Objective:To investigate the role and possible mechanism of triggering receptor expressed on myeloid cells-1(TREM-1)in the inflammatory response of rat vascular smooth muscle cells(VSMCs)mediated by trimethylamine N-oxide(TMAO).Methods:VSMCs were treated with TMAO at different concentrations(0,100,300,600,900,1 200,1 500 μmol/L)for 24 hours.VSMCs were transfected with the siRNA interference plasmid targeting the TREM-1 gene(si-TREM-1)and its negative control interference plas-mid(si-NC),and 600 μmol/L TMAO was used to induce inflammatory response in VSMCs,combined with the intervention with the nuclear factor-kappa B(NF-κB)activator phorbol myristate acetate(PMA)for 24 hours.CCK-8 assay was used to measure cell prolif-erative activity;ELISA was used to measure the levels of interleu-kin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in cell supernatant;qRT-PCR was used to measure the mRNA expression levels of TREM-1,cyclooxygenase-2(COX-2),intercellular adhesion molecule-1(ICAM-1),IL-1β,IL-6,and TNF-α in cells,and Western blot was used to measure the protein expression levels of TREM-1,COX-2,ICAM-1,NF-κB p65,and p-NF-κB p65(Ser536)in cells.Results:Treatment with TMAO at different concentrations had no significant impact on the prolifera-tive activity of VSMCs(P=0.375),but it significantly upregulated the levels of IL-1β,IL-6,and TNF-α in supernatant and the mRNA and protein expression levels of TREM-1,COX-2,and ICAM-1 in cells(all P<0.01)in a concentration-dependent manner.Silencing of the TREM-1 gene significantly inhibited the increases in the levels of IL-1β,IL-6,and TNF-α in the supernatant of VSMCs in-duced by TMAO,and it also suppressed the upregulation of the mRNA expression levels of COX-2,ICAM-1,IL-1β,IL-6,and TNF-α and the ratio of p-NF-kB p65/NF-kB p65 in VSMCs(all P<0.01).However,PMA intervention significantly reversed the role of si-lencing the TREM-1 gene on TMAO-induced inflammatory response in VSMCs.Conclusion:Silencing of the TREM-1 gene can in-hibit TMAO-induced inflammatory response in VSMCs,possibly by inhibiting the activation of the NF-κB pathway.

For rare real-world data involving off-label drug use or comorbidity-associated polypharmacy,researchers have increasingly adopted target trial emulation to investigate drug repurposing for target indications.The success of such studies hinges on rigorous trial design and strict adherence to predefined protocols and standardized pipelines.Key elements in the trial design include the precise definition of inclusion and exclusion criteria,the selection of trial and control drugs and determination of treatment allocation time,the determination of appropriate efficacy endpoints for the target indication,the identification of causal estimands,and the development of robust strategies for confounding adjustment.The execution of the trial follows a structured process:screening eligible subjects,extracting relevant drug exposure data,constructing treatment and control groups,emulating the target trial,and ultimately generating hypotheses for drug repurposing through statistical inference.Propensity score methods,including stratification,matching and weighting techniques,are critical tools for addressing confounding bias and ensuring accurate estimation of causal effects.In recent years,creative progress has been made in target trial emulation,particularly in the calculation of propensity scores.Researchers have adopted advanced machine learning techniques,to enhance variable selection and have actively explored the use of innovative methods of digital intelligence technology like classification and regression trees,support vector machines,and deep learning for the application of propensity score calculation.Target trial emulation based on real-world data has achieved remarkable advancements in drug repurposing,demonstrating broad application prospects,particularly in cardiovascular diseases,metabolic disorders,Alzheimer's disease,and cancer.

