1.Four Weeks of HIIT Modulates Lactate-mediated Synaptic Plasticity to Improve Depressive-like Behavior in CUMS Rats
Yu-Mei HAN ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Chun-Hui BAO ; Jun-Sheng TIAN ; Shi ZHOU ; Huan XIANG ; Yong-Hong YANG
Progress in Biochemistry and Biophysics 2025;52(6):1499-1510
ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, Smax) alternated with one minute at low speed (50%-55% Smax), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.
2.Chemical composition and efficacy of warming lung and resolving fluid retention of Asarum forbesii grown under different shading conditions.
Lu LIAO ; Li-Xian LU ; Hong-Zhuan SHI ; Qiao-Sheng GUO ; Cheng-Hao FEI ; Kun ZHAO ; Yuan-Yuan XING ; Yong SU ; Chang LIU ; Xin-Yue YUAN
China Journal of Chinese Materia Medica 2025;50(2):384-394
Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals
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Mice
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Lung/pathology*
;
Drugs, Chinese Herbal/administration & dosage*
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Male
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Light
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Cytokines/genetics*
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Humans
3.Bone loss in patients with spinal cord injury: Incidence and influencing factors.
Min JIANG ; Jun-Wei ZHANG ; He-Hu TANG ; Yu-Fei MENG ; Zhen-Rong ZHANG ; Fang-Yong WANG ; Jin-Zhu BAI ; Shu-Jia LIU ; Zhen LYU ; Shi-Zheng CHEN ; Jie-Sheng LIU ; Jia-Xin FU
Chinese Journal of Traumatology 2025;28(6):477-484
PURPOSE:
To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI).
METHODS:
A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant.
RESULTS:
The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively).
CONCLUSIONS
The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans
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Spinal Cord Injuries/complications*
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Male
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Female
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Retrospective Studies
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Incidence
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Adult
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Bone Density
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Middle Aged
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Case-Control Studies
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Osteoporosis/etiology*
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Lumbar Vertebrae
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Bone Diseases, Metabolic/etiology*
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Aged
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Risk Factors
4.Impact of admission-blood-glucose-to-albumin ratio on all-cause mortality and renal prognosis in critical patients with coronary artery disease: insights from the MIMIC-IV database.
Yong HONG ; Bo-Wen ZHANG ; Jing SHI ; Ruo-Xin MIN ; Ding-Yu WANG ; Jiu-Xu KAN ; Yun-Long GAO ; Lin-Yue PENG ; Ming-Lu XU ; Ming-Ming WU ; Yue LI ; Li SHENG
Journal of Geriatric Cardiology 2025;22(6):563-577
BACKGROUND:
Blood glucose and serum albumin have been associated with cardiovascular disease prognosis, but the impact of admission-blood-glucose-to-albumin ratio (AAR) on adverse outcomes in critical ill coronary artery disease (CAD) patients was not investigated.
METHODS:
Patients diagnosed with CAD were non-consecutively selected from the MIMIC-IV database and categorized into quartiles based on their AAR. The primary outcome was 1-year mortality, and secondary endpoints were in-hospital mortality, acute kidney injury (AKI), and renal replacement therapy (RRT). A restricted cubic splines model and Cox proportional hazard models assessed the association between AAR and adverse outcomes in CAD patients. Kaplan-Meier survival analysis determined differences in endpoints across subgroups.
RESULTS:
A total of 8360 patients were included. There were 726 patients (8.7%) died in the hospital and 1944 patients (23%) died at 1 year. The incidence of AKI and RRT was 63% and 4.3%, respectively. High AAR was markedly associated with in-hospital mortality (HR = 1.587, P = 0.003), 1-year mortality (HR = 1.502, P < 0.001), AKI incidence (HR = 1.579, P < 0.001), and RRT (HR = 1.640, P < 0.016) in CAD patients in the completely adjusted Cox proportional hazard model. Kaplan-Meier survival analysis noted substantial differences in all endpoints based on AAR quartiles. Stratified analysis and interaction test demonstrated stable correlations between AAR and outcomes.
CONCLUSIONS
The results highlight that AAR may be a potential indicator for assessing in-hospital mortality, 1-year mortality, and adverse renal prognosis in critical CAD patients.
