1.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
2.Effect of Yudantong decoction on intestinal flora and intestinal barrier function in mice with cholestasis induced by α-naphthyl isothiocyanate
Xiaoming WU ; Qiang HE ; Linyi HOU ; Yan HU ; Xiaofang ZHEN ; Jing HAO ; Yan SHENG
Journal of Clinical Hepatology 2023;39(4):864-875
Objective To investigate the therapeutic effect of Yudantong decoction in mice with α-naphthyl isothiocyanate (ANIT)-induced cholestasis, as well as its targets and mechanism based on intestinal flora and intestinal barrier function. Methods A total of 24 C57BL/6 mice were randomly divided into control group, model group, Yudantong decoction group (YDTF group), and ursodeoxycholic acid (UDCA) group, with 6 mice in each group. The mice in the model group, the YDTF group, and the UDCA group were given ANIT 35 mg/kg/day by gavage on days 1, 4, 7, 10, and 13, and those in the YDTF group and the UDCA group were given Yudantong decoction or UDCA by gavage for 15 consecutive days; related samples were collected on day 16. Liver histopathology was observed, and liver function parameters were measured; immunohistochemistry was used to measure the protein expression levels of caspase-1, interleukin-1β (IL-1β), and FXR in the liver, and flow cytometry was used to measure the percentages of CD11b + , CD86 + , and CD45 + immune cells in the liver; 16S rDNA sequencing and information analysis were performed for fecal microorganisms; immunohistochemistry was used to measure the protein expression of the intestinal FXR/NLRP3 pathway, and immunofluorescence assay was used to measure the protein expression of intestinal E-cadherin and occludin. A one-way analysis of variance was used for comparison of continuous data with homogeneity of variance between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Welch test was used for comparison of data with heterogeneity of variance between multiple groups, and the Games-Howell test was used for further comparison between two groups. Results HE staining showed that the model group had partial hepatocyte fatty degeneration, massive necrosis of hepatocytes in hepatic lobules, damage of lobular structure, and massive inflammatory cell infiltration, and the YDTF group and the UDCA group had alleviation of hepatocyte fatty degeneration and hepatocyte necrosis in hepatic lobules, with a reduction in inflammatory cells. Compared with the control group, the model group had significantly higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and total bile acid (TBA) (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the serum levels of ALT, AST, GGT, ALP, TBil, DBil, and TBA (all P < 0.05), and the UDCA group had significant reductions in the serum levels of GGT, TBil, DBil, and TBA (all P < 0.05). Compared with the control group, the model group had significant increases in the levels of caspase-1 and IL-1β and a significant reduction in the expression of FXR in the liver (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the levels of caspase-1 and IL-1β in the liver and the UDCA group had a significant reduction in the level of IL-1β in the liver, and both the YDTF group and the UDCA group had a significant increase in the expression level of FXR in the liver (all P < 0.05). The model group had a significant change in the composition of intestinal flora compared with the control group ( P < 0.05); there was a significant difference in the structure of intestinal flora between the YDTF group and the model group ( P < 0.05), and there was also a significant difference in the composition of intestinal flora between the UDCA group and the control/model groups ( P < 0.05). Compared with the control group, the model group had a significant increase in the abundance of intestinal Akkermansia muciniphila and a significant reduction in the abundance of Lactobacillus johnsonii (both P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant reduction in the abundance of intestinal Akkermansia muciniphila , and the YDTF group had a significant increase in the abundance of Lactobacillus murinus , while the UDCA group had significant increases in the abundance of Lactobacillus murinus and Bifidobacterium pseudolongum (all P < 0.05). Compared with the control group, the model group had a significant reduction in the protein expression of intestinal FXR, a significant increase in the protein expression of intestinal NLRP3, and significant reductions in the expression of intestinal E-cadherin and occludin (all P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant increase in the protein expression of intestinal FXR, a significant reduction in the protein expression of intestinal NLRP3, and significant increases in the expression of intestinal E-cadherin and occludin (all P < 0.05). Conclusion Yudantong decoction can alleviate liver injury in mice with ANIT-induced cholestasis, possibly by improving intestinal flora and enhancing intestinal barrier function.
3.Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma.
Yuwei HAO ; Sheng GAO ; Xiaoyue ZHANG ; Mengqiu CUI ; Xiaohui DING ; He WANG ; Dawei YANG ; Huiyi YE ; Haiyi WANG
Journal of Southern Medical University 2023;43(5):800-806
OBJECTIVE:
To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM).
METHODS:
We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient.
RESULTS:
In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05).