For rare real-world data involving off-label drug use or comorbidity-associated polypharmacy,researchers have increasingly adopted target trial emulation to investigate drug repurposing for target indications.The success of such studies hinges on rigorous trial design and strict adherence to predefined protocols and standardized pipelines.Key elements in the trial design include the precise definition of inclusion and exclusion criteria,the selection of trial and control drugs and determination of treatment allocation time,the determination of appropriate efficacy endpoints for the target indication,the identification of causal estimands,and the development of robust strategies for confounding adjustment.The execution of the trial follows a structured process:screening eligible subjects,extracting relevant drug exposure data,constructing treatment and control groups,emulating the target trial,and ultimately generating hypotheses for drug repurposing through statistical inference.Propensity score methods,including stratification,matching and weighting techniques,are critical tools for addressing confounding bias and ensuring accurate estimation of causal effects.In recent years,creative progress has been made in target trial emulation,particularly in the calculation of propensity scores.Researchers have adopted advanced machine learning techniques,to enhance variable selection and have actively explored the use of innovative methods of digital intelligence technology like classification and regression trees,support vector machines,and deep learning for the application of propensity score calculation.Target trial emulation based on real-world data has achieved remarkable advancements in drug repurposing,demonstrating broad application prospects,particularly in cardiovascular diseases,metabolic disorders,Alzheimer's disease,and cancer.

Objective:To explore the value of magnetic resonance diffusion tensor imaging (DTI) in evaluating cerebrovascular small vessel disease (CSVD) in patients with systemic lupus erythematosus (SLE).Methods:Eighty-two patients with SLE combined with CSVD treated at Yixing People's Hospital from January to December 2022 were selected. They were divided into acute phase infarction group (16 cases), chronic phase infarction group (26 cases), and chronic ischemic lesion group (40 cases) based on routine MRI examination results. All patients underwent DTI examination to obtain the average diffusion coefficient (DCavg) and anisotropy score (FA) of the affected and contralateral normal white matter areas, and the evaluation value of DTI for CSVD in SLE patients was analyzed.Results:The DCavg value on the affected side of 82 patients was significantly higher than that on the healthy side: (11.10 ± 3.48) 10 -3 mm 2/s vs. (8.18 ± 2.42) 10 -3 mm 2/s, and the FA value on the affected side was significantly lower than that on the healthy side: 0.28 ± 0.05 vs. 0.45 ± 0.08, with a statistical significant differences ( P<0.05). The DCavg values of the acute infarction group, chronic infarction group, and chronic ischemic focus group were (11.88 ± 3.50), (9.69 ± 3.24) and (8.52 ± 2.34) 10 -3 mm 2/s, respectively, with statistical significant differences ( P<0.05). The FA values of the acute infarction group, chronic infarction group, and chronic ischemic focus group were 0.28 ± 0.04, 0.33 ± 0.06 and 0.40 ± 0.07, respectively, with statistical significant differences ( P<0.05). The receiver operating characteristic curve was drawn, and the results showed that the area under the curve (AUC) of the acute phase infarction group and the chronic phase infarction group evaluated by DCavg and FA alone and in combination were 0.757, 0.756, and 0.820, respectively. The AUC of the chronic phase infarction group and the chronic ischemic focus group evaluated by DCavg and FA were 0.772, 0.776, and 0.813, respectively. The AUC value of the combined evaluation was relatively large. Conclusions:DTI has good evaluation value for CSVD in SLE patients and can accurately determine the type of CSVD.

Objective:To explore the application of nasal aesthetic polygon theory in the reconstruction of new domes on nasal tip with autogenous costal cartilage.Methods:From June 2019 to June 2021, 116 patients (26 males and 90 females) received rhinoplasty, CT-assisted examination of the costal cartilage, nasal bone and nasal cartilage was performed, and the autogenous costal cartilaginous cortex was used to make dome reconstruction grafts that were transplanted to the original alar cartilage and partially fixed to the original nasal septum cartilage to form a satisfactory and natural nasal shape.Results:All the patients were followed up for 6-24 months. No cartilaginous, overrotated or underrotated appearance was found in nasal tip. The shape of nasal tip was clear and good, with an obvious performance point and full lower lobule. The nose was tall and straight, and looked natural and beautiful in three dimensions.Conclusions:The nasal aesthetic polygon theory is used to guide the reconstruction of new domes with autogenous costal cartilage in nasal tip surgery. Compared to the cap and shield grafts, the nasal tip is more close to the normal anatomical structure, the shape and texture are more similiar to the natural state and the nasal tip is softer by using autogenous costal cartilage, and so it is an ideal surgical procedure for nasal tip reconstruction.

