1.Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction
Xinhao TANG ; Bowen CHU ; Yuanyuan QIN ; Yeling LIU ; Xinyan SHU ; Mianhua WU ; Gang YIN ; Jianguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):176-185
In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.
2.Exosome and Its Function in Central Nervous System
Zi-Yuan WANG ; Yu-Xuan BAI ; Gang CAO ; Jin-Xia DAI
Progress in Biochemistry and Biophysics 2024;51(2):378-393
Exosome is a kind of extracellular vesicles secreted by cells to the outside. Biogenesis mainly involves two invaginations of the cytoplasmic membrane, the formation of multivesicular bodies, and the release of exosomes. Exosomes have abundant and diverse inclusions—including landmark membrane proteins, soluble proteins, various RNA molecules and DNA fragments, etc. Cells can achieve intercellular signal communication by secreting and receiving exosomes. Through interaction of ligand molecules on the exosome membrane with receptors on the surface of other cytoplasmic membranes, exosomes can activate cell signal transduction or fuse with the cell membrane to release its contents into the cytoplasm to exert regulatory functions. In the central nervous system, exosomes secreted by neurons and various glial cells can mediate wired synaptic signal transmission, but mainly play a role similar to neuromodulator by way of volume transmission. In this paper, the biogenesis of exosomes and important functional components are described in detail, and the characteristics of neural exosomes in the biogenesis, content sorting and controlled release are compared with those of synaptic vesicles. We further review the research progress on the physiological functions of neural exosomes on the central nervous system and their roles in the occurrence and development of neurodegenerative diseases and major depressive disorder. We also prospect the application of exosomes in the early diagnosis and targeted therapy of nervous system diseases.
3.Bioactive Determination of Anfibatide
Xiangrong DAI ; Jie LIANG ; Tao JIANG ; Gang LI ; Leiming XU
Herald of Medicine 2024;43(3):431-435
Objective To screen and establish a method for determining the biological activity of anfibatide.Meth-ods Three methods of light transmittance aggregometry(LTA),whole blood electrical impedance aggregometry,and continuous platelet count method were compared and studied.And the constant platelet counting method was chosen and verified to detect the biological activity of anfibatide.Results The RSD values of anfibatide biological activity detected by LTA,whole blood electri-cal impedance aggregometry,and continuous platelet count method were 10.3%,14.0%,and 3.6%,respectively.RSD of repeat-ability of 6 parallel test articles was 11.0%.The RSD of intermediate precision of 12 test articles for different personnel was 9.8%,and the inhibition rate of anfibatide was linear in the range of 0.3-0.5 U.The correlation coefficient was more than 0.990.The ac-tivity of three batches of anfibatide was determined,and the inhibition rate was 49.9%~53.6%.Conclusion The continuous platelet count method for determining anfibatide activity was established and verified,which can be used for quality control for an-fibatide activity since the precision and detection limit of the method met the requirement for activity assay of biological products.
4.Study on the Correlation between the Expression of VPS33A Level in Peripheral Blood of Elderly Patients with Pulmonary Tuberculosis and Clinical Prognosis
Jing HU ; Honghui GAN ; Xueli LIU ; Gang DAI
Journal of Modern Laboratory Medicine 2024;39(5):162-167
Objective To detect the expression of vacuolar protein sorting-associated protein 33A(VPS33A)in the peripheral blood of elderly patients with pulmonary tuberculosis,and explore its correlation with clinical prognosis.Methods A total of 95 elderly pulmonary tuberculosis patients admitted to Macheng City People's Hospital from February 2019 to February 2021 were collected as the research group,and 90 healthy subjects in the same period were selected as control group.The expression of VPS33A and Toll like receptor 2(TLR2)in peripheral blood was detected by real-time fluorescent quantitative PCR(qRT-PCR),and the level of interleukin-6(IL-6)in peripheral blood was detected by enzyme-linked immunosorbent assay.Patients with pulmonary tuberculosis were given standardized anti-tuberculosis regimen therapy(2HRZE/4HR)treatment,and they were followed