Objective To investigate the association between the number of periphery artery atherosclerotic stenosis and cardio-cerebrovascular events in elderly people.Methods Totally 163 subjects aged 60 years and over (median age 83 years) in special outpatient service of PUMC Hospital were retrospectively reviewed and underwent Doppler ultrasound of carotid,lower extremity,and renal artery.General conditions,cardio-cerebrovascular events,risk factors and results of periphery artery ultrasound were assessed.Results Age (F =13.413,P ＜ 0.001 ),hypertension,hyperlipidemia and the statin users(x2 =24.961、13.592、16.207,all P＜0.001) significantly enhanced along with increasing number of peripheral artery stenosis (P＜0.001).The more the peripheral arteries stenosis,the more cardio-cerebrovascular events occurred (x2 =15.258,P ＜ 0.001).Symptomatic peripheral artery obstructive disease increased the prevalence of cardio-cerebrovascular events.Conclusions Multiple periphery artery atherosclerotic stenosis is associated with cardiocerebrouascular events and Doppler ultrasound is effective to detect high-risk patients.

OBJECTIVE:To establish a method for the contents determination of triamcinolone acetonide acetate and tretinoin in Dimensional ointment. METHODS:HPLC was performed on the column of Diamonsil C18 with mobile phase of methanol-0.1%Phosphoric acid solution(87:13,V/V),detection wavelength was 254 nm(0-5 min)and 350 nm(5-20 min),at a flow rate of 1.0 ml/min,column temperature was 25℃,and volume injection was 10 μl. RESULTS:The linear range was 0.5-5 μg/ml for triamcin-olone acetonide acetate(r=0.999 9)and 4.96-49.6 μg/ml for tretinoin(r=0.999 8);RSDs of precision,stability and reproducibility tests were lower than 1%;recoveries were 98.37%-100.03%(RSD=0.58%,n=6)and 98.21%-100.38%(RSD=0.78%,n=6). CON-CLUSIONS:The method is simple,accurate and fast,and suitable for the contents determination of triamcinolone acetonide ace-tate and tretinoin in Dimensional ointment.

Objective To study the constituents of urinary stones in patients in Zhejiang,and analyze the composition difference between patients from northern Zhejiang province and southern Zhejiang province.Methods From October 2012 to October 2018,clinical data of 4 423 urinary stone patients treated in Sir Run Run Shaw Hospital,the Second Affiliated Hospital of Wenzhou Medical University,and Huzhou First People's Hospital was retrospectively analyzed.Infrared spectrum was used to analyze urinary calculi constituents.Among 4 423 patients,there were 3 041 males and 1 382 females,male to female ratio was 2.2∶ 1,and the mean age was (51.2 ±16.5) years.There were 2 974 northern Zhejiang patients and 1 449 southern Zhejiang patients.High incidence age group was 41-60 years [48.2％ (2 136/4 423)].The distribution characteristics of urinary calculi constituents in different groups of sex,age,and region were analyzed.Results Among the 4 423 cases,the mixed urinary stones were dominant in the urinary calculus [73.1％ (3 235/4 423)],in which,the most component was the calcium oxalate monohydrate + calcium oxalate dehydrate + carbonated apatite [36.2％ (1 604/4 423)];among the pure stones,the most component was the calcium oxalate monohydrate [16.3 ％ (719/4 423)].Carbonated apatite stones [70.1％ (970/1 382) vs.61.0％ (1 856/3 041),P ＜0.05] and magnesium ammonium phosphate stones [12.7％ (176/1 382) vs.4.9％ (150/3 041),P ＜ 0.05] were both more prevalent in females than males,but uric acid stones[10.6％ (325/3 041) vs.5.8％ (81/1 382),P ＜0.05] were more common in males than females.The proportions of calcium oxalate stones[90.6％ (961/1 060) vs.76.2％ (935/1 227),P ＜0.05],carbonated apatite stones [77.6％ (823/1 060) vs.50.7％ (623/1 227),P ＜ 0.05],and magnesium ammonium phosphate stones[9.1％ (97/1 060) vs.6.5％ (80/1 227),P ＜0.05] of 0-40 years group were all higher than ＞ 60 years group,however,uric acid stones were more frequent in ＞ 60 years group [3.5％ (38/1 060) vs.17.0％ (209/1 227),P ＜ 0.05].The proportion of calcium oxalate stones in southern Zhejiang was lower than northern Zhejiang [79.0％ (1 145/1 449) vs.89.4％ (2 661/ 2 974),P ＜ 0.05].However,carbonated apatite stones [71.5％ (1 037/1 449) vs.60.1％ (1 789/2 974),P ＜ 0.05],magnesium ammonium phosphate stones [15.1％ (220/1 449) vs.3.5％ (106/ 2 974),P ＜ 0.05],and uric acid stones [10.7％ (156/1 449) vs.8.4％ (250/2 974),P ＜ 0.05] were more prevalent in southern Zhejiang than northern Zhejiang.Conclusions The distribution of constituents of urinary stones in Zhejiang was different in genders,age,and regions.Carbonated apatite stones and magnesium ammonium phosphate stones were more prevalent in females and young people,and uric acid stones were more common in males and old people.Calcium oxalate stones were more common in youths.Moreover,calcium oxalate stones were more frequent in northern Zhejiang,and carbonated apatite stones,magnesium ammonium phosphate stones and uric acid stones were common in southern Zhejiang.

