This study aimed to investigate the potential mechanism and the compatibility significance of Tanyu Tongzhi Formula in treating atherosclerosis(AS) in mice based on the transforming growth factor-β(TGF-β)/Smad2/3 signaling pathway. Eight C57BL/6J mice were as assigned to a normal control group and fed a regular diet, while 35 ApoE~(-/-) mice of the same strain were fed a high-fat diet for 8 weeks to establish an AS model. The model mice were randomly divided into a model group, a Tanyu Tongzhi group(18.2 mg·kg~(-1)), a Huatan(phlegm-resolving) group(10.4 mg·kg~(-1)), and a Quyu(blood stasis-resolving) group(7.8 mg·kg~(-1)), with 8 mice in each group. Except for the normal group, all other groups continued to be fed a high-fat diet for 8 weeks to maintain the AS model, and then the mice were treated by gavage for 8 weeks. Plasma levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), interleukin-1β(IL-1β), and interleukin-18(IL-18) were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin and eosin(HE) staining, oil red O staining, and Russell-Movat pentachrome staining were performed to observe the pathological changes in the aortic tissue. The proportions of aortic plaque area, lipid-stained area, collagen fibers, and elastic fibers were calculated. Immunofluorescence was used to detect the protein expression levels of matrix metalloproteinase 2(MMP2) and tissue inhibitor of metalloproteinases 2(TIMP2). Western blot was used to detect the protein expression levels of TGF-β1, TGF-β2, Smad2/3, and Smad7 in aortic tissue. Real-time fluorescence quantitative PCR(RT-qPCR) was used to measure the mRNA expression levels of TGF-β receptor(TGF-βR), TGF-β1, Smad2/3, Smad7, intercellular adhesion molecule-1(ICAM-1), and vascular cell adhesion molecule-1(VCAM-1) in aortic tissue. The results showed that compared with the normal control group, the model group had increased plasma TC and LDL-C, significantly decreased HDL-C, and significantly elevated plasma IL-1β and IL-18 levels. The model group also exhibited an increased proportion of aortic plaque area, lipid-stained area, and collagen fiber area, along with significantly upregulated MMP2 and downregulated TIMP2 expression in the aortic arch. Additionally, the expression levels of TGF-βR, TGF-β1, and p-Smad2/3 proteins and mRNA in the aortic tissue were significantly elevated, while Smad7 expression was decreased. Compared with the model group, the Tanyu Tongzhi group showed significantly reduced plasma TC and LDL-C levels, significantly increased HDL-C levels, and significantly decreased plasma IL-1β and IL-18 levels. The Tanyu Tongzhi group also exhibited a significant reduction in aortic plaque size and severity, a significant downregulation of MMP2 expression in the aortic arch, and significantly decreased ICAM-1 and VCAM-1 mRNA expression levels. Moreover, the Tanyu Tongzhi group demonstrated significantly reduced expression levels of TGF-β1 and p-Smad2/3 proteins and mRNA in the aortic tissue, and an increased expression level of Smad7 protein to varying degrees. Compared with the Tanyu Tongzhi group, the Quyu group had significantly higher LDL-C levels and elevated plasma IL-1β and IL-18 levels. The Huatan group showed upregulated MMP2 expression and downregulated TIMP2 expression in the aortic arch. In conclusion, Tanyu Tongzhi Formula, which is composed based on the pathogenesis of phlegm and blood stasis, maintains vascular homeostasis by primarily regulating lipid metabolism and controlling inflammatory factors through the Huatan group, and maintaining vascular wall permeability, inhibiting plaque development, and stabilizing plaques through the Quyu group. The mechanism of action may involve inhibiting TGF-β1 expression in the aorta, reducing Smad2/3 phosphorylation, and simultaneously increasing Smad7 expression.
Animals ; Atherosclerosis/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Male ; Transforming Growth Factor beta/genetics* ; Humans ; Homeostasis/drug effects* ; Aorta/metabolism* ; Smad2 Protein/genetics* ; Smad3 Protein/genetics*

