Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective To analyze the prevalence of hyperuricemia (HUA) among adults in Hebei Province and its influencing factors related to comorbidities with ^“three highs^”, and to provide a theoretical basis for the prevention and control of HUA and multi-disease co-management. Methods Data were derived from the 2018 China Chronic Disease and Risk Factors Surveillance program conducted in Hebei Province. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. All statistical analyses were adjusted for complex weighting. Design-based logistic regression was employed to analyze factors influencing HUA prevalence, and ordinal logistic regression was used to analyze the influencing factors of HUA patients and their comorbidity with ^“three highs^”. Results The prevalence of HUA among adults in Hebei Province was 10.42%, with males showing higher rates than females (P<0.05). The highest prevalence of HUA was observed in the 18-39 age group, followed by a declining trend, and a resurgence in those aged ≥70 (P<0.05). Among HUA patients with comorbidities, isolated HUA, 1 comorbidity, 2 comorbidities, and 3 comorbidities accounted for 13.94%, 33.33%, 39.17%, and 13.56%, respectively. HUA combined with hypertension and dyslipidemia represented the highest proportion (31.07%). Analysis of the influencing factors of HUA revealed that higher education levels, obesity, central obesity, and dyslipidemia increased the risk of HUA (P<0.05). Ordinal logistic regression analysis of HUA combined with three highs showed that HUA patients aged ≥50 years, overweight individuals, and those with chronic kidney disease had a higher number of patients with three highs (P<0.05). Conclusion HUA exhibits insidious onset, and it is recommended to include uric acid testing in routine physical examinations. Targeted prevention measures, such as early uric acid testing and health education, should be implemented by Hebei authorities for populations with higher education levels, obesity, central obesity, and dyslipidemia to reduce HUA incidence. Additionally, health education and regular medical check-ups are recommended for overweight HUA patients and those with chronic kidney disease to prevent comorbidities and alleviate disease burden.

Coronary heart disease （CHD） has a distinct circadian rhythmicity in its onset， which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind"， this paper explores the pathogenic evolution rules of qi-blood disharmony， channel obstruction， interacting as cause and effect with circadian rhythm disorders in CHD. Clinically， CHD can be observed to attack in the early morning， at night， in the afternoon， and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation， yin deficiency with yang floating， qi and yin deficiency， and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time， regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages， and select the appropriate timing for administration to harness natural timing. At the Mao （卯） hour， yang ascends while yin descends， and taking medication at this time conforms to the ascending of yang qi. At the Wu （午） hour， the heart meridian is active， and taking medication at this time warms the channel passages and assists heart yang， which can be treated with modified Buzhong Yiqi Decoction （补中益气汤） or Shengyang Yiwei Decoction （升阳益胃汤）. At night， blood should be harmonized， when the channel passages are unblocked through nourishing， restraining， and searching， with Lianmei Decoction （连梅汤） combined with Dahuang Zhechong Pill （大黄䗪虫丸）. Following the temporal rhythm， the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises， resonating and corresponding with the natural rhythm.

Objective:Exploring the association rules of factors influencing high hospitalization costs for cancer patients, providing references for hospitals to optimize medical cost management measures.Methods:In the inpatient case information system of a tertiary general hospital, the medical record homepages of inpatients in the DRG groups of the oncology department in 2022 were obtained. The upper four scores of hospitalization costs was used as the threshold for patient grouping. Patients with hospitalization costs≥this threshold were the high-cost group, while other patients were control group; 12 factors, including age, gender, and admission condition, etc, were considered as potential influencing factors of high hospitalization costs. FP-Growth and Apriori algorithms were used to excavate the potential association rules between the influencing factors of high hospitalization costs. Logistic regression was used to analyze the independent influencing factors of high hospitalization costs.Results:A total of 5 512 hospitalized patients were included, including 1 378 patients in the high-cost group. Thirteen validated strong association rules for factors influencing high hospitalization costs were obtained, of which the rule antecedents included age (≥70 years), number of days in hospital (≥7 days), other diagnoses (≥5), surgery, planned readmission, use of antibiotics, admission (general/critical), living admission score (61~99), level of care (level 1/level 2), non-day ward, criticality during hospitalisation. Logistic regression results showed that all nine influencing factors except gender, use of antibiotics, and readmission plans were independent influences on high hospitalization costs ( P<0.05). Conclusions:The joint application of FP-Growth and Apriori algorithm could effectively explore the association rules of high hospitalization costs for oncology patients. The early warning information mainly included the number of hospitalization days, the number of other diagnoses, surgeries, and so on. It was suggested that medical institutions can reasonably control the high hospitalization costs through clinical pathway management, diagnosis and treatment process reengineering, admission risk assessment, and multidisciplinary collaborative diagnosis and treatment strategies.