Objective:To investigate the clinicopathological characteristics of early-onset colorectal cancer.Methods:The retrospective and descriptive study was conducted. The clincopatholo-gical data of 59 206 patients with colorectal cancer in the Surveillance, Epidemiology, and End Results Program of the United States of America From January 1,2010 to December 31,2019 were collected. There were 33 213 males, 25 993 males, aged (50±7)years. Observation indicators: (1) demographic and oncological characteristics of colorectal cancer patients; (2) comparison of clinico-pathological characteristics between early-onset and late-onset colorectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison among groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers, and comparison among groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter H test. Patients with early-onset colorectal cancer were segmented by age, and missing data for categorical variables is set as unknown. Results:(1) Demographic and oncological characteristics of colorectal cancer patients. Of 59 206 patients, there were 23 104 cases with early-onset colorectal cancer and 36 102 cases with late-onset colorectal cancer, and cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years, cases aged 55-59 years were 1 041, 1 740, 3 288, 6 050, 10 985, 15 303,20 799, respectively. (2) Comparison of clinicopathological charac-teristics between early-onset and late-onset colorectal cancer. ① There were significant differences in gender, tumor location, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, tumor M staging, preoperative carcinoembryonic antigen (CEA), perineural invasion, cancer nodule, tumor diameter between patients with early-onset and late-onset colorectal cancer ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, transverse colon were 2 329, 2 139, 579, 1 303 in the 6 350 patients with early-onset right colon cancer. The above indicators were 4 563, 3 945, 902, 1 951 in the 11 361 patients with late-onset right colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=114.27, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 553, 1 354, 6 404, 2 431 in the 10 742 patients with early-onset left colon cancer. The above indicators were 865, 1 798, 9 668, 3 610 in the 15 941 patients with late-onset left colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=35.60, P<0.01). ②Of 23 104 patients with early-onset colorectal cancer, cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years were 1 041, 1 740, 3 288, 6 050, 10 985, respectively. There were significant differences in gender, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, pre-operative CEA, perineural invasion, cancer nodule, tumor diameter among patients of different age groups ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, and transverse colon were 91, 117, 45, 69 in the 6 350 early-onset right colorectal cancer patients aged 13-29 years. The above indicators were 165, 136, 47, 115, 304, 313, 93,201, 614, 535, 151, 330, 1 155, 1 038, 243, 588 in early-onset right colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=36.63, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 32, 83, 260, 95 in the 10 742 early-onset left colorectal cancer patients aged 13-29 years. The above indica-tors were 53, 112, 452, 171, 95, 230, 867, 342, 149, 337, 1 702, 665, 224, 592, 3 123, 1 158 in the 10 742 early-onset left colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=47.84, P<0.01). Conclusions:Compared with late-onset colorectal cancer, early-onset colorectal cancer are more likely to occur in the left colon and rectum, with poorly differentiated and undifferentiated tumors, histological type of mucinous adenocarcinoma, TNM staging of stage Ⅲ and Ⅳ, higher proportion of nerve infiltration and cancer nodules, and larger tumor diameter. There are significant differences in clinicopathological characteristics of tumors among patients with early-onset colorectal cancer of different age groups.

Objective:To investigate the effect of pulmonary rehabilitation therapy on the exercise capacity and dyspnea of persons with chronic obstructive pulmonary disease (COPD).Methods:One hundred COPD patients were randomly divided into a control group and an observation group, each of 50. Both groups were given routine medication, while the observation group was additionally provided with health guidance, oxygen therapy, respiratory physiological therapy and exercise for 3 months. Before and after the intervention, both groups′ forced expiratory volume in 1 second (FEV1) and the first and second forced expiratory volume as a percentage of FEV (FEV1%) were measured. The subjects′ motor functioning was evaluated using the 6-minute walk test. Enzyme-linked immunosorbent assays and immunoturbidimetry quantified their expression of inflammatory factors. And their ability in the activities of daily living (ADL) was evaluated using the Barthel index. The COPD quality of life questionnaire (CRQ) was also used to assess their life quality.Results:After the intervention, the average clinical efficacy in the observation group was 96%, significantly higher than that of the control group (80%). Moreover, the average FEV1, FEV1%, 6-minute walk test time of the former group were all significantly better than before the intervention and better than the control group′s results after the intervention. Their average CRP, IL-6 and TNF-α levels were all significantly lower as well. After the intervention, the observation group′s average total CRQ score and its average scores on the instrument′s emotion, fatigue, wheezing and disease control components were all better than the control group′s averages. The observation group′s average ADL score was also significantly higher than that of the control group.Conclusions:Supplementing conventional medication with pulmonary rehabilitation therapy can effectively improve the lung function, motor functioning and life quality of COPD patients. It can also lower their level of serum inflammatory factors.