CONCLUSION
ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female
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Male
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Humans
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Adult
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Middle Aged
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Aged
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Carcinoma, Renal Cell/diagnosis*
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Retrospective Studies
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Kidney
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Carcinoma
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Kidney Neoplasms/diagnosis*
4.Tannin Components of Geranium Plants in Prevention and Treatment of Alzheimer's Disease: A Review
Linyi CHEN ; Bo HE ; Zhiqiang SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(20):257-264
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by mechanisms including excessive deposition of β amyloid (Aβ), neuroinflammatory responses, and hyperphosphorylation of microtubule-associated protein (Tau protein). Currently, there are no effective clinical treatments available for AD. Traditional Chinese herbal drugs have gained attention for their potential to exert anti-AD effects through multi-component, multi-target approaches. As a traditional Chinese herbal drug with over 600 years of clinical use, Geranii Herba has substantial medicinal potential and wide application prospects. Geranium medicinal plants contain chemical components such as tannins, flavonoids, organic acids, and volatile oils. Research has indicated that various tannin compounds found in Geranii Herba possess pharmacological activities like enhancing learning and memory abilities, and improving cognitive function. These effects are linked to mechanisms involving anti-Aβ effects, Tau protein regulation, antioxidation, anti-inflammation, and inhibition of acetylcholinesterase activity. These compounds can act through multiple pathways and targets to inhibit neurodegenerative changes in neurons, thus effectively preventing and treating neurodegenerative diseases like AD. Based on relevant literature, this study focused on reviewing various tannin components in Geranium plants and their role in preventing and treating AD and identified potential drug components for treating neurodegenerative diseases such as AD by exploring the tannin components and their mechanisms in Geranium plants, thereby providing a theoretical foundation and research direction for further development and clinical application.
5.Mechanism of pathogenesis of Jingfang Mixture in intervention of chronic spontaneous urticaria based on serum metabolomics.
He XIAO ; Guo-Liang CHENG ; Bing LI ; Xian-Zhen WANG ; Ran-Ran KONG ; Li-Hong PAN ; Gui-Min ZHANG
China Journal of Chinese Materia Medica 2022;47(20):5488-5493
This study aims to clarify the effect of Jingfang Mixture on the treatment of chronic urticarial and its mechanism, and investigate the regulatory effect of chronic urticaria on the metabolic disorder of endogenous metabolites in the blood. The mice were randomly divided into normal group, model group, and Jingfang Mixture group, and modeling and administration continued for 21 d. The changes in endogenous small molecules in rat serum were determined by ultra-high performance liquid chromatography-electrospray ionization-Q Exactive-Orbitrap-mass spectrometry(UHPLC-ESI-QE-Orbitrap-MS) metabolomics technology. The change trend of endogenous metabolites in rat serum was analyzed to find potential biomarkers. The results showed that Jingfang Mixture regulate 16 biomarkers, mainly including taurine, glutamate, succinic acid, docosahexaenoic acid, and arachidonic acid. Metabolic pathway analysis was carried out by MetaboAnalyst, and P<0.01 was taken as the potential key metabolic pathway. Ten metabolic pathways were closely related to the treatment of chronic urticarial by Jingfang Mixture, mainly involved in the glutamate metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, arachidonic acid metabolism, tricarboxylic acid cycle, unsaturated fatty acid biosynthesis, glutathione metabolism, phenylalanine metabolism, alanine, aspartic acid, and glutamate metabolism, and butyric acid metabolism. Glutamate metabolism and butyric acid metabolism involved more metabolic pathways than others. Therefore, it was speculated that Jingfang Mixture had a balanced regulating effect on the related metabolic pathways which caused the serum disorder in the rats with urticaria, and tended to regulate the metabolic differential to the normal level in the rats with urticaria. This paper provides references for studying the mechanism of Jingfang Mixture from the perspective of endogenous metabolites and metabolic pathways in vivo. At the same time, the endogenous substances explored in this paper can be used as important biomarkers for the prevention of urticaria.
Rats
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Mice
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Animals
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Chronic Urticaria
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Arachidonic Acid
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Butyric Acid
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Metabolomics/methods*
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Chromatography, High Pressure Liquid/methods*
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Biomarkers/metabolism*
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Taurine
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Glutamates
6.Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202).
Jianhua SHI ; Ying CHENG ; Qiming WANG ; Kai LI ; Lin WU ; Baohui HAN ; Gongyan CHEN ; Jianxing HE ; Jie WANG ; Haifeng QIN ; Xiaoling LI
Frontiers of Medicine 2022;16(5):766-772
Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans
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Lung Neoplasms/drug therapy*
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Treatment Outcome
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Neoplasm Recurrence, Local/chemically induced*
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Quinolines/adverse effects*
7.Metabonomics study of Shouhui Tongbian Capsules in slow transit constipation based on UPLC-ESI-QE-Orbitrap-MS.