OBJECTIVE To investigate the impact of inflammatory cytokines related to different endotypes of chronic rhinosinusitis on the transcriptome of nasal epithelial cells.METHODS Human primary nasal epithelial cells were cultured in vitro,and treated with type 1,type 2,and type 3 inflammatory cytokines IFN-γ(10 ng/ml),IL-4(50 ng/ml),and IL-17A(50 ng/ml),respectively.After 48 hours,cells were collected for RNA extraction and transcriptome analysis.Differentially expressed genes were identified,followed by functional annotation and pathway enrichment analysis.Additionally,common regulated genes among different cytokines were analyzed.RESULTS Treatment of primary nasal epithelial cells with IFN-γ,IL-4,and IL-17A induced significant transcriptomic alterations,with 650,540,and 192 differentially expressed genes,respectively,compared to the control group.Functional annotation and pathway enrichment analysis showed that IFN-γ was mainly associated with defense response to virus,antigen processing and presentation,leukocyte and lymphocyte mediated immunity,and NOD-like receptor signaling pathway;IL-4 was mainly related to the regulation of leukocyte chemotaxis,cell-cell adhesion,ECM-receptor interaction,and MAPK signaling pathway;IL-17A was involved in the regulation of neutrophil chemotaxis,response to molecule of bacterial origin,chemokine signaling pathway,and NF-κB signaling pathway.Genes commonly regulated by IFN-γ,IL-4,and IL-17A were identified,with DUOX2 being upregulated by all the three cytokines.CONCLUSION IFN-γ,IL-4,and IL-17A reshapes the transcriptomic profile of nasal epithelial cells,which mainly regulates signaling pathways related to defense response to virus,leukocyte chemotaxis,and response to bacteria,respectively.

Objective To investigate the effect of ubiquitin-specific peptidase(USP)44 and nuclear receptor co-inhibitor 1(NCOR1)expression on prognosis in non-small cell lung cancer.Methods A total of 98 pa-tients with non-small cell lung cancer admitted to a hospital from May 2019 to May 2021 were selected as the study objects,and non-small cell lung cancer tissues and adjacent tissues were collected to detect the expres-sion levels of USP44 and NCOR1 in these tissues by immunohistochemical staining.The relationship between USP44 and NCOR1 expression and pathological features of non-small cell lung cancer patients was analyzed,and the prognostic factors of non-small cell lung cancer patients were analyzed by multivariate Cox regression.Results The positive expression rates of USP44 and NCOR1 in non-small cell lung cancer tissues were higher than those in adjacent tissues,the difference was statistically significant(P<0.05).The positive expression rates of USP44 and NCOR1 in patients with medium-low differentiation,lymph node metastasis,clinical stageⅢ to Ⅳ,and pleural metastasis were higher than those in patients with highly differentiated,no lymph node metastasis,clinical stage Ⅰ to Ⅱ,and no pleural metastasis,and the difference was statistically significant(P<0.05).The 3-year overall survival rate of USP44 and NCOR1 negative non-small cell lung cancer patients was higher than that of USP44 and NCOR1 positive non-small cell lung cancer patients,and the difference was statistically significant(all P<0.05).Multivariate Cox regression analysis showed that pleural metastasis,USP44 positive and NCOR1 positive were prognostic factors in non-small cell lung cancer patients(P<0.05).Conclusion The expression of USP44 and NCOR1 in patients with non-small cell lung cancer can be used as biomarkers for prognosis assessment,and provide evidence for progression assessment and clinical de-cision making of non-small cell lung cancer.

