1.Reasons and strategies of reoperation after oblique lateral interbody fusion
Zhong-You ZENG ; Deng-Wei HE ; Wen-Fei NI ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Hong-Fei WU ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG ; Fei PEI
China Journal of Orthopaedics and Traumatology 2024;37(8):756-764
Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P<0.05).The ODI recovered from(40.60±7.01)%preoperatively to(9.14±2.66)%postoperatively(P<0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.
2.Effects of porcine acellular dermal matrix combined with human epidermal stem cells on wound healing of full-thickness skin defect in nude mice.
Xiao Hong ZHAO ; Yu Cheng GUO ; Hong Hao CHEN ; Xue LI ; Ying WANG ; Wen Qiang NI ; Meng Qiu XING ; Rui ZHANG ; Shi Cang YU ; Yin Gen PAN ; Ri Xing ZHAN ; Gao Xing LUO
Chinese Journal of Burns 2022;38(1):45-56
Objective: To explore the effects of porcine acellular dermal matrix (ADM) combined with human epidermal stem cells (ESCs) on wound healing of full-thickness skin defect in nude mice. Methods: The morphology of porcine ADM was analyzed by photograph of digital camera, the cell residues in porcine ADM were observed by hematoxylin-eosin (HE) staining, the surface structure of porcine ADM was observed by scanning electron microscope, the secondary structure of porcine ADM was analyzed by infrared spectrometer, the porcine ADM particle size was analyzed by dynamic light scattering particle size analyzer, and the porcine ADM potential was analyzed by nano-particle size potentiometer. The morphology of porcine ADM was observed by inverted fluorescence microscope when it was placed in culture medium for 30 min, 1 d, and 5 d (n=2). The porcine ADM was divided into 5 min group, 10 min group, 20 min group, 30 min group, 60 min group, and 120 min group according to the random number table (the same grouping method below) in static state at normal temperature for the corresponding time to calculate the water absorption by weighing method (n=3). Swiss white mouse embryonic fibroblasts (Fbs) were divided into blank control group (culture medium only), and 50.0 g/L ADM extract group, 37.5 g/L ADM extract group, 25.0 g/L ADM extract group, 12.5 g/L ADM extract group, and 6.5 g/L ADM extract group which were added with the corresponding final concentrations of ADM extract respectively. At post culture hour (PCH) 24, 48, and 72, the cell survival rate was detected by cell counting kit 8 and the cytotoxicity was graded (n=5). The erythrocytes of a 6-week-old male Sprague-Dawley male rat were divided into normal saline group, ultra-pure water group, and 5 mg/mL ADM extract group, 10 mg/mL ADM extract group, and 15 mg/mL ADM extract group which were treated with the corresponding final concentrations of porcine ADM extract respectively. After reaction for 3 h, the absorbance value of hemoglobin was detected by microplate reader to represent the blood compatibility of porcine ADM (n=3). ESCs were isolated and cultured from the discarded prepuce of a 6-year-old healthy boy who was treated in the Department of Urology of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) in July 2020, and then identified by flow cytometry. The porcine ADM particles of composite ESC (hereinafter referred to as ESC/ADM) were constructed by mixed culture. After 3 days of culture, the composite effect of ESC/ADM was observed by HE staining and laser scanning confocal microscope. Thirty-six 7-8-week-old male non-thymic nude mice were divided into phosphate buffer solution (PBS) alone group, ADM alone group, ESC alone group, and ESC/ADM group, with 9 mice in each group, and the wound model of full-thickness skin defect was established. Immediately after injury, the wounds were treated with the corresponding reagents at one time. On post injury day (PID) 1, 7, 11, and 15, the wound healing was observed and the wound healing rate was counted (n=3). On PID 7, the epithelialization of wounds was observed by HE staining and the length of un-epithelialized wound was measured (with this and the following sample numbers of 4). On PID 11, the dermal area and collagen deposition of wounds were observed by Masson staining and the dermal area of wound section was calculated, the number of cells expressing CD49f, a specific marker of ESC, was calculated with immunofluorescence staining, the mRNA expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in ESC after wound transplantation was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, and least significant difference t test. Results: The porcine ADM was white particles and composed of reticular structure, with no cells inside, disordered structure, and rough surface. The absorption peak of porcine ADM appeared at the wave numbers of 1 659, 1 549, and 1 239 cm-1, respectively. The main particle size distribution of porcine ADM in solution was 500 to 700 nm, with negative charge on the surface. The morphology of porcine