Organic anion transporting polypeptide 2A1 ( SLCO2A1) gene encodes the organic anion transporting polypeptide 2A1 (OATP2A1) . OATP2A1 is widely expressed in human tissues and organs, plays an important regulatory role in prostaglandin metabolism and participates in various pathophysiological processes. The abnormality of SLCO2A1 gene can affect the prostaglandin metabolism by OATP2A1, leading to the disease. At present, the known SLCO2A1 gene related diseases include primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with SLCO2A1 gene (CEAS) . More attention has been paid to these diseases in recent years. Based on the functional characteristics of SLCO2A1 gene, the article introduces the pathogenesis, clinical characteristics and treatment progress of SLCO2A1 gene related diseases.

Organic anion transporting polypeptide 2A1 ( SLCO2A1) gene encodes the organic anion transporting polypeptide 2A1 (OATP2A1) . OATP2A1 is widely expressed in human tissues and organs, plays an important regulatory role in prostaglandin metabolism and participates in various pathophysiological processes. The abnormality of SLCO2A1 gene can affect the prostaglandin metabolism by OATP2A1, leading to the disease. At present, the known SLCO2A1 gene related diseases include primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with SLCO2A1 gene (CEAS) . More attention has been paid to these diseases in recent years. Based on the functional characteristics of SLCO2A1 gene, the article introduces the pathogenesis, clinical characteristics and treatment progress of SLCO2A1 gene related diseases.

Objective:To investigate and compare the therapeutic effect of Foley catheter balloon dilation and the traditional open reduction in the treatment of intussusception in children.Methods:A total of 68 children with intussusception treated by Foley catheter balloon dilatation by laparoscopic surgery or traditional open reduction in Department of Pediatric Surgery, the Second Hospital of Lanzhou University from August 2015 to July 2019 were retrospectively analyzed.Among them, there were 32 cases in the Foley catheter group and 36 cases in the traditional laparotomy group.Foley catheter group were treated with laparoscopic Foley catheter balloon dilatation, while the traditional open group were treated with traditional open surgery which was performed with finger dilatation.The results of surgical treatment, postoperative recovery, short-term complications, patient satisfaction and long-term complications were compared between the two groups.Results:Among the indexes of surgical treatment effect, the operation time[(0.4±1.1) h], intraoperative bleeding volume[(10.2±3.4) mL], incision size[(0.5±0.4) cm] and incidence of the rupture of intestine[6.3%(2/32 cases)] in the Foley catheter group were significantly lower than those in the traditional open group[(1.3±2.9) h, (40.5±2.1) mL, (5.1±0.7) cm, 30.6%(11/36 cases)], and the differences were statistically significant (all P< 0.05). Among the indexes of postoperative recovery and short-term complications, recovery time of gastrointestinal function[(1.2±3.1) d], length of hospital stay[(6.7±1.8) d], incidence of incision infection[9.4%(3/32 cases)]and incidence of incisional hernia(0) in the Foley catheter group were significantly lower than those in the traditional open group[(3.3±6.4) d, (7.3±0.9) d, 36.1%(13/36 cases), 16.7%(6/36 cases)], and the differences were statistically significant (all P<0.05). Among the indexes of family satisfaction and long-term complications, the score of family satisfaction in the Foley catheter group [(8.7±1.2) scores]was significantly higher than that in the traditional open group[(6.6±3.1) scores], and the incidence of adhesive intestinal obst-ructionin the Foley catheter group (0)was significantly lower than that in the traditional open group[0 vs.19.4%(7/36例)], and the differences were statistically significant(all P<0.05). Conclusions:Compared with traditional open reduction in the treatment of intussusception in children, Foley catheter balloon dilation has the advantages of short operation time, safe operation, low incidence of intestinal injury, less bleeding, and so on, and also has the advantages of small incision, fast recovery, short hospitalization time, high satisfaction of parents.In addition, the Foley catheter balloon dilation has a lower incidence of incisional infection, incisional hernia, postoperative intestinal adhesion and other complications.