1.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
;
Heart Failure/drug therapy*
;
Peptide Fragments
;
Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
2.The effect of BMI and age on the outcomes of microsurgical vasoepididymostomy: a retrospective analysis of 181 patients operated by a single surgeon.
Shou-Yang WANG ; Yang-Yi FANG ; Hai-Tao ZHANG ; Yu TIAN ; Vera Yeung CHUNG ; Yin-Chu CHENG ; Kai HONG ; Hui JIANG
Asian Journal of Andrology 2023;25(2):277-280
To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.
Humans
;
Male
;
Adult
;
Retrospective Studies
;
Body Mass Index
;
Epididymis/surgery*
;
Vas Deferens/surgery*
;
Treatment Outcome
;
Sperm Motility
;
Microsurgery
;
Surgeons
;
Vasovasostomy
3.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
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Brain Abscess
;
Child
;
Child, Preschool
;
Escherichia coli
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Female
;
Humans
;
Hydrocephalus
;
Infant
;
Infant, Newborn
;
Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
;
Streptococcus agalactiae
;
Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
4.Analysis of clinical outcome of synchronous micro-dissection testicular sperm extraction and intracytoplasmic sperm injection in male infertility with Y chromosome azoospermia factor c region deletion.
Jia Ming MAO ; Lian Ming ZHAO ; De Feng LIU ; Hao Cheng LIN ; Yu Zhuo YANG ; Hai Tao ZHANG ; Kai HONG ; Rong LI ; Hui JIANG
Journal of Peking University(Health Sciences) 2022;54(4):652-657
OBJECTIVE:
To analyze the clinical treatment results of male infertility caused by Y chromosome azoospermia factor c region(AZFc) deletion after synchronous micro-dissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) and to guide the treatment of infer- tile patients caused by AZFc deletion.
METHODS:
The clinical data of infertile patients with AZFc deletion who underwent synchronous micro-TESE in Peking University Third Hospitalfrom January 2015 to December 2019 were retrospectively analyzed. The clinical outcomes of ICSI in the patients who successfully obtained sperm were followed up and we compared the outcomes between the first and second synchronous procedures, including fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate and live birth rate.
RESULTS:
A total of 195 male infertile patients with AZFc deletion underwent micro-TESE. Fourteen patients were cryptozoospermia and their sperms were successfully obtained in all of them during the operation, and the sperm retrieval rate (SRR) was 100%(14/14). The remaining 181 cases were non obstructive azoospermia, and 122 cases were successfully found the sperm, the SRR was 67.4%(122/181). The remaining 59 patients with NOA could not found mature sperm during micro-TESE, accounting for 32.6% (59/181). We followed up the clinical treatment outcomes of the patients with successful sperm retrieved by synchronous micro-TESE and 99 patients were enrolled in the study. A total of 118 micro-TESE procedures and 120 ICSI cycles were carried out. Finally 38 couples successfully gave birth to 22 male and 22 female healthy infants, with a cumulative live birth rate of 38.4% (38/99). In the fresh-sperm ICSI cycle of the first and second synchronous operation procedures, the high-quality embryo rate, clinical pregnancy rate of the fresh embryo transfer cycle and live birth rate of the oocyte retrieve cycle were 47.7% vs. 50.4%, 40.5% vs. 50.0%, and 28.3% vs. 41.2%, respectively. The second operation group was slightly higher than that of the first synchronous operation group, but there was no significant difference between the groups.
CONCLUSION
Male infertility patients caused by AZFc deletion have a high probability of successfully obtaining sperm in testis through micro-TESE for ICSI and give birth to their own offspring with their own biological characteristics. For patients who failed in the first synchronous procedure, they still have the opportunity to successfully conceive offspring through reoperation and ICSI.