ADM in static state at 30 min and on 1 and 5 d was relatively stable. The water absorption of porcine ADM remained relatively high level in static state from 30 min to 120 min. The cytotoxicity of mouse embryonic Fbs in 6.5 g/L ADM extract group, 12.5 g/L ADM extract group, and 25.0 g/L ADM extract group was grade 1 at PCH 24, and the cytotoxicity of the other groups was 0 grade at each time point. After reaction for 3 h, the absorbance value of hemoglobin of erythrocytes in ultra-pure water group was significantly higher than the values in normal saline group and 15 mg/mL ADM extract group (with t values of 8.14 and 7.96, respectively, P<0.01). After 3 days of culture, the cells of the fourth passage showed pebble-like morphology, with low expression of CD71 and high expression of CD49f, which were identified as ESCs. There was ESC attachment and growth on porcine ADM particles. On PID 1, the wound sizes of nude mice were almost the same in PBS alone group, ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, 11, and 15, the wound contraction of nude mice in each group was observed, especially in ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, the wound healing rates of nude mice in ESC alone group and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.83 and 4.72 respectively, P<0.05 or P<0.01). On PID 11, the wound healing rate of nude mice in ESC/ADM group was significantly higher than that in PBS alone group (t=4.86, P<0.01). On PID 15, the wound healing rates of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.71, 2.90, and 3.23 respectively, P<0.05). On PID 7, the length of un-epithelialized wound of nude mice in ADM alone group, ESC alone group, and ESC/ADM group was (816±85), (635±66), and (163±32) μm, respectively, which were significantly shorter than (1 199±43) μm in PBS alone group (with t values of 5.69, 10.19, and 27.54 respectively, P<0.01). On PID 11, the dermal areas of wound section of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly larger than the area in PBS alone group (with t values of 27.14, 5.29, and 15.90 respectively, P<0.01); the collagen production of nude mice in ADM alone group and ESC/ADM group was more obvious than that in PBS alone group, and the collagen production of nude mice in ESC alone group and PBS alone group was similar. On PID 11, in the wounds of nude mice in ESC alone group and ESC/ADM group, the cells with positive expression of CD49f were respectively 135±7 and 185±15, and the mRNA expressions of GAPDH were positive; while there were no expressions of CD49f nor mRNA of GAPDH in the wounds of nude mice in PBS alone group and ADM alone group. Conclusions: ESC/ADM particles can promote the wound healing of full-thickness skin defects in nude mice, which may be related to the improved survival rate of ESCs after transplantation and the promotion of dermal structure rearrangement and angiogenesis by ADM.
Acellular Dermis
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Animals
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Fibroblasts
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Humans
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Male
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Mice
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Mice, Nude
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Rats
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Rats, Sprague-Dawley
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Stem Cells
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Swine
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Wound Healing
3.The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study.
Yong Peng ZHANG ; Ya Xing WANG ; Jin Qiong ZHOU ; Qian WANG ; Yan Ni YAN ; Xuan YANG ; Jing Yan YANG ; Wen Jia ZHOU ; Ping WANG ; Chang SHEN ; Ming YANG ; Ya Nan LUAN ; Jin Yuan WANG ; Shou Ling WU ; Shuo Hua CHEN ; Hai Wei WANG ; Li Jian FANG ; Qian Qian WAN ; Jing Yuan ZHU ; Zi Han NIE ; Yu Ning CHEN ; Ying XIE ; J B JONAS ; Wen Bin WEI
Biomedical and Environmental Sciences 2022;35(7):613-621
Objective:
To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD.
Methods:
A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD.
Results:
The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD.
Conclusion
There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies
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Diabetes Mellitus/epidemiology*
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Humans
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Hyperlipidemias/epidemiology*
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Hypertension/epidemiology*
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Macular Degeneration/etiology*
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Risk Factors
4.Differences in non-suicidal self-injury behaviors between only-child and non-only-child adolescents with mood disorders: a cross-sectional study.