Cheng-Hong SUN ; Xiang-Zi LI ; He XIAO ; Li ZHANG ; Yun ZHAO ; Jing-Chun YAO ; Gui-Min ZHANG
China Journal of Chinese Materia Medica 2021;46(3):532-538
The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.
Animals
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Biomarkers
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Capsules
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Chromatography, High Pressure Liquid
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Constipation/drug therapy*
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Metabolomics
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Mice
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Mice, Inbred ICR
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Tandem Mass Spectrometry
8.Feasibility of cryopreservation of human corneal stromal lenticules
Qi WEI ; Hui DING ; Tan ZHONG ; Hanyang YU ; Zhenduo YANG ; Hongming FAN ; Linyi HE ; Xingwu ZHONG
Chinese Journal of Experimental Ophthalmology 2021;39(12):1031-1037
Objective:To observe the transparency and tissue structure changes of human corneal stromal lenticules after long-term cryopreservation and explore a simple and feasible method for long-term effective preservation of corneal stromal lenticules.Methods:Two hundred samples of intact human corneal stromal lenticules from 200 eyes were obtained during femtosecond laser small-incision lenticule extraction (SMILE) in Hainan Eye Hospital, Zhongshan Ophthalmic Center from 2013 to 2020.The samples were divided into 1-month, 24-month, 60-month and 80-month group and were stored in an ultra-low temperature freezer for 1, 24, 60 and 84 months respectively at -80 ℃ according to grouping, with 50 samples in each group.Transmittance of the corneal lenticules at wavelength of 300-800 nm was measured with an ultra-micro spectrophotometer and every lenticule was measured for 10 times with a 50 nm interval.The histomorphology and collagen fiber structure of the corneal lenticules were examined by hematoxylin-eosin staining and Masson staining, respectively.The arrangement of collagen fibers and ultrastructure changes of keratocytes in the samples were inspected with a transmission electron microscope.The apoptosis rate of keratocytes was determined by TUNEL staining.The study protocol was approved by an Ethics Committee of Hainan Eye Hospital at Zhongshan Ophthalmic Center (No.2013-003). This study complied with the Declaration of Helsinki.Written informed consent was obtained from each subject before surgery.Results:The corneal lenticules were clear and intact in all groups and no significant difference in the transmittance within 450-800 nm wavelength was seen among the 4 groups (all at P>0.05). Masson staining revealed that the collagen fibers in the lenticules were neatly arranged and tightly packed in the 1-month group.In the 24-month group, interfibrous vacuoles were found in some collagen fibers.The arrangement of the collagen fibers was loose and more vacuoles were displayed in the 60-month group, and the loss of some collagen fibers appeared and the lenticules were thinned in the 84-month group.It was found through hematoxylin-eosin staining that the morphological changes of corneal stromal lenticules corresponded to the alterations of collagen fibers.Transmission electron microscopy showed that in the 1-month group, the collagen fibers of the corneal stroma lenticules were neatly arranged and regular, and the corneal stromal cells were elongated and spindle-shaped, and the nuclear membrane was intact and the cytoplasm was abundant.In the 24-month group, the collagen fibers showed slightly loose arrangement, and the corneal stromal cells were deformed with incomplete nuclear membrane.In the 60-month group, the collagen fibers were in loose and irregular arrangement, and the nuclei were atrophied and deformed.The 84-month group showed disorganized arrangement of collagen fibers, wrinkled and atrophied corneal stromal cells, discontinuous nucleus membrane and nucleoplasmic lysis.TUNEL staining showed that the percentage of apoptotic corneal cells in lenticules was (87.80±1.17)%, (89.50±1.05)%, (89.30±1.51)% and (90.20±1.47)% in the 1-month, 24-month, 60-month and 84-month groups, respectively, with no statistically significant difference found in overall comparison ( F=4.525, P=0.053). Conclusions:The disorder of collagen fibers and apoptosis of keratocytes occur in the human corneal stromal lenticules till 84 months after cryopreservation, however, the transparency and integrity remain excellent.The ultra-low temperature preservation technique provides an effective and simple solution for long-term storage of human corneal stromal lenticule.
9.Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.
Jun-Bo GE ; Wei-Hu FAN ; Jing-Min ZHOU ; Hai-Ming SHI ; Fu-Sui JI ; Yang WU ; Yu-Lan ZHAO ; Jun QIAN ; Yuan-Zhe JIN ; Ying-Wu LIU ; Sheng-Huang WANG ; Sheng-Hu HE ; Ping YANG ; Jie WU ; Feng LU ; Zi-Shan HOU
Chinese Medical Journal 2020;134(2):185-192
BACKGROUND:
The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.
METHODS:
A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency.
RESULTS:
In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785).
