1.Progress of biomacromolecule drug nanodelivery systems in the treatment of rare diseases
Shu-jie WEI ; Han-xing HE ; Jin-tao HAO ; Qian-qian LV ; Ding-yang LIU ; Shao-kun YANG ; Hui-feng ZHANG ; Chao-xing HE ; Bai XIANG
Acta Pharmaceutica Sinica 2024;59(7):1952-1961
Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of
2.Difference in Nocturnal Erectile Function Between SRPE Patients and Normal People
Hai-bing HU ; Kun-kun ZHAO ; Yong-yi CHEN ; Yuan-hao LI ; Wen-jun BAI ; Ping LI
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(4):691-696
ObjectiveTo compare the nocturnal erectile function between SRPE patients and normal people. MethodsFrom July 1st, 2019 to December 15th, 2022, a clinical comparative study was conducted on 29 SRPE patients (experimental group) and 58 volunteers (control group) who visited our urology department. The Rigiscan System was used to monitor sleep monitoring time, the number of nocturnal erections and the rigidity, duration and circumference growth of the penis when the erection reached 60%~79% and 80%~100%, respectively. The patients and volunteers were asked to make written records when they woke up, and then the total number of awakenings and the number of awakenings when the penis erection reached 60% and 80% were compared between the two groups. ResultsAge was eliminated by matching. There was no statistically significant difference in sleep monitoring time, rigidity, circumference growth and duration of the penis when the erection reached 60%~79% and 80%~100%. between the two groups. In terms of sleep, there was a statistically significant difference in the total number of awakenings between the two groups[3(2 ~ 4)vs 0(0 ~ 0),P<0.01] .And the same was true for the number of awakenings when the penis erection exceeded 60%~79% [1(0 ~ 1)vs 0(0 ~ 0),P<0.01]and 80%~100% [2(1 ~ 3)vs 0(0 ~ 0),P<0.01]. ConclusionRigiscan monitoring showed that there was no difference between SRPE patients and normal male in nocturnal penile erection function. Painful awakening usually occurs when the penis erection reaches 60%~79% or 80%~100%, which reveals that SRPE may be caused by abnormal sensation of nocturnal erections or pain sensitivity in some of these patients.
3.Influence of age on advanced neoplasia detection in colorectal cancer screening in population at high risk.
Jin Hua YANG ; Xing Lin FEI ; Qi Long LI ; Zeng Hao XU ; Kai GAO ; Hao BAI ; Jia Yu LI ; Meng Ling TANG ; Jian Bin WANG ; Ming Juan JIN ; Kun CHEN
Chinese Journal of Epidemiology 2022;43(8):1282-1287
Objective: To compare the detection rate of advanced neoplasia and the number of people needing endoscopy in colorectal cancer screening giving at different starting age in population at high risk. Methods: Based on the screening project of early diagnosis and treatment of colorectal cancer in Jiashan county, Zhejiang province, two rounds of colorectal cancer screening were conducted between January 2007 and December 2020. After excluding participants who were not at high risk or had incomplete information, 27 130 participants and 31 205 participants were finally enrolled in round one and in round two, respectively. The spline analysis based on the generalized additive model was used to describe the trend of detection rate of advanced neoplasia with age. The detection rate and number of people needing endoscopy for the groups with starting age at 50, 45 and 40 years were calculated, and the differences in the detection rate were tested by χ2 goodness of fit test. Results: A total of 21 077 (77.69%) participants in round one and 25 249 (80.91%) participants in round two received endoscopy, in whom 1 097 (detection rate=52.05‰) and 1 151 (detection rate=45.59‰) had advanced neoplasia (cancers and advanced adenomas), respectively. The detection rate increased significantly with age, and the detection rate in round one were significantly higher than that in round two (P<0.05). The overall detection rates of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 61.11‰, 56.14‰ and 52.05‰ in round one, and 49.10‰, 46.75‰ and 45.59‰ in round two, respectively. The rates were significantly higher for the group with starting age at 50 years than that with starting age at 40 years in both round one and round two (P<0.05). The numbers of people needing endoscopy of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 17, 18, and 20 in round one, and 21, 22 and 22 in round two. Conclusions: The detection rate of advanced neoplasia increased with age. Starting screening at lower age might contribute to decreased detection rate and increased number of people needing endoscopy. However, the difference was limited.