Objective To study the correlation between intestinal flora imbalance and serum interleukin-6(IL-6),serum amyloid A(SAA)and D-lactic acid levels in chronic obstructive pulmonary disease(COPD)pa-tients with pulmonary infection.Methods The case data of totally 148 COPD patients with pulmonary infec-tion who were treated in the hospital from June 2022 to June 2023 were collected.According to the presence or absence of intestinal flora imbalance,they were divided into intestinal flora imbalance group(n=41)and in-testinal flora non-imbalance group(n=107).The levels of serum IL-6,SAA and D-lactic acid and distribution of intestinal flora in the two groups were detected,and the correlation between intestinal flora imbalance and levels of serum IL-6,SAA and D-lactic acid was analyzed.Results The levels of serum IL-6,SAA and D-lactic acid in intestinal flora imbalance group were higher than those in intestinal flora non-imbalance group(P<0.05).Eubacterium,Lactobacillus and Bifidobacterium counts in intestinal flora imbalance group were less than those in intestinal flora non-imbalance group(P<0.05),while Enterococcus and Escherichia coli counts were more than those in intestinal flora non-imbalance group(P<0.05).In intestinal flora imbalance group,there were 14 cases with degree Ⅰ imbalance(degree Ⅰ group),6 cases with degree Ⅱ imbalance(degree Ⅱgroup)and 21 cases with degree Ⅲ imbalance(degree Ⅲ group).The levels of serum IL-6,SAA,and D-lac-tate increased sequentially in the degree Ⅰ group,degree Ⅱ group and degree Ⅲ group(P<0.05).Eubacteri-um,Lactobacillus and Bifidobacterium counts were negatively correlated with serum IL-6,SAA and D-lactic acid levels(P<0.05),while Escherichia coli and Enterococcus counts were positively correlated with serum IL-6,SAA and D-lactic acid levels(P<0.05).Conclusion There is a correlation between intestinal flora im-balance and serum IL-6,SAA and D-lactic acid levels in COPD patients with pulmonary infection,and IL-6,SAA and D-lactic acid levels could be used as effective indicators to evaluate the degree of intestinal flora im-balance.

BACKGROUND:Allogeneic tendons are often used in clinical treatment of tendon and ligament injuries,which need to be treated before clinical application.At present,allogeneic tendons will face multiple freeze-thaw cycles after cryopreservation,but there is no relevant research on the changes in the properties of the treated allogeneic tendon after several freeze-thaw cycles.OBJECTIVE:To explore the changes in mechanical properties and composition of allogeneic tendon after multiple freeze-thaw cycles.METHODS:The treated allogeneic tendon was frozen and thawed 3,6,and 10 times at-40 ℃(or-80 ℃),respectively.The mechanical test,DNA content,glycosaminoglycan sulfate,hydroxyproline content and total protein content of the allogeneic tendon after freezing and thawing were detected.RESULTS AND CONCLUSION:(1)There was no significant difference in the maximum load,maximum load elongation,tensile strength and elastic modulus between groups after freezing-thawing cycles for 3,6,and 10 times at-40 ℃(P＞0.05).There was no significant difference in the maximum load and maximum load elongation between the groups after freezing-thawing cycles for 3,6,and 10 times at-80 ℃(P＞0.05).The tensile strength of the group with 3 cycles of freezing and thawing was higher than that of the groups with 6 and 10 cycles of freezing and thawing(P＜0.05).The elastic modulus of the group with 3 cycles of freezing and thawing was higher than that of the group with 10 cycles of freezing and thawing(P＜0.05).(2)The freezing and thawing times did not affect the contents of DNA,hydroxyproline,total protein,and sulfated glycosaminoglycan in allogeneic tendon when stored at-40 ℃(or-80 ℃).(3)These findings suggest that in-40℃ storage,the performance of the allogeneic tendon should not be affected by taking out and putting back the tendon less than 10 times,while in-80 ℃ storage,the allogeneic tendon should be taken out and put back less than 6 times.

Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.