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

ObjectiveTo explore the formulation rules for the treatment of heart pain in the Medical Heart Enlightenment （《医学心悟》） from the perspective of the "Tangye Jingfa Tu"， thereby providing a way of thinking about the treatment of heart pain in traditional Chinese medicine （TCM） and the study of the Medical Heart Enlightenment. MethodThe "Tangye Jingfa Tu" contained in the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） was used to analyze the nine prescriptions for heart pain in Volume Ⅲ of the Medical Heart Enlightenment by CHENG Guopeng in the Qing dynasty. A "table for analyzing the formulation of the nine prescriptions for heart pain" was developed. The analysis diagrams for decoction and meridian rules in nine prescriptions for heart pain were plotted and the compatible structure of the medicinal flavors was analyzed. ResultThe composition of Chenxiang Jiangqisan for the treatment of Qi-induced heart pain is "five pungent， four bitter， and two sweet drugs"， the composition of Shouniansan for the treatment of blood-induced heart pain is "five bitter， four pungent， three sweet， and one salty drugs"， the composition of Qingzhongtang for the treatment of heat-induced heart pain is "six bitter， three pungent， and two sweet drugs”， the composition of Jiangfutang with Cinnamomi Cortex for cold-induced heart pain is "three pungent and two sweet drugs"， the composition of Xiaobanxia modified with Fuling Tang for treating fluid retention-induced heart pain is "two pungent and two sweet drugs"， the composition of Baohetang for treating heart pain due to dietary stagnation is "five sweet， four pungent， four bitter， and one sour drugs"， the composition of Guipitang for the treatment of deficiency-induced heart pain is "eight sweet， four bitter， three pungent， and one sour drugs"， the combination of Huachongwan for the treatment of worm-induced heart pain is "seven bitter， six pungent， and four sweet drugs"， the composition of Shenzhusan， Congbaijiu， and Shengjiangtang for the treatment of resistance-induced heart pain is "eight pungent， four bitter， and two sweet drugs". ConclusionFrom the perspective of the "Tangye Jingfa Tu"， the Medical Heart Enlightenment is based on the compatibility principle of "pungent-bitter-sweet drugs" in the treatment of heart pain， with heart deficiency treated with salty drugs for tonifying， or bitter-sweet-salty drugs， and heart excess treated with bitter drugs for purging， or sweet-pungent-bitter drugs， mostly applying the transformation rules of five medicinal flavors， i.e.， "sweet-pungent-bitter drugs" and promoting the action of the pungent and sweet drugs acting on the spleen into the heart to relieve and purge the heart. In most cases， the treatment focuses on harmonizing the heart， liver， spleen， and kidneys， with an emphasis on the mother-child relationship and the application of the principles of the five elements generating and controlling each other. If the progression of the disease involves both the mother and child organs， the formulation should adhere to the compatibility rule of "the child organ makes the mother organ excess and the mother organ makes the child organ deficient".

Upon penetration into the host organism,the decapsulated larvae(intestinal infective stage 1 larvae)of Trichinella spiralis(T.spiralis)proceed to invade the host's small intestinal epithelial cells to continue their development,which is a critical step for T.spiralis infection and pathogenesis.Based on our prior research,the Ts-DNase Ⅱ-7 protein,which is present in the adult stage of T.spiralis,has a role in promoting the parasite's invasion of the intestinal epithelium.This is achieved by disrupting the integrity of the intestinal barrier,consequently promoting the parasitization of these cells in the host organism.Ts-DNase Ⅱ-7 can induce differential expression of various miRNAs,among which miR-142-5p has been reported to be involved in disrupting the intestinal barrier.Therefore,in this study,we investigated the mechanism by which Ts-DNase Ⅱ-7-induced miR-142-5p regulates intestinal epithelial cell barrier function by affecting target genes.The experiment was divided into Ts-DNase Ⅱ-7-treated group,miR-142-5p overexpression group(OE),miR-142-5p inhibition group(Inhibition),negative control group(NC)and control group(Control),lentiviral vectors for overexpression and suppression of miR-142-5p expression were used to infect human colorectal adenocarcinoma cells Caco-2 at an MOI of 80,and puromycin(8 mg/L)was used to screen cells to obtain cell lines that stably suppressed the expression of miR-142-5p and cell lines that miR-142-5p was overexpressed,cell transfection efficiency was assessed by fluorescence microscopy,and the relative expression of miR-142-5p was detected by RT-qPCR in each group of cells.The target gene Claudin-1(CLDN1)was predicted and validated using miR target prediction database,RT-qPCR,Western blot and dual luciferase assay.HE staining,Western blot and quantitative analysis of monolayer transmembrane electrical resistance(TEER)and FITC permeability were then applied to elucidate the mechanism of action of miR-142-5p.Caco-2 cells were lentivirally infected and successful transfection was verified by fluorescence microscopy and RT-qPCR.Dual luciferase and Western blot results showed that CLDN1 was a direct target gene of miR-142-5p(P＜0.001).Compared to the Ts-DNaseⅡ-7 alone treatment group and the OE+Ts-DNase Ⅱ-7 group,the miR-142-5p inhibited expression group and alleviated Ts-DNase Ⅱ-7-induced down-regulation of CLDN1 mRNA and protein levels(P＜0.01 and P＜0.05,respectively)and re-versed the decrease in TEER and elevated permeability(P＜0.01).Ts-DNase Ⅱ-7 up-regulates miR-142-5p expression,causing reduced CLDN1 expression and impaired intestinal barrier function in Caco-2 monolayer cells,which in turn promotes T.spiralis invasion of the intestinal epithelium to achieve further development.

Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer's lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer's lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.
Aged ; Ankle/physiology* ; Ankle Joint/physiology* ; Biomechanical Phenomena/physiology* ; Electromyography ; Exoskeleton Device ; Gait/physiology* ; Humans ; Muscle Contraction ; Muscle, Skeletal/physiology* ; Walking/physiology*

OBJECTIVE：To compare the protective effects of different effective components of Astragali radix against DNA damage of human bone marrow mesenchymal stem cells （BMSCs）induced by ionizing radiation. METHODS ：2 Gy X-rays were used to directly irradiate BMSCs to establish a radiation model. CCK- 8 method was used to detect the effects of different mass concentrations（25，50，75，100 μg/mL）of astragalus polysaccharide ，astragalus saponin and astragalus flavonoids for 1 day before radiation + 1 to 5 days after radiation on the proliferation of BMSCs. The dose concentration and the duration of intervention after radiation were selected. The irradiated BMSCs were divided into radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group. The last three groups were treated with appropriate dosage of corresponding drugs before and 2 days after radiation ，and a blank groupwas set for comparison. Cytoplasmic division arrest qq.com micronucleus method was used to detect micronucleus cell rate and cell micronucleus rate after appropriate time of was used to detect th e number of 53BP1 foci in cells after appropriare time of intervention following radiation ；the number of 53BP1 foci were compared among different time points （0.5，2，12，24 h）. RESULTS ：Compared with blank group ，OD values of BMSCs were decreased significantly in radiation group （P＜0.05 or P＜0.01）. Compared with radiation group ，the OD values of BMSCs were significantly increased when 50 μ g/mL astragalus polysaccharide，astragalus saponin and astragalus flavonoids continuously intervened radiation for 2-3 days，there was significant difference in other groups at some time point （P＜0.05 or P＜ 0.01）. After consideration ，drug concentration was determined to be 50 μg/mL，and the continuous intervention time was 2 days after radiation. Compared with blank group ，the micronucleus cell rate and cell micronucleus rate of radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group increased significantly ，and the number of 53BP1 focus cluster in radiation group and astragalus polysaccharide group increased significantly （P＜0.01）. Compared with radiation group and astragalus flavonoids group ，the micronucleus cell rate ，cell micronucleus rate and the number of 53BP1 focus cluster （continued intervention for 0.5，2，12 h）in the astragalus polysaccharide group and astragalus saponin group were significantly reduced，and the micronucleus cell rate and cell micronucleus rate in the astragalus polysaccharide group were significantly lower than astragalus saponin group （P＜0.05）. 53BP1 focus cluster could not be detected 24 h later （P＜0.05）. CONCLUSIONS ： Astragalus polysaccharide and astragalus saponin both have protective effects on BMSCs DNA damage induced by radiation ，and the protective effect of astragalus polysaccharide is better than that of astragalus saponin ；astragalus flavonoids has no protective effect on radiation-induced DNA damage.

Rare diseases have been a major challenge for clinical medicine and public health challenge in China. One of the effective measures is to conduct proactive research on rare diseases to deal with the disease burden of the diseases. However, low prevalence, disperse distribution of patients, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of research for rare diseases. Recently, it has been found that patients registry is effective in understanding the course of the disease and accu- mulating the cases and data of clinical research or clinical trial design. At present, most of developed countries or regions in the world have promoted clinical research and clinical trials of new medications on rare diseases by using the registration of rare disease. In 2016, Peking Union Medical College Hospital established China's first registry system at the national level-National Rare Disease Registry System of China(NRDRS). NRDRS has accumulated 68 137 cases data registered by the researchers from China's 101 collaborating hospitals in 29 provinces/municipalities/autonomous regions, covering 171 different, and forming 188 cohorts. To date, NRDRS complete the initial stage of resources buildup.Nex stage will be focused on clinical research and clinical trials related to rare diseases based on NRDRS. This article is on the process of building NRDRS, the potential support for conducting clinical research and clinical trials related to rare diseases, and the challenges will be faced.