5.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
6.Regulatory Effect of Mahuang Dingchuan Decoction Adjuvant Therapy on Airway Inflammation,Airway Remodeling and Th1/Th2 Imbalance in Children with Allergic Asthma
Yong-Sheng MA ; Feng-Ran ZHOU ; Man-Man SHI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1479-1486
Objective To investigate the regulatory effect of Mahuang Dingchuan Decoction on airway inflammation,airway remodeling and imbalance of helper T cell 1(Th1)/helper T cell 2(Th2)in children with allergic asthma.Methods A total of 126 children with allergic asthma of phlegm-heat obstructing the lung type at acute attack stage were randomly divided into observation group and control group,with 63 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Mahuang Dingchuan Decoction on the basis of treatment for the control group.The total course of treatment for the two groups covered 14 days.Before and after treatment,the two groups were observed in the changes of lung function indicators of forced expiratory volume in one second(FEV1)and peak expiratory flow(PEF),airway inflammation indicators of neutrophil count,lymphocyte count,eosinophil count,monocyte percentage and levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the sputum,airway remodeling indicators of airway wall area(WA),airway lumen area(LA)and airway total area(TA),and levels of Th1/Th2 cytokines of gamma-interferon(IFN-γ)and interleukin 4(IL-4).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 14 days of treatment,the total effective rate of the observation group was 93.65%(59/63),and that of the control group was 80.95%(51/63).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the values of pulmonary function indicators of FEV1 and PEF in the two groups were significantly higher than those before treatment(P<0.01),and the increase in the observation group was significantly superior to that in the control group(P<0.05).(3)The analysis of airway inflammation indicators showed that the percentages of neutrophils,eosinophils and monocytes and the levels of IL-6 and TNF-α in the sputum of the two groups after treatment were significantly lower than those before treatment(P<0.05),and the percentage of lymphocytes was significantly higher than that before treatment(P<0.05).The decrease of the percentages of neutrophils,eosinophils and monocytes and the levels of IL-6 and TNF-α in the sputum as well as the increase of the percentage of lymphocytes in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the value of airway remodeling indicator of WA in the two groups was lower(P<0.05)and the values of LA and TA were higher than those before treatment(P<0.05).The decrease of WA value and the increase of LA and TA values in the observation group were significantly superior to those in the control group(P<0.05).(5)The observation of Th1/Th2 cytokines showed that the serum IFN-γ level and IFN-γ/IL-4 ratio in the two groups after treatment were significantly higher than those before treatment(P<0.05),and the serum IL-4 level was significantly lower than that before treatment(P<0.05).The increase of serum IFN-γ level and IFN-γ/IL-4 ratio and the decrease of serum IL-4 level in the observation group were significantly superior to those in the control group(P<0.05).(6)No serious adverse reactions were found in the two groups during the treatment,or no obvious abnormalities were found in the safety indicators such as electrocardiogram,blood routine test,liver function examination,heart rate and blood pressure.Conclusion Mahuang Dingchuan Decoction is beneficial to alleviating airway inflammation and airway remodeling in children with allergic asthma,regulating Th1/Th2 imbalance,and improving lung function in children,with definite effective and high safe.
7.Design,numerical simulation and experimental study of novel oxygenator
Ming-Hao YUE ; Shi-Yao ZHANG ; Ji-Nian LI ; Hui-Chao LIU ; Zi-Hua SU ; Ya-Wei WANG ; Zeng-Sheng CHEN ; Shi-Hang LIN ; Jin-Yu LI ; Ya-Ke CHENG ; Yong-Fei HU ; Cun-Ding JIA ; Ming-Zhou XU
Chinese Medical Equipment Journal 2024;45(3):23-28
Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]
8.An analysis of long-term survival trends for nasopharyngeal carcinoma in Qidong, Jiangsu.
Yong Sheng CHEN ; Jian ZHU ; Jun WANG ; Hai Hui SHI
Chinese Journal of Oncology 2023;45(9):773-778
Objective: To analyze the survival of nasopharyngeal carcinoma patients in Qidong from 1972 to 2016, and provide a basis for the prognosis evaluation and prevention for nasopharyngeal carcinoma patients. Methods: A total of 1 060 registered nasopharyngeal carcinoma patients were followed up for survival outcomes until December 31, 2021. Observed survival rate (OSR) and relative survival rate (RSR) was calculated by Hakulinen method in SURV3.01 software, and Hakulinen's likelihood ratio test was used for statistical difference comparison. Age-standardized relative survival rate (ARSR) was calculated according to the International Cancer Survival Standard (ICSS). Joinpoint 4.7.0.0 software was used to conduct the annual average percentage change (AAPC) in nasopharyngeal carcinoma survival rate. The period from 1972 to 2016 is divided into 9 periods for grouping processing according to 5 years. Results: The OSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.02%, 34.70% and 24.72%, the RSR at 1, 5, 10 years were 64.44%, 38.98% and 31.64%, respectively. The uptrends of RSR in the nine periods were statistically significant (χ(2)=112.16, P<0.001). The 1, 5, 10 years RSR for males were 62.66%, 35.89% and 27.94%, while the 1, 5, 10 years RSR for females were 68.30%, 45.67% and 39.68%, respectively. There was no statistically significant difference in RSR between males and females (χ(2)=14.16, P=0.656). The 5-year RSR for the age groups of 25-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 52.83%, 40.92%, 42.64%, 38.65%, 27.23% and 28.88%, respectively. There was a statistically significant difference in RSR among different age groups (χ(2)=42.33, P=0.003). Moreover, the ARSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.64%, 37.33% and 27.10%, for males were 61.82%, 35.60% and 25.20%, for females were 68.36%, 43.12% and 32.93%. Period trend showed that the AAPC of 5-ARSR was 2.71% (t=7.47, P<0.001) from 1972 to 2016 in Qidong. The AAPC of 5-ARSR in males and females were 2.63% (t=4.98, P=0.002) and 2.71% (t=6.08, P=0.001). There was statistically significant increase in 5-year ARSR among both genders. Furthermore, the AAPC of 5-year RSR among 25-34, 35-44, 45-54, 55-64, 65-74 and 75+ years old were 2.16% (t=4.28, P=0.004), 3.38% (t=5.06, P=0.001), 1.99% (t=2.82, P=0.026), 2.82% (t=3.39, P=0.012), 2.20% (t=2.82, P=0.026) and -0.91% (t=-0.42, P=0.689), respectively. Except for the 75+ years old age group, the other age groups were significantly upward trend. Conclusions: The overall survival rate of nasopharyngeal carcinoma in Qidong from 1972 to 2016 has shown an upward trend. It is necessary to introduce standardized multi-disciplinary treatment mode to improve treatment effect and survival rate.