Objective:To investigate the regulatory effect of follistatin-like 1 protein (FSTL1) on the differentiation of mesenchymal stem cells (MSCs) into myofibroblasts in renal tissue and on renal fibrosis induced by renal ischemia-reperfusion injury (IRI).Method:In animal experiments, a unilateral renal IRI-induced fibrosis model was established by clamping the left renal pedicle (IRI 7 d group, n=3), with a sham-operated group as control (Sham 7 d group, n=3). Twelve male C57BL/6 mice were randomly assigned to sham operation (Sham group, n=4), model (IRI group, n=4) and FSTL1 treatment (IRI+FSTL1 group, n=4) groups. The Sham group underwent laparotomy sham surgery, while the IRI group and IRI+FSTL1 group underwent unilateral renal IRI surgery. From 1 day before surgery to 7 days after surgery, mice received daily intraperitoneal injections of phosphate buffered saline (Sham group and IRI group) or recombinant FSTL1 protein (IRI+FSTL1 group). The mice were sacrificed 14 days after surgery. Renal histopathological damage was evaluated by hematoxylin-eosin (HE) staining. Collagen fiber deposition and fibronectin (FN) accumulation in renal interstitium were assessed by Sirius red staining, Masson’s trichrome staining and immunohistochemical staining. The co-expression level of stem cell antigen-1 (SCA-1) and α-smooth muscle actin (α-SMA) was detected by double immunofluorescence staining. The mRNA expression levels of fibrosis-related genes ( Col1a1, Col3a1, Fn1) and myofibroblast marker gene ( Acta2) were detected by real time quantitative polymerase chain reaction (RT-qPCR). In cell experiments, a differentiation model of mouse MSCs into myofibroblasts was established through TGF-β1 induction (MSC+TGF-β1 group, n=3), with a blank control group (MSC group, n=3) set up for comparison. Bone marrow MSCs from C57BL/6 mice were randomly divided into 4 groups: the TGF-β1 induction group (MSC+TGF-β1, n=6), the FSTL1 treatment group (MSC+TGF-β1+FSTL1, n=6), the negative control siRNA transfection group (MSC-siNC+TGF-β1, n=6), and the Fstl1-targeted siRNA transfection group (MSC-si Fstl1+TGF-β1, n=6). The mRNA and protein expression levels of Col1a1, Col3a1, Fn1 and Acta2 were detected by RT-qPCR and Western blot respectively. The concentration of FSTL1 protein in cell culture supernatant was measured by enzyme-linked immunosorbent assay. Result:The expression of Col1a1 and Acta2 mRNA in the kidney tissue of IRI 7 d group mice was higher than that of the Sham 7 d group (both P<0.05), successfully establishing a mouse model of renal fibrosis. The mRNA expression of Fstl1 in kidney tissues of the IRI 7 d group mice was upregulated ( P<0.01). Immunofluorescence double staining revealed increased co-expression of SCA-1/α-SMA and SCA-1/FSTL1 in the renal interstitium. At 14 days after surgery, HE staining results showed reduced pathological damage in kidney tissues of the IRI+FSTL1 group compared to the IRI group, and Sirius Red and Masson staining revealed decreased collagen fiber deposition in the renal interstitium, while immunohistochemical staining demonstrated reduced FN accumulation in the renal interstitium (all P<0.05). The mRNA expression levels of Col1a1, Col3a1, Fn1 and Acta2 in renal tissue of IRI+FSTL1 group were lower than IRI group (all P<0.05). Double immunofluorescence staining showed a decrease in the co-expression of SCA-1 and α-SMA in renal interstitium. In cell experiments, the mRNA expression levels of Col1a1, Col3a1, Fn1, and Acta2 in the MSC+TGF-β1 group were higher than those in the MSC group (all P<0.05), confirming successful TGF-β1-induced myofibroblast differentiation of MSCs. Additionally, both intracellular FSTL1 protein expression and FSTL1 protein concentration in the cell supernatant were elevated in the MSC+TGF-β1 group (both P<0.05). Compared with MSC+TGF-β1 group, the mRNA levels of Acta2 and Col1a1 in MSC+TGF-β1+FSTL1 group were decreased (both P<0.01), and the protein expression levels of collagen Ⅰ and α-SMA were significantly decreased (both P<0.001). Compared with MSC-siNC+TGF-β1 group, the protein level of FSTL1 in cell culture supernatant of MSC-si Fstl1+TGF-β1 group were decreased ( P<0.001), while the protein expression levels of FN and α-SMA were increased (both P<0.001), and the mRNA expression levels of Fn1 and Acta2 were increased (both P<0.05). Conclusions:During unilateral renal IRI-induced renal fibrosis, MSCs in renal interstitium may differentiate into myofibroblasts. FSTL1 may alleviate renal fibrosis after unilateral renal IRI by inhibiting the differentiation of MSCs into myofibroblasts.