BACKGROUND:Plasma coagulation factors have been shown to be strongly associated with chronic kidney disease in many observational studies.Nevertheless,the causal relationship between plasma coagulation factors and chronic kidney disease has not been fully revealed.OBJECTIVE:To assess and explore the association between plasma coagulation factors and chronic kidney disease risk using a two-sample Mendelian randomization approach.METHODS:Genome-wide association study data of 39 plasma coagulation factors with different ID numbers were obtained from the GWAS Catalog database and chronic kidney disease genome-wide association analysis data(ebi-a-GCST003374)were obtained from the Open Genome-Wide Association Study database(IEU Open GWAS),where the sample size of the chronic kidney disease dataset was 117 165 cases and the number of single nucleotide polymorphisms was 2 179 497.Inverse variance weighting,MR-Egger regression,weighted median,weighted mode,and simple mode were used to explore causality.Meanwhile,Cochran Q test was used to assess the variability of single nucleotide polymorphism loci.Horizontal pleiotropy of single nucleotide polymorphisms was verified by MR-Egger intercept test.Sensitivity analyses were performed using the"leave-one-out"method to determine whether the Mendelian randomization results would be confounded by a single single nucleotide polymorphism site.RESULTS AND CONCLUSION:(1)A total of four plasma coagulation factors were associated with chronic kidney disease by Mendelian randomization analysis of 39 plasma coagulation factors and chronic kidney disease.Plasma coagulation factor V(FV)level(odds ratio[OR]=0.922,95％confidence interval[CI]:0.875-0.971,P=0.002),plasma FVII level(OR=0.719,95％CI:0.521-0.991,P=0.044),plasma FXa level(OR=1.113,95％CI:1.009-1.227,P=0.032),plasma antithrombin-level(OR=0.849,95％CI:0.739-0.975,P=0.020)were significantly associated with chronic kidney disease(all P＜0.05).Horizontal pleiotropy and heterogeneity were not detected.(2)Based on the two-sample Mendelian randomization in the genetic epidemiologic method,plasma FVII level,plasma antithrombin-level,and plasma FV level of coagulation factors were protective factors for the risk of chronic kidney disease,and plasma FXa level was a risk factor of chronic kidney disease.(3)The above results confirm that there is a significant potential causal relationship between plasma coagulation factors and chronic kidney disease.Although we analyzed the data of European populations from international databases,these data analyses have a reference value for the study of chronic kidney disease and coagulation factors in China,and they also provide innovative insights into the study of the genetic epidemiology of chronic kidney disease,and they also provide a certain reference value for the in-depth study of the related databases in China,including the China Health and Retirement Longitudinal Study database.Future studies can focus on the assessment of hypocoagulability or hypercoagulability of related coagulation factors in patients with chronic kidney disease.

BACKGROUND:Plasma coagulation factors have been shown to be strongly associated with chronic kidney disease in many observational studies.Nevertheless,the causal relationship between plasma coagulation factors and chronic kidney disease has not been fully revealed.OBJECTIVE:To assess and explore the association between plasma coagulation factors and chronic kidney disease risk using a two-sample Mendelian randomization approach.METHODS:Genome-wide association study data of 39 plasma coagulation factors with different ID numbers were obtained from the GWAS Catalog database and chronic kidney disease genome-wide association analysis data(ebi-a-GCST003374)were obtained from the Open Genome-Wide Association Study database(IEU Open GWAS),where the sample size of the chronic kidney disease dataset was 117 165 cases and the number of single nucleotide polymorphisms was 2 179 497.Inverse variance weighting,MR-Egger regression,weighted median,weighted mode,and simple mode were used to explore causality.Meanwhile,Cochran Q test was used to assess the variability of single nucleotide polymorphism loci.Horizontal pleiotropy of single nucleotide polymorphisms was verified by MR-Egger intercept test.Sensitivity analyses were performed using the"leave-one-out"method to determine whether the Mendelian randomization results would be confounded by a single single nucleotide polymorphism site.RESULTS AND CONCLUSION:(1)A total of four plasma coagulation factors were associated with chronic kidney disease by Mendelian randomization analysis of 39 plasma coagulation factors and chronic kidney disease.Plasma coagulation factor V(FV)level(odds ratio[OR]=0.922,95％confidence interval[CI]:0.875-0.971,P=0.002),plasma FVII level(OR=0.719,95％CI:0.521-0.991,P=0.044),plasma FXa level(OR=1.113,95％CI:1.009-1.227,P=0.032),plasma antithrombin-level(OR=0.849,95％CI:0.739-0.975,P=0.020)were significantly associated with chronic kidney disease(all P＜0.05).Horizontal pleiotropy and heterogeneity were not detected.(2)Based on the two-sample Mendelian randomization in the genetic epidemiologic method,plasma FVII level,plasma antithrombin-level,and plasma FV level of coagulation factors were protective factors for the risk of chronic kidney disease,and plasma FXa level was a risk factor of chronic kidney disease.(3)The above results confirm that there is a significant potential causal relationship between plasma coagulation factors and chronic kidney disease.Although we analyzed the data of European populations from international databases,these data analyses have a reference value for the study of chronic kidney disease and coagulation factors in China,and they also provide innovative insights into the study of the genetic epidemiology of chronic kidney disease,and they also provide a certain reference value for the in-depth study of the related databases in China,including the China Health and Retirement Longitudinal Study database.Future studies can focus on the assessment of hypocoagulability or hypercoagulability of related coagulation factors in patients with chronic kidney disease.

