1.Dawn of CAR-T cell therapy in autoimmune diseases
Yuxin LIU ; Minghao DONG ; Yunhui CHU ; Luoqi ZHOU ; Yunfan YOU ; Xiaowei PANG ; Sheng YANG ; Luyang ZHANG ; Lian CHEN ; Lifang ZHU ; Jun XIAO ; Wei WANG ; Chuan QIN ; Daishi TIAN
Chinese Medical Journal 2024;137(10):1140-1150
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.
2.Effects of GanoExtra combined with CTX on lung metastasis and immune function in mice
Shu LIAN ; Ting-Jian WU ; Jie CHEN ; Chun-Lian ZHONG ; Yu-Sheng LU ; Ye LI ; Chang-Hui WU ; Kun ZHANG ; Li JIA ; Xiao-Dong XIE
Chinese Pharmacological Bulletin 2024;40(7):1335-1342
Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.
3.Guidelines for management of pediatric acute hyperextension spinal cord injury.
Lian ZENG ; Yu-Long WANG ; Xian-Tao SHEN ; Zhi-Cheng ZHANG ; Gui-Xiong HUANG ; Jamal ALSHORMAN ; Tracy Boakye SEREBOUR ; Charles H TATOR ; Tian-Sheng SUN ; Ying-Ze ZHANG ; Xiao-Dong GUO
Chinese Journal of Traumatology 2023;26(1):2-7
Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.
Child
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Humans
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Spinal Cord Injuries/complications*
;
Spinal Cord
4.Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.
Xiao-Yun YIN ; Yun-Mei ZHANG ; Ai-Dong SHEN ; Jing-Ping WANG ; Zhe-Xun LIAN ; Yi-Bing SHAO ; Wen-Qi ZHANG ; Shu-Ying ZHANG ; Yang ZHENG ; Kang CHENG ; Biao XU ; Cheng-Xing SHEN ; Rong-Chong HUANG ; Jin-Cheng GUO ; Guo-Sheng FU ; Dong-Kai SHAN ; Dan-Dan LI ; Yun-Dai CHEN
Journal of Geriatric Cardiology 2023;20(4):256-267
OBJECTIVE:
To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).
METHODS:
In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.
RESULTS:
Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.
CONCLUSIONS
In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.
5.Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia.
De Peng WU ; Jun BAI ; Song Lin CHU ; Zheng Dong HAO ; Xiao Jia GUO ; Lian Sheng ZHANG ; Li Juan LI
Chinese Journal of Internal Medicine 2023;62(6):688-692
Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.
Humans
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Longevity
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Clinical Relevance
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Prospective Studies
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Erythrocytes
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Anemia, Megaloblastic
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Folic Acid
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Bilirubin
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Vitamins
6.Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.
Ying-Ying JIANG ; Fang-Chao LIU ; Chong SHEN ; Jian-Xin LI ; Ke-Yong HUANG ; Xue-Li YANG ; Ji-Chun CHEN ; Xiao-Qing LIU ; Jie CAO ; Shu-Feng CHEN ; Ling YU ; Ying-Xin ZHAO ; Xian-Ping WU ; Lian-Cheng ZHAO ; Ying LI ; Dong-Sheng HU ; Jian-Feng HUANG ; Xiang-Feng LU ; Dong-Feng GU
Journal of Geriatric Cardiology 2023;20(11):779-787
BACKGROUND:
The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).
METHODS:
A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.
RESULTS:
A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).
CONCLUSIONS
Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
7.Association between metabolically healthy obesity and incident risk of stroke in adult aged over 40 from rural Henan province.
Hong Chao LIAN ; Xiao Kang XIE ; Ruo Xi ZHOU ; Rui LIN ; Shang Xin SHI ; Xue Ru FU ; Dong Sheng HU ; Yang ZHAO
Chinese Journal of Preventive Medicine 2022;56(3):295-301
Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q1, Q3) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.
Adolescent
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Adult
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Body Mass Index
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Humans
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Male
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Middle Aged
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Obesity/complications*
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Obesity, Metabolically Benign/epidemiology*
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Risk Factors
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Stroke/epidemiology*
8. Ancient DNA Damage Analysis of Late Quaternary Mammalian Fossil Samples in Northeast China
Shi-Wen SONG ; Gui-Lian SHENG ; Miao-Xuan DENG ; Xin-Dong HOU ; Gui-Lian SHENG ; Xu-Long LAI ; Jun-Xia YUAN ; Guo-Jiang SUN ; Lin-Ying WANG ; Bo XIAO ; Jia-Ming HU ; Xu-Long LAI
Chinese Journal of Biochemistry and Molecular Biology 2022;38(4):465-473
The advancement of the next generation sequencing (NGS) technology has promoted the development of ancient DNA research. Ancient DNA has made outstanding contributions in various fields such as human origin, animal evolution, etc. How to effectively extract and mine the genetic information from fossil and sub-fossil remains excavated from specific locations is a prerequisite for optimizing their important roles in many fields. In this study, we correlated the two main indicators of DNA damage (terminal base replacement rate, average fragment length) with the possible factors such as the burial time, geological epochs, tissue types, and sequencing library construction methods. The results show that the end base replacement rate of ancient DNA from Northeastern China is positively correlated with the water content of the environment and the ages of the samples. Among samples of different geological epochs, ancient DNA end base replacement rates have significant differences. On the contrary, different tissue types of the remains have no significant effects on the end base replacement rate of ancient DNA. The average fragment size of the molecules has no obvious correlation with the factors mentioned above. The results provide both solid data for investigating the characteristics of ancient DNA from specimens collected in Northeastern China, and valuable information for collecting appropriate samples from different geographical locations and the downstream storage before wet lab procedures after excavation.
