Objective To investigate the investigation of co-morbidity etiology and prognosis analysis of chronic diseases in the elderly population. Methods The data of 1 475 elderly patients who were seen and treated in Chengdu Fifth People's Hospital from January 2019 to December 2021 were screened to analyze their disease status, co-morbidity combinations and patterns, co-morbidity influencing factors, and prognosis. Results The top four prevalence rates among 1 475 elderly patients with chronic diseases were hypertension 555 (37.63%), gastric or gastrointestinal diseases 445 (30.17%), arthritis or rheumatism 427 (28.95%), and diabetes 329 (26.58%). 1034 co-morbidities were found in 1475 elderly patients with chronic diseases, with a co-morbidity rate of 70.10%. The binary disease combination accounted for 58.41% and the ternary disease combination accounted for 41.59%. Female, age >70 years, family history of chronic diseases, overweight/obesity, daily physical inactivity, history of alcohol/smoking, poor sleep quality, and poor dietary habits were the independent influencing factors for co-morbidity in elderly patients with chronic diseases (OR_female=2.413, ORage ≥ 70=1.670, OR_{history of alcohol consumption}family history of chronic diseases=2.846, OR_{history of alcohol consumption}overweight/obesity=2.570, ORdaily inactivity=1.802, OR_{history of alcohol consumption}=3.543, ORhistory of smoking=1.784, OR_{poor sleep quality}=2.128, OR_{unhealthy dietary habits}=2.085, all P<0.05). Compared with elderly patients with chronic diseases without co-morbidity, patients with co-morbidity had higher odds of exacerbation of the original disease/acute readmission and lower odds of new chronic disease (χ²_{primary exacerbation/emergency readmission}=10.726, χ²_{new chronic disease}=5.873 , all P<0.05). Conclusion Gender, age, chronic disease history, BMI, and lifestyle habits are important factors influencing co-morbidity in elderly patients with chronic diseases, and patients with co-morbidity have a relatively poor prognosis.

Objective We aimed to investigate the TCM syndrome characteristics and risk factors of early death in higher-risk patients with myelodysplastic syndromes with excess blasts (HR-MDS-EB). Methods The data of 57 HR-MDS-EB patients in the hematology ward of Xiyuan Hospital, China Academy of Chinese Medical Sciences admitted between January 2013 and August 2020 were analyzed. Patients were divided into an early death group and a non-early death group according to the survival time. The basic information, clinical characteristics, specialized examination, complete blood cell counts and laboratory examination result for first diagnosis, TCM syndrome characteristics, and other data of patients were collected and analyzed to screen the risk factors of death.Results There were statistically significant differences in Charlson comorbidity index (CCI) score, Barthel index score, platelet count at first diagnosis, blast ratio in peripheral blood, lactate dehydrogenase levels, blazing pathogenic heat pattern, and constipation between the early death group and the non-early death group (P<0.05). According to the result of the above univariate analysis, logistic multivariate regression analysis was performed for significant factors P<0.05. CCI score had statistically significant effects on the risk of death (P<0.05).Conclusion Higher CCI score is an independent risk factor for early death in HR-MDS-EB patients.

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36⁺ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36⁺ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Humans ; Adenoma, Pleomorphic/genetics* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Transcriptome ; Myoepithelioma

Objective:To investigate the risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS), and the predictive value of Neutrophil to lymphocyte ratio (NLR).Methods:Consecutive patients with AIS received IVT in Zhengzhou People’s Hospital from January 2021 to December 2022 were retrospectively enrolled. HT was defined as no intracranial hemorrhage was found on the first imaging examination after admission, and new intracranial hemorrhage was found on the imaging examination 24 h after IVT or when symptoms worsened. sHT was defined as HT and the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 compared to admission or required surgical treatment such as intubation and decompressive craniectomy. The baseline clinical and laboratory data of the patients were collected, and NLR, lymphocyte to monocyte ratio (LMR), and platelet to neutrophil ratio (PNR) were calculated. Multivariate logistic regression analysis was used to identify the independent predictors of HT and sHT, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT and sHT after IVT. Results:A total of 196 patients were included (age 65.37±13.10 years, 124 males [63.3%]). The median baseline NIHSS score was 4 (interquartile range: 2-10). Twenty patients (10.2%) developed HT, and 12 (6.1%) developed sHT. Univariate analysis showed that there were statistically significant differences in age, baseline NIHSS score, creatinine, NLR, and stroke etiology type between the HT group and the non-HT group (all P<0.05); there were statistically significant differences in age, NLR, PNR, creatinine, baseline NIHSS score, and stroke etiological type between the sHT group and the non-sHT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent predictor of HT (odds ratio [ OR] 1.375, 95% confidence interval [ CI] 1.132-1.670; P=0.001) and sHT ( OR 1.647, 95% CI 1.177-2.304; P=0.004) after IVT. The ROC curve analysis showed that the area under the curve for predicting HT by NLR was 0.683 (95% CI 0.533-0.833; P=0.007), the optimal cutoff value was 5.78, the sensitivity and specificity were 55.0% and 84.1%, respectively. The area under the curve for predicting sHT by NLR was 0.784 (95% CI 0.720-0.839; P=0.001), the optimal cutoff value was 5.94, the sensitivity and specificity were 66.67% and 84.24%, respectively. Conclusions:A higher baseline NLR is associated with an increased risk of HT and sHT after IVT in patients with AIS, and can serve as a biomarker for predicting HT and sHT after IVT.