Humans
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Male
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Female
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Aged
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Nasopharyngeal Carcinoma
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Survival Rate
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Prognosis
;
Software
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Nasopharyngeal Neoplasms
;
China/epidemiology*
;
Incidence
9.An analysis of long-term survival trends for nasopharyngeal carcinoma in Qidong, Jiangsu.
Yong Sheng CHEN ; Jian ZHU ; Jun WANG ; Hai Hui SHI
Chinese Journal of Oncology 2023;45(9):773-778
Objective: To analyze the survival of nasopharyngeal carcinoma patients in Qidong from 1972 to 2016, and provide a basis for the prognosis evaluation and prevention for nasopharyngeal carcinoma patients. Methods: A total of 1 060 registered nasopharyngeal carcinoma patients were followed up for survival outcomes until December 31, 2021. Observed survival rate (OSR) and relative survival rate (RSR) was calculated by Hakulinen method in SURV3.01 software, and Hakulinen's likelihood ratio test was used for statistical difference comparison. Age-standardized relative survival rate (ARSR) was calculated according to the International Cancer Survival Standard (ICSS). Joinpoint 4.7.0.0 software was used to conduct the annual average percentage change (AAPC) in nasopharyngeal carcinoma survival rate. The period from 1972 to 2016 is divided into 9 periods for grouping processing according to 5 years. Results: The OSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.02%, 34.70% and 24.72%, the RSR at 1, 5, 10 years were 64.44%, 38.98% and 31.64%, respectively. The uptrends of RSR in the nine periods were statistically significant (χ(2)=112.16, P<0.001). The 1, 5, 10 years RSR for males were 62.66%, 35.89% and 27.94%, while the 1, 5, 10 years RSR for females were 68.30%, 45.67% and 39.68%, respectively. There was no statistically significant difference in RSR between males and females (χ(2)=14.16, P=0.656). The 5-year RSR for the age groups of 25-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 52.83%, 40.92%, 42.64%, 38.65%, 27.23% and 28.88%, respectively. There was a statistically significant difference in RSR among different age groups (χ(2)=42.33, P=0.003). Moreover, the ARSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.64%, 37.33% and 27.10%, for males were 61.82%, 35.60% and 25.20%, for females were 68.36%, 43.12% and 32.93%. Period trend showed that the AAPC of 5-ARSR was 2.71% (t=7.47, P<0.001) from 1972 to 2016 in Qidong. The AAPC of 5-ARSR in males and females were 2.63% (t=4.98, P=0.002) and 2.71% (t=6.08, P=0.001). There was statistically significant increase in 5-year ARSR among both genders. Furthermore, the AAPC of 5-year RSR among 25-34, 35-44, 45-54, 55-64, 65-74 and 75+ years old were 2.16% (t=4.28, P=0.004), 3.38% (t=5.06, P=0.001), 1.99% (t=2.82, P=0.026), 2.82% (t=3.39, P=0.012), 2.20% (t=2.82, P=0.026) and -0.91% (t=-0.42, P=0.689), respectively. Except for the 75+ years old age group, the other age groups were significantly upward trend. Conclusions: The overall survival rate of nasopharyngeal carcinoma in Qidong from 1972 to 2016 has shown an upward trend. It is necessary to introduce standardized multi-disciplinary treatment mode to improve treatment effect and survival rate.
Humans
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Male
;
Female
;
Aged
;
Nasopharyngeal Carcinoma
;
Survival Rate
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Prognosis
;
Software
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Nasopharyngeal Neoplasms
;
China/epidemiology*
;
Incidence
10.Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study
Lu WANG ; Ying-Jie DAI ; Yu CUI ; Hong ZHANG ; Chang-Hao JIANG ; Ying-Jie DUAN ; Yong ZHAO ; Ye-Fang FENG ; Shi-Mei GENG ; Zai-Hui ZHANG ; Jiang LU ; Ping ZHANG ; Li-Wei ZHAO ; Hang ZHAO ; Yu-Tong MA ; Cheng-Guang SONG ; Yi ZHANG ; Hui-Sheng CHEN
Journal of Stroke 2023;25(3):371-377
Background:
and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset.
Methods:
In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH).
Results:
Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group.
Conclusion
This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

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