Objective:To analyze the blood flow parameters of the cavernous arteries of ED patients after injection of vasoac-tive drugs,and to explore the differences in blood flow of the cavernous arteries in different erectile states.Methods:Retrospectively analyzed the penile cavernous arterial blood flow parameters of 2568 adult male ED patients after injection of the vasoactive drug(al-prostadil).The patients were divided into three groups:maintaining erection group with EHS(erection hardness score)≥3 and sus-tained erection time≥20 minutes(967 cases),nonpersistent erection group with EHS ≥3 and sustained erection time＜5 minutes(788 cases),and incomplete erection group with EHS＜3(813 cases).Compared the parameters of age,EHS,duration of erection,cavernous artery peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)among the three groups re-spectively.The maintaining erection group was divided into the youth group(757 cases)which aged less than 40 years old and the middle-aged and elderly group(210 cases)with 40 years old or over.The parameters of PSV,EDV and RI between the two groups were compared.The incomplete erection group were divided into the good blood supply group(407 cases)with the bilateral PSV 35cm/s and the insufficient blood supply group(252 cases)with the bilateral PSV＜35cm/s.The parameters of age,EHS,EDV and RI between the two groups were compared.Results:The age,PSV,EDV and RI of the three groups were significantly different(P＜0.01).In the maintaining erection group,the PSV of the young group was significantly higher than that of the middle-aged and eld-erly group(P＜0.05),but there was no statistically significant difference in EDV and RI(P＞0.05).In the incomplete erection group,the EHS,PSV,EDV,and RI of the good blood supply group were significantly higher than those of the insufficient blood supply group(P＜0.05),while the age was significantly lower than that of the latter(P＜0.01).Conclusion:The injection of vasoactive drugs combined with color Doppler ultrasound can directly reflect the blood supply of the cavernous arteries of the penis.The better the erection state,the better the blood supply of cavernous arteries.The middle-aged and elderly people are more likely to have cavernous arteries problem of insufficient blood supply than the young people.

Objective:To evaluate and compare the foveal microvascular morphology and central foveal thickness (CFT) after laser retinal photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (VEGF) in patients with retinopathy of prematurity (ROP), and to explore the factors affecting the prognosis of vision.Methods:A cohort study was conducted.Forty children (40 eyes) aged 4-6 years, who had been treated in Peking University People's Hospital for type 1 ROP from January 2019 to December 2020, were enrolled.Optical coherence tomography angiography (OCTA), best corrected visual acuity (BCVA) and refractive status of the patients were examined.The patients were divided into laser retinal photocoagulation group and anti-VEGF group according to they received a single laser retinal photocoagulation therapy or a single intravitreal injection of anti-VEGF drugs (conbercept or ranibizumab 0.25 mg/0.025 mL) after birth.Twenty age-matched full-term healthy children (20 eyes) were enrolled as the normal control group.The FAZ area, superficial and deep foveal vessel density (VD) and CFT of the affected eyes were measured by OCTA at 4-6 years after treatment to investigate the influence of gestational age, birth weight, morphological characteristics of foveal microvessels and CFT on the prognosis of BCVA.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Peking University People's Hospital (No.2017PHB179-01). Written informed consent was obtained from the guardians prior to any medical examination.Results:There were statistically significant differences in FAZ area, superficial foveal VD and deep foveal VD among the three groups ( F=12.321, 8.436, 5.497; all at P<0.05). The FAZ area was smaller, and the superficial and deep foveal VD of the laser photocoagulation group and the anti-VEGF group were greater than those in the normal control group, and the difference was statistically significant (all at P<0.05). The CFT of the laser photocoagulation group was (267.6±11.8)μm, greater than (259.5±12.9)μm of the anti-VEGF group and (242.4±12.3)μm of normal control group, and the CFT value of the anti-VEGF group was greater than that of the normal control group, and the differences were statistically significant (all at P<0.05). There was a strong negative correlation between the superficial foveal VD and FAZ area ( r=-0.713, P<0.05), a moderate negative correlation between the deep foveal VD and FAZ area ( r=-0.565, P<0.05), and a moderate positive correlation between gestational age and FAZ area ( r=0.485, P<0.05). Pearson correlation analysis results showed that gestational age, FAZ, superficial foveal VD, deep foveal VD, CFT were all correlated with BCVA (all at P<0.05). The effects of gestational age and FAZ on BCVA were both statistically significant ( R2=0.615, both at P<0.05). Conclusions:The morphology of microvessels in macular fovea and the prognosis of BCVA in the affected eye is similar at 4-6 years after laser retinal photocoagulation and intravitreal injection of anti-VEGF drugs for type 1 ROP.The CFT of the affected eye after anti-VEGF drug therapy is better than those after laser retinal photocoagulation.Gestational age and FAZ are the influencing factors of visual acuity after treatment in children with type 1 ROP.

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.

Objective:To explore the current situation of the demand for home care services for the elderly in communities in Jiangsu Province, and to analyze its influencing factors.Methods:From May to August 2020, convenience sampling was used to select 592 community elderly people in Jiangsu Province for a survey. The survey tools included the General Information Questionnaire and Home Care Service Demands Questionnaire.Results:A total of 588 valid questionnaires were recovered, with a valid recovery rate of 99.32%. The demands of the elderly in the community for home care services from high to low were medical care needs (87.07%) , life care needs (68.37%) , spiritual comfort needs (58.16%) , cultural and leisure needs (34.18%) , policy and regulation needs (31.63%) . Logistic regression analysis showed that age, gender, region, type of chronic disease, monthly income and payment method of medical expenses were the main influencing factors of the demand for home care services ( P<0.05) . Conclusions:The elderly in the community have real needs for home care services. It is recommended to establish a diversified, multi-path and layered service system for the needs of the elderly, and strive to improve the effectiveness and efficiency of home elderly care services.