Wei HUANG ; Yong-Jie ZHOU ; Hong-Yu ZOU ; Xing YANG ; Hong XU ; Guo-Hua LI ; Yan-Ni WANG ; Rui-Fen LI ; Ling-Yun ZENG
Chinese Journal of Contemporary Pediatrics 2022;24(7):806-811
OBJECTIVES:
To investigate the differences in non-suicidal self-injury (NSSI) behaviors between only-child and non-only-child adolescents with mood disorders.
METHODS:
A three-stage sampling method was used to perform a cross-sectional survey of 529 adolescents, aged 12-18 years, who had mood disorders and NSSI behaviors. These adolescents were sampled from the outpatient service of 20 mental hospitals in 9 provinces of China from August to November 2020. A self-made questionnaire was used to collect general demographic data. The Functional Assessment of Self-Mutilation, Beck Scale for Suicide Ideation, Kessler Psychological Distress Scale, Stress Mindset Measure-General, Multidimensional Scale of Perceived Social Support, Multidimensional Students' Life Satisfaction Scales, and Rosenberg Self-Esteem Scale were used to collect the information on self-injury behaviors and psychological factors in these adolescents.
RESULTS:
A total of 529 adolescents with mood disorders and NSSI behaviors were surveyed, among whom 375 were only-child adolescents and 154 were non-only-child adolescents. Compared with the non-only-child group, the only-child group had a significantly higher total score of Functional Assessment of Self-Mutilation (P<0.05) .The type and frequency of self-injury in the only-child group were significantly higher than those in the non-only-child group (P<0.05). Psychological analysis showed that compared with the non-only-child group, the only-child group had a significantly lower score of self-esteem (P<0.05) and significantly higher scores of psychological distress and depressive symptoms (P<0.05). The multiple linear regression analysis showed that the score of suicidal ideation was positively correlated with the frequency of NSSI behaviors in both only-child and non-only-child adolescents with mood disorders (P<0.05); in the only-child adolescents, the level of self-esteem was negatively correlated with the frequency of NSSI behaviors (P<0.05), and the score of stress perception was positively correlated with the frequency of NSSI behaviors (P<0.05); in the non-only-child adolescents, the score of anxious emotion was positively correlated with the frequency of NSSI behaviors (P<0.05).
CONCLUSIONS
Among the adolescents with mood disorders and NSSI behaviors, the only-child adolescents tend to have a higher frequency of self-injury and poorer mental health, and therefore, the only-child adolescents with mood disorders and NSSI behaviors need more attention.
Adolescent
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Cross-Sectional Studies
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Humans
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Mood Disorders
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Risk Factors
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Self Mutilation
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Self-Injurious Behavior/psychology*
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Suicide, Attempted/psychology*
5.Transcriptome Analysis of Xianlian Jiedu Prescription in Intervention of Colorectal Carcinoma Due to Dampness, Heat, Stasis, and Toxin in Mice
Tong-qing CHEN ; Cheng-tao YU ; Hui-qin XU ; Hai-bo CHENG ; Wei-xing SHEN ; Jia-ni TAN ; Chang-liang XU ; Yue-yang LAI ; Min-min FAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):63-71
ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription (XLJDP) in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing (RNA-seq). MethodNinety male C57BL/6 mice were randomly divided into the control group, colorectal carcinoma due to dampness, heat, stasis, and toxin model group, and XLJDP group, with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate (AOM/DSS) for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin (HE) and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling, followed by gene oncology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group, XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci (ACF,P<0.01). As revealed by HE staining, XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes (446 up-regulated and 169 down-regulated) between the model group and the blank group and 54 differentially expressed genes (29 up-regulated and 25 down-regulated) between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene (Nek7, P<0.01), Mucin 16 (Muc16, P<0.01), SiahE3 ubiquitin protein ligase family member 3 (Siah3, P<0.01), regenerating islet-derived protein 3-gamma (Reg3g, P<0.01), RNA polymerase Ⅱ elongation factor-associated factor 2 (Eaf2, P<0.01), transforming growth factor‐alfa gene (TGF-α, P<0.05), secretoglobin family 1A member 1 (Scgb1a1, P<0.05), family with sequence similarity 227 member B (Fam227B, P<0.05), cytochrome P450 family 2 subfamily c polypeptide 40 (Cyp2c40, P<0.01), and ankyrin repeat and EF-hand domain containing protein 1 (Ankef1, P<0.05). Enrichment analysis showed that intestinal epithelial cell proliferation, metabolism of xenobiotics by cytochrome P450, and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness, heat, stasis, and toxin in mice, which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.