Azoospermia/therapy*
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Chromosome Deletion
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Chromosomes, Human, Y
;
Female
;
Humans
;
Infertility, Male/therapy*
;
Male
;
Pregnancy
;
Retrospective Studies
;
Semen
;
Sex Chromosome Aberrations
;
Sex Chromosome Disorders of Sex Development
;
Sperm Injections, Intracytoplasmic/methods*
;
Sperm Retrieval
;
Spermatozoa
;
Testis
5.Interpretation of Intelligence Attribute of Supramolecular "Qi Chromatography" Theory of Traditional Chinese Medicine and Its Combined Application with Artificial Intelligence
Hai-ying LI ; Kai-wen DENG ; Xue PAN ; Ding-fang CHEN ; Yue-feng WU ; Min-cun WANG ; Yan-zi ZHOU ; Yan-tao YANG ; Fu-yuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(5):227-233
In the era of artificial intelligence based on big data, data acquisition, storage and processing are more convenient, which provides a guarantee for accelerating the development of traditional Chinese medicine (TCM), but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM, combined with the current development trend of artificial intelligence, this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template", in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template", the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM, in which the self-recognition, self-assembly, self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes:the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM, and store the memory information database in the meridian and collateral organs in the form of "imprinting template", and then pass the "imprinting template". The comparison, analysis, and judgment of imprinting templates guide the self-assembly, self-organization and self-replication among "molecular society", synthesize biological machines, produce biological functions, repair or strengthen biological supramolecular bodies, and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence", while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world, artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world, suggesting the development direction of "intelligence" functionalization of drug innovation mode.
6.Evolution Characteristics and Clinical Significance of Blood Separation in Patients with Multiple Myeloma.
Ze-Wen FAN ; Na-Li CHU ; Jing-Yu ZHANG ; Hua ZHANG ; Hai-Tao HU ; Kai JI ; Hong FAN
Journal of Experimental Hematology 2022;30(2):449-454
OBJECTIVE:
To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis.
METHODS:
The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed.
RESULTS:
In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and β2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05).
CONCLUSION
Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.
Humans
;
Interleukin-17
;
Interleukin-6
;
Multiple Myeloma
;
Prognosis
;
Retrospective Studies
;
Tumor Necrosis Factor-alpha
7.Effects of exosomes from human adipose-derived mesenchymal stem cells on inflammatory response of mouse RAW264.7 cells and wound healing of full-thickness skin defects in mice.
Kuo SHEN ; Xu Jie WANG ; Kai Tuo LIU ; Shao Hui LI ; Jin LI ; Jin Xin ZHANG ; Hong Tao WANG ; Da Hai HU
Chinese Journal of Burns 2022;38(3):215-226
Objective: To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on inflammatory response of mouse RAW264.7 cells and wound healing of full-thickness skin defects in mice. Methods: The experimental research methods were adopted. The discarded adipose tissue was collected from 3 female patients (aged 10-25 years) who underwent abdominal surgery in the First Affiliated Hospital of Air Force Medical University. ADSCs were extracted from the adipose tissue by collagenase Ⅰ digestion and identified with flow cytometry. Exosomes were extracted from the human ADSCs by differential ultracentrifugation, the morphology of the exosomes was observed by transmission electron microscopy, the particle diameter of the exosomes was detected by nanoparticle tracking analyzer, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin were detected by Western blotting. The human ADSCs exosomes (ADSCs-Exos) and RAW264.7 cells were co-cultured for 12 h, and the uptake of RAW264.7 cells for human ADSCs-Exos was observed. The RAW264.7 cells were divided into phosphate buffer solution (PBS) group stimulated with PBS for suitable time, endotoxin/lipopolysaccharide (LPS) stimulation 2 h group, LPS stimulation 4 h group, LPS stimulation 6 h group, LPS stimulation 12 h group, and LPS stimulation 24 h group stimulated with LPS for corresponding time, with 3 wells in each group, and the mRNA expressions of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-6, and IL-10 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) method. The RAW264.7 cells were divided into PBS group, LPS alone group, and LPS+ADSCs-Exos group, with 3 wells in each group, which were dealt correspondingly for the time screened out in the previous experiment, the mRNA expressions of IL-1β, TNF-α, IL-6, IL-10, trasforming growth factor β (TGF-β,) and vascular endothelial growth factor (VEGF) were detected by real time fluorescence quantitative RT-PCR method, and the protein expressions of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) were