Ambystoma mexicanum/immunology* ; Amputation ; Animals ; Biomarkers/metabolism* ; Blastomeres/immunology* ; Cell Lineage/immunology* ; Connective Tissue Cells/immunology* ; Epithelial Cells/immunology* ; Forelimb ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunity ; Peroxiredoxins/immunology* ; Regeneration/immunology* ; Regenerative Medicine/methods* ; Single-Cell Analysis/methods*

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

BACKGROUND: Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon's experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy. METHODS: The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis. RESULTS: The final multivariable model included the following three factors: open operative approach (P < 0.001), Neves classification IV (P < 0.001), inferior vena cava resection (P = 0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280 mL (interquartile range [IQR] 100-600 mL), 1250 mL (IQR 575-2700 mL), 2000 mL (IQR 1250-2900 mL), and 5000 mL (IQR 4250-8000 mL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (P = 0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0 vs. 1 to 3 (P = 0.098). CONCLUSION We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.

Objective:To evaluated the indications, methods, outcomes and prognosis of surgical treatment for post-traumatic epiphyseolisthesis at odontoid process in children.Methods:Retrospective analysis was performed on 5 cases of children with delayed epiphyseolisthesis of odontoid process in our institution from July 2009 to October 2016, including 1 male and 4 females. Initial surgery age were at1.7~5.4 years old, averaged (39.6±19.4) months and were 0.67-8 months, averaged (87.0±95.1) days. Disease duration ranged from 23 days to 8 months, with an average of 88 days. X-ray, CT and MRI examinations of the occipital-cervical area were taken to evaluate the type of the fracture and the severity of spinal cord compression. Children were treated with anterior loosening combined with posterior fixation fusion or posterior loosening reduction and internal fixation respectively.The function of spinal cord was evaluated by Frankel scale at pre- and post- operation. During the follow-up, X-ray and CT were performed to assess the fusion condition of the grafted bone.Results:The duration of operation was ranged from 75-145 months, with an average of (101.0±20.7) months; Blood loss ranged from 50-100 ml, with an average of (70.0±21.2) ml; follow-up duration ranged from 6 to 48 months, with an average of (23.5±17.6) months. Two cases preoperatively evaluated as Frankel C and D recovered to postoperative Frankel E. Among the five cases, two received satisfactory reduction, two cases received incomplete reduction, and one experienced failure reduction. The epiphyseolisthesis and bone grafted sites achieved solid fusion at 6-15 months after surgery, with an average of (9.5±3.4) months. The physiological curvature of cervical remained well without bone resorption, nonunion, pseudoarthrosis, as well as screw loosening or broken. Internal fixation of 2 cases were removed.Conclusion:Children with post-traumatic epiphyseolisthesis at odontoid process are not common in clinical practice. The detailed diagnosis of medical history, physical examination and comprehensive imaging evaluation. The posterior approach technique of C1-2 was feasible and effective, which could obtain decompression, reconstruction andstability all together.

Background: Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations. But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear. This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus. Methods: The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed. Among these 67 cases, 21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level II–IV), while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0–I). Clinical features, operation details, and pathology data were collected. Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus. Results: Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs. 282.2 ± 101.9 min, t = 4.685, P < 0.001), more surgical bleeding volume (1200 [325, 2900] mL vs. 500 [180, 1000] mL, U = 270.000, P = 0.004), more surgical blood transfusion volume (800 [0, 1400] mL vs. 0 [0, 800] mL, U = 287.500, P = 0.004), more plasma transfusion volume (0 [0, 800] mL vs. 0 [0, 0] mL, U = 319.000, P = 0.004), higher percentage of open operative approach (76.2% vs. 32.6%, χ² = 11.015, P = 0.001), higher percentage of IVC resection (33.3% vs. 0%, χ² = 17.122, P < 0.001), and higher percentage of post-operative complications (52.4% vs. 19.6%, χ² = 7.415, P = 0.010) than patients with large tumors and low-level thrombus. In multivariate analysis, decreased hemoglobin (Hb) (odds ratio [OR]: 0.956, 95% confidence interval [CI]: 0.926–0.986, P = 0.005) and non-sarcomatoid differentiation (OR: 0.050, 95% CI: 0.004–0.664, P = 0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with small tumor thrombus. The estimated mean cancerspecific survival times of small tumor with high-level thrombus and large tumor with low-level thrombus were 31.6 ± 3.8 months and 32.5 ± 2.9 months, without statistical significance (P = 0.955). After univariate and multivariate Cox proportional hazard survival regression analyses, only distant metastasis (hazard ratio [HR]: 3.839, P = 0.002), sarcomatoid differentiation (HR: 7.923, P < 0.001), alkaline phosphatase (HR: 2.661, P = 0.025), and severe post-operative complications (HR: 10.326, P = 0.001) were independent predictors of prognosis. Conclusions The level of the tumor thrombus was more important than the diameter of the primary kidney tumor in affecting the complexity of surgery. In the same T3 stage, neither the renal tumor diameter nor the tumor thrombus level was an independent risk factor for prognosis.