Objective:To investigate the relationship between the overall burden score of cerebral small vessel disease (CSVD) and sudden sensorineural hearing loss (SSNHL) and its severity.Methods:Patients with SSNHL admitted to Zhengzhou People’s Hospital from January 2019 to June 2022 were used as the case group, and age- and gender-matched patients with tension headache or benign positional vertigo were used as the control group. MRI was used to evaluate the phenotype of CSVD, including white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), and lacune of presumed vascular origin, and then the total burden score of CSVD was calculated. Multivariate logistic regression analysis was used to determine the independent factors of SSNHL. Ordinal logistic regression analysis was used to investigate the relationship between the overall burden of CSVD and the severity of hearing loss in patients with SSNHL. Results:A total of 86 patients with SSNHL and 90 age- and gender-matched controls were included. There were statistically significant differences in triglycerides, high-density lipoprotein cholesterol, fasting blood glucose levels, WMHs overall score classification, periventricular WMHs score classification, deep WMHs score classification, CMBs, moderate to severe EPVS, CSVD overall burden score and classification between the two groups (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for high-density lipoprotein cholesterol, fasting blood glucose ≥6.1 mmol/L (odds ratio [ OR] 2.149, 95% confidence interval [ CI] 1.042-4.432; P=0.038), triglycerides ≥1.7 mmol/L ( OR 7.012, 95% CI 2.962-16.597; P=0.000), CSVD overall burden score >1 (compared to 0 point, 2 points: OR 4.095, 95% CI 1.364-12.291, P=0.012; 3 points: OR 5.776, 95% CI 1.888-17.614, P=0.002; 4 points: OR 7.900, 95% CI 2.526-24.706; P=0.000) were significantly independently correlated with SSNHL. Ordinal logistic regression analysis showed that after adjusting for age and fasting blood glucose, the flat decline type hearing loss ( OR 1.276, 95% CI 1.131-1.618; P=0.044) and total deafness type hearing loss ( OR 1.029, 95% CI 1.002-1.058; P=0.038), and the overall burden of CSVD being moderate ( OR 1.318, 95% CI 1.036-1.677; P=0.025) and severe ( OR 2.330, 95% CI 1.232-4.406; P=0.009) were significantly independent associated with the degree of hearing loss in patients with SSNHL. Conclusion:The CSVD total burden score of moderate to severe degree is independently associated with SSNHL and the degree of hearing loss.

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and collateral circulation in patients with stroke caused by anterior circulation large vessel occlusion (aLVO).Methods:Patients with stroke caused by aLVO treated with endovascular mechanical thrombectomy in the Department of Neurology, Zhengzhou People's Hospital from December 2017 to April 2021 were retrospectively enrolled. Their demography, vascular risk factors, baseline clinical data and Fazekas scale score were collected. Multivariate logistic regression analysis was used to determine the independent correlation between WMHs and the collateral circulation status in patients with aLVO. Results:During the study, 166 patients with aLVO were included (77 males, 46.39%; aged 69.62±5.91 years). Their baseline National Institutes of Health Stroke Scale (NIHSS) score was 9.33±4.42. There were 120 patients (72.29%) in the good collateral circulation group and 46 (27.71%) in the poor collateral circulation group. Univariate analysis showed that there were significant differences in baseline NIHSS score, total Fazekas score and periventricular Fazekas score between the good collateral circulation group and the poor collateral circulation group (all P<0.05). Multivariate logistic regression analysis showed that total Fazekas score (odds ratio 2.583, 95% confidence interval 1.445-4.619; P=0.001) and periventricular Fazekas score (odds ratio 2.190, 95% confidence interval 1.022-4.692; P=0.044) were the independent risk factors for the poor collateral circulation. Conclusion:The severity of WMHs is associated with the poor collateral circulation in patients with aLVO.