Adult
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Colorectal Neoplasms/epidemiology*
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Early Detection of Cancer
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Humans
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Mass Screening
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Middle Aged
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Occult Blood
4.Protective Effect of Ficus pandurata Extract on Alcohol-induced Acute Liver Injury Base on Pyroptosis
Hui-ting FENG ; Wei-bo DAI ; Sha-sha BAI ; Chong-kun SHEN ; Wen-hao WEN ; Sai-nan CUI ; Yong-fei CUI ; Rong ZHANG ; Wei-wen PENG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(13):125-131
Objective:To study the protective effect of
5.Incidence and risk factors of liver abscess after radiofrequency ablation for liver cancer
Song WANG ; Yanhong HAO ; Wei YANG ; Wei WU ; Kun YAN ; Jung-Chieh LEE ; Zhongyi ZHANG ; Xiumei BAI ; Binbin JIANG ; Minhua CHEN
Chinese Journal of Interventional Imaging and Therapy 2018;15(1):37-41
Objective To investigate the incidence and risk factors of liver abscess after radiofrequency ablation (RFA) for liver cancer.Methods A retrospective study was performed on 1 643 patients from January 2000 to June 2016.All the patients were diagnosed with hepatocellular carcinoma (HCC,n =942),cholangiocellular carcinoma (CCC,n =31) or metastatic liver carcinoma (MLC,n=670).Univariate and multiple Logistic regression analysis were used to evaluate the risk factors of liver abscess.Results The incidence of liver abscess after RFA was 0.79%% (13/1 643).Univariate analysis indicated that the liver abscess was significantly correlated with the history of diabetic mellitus (DM),Child-Pugh level,history of surgery and tumor location (all P<0.05).Multivariate analysis showed that the history of DM,history of surgery and tumor location were independent risk factors of liver abscess after RFA for liver cancer.Conclusion History of DM,surgery and tumor location are important factors that result in liver abscess after RFA.
6.Anatomical and biomechanical characteristics of sternoclavicular joint
Kun YANG ; Tian-Hao WU ; Gen LI ; Yun-Kang YANG ; Jian-Hua GE ; Rui BAI ; Fei-Fan XIANG ; Yuan-Lin SUN
Chinese Journal of Tissue Engineering Research 2018;22(11):1695-1700
BACKGROUND: The clinical experience of the treatment of the sternoclavicular joint dislocation and peripheral fracture is relatively lacking, but its incidence is increasing yearly. At present, there are few studies on the anatomy and biomechanics of the sternoclavicular joint in and outside China, and no systematic anatomical measurements of the sternoclavicular joint are reported. OBJECTIVE: To provide a biological reference for the clinical diagnosis and treatment of sternoclavicular joint dislocation or peripheral fractures by studying the anatomy and biomechanics of the sternoclavicular joint. METHODS: (1) A total of 16 specimens (32 sides) of adult antiseptic and moist cadaveric specimens were selected. The complete manubrium, bilateral clavicle and surrounding tissues of sternoclavicular joint were anatomically separated, and repair to bone-ligament-bone specimen models. (2) The areas of manubrium articular surface and the medial clavicular articular surface of all specimens were measured by the ink pattern combined with grid counting method. (3) The morphological features of the anterior and posterior sternoclavicular ligaments of the specimens in this group were observed, and the length, width and thickness were measured and analyzed statistically. (4) The left and right sternoclavicular joints of each specimen were randomly paired into A and B groups. Group A received simply cutting of anterior sternoclavicular ligament. Group B received simply cutting of posterior sternoclavicular ligament. Before and after cuting off the ligament, the anterior and posterior load experiments were performed on the anatomical sites with the same force arm length and perpendicular to the distal clavicle. The angles of joints and load-angle regression line slopes were compared between the two groups in the anterior and posterior directions load. RESULTS AND CONCLUSION: (1) The area of articular surface of manubrium (239.00±28.78 mm2) was smaller than the area of medial articular surface of the clavicle (482.56±44.89 mm2), and the difference was statistically significant (t=-40.105, P < 0.001). (2) The length, width and thickness of the anterior sternoclavicular ligament were (17.56±1.94 mm), (15.54±1.42 mm) and (1.93±0.32 mm), and the length, width and thickness of the posterior sternoclavicular ligament were (17.21±1.86 mm), (15.97±1.17 mm), and (2.07±0.29 mm) respectively;there was no significantly statistical difference in the length, width and thickness between them (P > 0.05). (3) Before cutting the ligaments, when the loads were 2, 4, 6, 8, and 10 N, the angle backwards of joint caused by loads in the forward direction was less than the angle of forwards of joints caused by loads in the backward direction, but only when the loads were 6, 8, and 10 N, the difference between them was statistically significant (P < 0.05). The slope of the regression line of load-angle for the loads in the forward direction was less than the slope of the regression line of load-angle for the loads in the backward direction, with statistical difference (F=31.413, P < 0.001). After the ligaments were cut, when the loads were 2, 4, 6, 8 and 10 N in the forward direction in group A and group B, the backward angulation of joint in group A was less than that in group B (P < 0.05). The slope of the load-angled regression line in group A was less than that in group B (F=52.224, P <0.001). When the loads in the backward direction in group A and group B were 2, 4, 6, 8 and 10 N, the forward angulation of joint in group A was greater than that in group B (P < 0.05), and the slope of the load-angled regression line in group A was greater than that in group B (F=12.503, P=0.008). (4) These results suggest that contact area between the articular surface of the medial clavicle and the articular surface of the manubrium is narrow, which determines the instability of the joint itself. The sternoclavicular ligament is extremely important for maintaining the joint stability. The forward angulation of joint restriction effect of sternoclavicular ligament was weaker than that of the backward angulation, also because of the joint in the anatomical position of the natural forward angulation, so the sternoclavicular joint was prone to anterior dislocation. It is necessary to pay attention to the repair and reconstruction of sternoclavicular ligament when sternoclavicular joint dislocation or peripheral fractures are treated by operations.
