked with influenza vaccination willingness (aOR 0.68 for 70-79 years, P = .003; aOR 0.55 for≥80 years, P = .025) in contrast to those aged 60-69. High willingness to get vaccinated was more frequent in people with a high school diploma (aOR 1.33, P = .037). In this work, we observed that the coverage is poor but the immunization desire is high regarding influenza vaccination. Interestingly, older age was associated with higher coverage and lower willingness. These suggest that raising immunization rates among older people with chronic conditions and strengthening health education for caregivers should be the primary concerns.

Parechovirus A infection and risk of gastroenteritis in children: A systematic review and meta-analysis.

Parechovirus A (PeV-A) belongs to the genus Parechovirus in the family Picornaviridae associated with gastroenteritis illness, particularly in children, but prior studies have produced ambiguous results. This study aimed to provide a systematic review of the PeV-A prevalence in paediatric patients with gastroenteritis and the association between PeV-A infection and the risk of gastroenteritis. A systematic search of the literature was conducted in Embase, PubMed, Scopus, and Web of Science, in combination with the reference lists of potentially relevant articles. A random effect-based model was applied to analyse data from included studies. The pooled odds ratio (OR) and 95% confidence interval (CI) were used for assessing the risk between PeV-A and gastroenteritis. A total of 41 studies assessing 21,850 cases and 1746 healthy controls were analysed. The overall prevalence of PeV-A among paediatric patients with gastroenteritis was 10.4% (95% CI: 7.9%-13.2%), while it was estimated at 8.1% (95% CI: 5.1%-11.7%) based on studies only investigating children without gastroenteritis. The pooled OR for all eight case-control studies was 1.079 (95% CI: 0.730-1.597), indicating there was no statistically significant association. PeV-A genotype 1 was the most frequent genotype of PeV-A infection in children with gastroenteritis. The PeV-A prevalence in cases of gastroenteritis is higher than that in children without gastroenteritis. However, the present meta-analysis did not indicate a statistically significant association between PeV-A infection and risk of gastroenteritis. Given the considerable heterogeneity and various sample sizes among the included studies, relevant investigations in the future should be carried out based on a large-scale population.

Influenza Vaccination Coverage among Older Adults with Hypertension in Shenzhen, China: A Cross-Sectional Survey during the COVID-19 Pandemic.

BACKGROUND: Older individuals with hypertension are at a high risk of being infected with influenza. However, there have been few studies investigating the influenza vaccination status among older people with hypertension. The present work aimed to estimate the vaccination coverage and determine the predictors of seasonal influenza vaccinations among hypertensive patients aged over 60 years in Shenzhen, China. METHOD: The study used data from an online cross-sectional survey that was conducted in Shenzhen City, China, in October 2020. Frequencies and proportions of all the variables including sociodemographic characteristics and health-related information were described and tabulated based on the influenza vaccination status. Bivariate and multivariable logistic regression analyses were used to identify independent predictors associated with the influenza vaccination. RESULTS: A total of 5216 older people with hypertension aged above 60 years were recruited. Overall, only 4.7% had received an influenza vaccine in the latest influenza season. Using the action toward being vaccinated as the primary outcome, the multivariable regression analysis showed that participants aged over 80 years (aOR 2.957, 95% CI: 1.784-4.900), obtaining higher education levels (aOR 1.424, 95% CI: 1.060-1.914 for high school, aOR 1.681, 95% CI: 1.066-2.650 for college or above), living with a partner (aOR 1.432, 95% CI: 1.068-1.920), using a family doctor (aOR 2.275, 95% CI: 1.744-2.968), and taking a physical examination 1-2 and ≥3 times each year (aOR 2.107, 95% CI: 1.601-2.772 and aOR 2.118, 95% CI: 1.083-4.143, respectively) were more likely to be vaccinated. In contrast, smokers had less likelihood of having the influenza vaccination than non-smokers (aOR 1.829, 95% CI: 1.208-2.767). CONCLUSIONS: The coverage rate of influenza vaccinations is far away from optimistic among older adults with hypertension. Additional works should be undertaken immediately to improve the influenza vaccination status.

