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 investigate the dynamic changes of signal transducer and activator of transcription 6(STAT6)and peroxisome proliferator-activated receptor alpha(PPARα)in peripheral blood of patients with acute cerebral in-farction(ACI)and their association with disease severity and prognosis.Methods A total of 86 ACI patients who were hospi-talized in our hospital from January 2021 to June 2022 were enrolled as ACI group,and according to the National Institutes of Health Stroke Scale(NIHSS)score,they were divided into mild group with 33 patients,moderate group with 35 patients,and severe group with 18 patients;a total of 85 individuals who underwent physical examination were enrolled as control group.ELISA was used to measure the level of STAT6 in peripheral blood;quantitative real-time PCR was used to measure the mRNA level of PPARα in peripheral blood;an automatic biochemical analyzer was used to measure blood-related biochemical param-eters,and an automatic blood pressure instrument was used to measure blood pressure parameters;a Pearson correlation analy-sis was used to investigate the correlation of STAT6 and PPARα levels with NIHSS score on admission.Results There were significant differences between the control group and the ACI group in triglycerides,low-density lipoprotein cholesterol,lipo-protein,diastolic pressure,and systolic pressure(P<0.05).The ACI group showed gradual reductions in the levels of STAT6 and PPARα in peripheral blood on days 1,3,and 7 of stroke,with the lowest levels observed on day 7 of stroke,and there were increases in the levels of STAT6 and PPARα on day 14 of stroke,which was still lower than the levels in the control group(P<0.05).For the ACI patients,the expression levels of STAT6 and PPARα in peripheral blood tended to decrease gradually with the aggravation of disease conditions at different time points of stroke.The Pearson correlation analysis showed that the levels of STAT6 and PPARα in peripheral blood of ACI patients on day 1 of stroke were negatively correlated with NIHSS scores(P<0.05).The good prognosis group had significantly higher levels of STAT6 and PPARα than the poor progno-sis group at different time points of stroke(P<0.05).Conclusion There are reductions in the levels of STAT6 and PPARα in peripheral blood of ACI patients after the onset of ACI,which tend to first decrease and then increase over the time of stroke,and the changes in the levels of STAT6 and PPARα are associated with the severity and prognosis of ACI patients.

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 effect of autologous costal cartilage cortex as nasal tip support and modified graft for nasal tip contour improvement.Methods:From June 2020 to June 2021, 116 patients (male 26, female 90, aged 20-45 years) who received rhinoplasty in the cosmetic surgery department of Myoung Beaucare Clinic of Beijing, were examined the costal cartilage by CT, and the costal cartilage was cut. The costal cartilage cortex was made into " strip" and " cap" grafts to shape the nasal tip, and the nasal dorsum was raised by polytetrafluoroethylene or silicone prosthesis for comprehensive rhinoplasty.Results:A total of 116 patients were followed up for an average of 11.7 months. After the operation, there was no space occupying in the nasal cavity, no graft protrusion, no obvious foreign body feeling in the nasal valve, and the nasal tip could swing left and right. At the same time, the nasal tip showed obvious signs, the lower lobule was full, and there were no complications such as cartilage appearance, exposure, infection, etc. Due to the untreated deviation of nasal septum, 3 cases had deviation of nasal columella and asymmetric nostrils. The shape of nasal tip was stable in the remaining 113 cases, and satisfactory results were obtained.Conclusions:By using autologous costal cartilage cortex as nasal tip support and modification graft for nasal tip contour improvement, the shaped nasal tip is soft and movable, and does not affect the airway. It is a good surgical technique in nasal tip plastic surgery, which is worthy of clinical application.

Objective:To measure and analyze the morphological parameters of nasal septal cartilage obtained by rhinoplasty in Chinese, so as to provide theoretical guidance for clinical acquisition and application of nasal septal cartilage.Methods:From March 2014 to June 2021, 732 patients were received rhinoplasty in Myoung Beaucare Clinic of Beijing-Cosmetic Surgery. During the operation, 12 mm L-shaped nasal septal cartilage scaffold was obtained from nasal septal cartilage for transplantation. Measurement of the length, width, area, maximum thickness and minimum thickness of nasal septal cartilage was performed for further analysis.Results:For nasal septal cartilage obtained from comprehensive rhinoplasty, its length was 1.2 to 3.5 cm, with an average of 2.16 cm; the width was 1 to 3 cm, with an average of 1.84 cm; the area was 1.43 to 10.5 cm 2, with an average of 4.04 cm 2, with a maximum thickness of 0.5 to 3 mm, with an average of 1.92 mm and a minimum thickness of 0.2 to 0.5 mm, with an average of 0.92 mm. Conclusions:In the comprehensive rhinoplasty of nasal septal cartilage for Chinese, the 12 mm L-shaped nasal septal cartilage scaffold is retained, and the average length, width and area of nasal septal cartilage for transplantation are 2.16 cm, 1.84 cm, 4.04 cm 2, 1.92 mm and 0.92 mm respectively.

Objective:To investigate the surgical method and clinical outcome of using nasal septal cartilage combined with auricular cartilage for management of nasal tip shape.Methods:A clinical study was conducted from April 2014 to June 2019, in which we managed nasal tip shape with nasal septal cartilage and auricular cartilage, and these materials were used as septal extension graft, spreader graft and cap graft. In total, 622 patients (28 males, 594 females; age from 18 to 42 years, mean age 27.47 years) were assessed for eligibility.Results:The follow-up period was from 6 months to 6 years. Nasal shape of all 622 patients was improved significantly after the operation. The nasal tip was natural and round, and there were no complications such as damage of nasal septum mucosa, exposure of prosthesis and infection of surgical site. Only 12 patients were found downward rotation of nasal tip, and 610 patients achieved satisfactory aesthetic results.Conclusions:Using septal cartilage combined with auricular cartilage is a safe, effective and suitable method for management of nasal tip shape.

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.