7.Impact of anemia and chronic kidney disease on the risk of cardiovascular disease and all-cause mortality among diabetic patients.
Chao YANG ; Jin Wei WANG ; Yao Zheng YANG ; Kun Hao BAI ; Bi Xia GAO ; Ming Hui ZHAO ; Lu Xia ZHANG ; Shou Ling WU ; Fang WANG
Journal of Peking University(Health Sciences) 2018;50(3):495-500
OBJECTIVE:
To explore the association between anemia and cardiovascular disease and all-cause mortality among diabetic patients, and whether the association is modified by the presence of chronic kidney disease (CKD).
METHODS:
Physical examination data of 8 563 patients with diabetes who met the inclusion and exclusion criteria between 2010 and 2011 were collected, based on the prospective cohort data of Kailuan study. The deadline of the follow-up was December 31, 2015, and the endpoints comprised all-cause mortality and cardiovascular disease. Survival analysis was performed by Kaplan-Meier method. Cox proportional hazards regression model was used to assess the association between anemia with or without CKD, and cardiovascular events and all-cause mortality after adjustment for confounding factors.
RESULTS:
The average age of the subjects was (57.3±10.3) years, of whom the patients with anemia accounted for 5.2%. The proportion of the patients with anemia combined with CKD was higher than that of the patients without anemia (27.2% vs. 20.8%, P=0.001). The median follow-up time was 4.9 years (interquartile range: 4.6-5.2 years). During the follow-up period, 559 patients died, and 434 patients had cardiovascular disease. Compared with the patients without anemia, the all-cause mortality rate of the patients with anemia was higher (3 220.3/100 000 person-years vs. 1 257.9/100 000 person-years, P<0.001). There was no statistically significant difference in the incidence of cardiovascular disease between the above two groups (999.8/100 000 person-years vs. 1 081.2/100 000 person-years, P>0.05). The mortality and incidence of cardiovascular disease among the patients with CKD were higher than those of the patients without CKD (2 558.3/100 000 person-years vs. 1 044.0/100 000 person-years, P<0.001; 1 605.9/100 000 person-years vs. 941.6/100 000 person-years, P<0.001). Results of Cox regression model showed that, after adjustment for confounding factors, the all-cause mortality risk increased by 95% in the diabetic patients with anemia (HR=1.95, 95% CI: 1.50-2.54). Anemia and CKD significantly increased the mortality risk among diabetic patients (HR=3.61, 95% CI: 2.48-5.26). The CKD patients without anemia had an increased risk of cardiovascular disease (HR=1.41, 95% CI: 1.13-1.74).
CONCLUSION
Anemia is associated with an increased mortality risk in Chinese diabetic patients. Patients with CKD have an increased risk of cardiovascular disease and mortality. The all-cause mortality risk increases significantly in anemia patients with the presence of CKD, which indicates that we should focus on the prevention and treatment of diabetic patients with anemia and CKD.
Anemia/epidemiology*
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Cardiovascular Diseases/epidemiology*
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Diabetes Mellitus, Type 2
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Humans
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Proportional Hazards Models
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Prospective Studies
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Renal Insufficiency, Chronic/epidemiology*
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Risk Factors
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Survival Analysis
8.Study on the mechanism of PPAR-γ dependent immunological idiosyncrasy liver injury induced by Polygonum multiflorum
Lan-zhi HE ; Ping YIN ; Ya-kun MENG ; Zhen-fang ZHANG ; Hui-min LIU ; He-rong CUI ; Hao-tian NI ; Jia-bo WANG ; Xiao-he XIAO ; Zhao-fang BAI
Acta Pharmaceutica Sinica 2017;52(7):1027-1032
To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.