[Clinicopathological features and types of microsatellite instability in 1394 patients with colorectal cancer].

OBJECTIVE: To explore the clinicopathological features and types of genic mutations in DNA mismatch repair (MMR) in colorectal cancer (CRC). METHODS: Immunohistochemistry was used to determine the expression of MMR proteins in 1394 patients with CRC, and PCR-capillary electrophoresis (PCR-CE) was used to detect microsatellite instability (MSI) in 106 cases of defective MMR (dMMR), 46 cases of proficient MMR (pMMR) with heterogeneous expression and 147 randomly selected cases of pMMR. The relationship between the expressions of MMR proteins and the clinicopathological features of the patients was evaluated. The consistency between the results of immunohistochemistry and PCR-CE was assessed. RESULTS: Immunohistochemical staining showed an incidence of dMMR of 7.6% in the patients. The main type of dMMR was co-deletion of MLH1 and PMS2, accounting for 55.7% of the total dMMR cases. The deletion of MMR proteins was significantly correlated with the patients' age, tumor location, tumor size, gross type, histological type, degree of differentiation, lymph node status and TNM stage (P < 0.05), but not with gender (P > 0.05). The total accordance rate of immunohistochemistry and PCR-CE was 98.7% in these patients. CONCLUSIONS: The main type of dMMR is co-deletion of MLH1 and PMS2 in patients with colorectal cancer. dMMR colorectal cancer has typical clinicopathological features and a lower incidence in China than in Western countries. The results of immunohistochemistry and PCR-CE are highly consistent for detecting dMMR in colorectal cancer patients.

Effect of Variations in the Fatty Acid Residue of Lactose Monoesters on Their Emulsifying Properties and Biological Activities.

Lactose fatty acid esters are high-value-added derivatives of lactose and represent a class of biodegradable, non-ionic, low-molecular-weight surfactants (emulsifiers) that have considerable potential in the food, cosmetic, and pharmaceutical industries. Certain lactose esters have also garnered attention for their biological activities. In this work, we detail syntheses of a homologous series of 6'- O-acyllactose esters of varying alkyl chain length (from 6 to 18 carbons) and report on their activities as surfactants as well as their antimicrobial and cytotoxic properties. The structure-property profiles established in this work revealed that while the medium-chain esters displayed excellent emulsifying properties and moderate antimicrobial activities, their longer chain congeners exhibited the highest cytotoxicities. As such, we have established that certain 6'- O-acyllactose esters are superior to their sucrose-derived and commercially exploited counterparts. These results will serve as a useful guide for the development of lactose esters as, inter alia, emulsifiers in the food industry.

Enzymatic Preparation of a Homologous Series of Long-Chain 6- O-Acylglucose Esters and Their Evaluation as Emulsifiers.

Sugar fatty acid esters are nonionic surfactants that are widely exploited in the food and cosmetics industries, as well as in the oral care and medical supply fields. Accordingly, new methods for their selective synthesis and the "tuning" of their emulsifying properties are of considerable interest. Herein we report simple and irreversible enzymatic esterifications of d-glucose with seven fatty acid vinyl esters. The foaming and emulsifying effects of the resulting 6- O-acylglucose esters were then evaluated. In accord with expectations, when the length of the alkyl side chain associated with the 6- O-acylglucose esters increases, then their hydrophilic-lipophilic balance (HLB) values decrease, while the stabilities of the derived emulsions improve. In order to maintain good foaming properties, alkyl side chains of at least 9 to 11 carbons in length are required. In the first such assays on 6- O-acylglucose esters, most of those described herein are shown to be nontoxic to the HepG2, MCF-7, LNacp, SW549, and LO-2 cell lines.