detected by Western blotting. Twenty-four 8-week-old male BALB/c mice were divided into PBS group and ADSCs-Exos group according to the random number table, with 12 mice in each group, and a full-thickness skin defect wound with area of 1 cm×1 cm was inflicted on the back of each mouse. Immediately after injury, the wounds of mice in the two groups were dealt correspondingly. On post injury day (PID) 1, the concentration of IL-1β and TNF-α in serum were detected by enzyme-linked immunosorbent assay, and the mRNA expressions of IL-1β, TNF-α, and IL-6 were detected by real time fluorescence quantitative RT-PCR method. On PID 3, 6, 9, 12, and 15, the wound healing was observed and the wound non-healing rate was calculated. On PID 15, the defect length of skin accessory and collagen volume fraction (CVF) were detected by hematoxylin eosin staining and Masson staining, respectively, the CD31 expression and neovascularization were detected by immunohistochemistry, and the ratio of Ki67 positive cells, the ratio of iNOS and Arg1 double positive cells, and the ratio of iNOS positive cells to Arg1 positive cells and their fluorescence intensities were detected by immunofluorescence method. The number of samples in animal experiments was 6. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and independent sample t test. Results: At 12 h of culture, the cells exhibited a typical spindle shape, which were verified as ADSCs with flow cytometry. The exosomes with a vesicular structure and particle diameters of 29-178 nm, were positively expressed CD9, CD63, and TSG101 and negatively expressed β-actin. After 12 h of co-culture, the human ADSCs-Exos were endocytosed into the cytoplasm by RAW264.7 cells. The mRNA expressions of IL-1β, TNF-α, IL-6, and IL-10 of RAW264.7 cells in LPS stimulation 2 h group, LPS stimulation 4 h group, LPS stimulation 6 h group, LPS stimulation 12 h group, and LPS stimulation 24 h group were significantly higher than those in PBS group (with t) values of 39.10, 14.55, 28.80, 4.74, 48.80, 22.97, 13.25, 36.34, 23.12, 18.71, 29.19, 41.08, 11.68, 18.06, 8.54, 43.45, 62.31, 22.52, 21.51, and 37.13, respectively, P<0.01). The stimulation 12 h with significant expressions of all the inflammatory factors was selected as the time point in the following experiment. After stimulation of 12 h, the mRNA expressions of IL-1β, TNF-α, IL-6, and IL-10 of RAW264.7 cells in LPS alone group were significantly higher than those in PBS group (with t values of 44.20, 51.26, 14.71, and 8.54, respectively, P<0.01); the mRNA expressions of IL-1β, TNF-α, and IL-6 of RAW264.7 cells in LPS+ADSCs-Exos group were significantly lower than those in LPS alone group (with t values of 22.89, 25.51, and 8.03, respectively, P<0.01), while the mRNA expressions of IL-10, TGF-β, and VEGF were significantly higher than those in LPS alone group (with t values of 9.89, 13.12, and 7.14, respectively, P<0.01). After stimulation of 12 h, the protein expression of iNOS of RAW264.7 cells in LPS alone group was significantly higher than that in PBS group and LPS+ADSCs-Exos group, respectively (with t values of 11.20 and 5.06, respectively, P<0.05 or P<0.01), and the protein expression of Arg1 was significantly lower than that in LPS+ADSCs-Exos group (t=15.01, P<0.01). On PID 1, the serum concentrations of IL-1β and TNF-α and the mRNA expressions of IL-1β, TNF-α, and IL-6 in wound tissue of mice in ADSCs-Exos group were significantly those in lower than PBS group (with t values of 15.44, 12.24, 9.24, 7.12, and 10.62, respectively, P<0.01). On PID 3, 6, 9, 12, and 15 d, the wound non-healing rates of mice in ADSCs-Exos group were (73.2±4.1)%, (53.8±3.8)%, (42.1±5.1)%, (24.1±2.8)%, and 0, which were significantly lower than (82.5±3.8)%, (71.2±4.6)%, (52.9±4.1)%, (41.5±3.6)%, and (14.8±2.5)% in PBS group, respectively (with t values of 4.77, 8.93, 5.54, 7.63, and 7.59, respectively, P<0.01). On PID 15, the defect length of skin accessory in wounds of mice in PBS group was significantly longer than that in ADSCs-Exos group (t=9.50, P<0.01), and the CVF was significantly lower than that in ADSCs-Exos group (t=9.15, P<0.01). On PID 15, the CD31 expression and the number of new blood vessels (t=12.99, P<0.01), in wound tissue of mice in ADSCs-Exos group were significantly more than those in PBS group, and the ratio of Ki67 positive cells was significantly higher than that in PBS group (t=7.52, P<0.01). On PID 15, the ratio of iNOS and Arg1 double positive cells in wound tissue of mice in PBS group was (12.33±1.97)%, which was significantly higher than (1.78±0.29)% in ADSCs-Exos group (t=13.04, P<0.01), the ratio of iNOS positive cells and the fluorescence intensity of iNOS were obviously higher than those of ADSCs-Exos group, and the ratio of Arg1 positive cells and the fluorescence intensity of Arg1 were obviously lower than those of ADSCs-Exos group. Conclusions: The human ADSCs-Exos can alleviate inflammatory response of mouse RAW264.7 cells, decrease macrophage infiltration and secretion of the pro-inflammatory cytokines, increase the secretion of anti-inflammatory cytokines to promote neovascularization and cell proliferation in full-thickness skin defect wounds of mice, hence accelerating wound healing.