9.Anti-cancer Mechanism of "Clematis Radix et Rhizoma-Trichosanthis Radix" Based on Network Pharmacology
Hong-mei SI ; Xu-dong YU ; Jian-wei SHANG ; Lian-ying SONG ; Fan-chao MENG ; Yao-sheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(5):182-190
Objective:To explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology. Method:Chinese Medicine System Pharmacology Analysis Platform(TCMSP) was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability(OB) and drug likeness(DL),cancer disease targets were screened out using GeneCards and OMIM databases,R language software was used to screen out common targets of clematis,trichosanthin and cancer diseases, Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target", STRING database was used to draw protein protein interaction(PPI)of common target proteins, R language software was used to perform enrichment analysis of gene ontology(GO) functions and Kyoto encyclopedia of genes and genomes(KEGG) channels on effective targets. Result:A total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched,and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes,which mainly involved endopeptidase,cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes,and played a role in the treatment of cancers by regulating apoptosis,measles,hepatitis B,kaposi sarcoma-associated herpesvirus infection,p53,interleukin-17(IL-17),tumor necrosis factor(TNF) and many other pathways. Conclusion:The mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.
10.Radioanatomic study on the role of Hadad-Bassagasteguy flap in skull base reconstruction in endoscopic endonasal approach.
Dong Sheng GU ; Pei Zhong LI ; Lian Shu DING ; Xiao Yang SUN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(1):69-74
Objective: To evaluate the value of Hadad-Bassagasteguy flap (HBF) in endoscopic endonasal approaches (EEA) skull base reconstruction by radioanatomic measurements on CT of the skull base of Chinese adults. The following data in terms of anterior skull base defect and reconstruction, sphenoid platform area and middle skull base defect and reconstruction including sphenoid platform and sella area, clivus area defect and reconstruction, and HBF were collected and assessed. Methods: CT image data of 42 Chinese adults were selected to obtain radioanatomic measurement data related to HBF, anterior skull base defect and reconstruction, middle skull base defect and reconstruction, and defect and reconstruction of clivus area. SPSS 26.0 software was used to analyze the data. Results: The radioanatomic measurement data about HBF and skull base of 42 Chinese adults were obtained. The width of the leading edge of HBF [(37.49±2.86) mm] was 6 mm more than the anterior skull base width at the level of the anterior ethmoidal artery [(30.87±8.61) mm], and the width of the trailing edge of HBF [(42.61±3.95) mm] was also 6 mm more than the anterior skull base width at the level of the sphenoethmoidal junction [(26.79±2.79) mm]. The total length of HBF including the pedicle [(79.68±4.96) mm] was 6 mm more than the length of the anterior skull base reconstruction [(54.06±8.67) mm], and the length of HBF without pedicle [(46.27±3.14)] mm was 6 mm more than the length of anterior skull base defect [(30.87±8.61) mm]. The trailing edge width was 6 mm more than the planum sphenoidal width at the level of the optic strut [(30.87±8.61) mm]. The total length of HBF including the pedicle was 6 mm more than the length of the planum sphenoidal, and the sella reconstruction [(64.44±10.25) mm], also was 6 mm more than the length of the planum sphenoidal reconstruction [(73.61±8.28) mm]. The length of HBF without pedicle was 6 mm more than the length of the planum sphenoidal, and the sella defect [(27.88±3.74) mm], also was 6 mm more than the length of the planum sphenoidal defect [(15.50±3.38) mm]. The width of the leading edge of HBF and the width of the trailing edge were both 6 mm more than the width of clivus reconstruction at the level of the foramen lacerum [(21.68±2.30) mm]. The total length of HBF including pedicles was 6 mm more than the clivus reconstruction length [(67.09±5.44) mm], while the length of HBF without pedicles was also 6 mm more than the clivus defect length [(37.19±3.80) mm]. Conclusions: In this study, the radiosanatomic measurements ensured that HBF could provide sufficient tissue flap for the reconstruction of the anterior skull base and sphenoid plateau and extend the reconstruction area to sella and clivus. Preoperative radiosanatomic measurement can be used to predict the size of HBF required for skull base reconstruction, which provides important guidance for flap harvest.
Adult
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Endoscopy
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Humans
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Nose/surgery*
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Reconstructive Surgical Procedures
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Skull Base/surgery*
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Skull Base Neoplasms/surgery*
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Sphenoid Bone
;
Surgical Flaps

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