9.The level of serum lipids,body-fat content of obesity rats,and the relationship between intracellular calciumand ventricular arrhythmia
Lin-chuan, LANG ; Xing, JIANG ; Yan-kun, HAO ; Yun-Long, BAI ; Yan-jie, LV ; Bao-feng, YANG
Chinese Journal of Endemiology 2008;27(6):632-635
Objective To study the level of serum lipids and body-fat content of high-fat diet induced pbesity rats(DIO).explore the relationship between intracellular caleium and ventrieufar arrhythmia.Methods Sixty male Sprague-Dawley(SD)rats were divided into control group(15)and experiment group(45),high-fat diet was administrated for 12 weeks to established obesity model,15 rats were selected into obesity group according to their body weight gain.The standard 2-lead electrocardiograph was used to detect the incidence and scores of arrhythmia induced by barium chloride(BaCl2,0.1 mg/kg)for 1 hour on every 8 rats from different groups respectively.Body-fat content.the level of serum total cholesterol(TC),triglyceride(TG),low density lipopmtein cholesterol (LDL-C) and high density lipopmtein cholesterol (HDL-C)were measured.The epididymal(EP),retroperitoneal (RE) and mesenteric(ME)white adipose pads was measured to obtain the body fat content.Single ventricular myrocytes of rats were isolated by enzymatic dissociation.The confocal laser scanning microscope was used to record basic intraceUular calcium level([Ca2+]i).Results The body-fat content in obesity group[(7.71±0.74)%] was significantly higher than control group[(4.69±0.37)%](t=3.650,P<0.05).The level of serum TC,TGand LDL-C were significantly higher(t=3.801,2.778,3.536.P<0.05) in obesity group[(1.26±0.04),(0.58±0.10),(0.51±0.04)mmol/L]than those in control group[(0.92±0.08),(0.29+0.03),(0.31±0.04) mmol/L].The level of serum HDL-C wa8 decreased gradually from control group[(0.53±0.05)mmol/L] toobesity group[(0.52±0.02)mmol/L],but there waft no significant difference between them(t=0.186,P>0.05).The incidence of arrhythmia induced by BaCl2(0.1 mg/kg)in obesity group was significantly higher than controlgroup(X2=5.333,P<0.05),and the scores of arrhythmla was increased in obesity group(2.5±0.6)too.The fluorescence intensity standing for[Ca2+]i was increased significantly(t=2.409,P<0.05)from obesity group(247.96±20.03)to control group (174.25±23.13).Conclusion As the free cytosolic calcium begin to accumulate,the arrhythmia morbidity is increased in obesity rats.
10.Improvement of the thermostability of xylanase by N-terminus replacement.
Hao-Meng YANG ; Kun MENG ; Hui-Ying LUO ; Ya-Ru WANG ; Tie-Zheng YUAN ; Ying-Guo BAI ; Bin YAO ; Yun-Liu FAN
Chinese Journal of Biotechnology 2006;22(1):26-32
The hybrid xylanase TB was constructed by the substitution of the N-terminus segment of the Streptomyces olivaceoviridis xylanase XYNB with corresponding region of Thermomonosporafusca xylanase TfxA. The hybrid gene tb, encoding the TB, was correctly expressed in Escherichia coli BL21 and Pichia pastoris GS115. TB was purified and its enzymatic properties were determined. The results revealed that the optimal temperature and optimal pH of TB were at 70 degrees C and 6.0, which have been obviously improved compared with those of XYNB. The thermostability of TB were all about six-fold of XYNB's after incubating the properly diluted enzyme solutions at 80 degrees C and 90 degrees C for 3min, respectively. The pH stability of TB was 5 to approximately 9, which was narrower than that of XYNB. Still, TB remains a high specific activity as XYNB does. Analysis of a homology modeling and sequence similarity were used to reveal the factors influencing the enzymatic properties of TB and the discussion for the relationship between structure and function of xylanase was given.
Amino Acid Sequence
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Base Sequence
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Desulfurococcaceae
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enzymology
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genetics
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Endo-1,4-beta Xylanases
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genetics
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metabolism
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Enzyme Stability
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Escherichia coli
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enzymology
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genetics
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Hot Temperature
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Molecular Sequence Data
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Pichia
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enzymology
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genetics
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Protein Engineering
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methods
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Recombinant Fusion Proteins
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genetics
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metabolism
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Streptomyces
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enzymology
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genetics
;
Structure-Activity Relationship

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