Animals
;
Exosomes
;
Female
;
Humans
;
Male
;
Mesenchymal Stem Cells
;
Mice
;
Skin
;
Vascular Endothelial Growth Factor A
;
Wound Healing
8.A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data.
Xue Wei DING ; Zhi Chao ZHENG ; Qun ZHAO ; Gang ZHAI ; Han LIANG ; Xin WU ; Zheng Gang ZHU ; Hai Jiang WANG ; Qing Si HE ; Xian Li HE ; Yi An DU ; Lu Chuan CHEN ; Ya Wei HUA ; Chang Ming HUANG ; Ying Wei XUE ; Ye ZHOU ; Yan Bing ZHOU ; Dan WU ; Xue Dong FANG ; You Guo DAI ; Hong Wei ZHANG ; Jia Qing CAO ; Le Ping LI ; Jie CHAI ; Kai Xiong TAO ; Guo Li LI ; Zhi Gang JIE ; Jie GE ; Zhong Fa XU ; Wen Bin ZHANG ; Qi Yun LI ; Ping ZHAO ; Zhi Qiang MA ; Zhi Long YAN ; Guo Liang ZHENG ; Yang YAN ; Xiao Long TANG ; Xiang ZHOU
Chinese Journal of Gastrointestinal Surgery 2021;24(5):403-412
Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant
;
Female
;
Gastrectomy
;
Humans
;
Male
;
Neoadjuvant Therapy
;
Neoplasm Staging
;
Prognosis
;
Retrospective Studies
;
Stomach Neoplasms/surgery*
9.Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study.
Peng ZHANG ; Jun ZHANG ; Bo ZHANG ; Wen Chang YANG ; Jun Bo HU ; Xiao Feng SUN ; Gang ZHAI ; Hao Ran QIAN ; Yong LI ; Hao XU ; Fan FENG ; Xing Ye WU ; He Li LIU ; Hong Jun LIU ; Hai Bo QIU ; Xiao Jun WU ; Yan Bing ZHOU ; Kun Tang SHEN ; You Wei KOU ; Yang FU ; Zhi Gang JIE ; Xiao Ming ZOU ; Hui CAO ; Zhi Dong GAO ; Kai Xiong TAO
Chinese Journal of Gastrointestinal Surgery 2021;24(9):775-782
Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged
;
Aged, 80 and over
;
Antineoplastic Agents/therapeutic use*
;
Chemotherapy, Adjuvant
;
Cross-Sectional Studies
;
Female
;
Gastrointestinal Stromal Tumors/drug therapy*
;
Humans
;
Imatinib Mesylate/therapeutic use*
;
Male
;
Middle Aged
;
Neoplasm Recurrence, Local/drug therapy*
10.Utilization of facility-based HIV testing and associated factors among men who have sex with men in Shanghai
Yan BAO ; Zhen NING ; Kai-kan GU ; Yun YANG ; Hai-tao WANG ; Lei HAN ; Bing SHEN
Shanghai Journal of Preventive Medicine 2021;33(8):687-691
Objective:To determine the prevalence of facility-based HIV testing and its associated factors among men who have sex with men (MSM) in Shanghai. Methods:From June 2018 to December 2020, MSM were recruited by a community organization “Shanghai CSW&MSM Center (SCMC)”. A total of 3 251 MSM were included as follows: being 18 years old and above, being HIV-negative or with unknown HIV status, living in Shanghai, had homosexual behavior in the past year, and completed informed consent. Using a self-designed questionnaire, we performed an online survey powered by www.wjx.cn to collect information on demographics, sexual behavior, and facility-based HIV testing. A total of 3 240 valid questionnaires were collected. Univariate and multivariate logistic regression were used to determine the factors associated with facility-based HIV testing. Results:A total of 3 240 MSM participated in the study with mean age of (29.7±6.2) years .The prevalence of facility-based HIV testing was 63.2% (2 049/3 240), Multivariate logistic regression showed that the participants with a college degree or above were less likely to have facility-based HIV testing(

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