6.Effect of Xianlian Jiedu Prescription on Proliferation and Glycolysis of Human Colorectal Cancer HCT-116 Cells and Mechanism
Li-huiping TAO ; Yue-yang LAI ; Hai-bo CHENG ; Wei-xing SHEN ; Jia-ni TAN ; Chang-liang XU ; Cheng-tao YU ; Min-min FAN ; Liu LI ; Zheng-jie SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):72-78
ObjectiveTo explore the effect of Xianlian Jiedu prescription (XLJDP) on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium (MTT) assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine (EDU) incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit, and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), glucose transporter 1 (GLUT1), and lactate dehydrogenase (LDHA) was detected by Western blot. ResultThe half-maximal inhibitory concentration (IC50) of XLJDP against HCT-116 cells was 6.82 g·L-1. Compared with the blank group, XLJDP (1.625, 3.25, 6.50 g·L-1) inhibited the proliferation of HCT-116 cells (P<0.05, P<0.01). Moreover, compared with the blank group, XLJDP (1.625, 3.25, 6.50 g·L-1) suppressed glucose uptake and lactic acid production in a dose-dependent manner (P<0.05, P<0.01). The expression of p-mTOR/mTOR, LDHA, and GLUT1 was down-regulated by XLJDP (P<0.05, P<0.01). ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA, GLUT1, and other key proteins and enzymes in glycolysis.
7.Effect and Mechanism of Xianlian Jiedu Prescription Against Proliferation of Colorectal Cancer Cells in Hypoxic Microenvironment
Rui-yang JIANG ; Chang-liang XU ; Hai-bo CHENG ; Wei-xing SHEN ; Min-min FAN ; Jia-ni TAN ; Yue-yang LAI ; Cheng-tao YU ; Dong-dong SUN ; Liu LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):79-85
ObjectiveTo study the effect of Xianlian Jiedu prescription (XLJDP) on the activation of nuclear transcription factor-κB (NF-κB) signaling pathway induced by bromodomain-containing protein 4 (Brd4) in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8,1,1.2,1.6,3.2,6.4,and 12.8 g·L-1 for 48 h, respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium (MTT) colorimetry, the effects of XLJDP (1.25,2.5,and 5 g·L-1) on the cell mitochondrial membrane potential were determined using a fluorescent probe (JC-1), and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine (EDU) staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 (HEXIM1), as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group, XLJDP at 0.8,1,1.2,1.6,3.2,6.4,and 12.8 g·L-1 inhibited the vitality of colorectal cancer HT-29 cells (P<0.05 , P<0.01), with the median inhibitory concentration (IC50) under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group, XLJDP at 1.25,2.5,and 5 g·L-1 significantly decreased the mitochondria membrane potential, enhanced the apoptosis (P<0.05,P<0.01), and lowered the number of cell colonies and also the EDU-positive cells (P<0.05, P<0.01). The results of Western blot showed that compared with the blank control group, XLJDP at 1.25,2.5,and 5 g·L-1 down-regulated Brd4, c-Myc, p-NF-κB p65, and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 (P<0.05, P<0.01). ConclusionIn the hypoxic microenvironment, XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4, which may be related to its inhibition of the activation of NF-κB signaling pathway.
8.Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer.
Yu-Chao NI ; Jin-Ge ZHAO ; Meng-Ni ZHANG ; Yi-Jun ZHANG ; Zhen-Yu YANG ; Ni CHEN ; Jun-Ru CHEN ; Peng-Fei SHEN ; Guang-Xi SUN ; Xing-Ming ZHANG ; Yong-Hong LI ; Hao ZENG
Asian Journal of Andrology 2022;24(2):154-160
Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.