Objective To establish the three-dimensional (3D) finite element model of unicompartmental knee arthroplasty (UKA) with 3° and 7° posterior tibial slope at different knee flexion angles, and to study biomechanical properties and prosthetic wear of the knee joints with two types of posterior tibia slope and their effects on knee function. Methods Combining CT and MRI images of human knee joints with the 3rd-generation Oxford prosthesis, the finite element UKA model with 3° and 7° posterior tibia slope were established. The 1 kN load was applied to center point of the medial and lateral condyles of the femur to simulate the standing load of human body. The maximum stresses and distributions of the prosthesis and articular cartilage at different knee flexion angles were analyzed. ResultsThe maximum stress of the meniscus liner with 3° posterior tibia slope at 0°, 30°, 60°, 90°, 120° knee flexion angles increased by 28.06%, 68.99%, 19.45%, 21.06% and 53.38%, the distribution area was concentrated from the side of the meniscus liner to the central area, and the stress concentration was obvious at 120° knee flexion. The maximum stress of prosthesis with 3° posterior tibia slope was greater than that with 7 ° posterior tibia slope. The expansion of stress concentration area would cause wear and loosening of the prosthesis, contact stress and concentration area of the articular cartilage would subsequently increase with posterior tibia slope increasing, and stress concentration would be more obvious at high knee flexion angles. Conclusions Tibial prosthesis has the higher stress and greater wear under the condition of 3° posterior tibia slope than 7° posterior tibia slope. The research findings provide theoretical basis for the UKA design in clinic.

Objective To develop a chemiluminescence imaging DNA microarray method for simultaneous,quick and accurate detection of serotypes of human adenovirus (HAdV ),namely,HAdV3,HAdV7,HAdV11,HAdV14 and HAdV55.Methods Based on the specific gene sequences in the conserved region of adenovirus from GenBank, oligonucleotide primers and probes were designed and synthesized to prepare the oligonucleotide microarray.The specific genomic sequences were amplified by multiplex PCR method.The multiplex PCR amplification products were hybridized with the specific probes of microarray that was scanned after washing and chemiluminescenceb before the result was analyzed.After optimization of the multiple PCR system,hybridization reactions and conditions of chemiluminescence,the specificity,sensitivity and reproducibility of the chip were evaluated.Results The microarray displayed high sensitivity, specificity and reproducibility.The minimum detection limit of plasmidg DNA was 3 ×103 copies/reaction.The microarray detection results of 38 clinical samples were approximately consistent with those using the direct sequencing method(37 /38).Conclusion A chemiluminescence imaging DNA microarray method for quick,sensitive and specific detection of five serotypes of HAdV is established,which can provide a new means for detecting serotypes of HAdV.

Objective To develop a chemiluminescence imaging DNA microarray method for simultaneous,fast and accurate detection of nine rash-and fever-causing pathogens,namely,Measles virus,Rubella virus,Enterovirus type 71, Varicella zoster virus,Dengue fever virus,Human small FDNA virus B19,Coxsackie virus type A16,A-βStreptococcus pyogenes (hemolytic streptococcus)and Salmonella typhi.Methods Primers and probes were designed based on the specific sequence in the conserved region of genomes of the nine pathogens.The nucleic acids of the nine pathogens were amplified and labelled by multiplex PCR method.The multiplex PCR amplification products were hybridized with specific probes of microarray that was scanned after washing and chemiluminescence coloration to identify the nine pathogens.After the optimization of the multiplex PCR system,hybridization and chemiluminescence imaging,the specificity,sensitivity and reproducibility of the chip were evaluated.The serial diluted nucleic acid of Enterovirus type 71 was detected using microarray and real-time PCR approach to compare the sensitivity of these two methods.Results Nine specific primers and eleven specific probes were selected.The microarray demonstrated high sensitivity and specificity.The minimum detection limit of plasmid DNA and in vitro transcribed RNAs was 3 ×103 copies per reaction.The detection sensitivity of this microarray was 10 percent of that by the real-time PCR method.The rate of sensitivity and specificity of clinical sample detection was 95% and 85.7% respectively,and the rate of accuracy was 93.2%.Conclusion A chemiluminescence imaging DNA microarray method for simultaneous,fast and accurate detection of nine pathogens that cause rash and fever illnesses is established successfully,which can serve as a new high throuthput screening method for clinical diagnosis and epidemiological investigation of rash and fever illnesses.

OBJECTIVETo evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally.

METHODSBased on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively.

RESULTSIn Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group.

CONCLUSIONCo-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

Administration, Oral ; Animals ; Biological Availability ; Biological Transport ; Chromatography, High Pressure Liquid ; Euphorbiaceae ; chemistry ; Paclitaxel ; pharmacokinetics ; Permeability ; Plant Extracts ; pharmacology ; Plant Roots ; chemistry ; Rats ; Tandem Mass Spectrometry ; Verapamil