CONCLUSIONS:
As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD.
TRIAL REGISTRATION
chictr.org.cn, No. ChiCTR-TRC-12003513.
Angina Pectoris
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China
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Coronary Artery Disease/drug therapy*
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Double-Blind Method
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Drugs, Chinese Herbal/adverse effects*
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Humans
10.Implementation of enhanced recovery after surgery protocols to robotic assisted radical cystectomy with intracorporeal urinary diversion using orthotopic U-shape ileal neobladder
Qijun WO ; Xiaolong QI ; Feng LIU ; Qi ZHANG ; Zujie MAO ; Fei XIANG ; Jia LYU ; Linyi HU ; Liping WANG ; Xiang HE ; Dahong ZHANG
Chinese Journal of Urology 2020;41(2):95-101
Objective To discuss outcome and safety after implementation of enhanced recovery after surgery(ERAS) protocols to patients who underwent robotic assisted radical cystectomy (RARC) with intracorporeal orthotopic "U" shaped ileal neobladder creation using STAPLER technique.Methods Between October 2014 and April 2019,71 patients(59 males and 12 females)with MIBC (Muscle Invasive Bladder Cancer) who underwent RARC with intracorporeal urinary diversion using orthotopic "U" shaped ileal neobladder in Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College) were studied retrospectively.They had an average age of (65.2 ± 5.6)y and BMI of (22.18 ± 3.75) kg/m2.The median age-adjusted charlson comorbidity index (aCCI) was 4,median ASA score was 2.All patients underwent these inspections pre-RARC:chest Xray,vascular ultrasound (jugular vein included),abdominal ultrasound,CT urography,cystoscopy with biopsy or TURBT(trans-urethral resection of a bladder tumour).All patients were pathological diagnosed with MIBC,with no evidence of systemic metastasis and no history of radiotherapy,systemic chemotherapy and open abdominal surgery before RARC.All 71 patients received RARC with intracorporeal orthotopic "U" shaped ileal neobladder creation using STAPLER technique.Between October 2014 and September 2016,37 cases (29 males and 8 females) were managed without ERAS protocols perioperatively.They had an average age of (65.3 ±5.7)y and BMI of (23.66 ± 3.47)kg/m2.The median aCCI was 4,median ASA score was 2.Between October 2016 and April 2019,another group of 34 cases (30 males and 4 females) were managed with ERAS protocols including nutritional assessment,thrombosis prevention,pain assessment and management,perioperative diet management etc.They had an average age of (64.5 ± 4.3) y and BMI of (21.87 ± 4.85) kg/m2.The median aCCI was 4,median ASA score was 2.There were no statistical significance between the two groups with regard to general information.Surgical and follow-up data were collected for all patients.Results Surgeries were successful in all 71 cases with postoperative follow up for 3-51 months.In ERAS group,there were 22 cases in pT2 and 12 cases pT3 according to classification of malignant tumours:with 2 cases of incidental prostate cancer (IPCa).In non-ERAS group,pT2 in 25 cases and pT3 in 12 cases:with 1 case of IPCa.Statistical significance were observed between groups with regard to the first anal exhaust time [(20.5 ± 18.7) h vs.(29.9 ± 17.4)h,P =0.032],the first defecation time [(72.6 ±27.1)h vs.(88.7 ±35.8)h,P =0.004],length of hospital stay after surgey [(14.1 ± 3.3) d vs.(16.2 ± 4.8) d,P =0.037],numeric rating scales (NRS) Pain Score 8.0,24.0,48.0 h after surgery [(3.2 ±0.5)vs.(3.6 ±0.8),P =0.015;(1.9 ±0.3) vs.(2.2 ± 0.6),P =0.011;(1.3 ± 0.4) vs.(1.6 ± 0.7),P =0.032],respectively.There were no significance between groups with regard to operating time [(290 ± 65) min vs.(282 ± 46) min,P =O.549],intraoperative blood loss [(190.5 ± 235.6) ml vs.(221.1 ± 250.3) ml,P =0.438],transfusion rate [5.9% (2/34) vs.8.1% (3/37),P =0.922],readmission within 30 days after surgery [2.9% (1/34) vs.5.4% (2/37),P =0.940],early severe complications(within 30 days) [2.9% (1/34) vs.2.7% (1/37),P =0.940],late severe complications (after 30 days) [5.9% (2/34) vs.8.1% (3/37),P =0.922].Conclusions The implementation of ERAS protocols to patients who underwent RARC with intracorporeal orthotopic "U" shaped ileal neobladder using STAPLER technique is safe and effective.It can reduce postoperative pain and hospital stay,shorten bowel recovery time,improve early functional recovery without increasing major complications.This adoption should be encouraged.

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