Chinese materia medica has a wide range of clinical applications， but it has many active ingredients with different physicochemical properties， and the target organs， action pathways and mechanisms for different ingredients to exert their efficacy are not the same. Therefore， it is difficult to design and develop a co-delivery system loading multiple components of Chinese materia medica to maximize the synergistic therapeutic efficiency. Based on the characteristics of effectiveness and functionality of active ingredients， the strategies for multi-component co-delivery of Chinese materia medica can be categorized into two types：firstly， based on the effectiveness of active ingredients， new carriers such as liposomes， nanoparticles can be constructed to load multi-components of Chinese materia medica. secondly， based on the functionality of some active ingredients of Chinese materia medica， they are employed in the construction of co-delivery system， which can give play to the dual characteristics of their own efficacy and preparation functions. In this paper， we summarized the relevant research progress of the above two types of multi-component co-delivery strategies， and mainly discussed the pharmaceutical functions of the active ingredients in co-delivery systems， in order to find a more suitable multi-component co-delivery strategy， promoting the design and development of new delivery systems of Chinese materia medica.

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective To observe the changes of liver function,blood cell,and lung function of healthy young and middle-aged men before and after fast-advancing short-term high altitude exposure(FSHAE);and to explore the effects and possible mechanisms of FSHAE on the function of liver,blood cells,and lung tissues.Methods This study included 48 healthy young and middle-aged male volunteers,who collected physiological indicators,tested liver function indicators,blood cell indicators,and lung function-related indicators 1 day before entering the plateau(100m above sea level),and 15 days after FSHAE(3000m above sea level).Differences in the relevant parameters of each system were compared before and after FSHAE.Results Compared with those before entering the plateau,the physiological parameters of young and middle-aged men after 15 days of FSHAE heart rate increased significantly,respiratory rate increased,systolic blood pressure increased,mean arterial blood pressure increased,oxygen saturation decreased(P＜0.01),and diastolic blood pressure increased(P＜0.05),all of which were statistically significant;and the indicators of liver function:glutamic oxaloacetic aminotransferase,glutamic alanine aminotransferase increased(P＜0.01),glutamylamine aminotransferase,glutamate aminotransferase,glutaminase,and pulmonary function were increased(P＜0.01),glutamyl transpeptidase,alkaline phosphatase,and total bile acids were elevated,and total protein decreased(P＜0.05),and the differences were statistically significant.Hemocyte-related indexes:erythrocyte count,erythrocyte pressure volume,mean erythrocyte volume,mean hemoglobin volume,mean hemoglobin concentration,and hemoglobin were elevated,and platelet count decreased(P＜0.01),and the differences were statistically significant.although there was an elevation of leukocyte count(P＞0.05);Lung function-related indexes:decreased exertion lung volume(P＜0.05).There were decreased exertion expiratory volume in the first second,increased one-second rate(P＞0.05).Conclusion FSHAE can lead to oxidative stress in the organism,and acute hypoxic multisystemic injury will occur,with the simultaneous emergence of hypoxic adaptive regulation of various systems,self-compensatory repair of various organs of the organism,and there may be the possibility of interactions between various systems.