Abiraterone Acetate/therapeutic use*
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Adrenal Cortex Hormones/therapeutic use*
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Androstenes
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Dexamethasone/therapeutic use*
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Disease-Free Survival
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Humans
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Male
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Prednisone/therapeutic use*
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Prostate-Specific Antigen
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Prostatic Neoplasms, Castration-Resistant/pathology*
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Retrospective Studies
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Treatment Outcome
9.Study on characteristic chromatogram and content determination of Wuzhuyu Decoction reference sample.
Meng-Ru CAI ; Dong-Ge YIN ; Hu-Lin-Yue PENG ; Kai-Xin WANG ; Yu-Chen XU ; Xing-Bin YIN ; Chang-Hai QU ; Chang-Qing SUN ; Jin-Cai HOU ; Jian NI ; Xiao-Xu DONG
China Journal of Chinese Materia Medica 2022;47(15):4015-4024
In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb_1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb_1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.
Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal/chemistry*
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Ginsenosides/analysis*
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Limonins/analysis*
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Quality Control
10.Shenbai Jiedu Fang inhibits AOM/DSS-induced colorectal adenoma formation and carcinogenesis in mice via miRNA-22-mediated regulation of the PTEN/PI3K/AKT signaling pathway.
Jian Rong LIU ; Wei Xing SHEN ; Hai Bo CHENG ; Min Min FAN ; Jun XIAO ; Chang Liang XU ; Jia Ni TAN ; Yue Yang LAI ; Cheng Tao YU ; Dong Dong SUN ; Liu LI
Journal of Southern Medical University 2022;42(10):1452-1461
OBJECTIVE:
To observe the inhibitory effect of Shenbai Jiedu Fang (SBJDF, a compound recipe of traditional Chinese herbal drugs) on chemically induced carcinogenesis of colorectal adenoma in mice and explore the role of PTEN/PI3K/AKT signaling pathway in mediating this effect.
METHODS:
Four-week-old male C57BL/6 mice were randomly divided into control group (n=10), AOM/DSS model group (n=20), low-dose (14 g/kg) SBJDF group (n=10) and high-dose (42 g/kg) SBJDF group (n= 10). In the latter 3 groups, the mice were treated with azoxymethane (AOM) and dextran sodium sulphate (DSS) to induce carcinogenesis of colorectal adenoma. In the two SBJDF treatment groups, SBJDF was administered daily by gavage during the modeling. The survival rate, body weight, general condition of the mice, and intestinal adenoma formation and carcinogenesis were observed. The expressions of proteins associated with the PTEN/PI3K/AKT signaling pathway in the intestinal tissue were detected using immunohistochemistry.
RESULTS:
Compared with those in the model group, the mice treated with SBJDF, especially at the high dose, showed a significantly lower incidence of intestinal carcinogenesis and had fewer intestinal tumors with smaller tumor volume. Pathological examination showed the occurrence of adenocarcinoma in the model group, while only low-grade and high-grade neoplasia were found in low-dose SBJDF group; the mice treated with high-dose SBJDF showed mainly normal mucosal tissues in the intestines with only a few lesions of low-grade neoplasia of adenoma. Compared with those in the control group, the mice in the model group had significantly elevated plasma miRNA-222 level (P < 0.05), which was obviously lowered in the two SBJDF groups (P < 0.01). The results of immunohistochemistry revealed that compared with the model group, the two SBJDF groups, especially the high-dose group, had significantly up-regulated expressions of PTEN, P-PTEN and GSK-3β and down-regulated expressions of p-GSK-3 β, PI3K, AKT, P-AKT, β-catenin, c-myc, cyclinD1 and survivin in the intestinal tissues.
CONCLUSION
SBJDF can significantly inhibit colorectal adenoma formation and carcino-genesis in mice possibly through regulating miRNA-222 and affecting PTEN/PI3K/AKT signaling pathway.
Animals
;
Male
;
Mice
;
Adenoma/prevention & control*
;
Azoxymethane/adverse effects*
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Carcinogenesis/drug effects*
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Colorectal Neoplasms/prevention & control*
;
Dextran Sulfate/adverse effects*
;
Disease Models, Animal
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Glycogen Synthase Kinase 3 beta/metabolism*
;
Mice, Inbred C57BL
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MicroRNAs/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Signal Transduction
;
Drugs, Chinese Herbal/therapeutic use*

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