Objective To build a whole-course nursing quality evaluation system for liver transplanta-tion in children,so as to provide a basis for nursing quality evaluation and management.Methods With Donabedian's"structure-process-outcome"model as the theoretical framework,we employed literature analysis,Delphi method,and hierarchical analysis to determine the contents and weights of indexes in the whole-course nursing quality evaluation system for liver transplantation in children.Results The three rounds of survey based on questionnaires showed the questionnaire recovery rate of 100% ,the expert authority coefficients of 0.95,0.96,and 0.98,and the Kendall's coefficients of concordance of 0.165,0.209,and 0.220,respectively(all P<0.001).The established nursing quality evaluation system included 3 first-level indexes,15 second-level inde-xes,and 67 third-level indexes.Conclusion The whole-course nursing quality evaluation system for liver trans-plantation in children that was built in this study can provide a basis for the evaluation of the nursing quality.

Objective:To investigate the effects of rapid short-term altitude exposure on thyroid related hormone parameters in healthy male pilots.Methods:A total of 132 healthy male pilots who lived in the plain were selected by random number table method to enter the plateau, with an average altitude of 3 000 m, within 3 h by plane from the plain, with an average altitude of 100 m, from March 2023 to April 2023, and returned to the plain within 3 h by plane 15 d later. General physiological indices, thyroid related hormone parameters [thyroid stimulating hormone (TSH), total thyroid hormone (TT 4), free thyroxine (FT 4), free triiodothyronine (FT 3), total triiodothyronine (TT 3), thyroglobulin antibody (TgAb), anti-thyroid peroxidase antibody (TPOAb), and thyroglobulin (Tg)] were collected from the pilots 1 day before the rush into plateau exposure and after 15-day plateau exposure. The differences in thyroid related hormone parameters of the pilots before and after acute short-term plateau exposure were compared. Results:As compared with the parameters before entering the plateau, the heart rate, respiratory rate, systolic and diastolic blood pressure of pilots were increased and oxygen saturation was decreased after 15 d plateau exposure, and the differences were statistically significant ( t=8.65, 10.78, 13.39, 12.49, 17.72, all P<0.001). The levels of TSH, FT 4, TPOAb and Tg of pilots were all decreased after 15 d plateau exposure, and the differences were significant ( t=3.67, 2.17, Z=-4.63, -7.49, P=0.003, 0.049, <0.001, <0.001). The levels of TT 4 and TT 3 were elevated, with significant differences ( t=4.08, 2.55, P<0.001, =0.024). TgAb level was less discrete, but the difference was significant ( Z=-2.36, P=0.018). Conclusions:By rush into plateau and short-term exposure, the healthy male pilots showed decreased TSH, FT 4, TPOAb and Tg, and increased TT 4 and TT 3, and those may result in the thyroid gland due to acute stress and low-pressure hypoxia appeared related to the hormone metabolism and protein changes.

Objective:To investigate the effects of rapid short-term altitude exposure on thyroid related hormone parameters in healthy male pilots.Methods:A total of 132 healthy male pilots who lived in the plain were selected by random number table method to enter the plateau, with an average altitude of 3 000 m, within 3 h by plane from the plain, with an average altitude of 100 m, from March 2023 to April 2023, and returned to the plain within 3 h by plane 15 d later. General physiological indices, thyroid related hormone parameters [thyroid stimulating hormone (TSH), total thyroid hormone (TT 4), free thyroxine (FT 4), free triiodothyronine (FT 3), total triiodothyronine (TT 3), thyroglobulin antibody (TgAb), anti-thyroid peroxidase antibody (TPOAb), and thyroglobulin (Tg)] were collected from the pilots 1 day before the rush into plateau exposure and after 15-day plateau exposure. The differences in thyroid related hormone parameters of the pilots before and after acute short-term plateau exposure were compared. Results:As compared with the parameters before entering the plateau, the heart rate, respiratory rate, systolic and diastolic blood pressure of pilots were increased and oxygen saturation was decreased after 15 d plateau exposure, and the differences were statistically significant ( t=8.65, 10.78, 13.39, 12.49, 17.72, all P<0.001). The levels of TSH, FT 4, TPOAb and Tg of pilots were all decreased after 15 d plateau exposure, and the differences were significant ( t=3.67, 2.17, Z=-4.63, -7.49, P=0.003, 0.049, <0.001, <0.001). The levels of TT 4 and TT 3 were elevated, with significant differences ( t=4.08, 2.55, P<0.001, =0.024). TgAb level was less discrete, but the difference was significant ( Z=-2.36, P=0.018). Conclusions:By rush into plateau and short-term exposure, the healthy male pilots showed decreased TSH, FT 4, TPOAb and Tg, and increased TT 4 and TT 3, and those may result in the thyroid gland due to acute stress and low-pressure hypoxia appeared related to the hormone metabolism and protein changes.