up for 12 months.According to their prognosis,they were divided into good prognosis group(n=58)and bad prognosis group(n=37).The predictive value of VPS33A for poor prognosis was analyzed by ROC curve.The correlation between serum VPS33A,IL-6 and TLR2 in poor prognosis group was analyzed by Pearson method.Logistic regression analysis was used to explore the factors influencing poor prognosis in elderly patients with pulmonary tuberculosis.Results Compared with the control group,VPS33A level(0.87±0.22 vs 1.02±0.23)in peripheral blood was lower,but IL-6(22.13±5.36 pg/ml vs 18.53±4.68 pg/ml)and TLR2 levels(1.26±0.25 vs 0.99±0.21)were higher in the pre-treatment study group,with significant differences(t=6.170,6.682,11.241,all P<0.05).Compared with the pre-treatment study group,VPS33A level(0.95±0.25)in peripheral blood was higher,but IL-6(19.66±5.44 pg/ml)and TLR2 levels(1.11±0.2)were lower in the post-treatment study group,with significant differences(t=3.336,4.648,6.331,all P<0.05).The level of VPS33A(0.71±0.16)in peripheral blood of poor prognosis group was lower than that of good prognosis group(0.97±0.22),while the levels of IL-6(26.41±7.16 pg/ml)and TLR2(1.35±0.26)were higher than those of good prognosis group(19.40±4.21pg/ml,1.20±0.24),with significant differences(t=5.555,6.012,2.875,all P<0.05).Pearson correlation analysis showed that VPS33A in the pre-treatment study group was negatively correlated with IL-6 and TLR2 levels(r=-0.649,-0.634,all P<0.05).ROC curve analysis results showed that the AUCs of VPS33A,IL-6 and TLR2 for predicting the prognosis of tuberculosis in the elderly were 0.805,0.842 and 0.882,respectively.The combined AUC of the three was 0.971,which was higher than that predicted by the three alone(Z=4.010,3.136,2.285,P=0.001,0.002,0.022).Logistic regression analysis showed that VPS33A,IL-6 and TLR2 were the influencing factors for poor prognosis of elderly pulmonary tuberculosis patients(all P<0.05).Conclusion The expression of VPS33A is down-regulated in the peripheral blood of elderly patients with pulmonary tuberculosis,which may be a good predictive value for the prognosis of elderly patients with pulmonary tuberculosis,and be a factor affecting bad prognosis.
5.Molecular characteristics and drug resistance analysis of H3N2 influenza virus in Jiangsu Province from 2022 to 2023
Fei DENG ; Shen-Jiao WANG ; Hui-Yan YU ; Xian QI ; Li-Guo ZHU ; Qi-Gang DAI
Chinese Journal of Zoonoses 2024;40(9):848-854
On the basis of the laboratory detection results of influenza viruses in Jiangsu Province from 2022 to 2023,this study was aimed at conducting a analysis of the genetic characteristics and resistance of the H3N2 influenza virus,and evalua-ting the effectiveness of vaccines and drugs.The full genome of 29 H3N2 isolates submitted by provincewide influenza surveil-lance network laboratories was amplified and sequenced.Phylogenetic trees of the HA and NA genes were constructed.The mutation characteristics of antigenic sites,glycosylation sites,and resistance sites were analyzed,and the influenza virus neura-minidase was detected with a fluorescence luminescence method.The homology of the 29 H3N2 isolates in Jiangsu Province was relatively high.The isolates belonged to the same evolutionary branch as domestic reference strains and the 2021-2022 vaccine strains,but were in different evolutionary branches from foreign reference strains and the 2022-2023 vaccine strains.Compared with the 2021-2022 vaccine strain A/Cambodia/e0826360/2020,the H3N2 influenza viruses isolated in Jiangsu Province during 2022-2023 had four amino acid substitutions in the HA protein and two amino acid substitutions in the NA protein.No changes in glycosylation sites,receptor-binding sites,and conserved amino acid residue regions were observed.IC50 analysis indicated that the 29 H3N2 isolates were not resistant to the antiviral drugs oseltamivir and zanamivir.The pre-dominant influenza viruses detected in Jiangsu Province during 2022-2023 were type A H3N2 influenza viruses.Monitoring of variations in HA and NA gene sites and influenza virus resistance aids in rapid understanding gene mutations,and can inform the selection of effective vaccine strains,and contribute to the prevention and control of influenza virus outbreaks.
6.Clinical application value of single pass scanning using multi-slice spiral CT for polytrauma patients
Gang WANG ; Ying ZHANG ; Teng TANG ; Hongyang DAI ; Nan WANG ; Mimi QIU ; Hongwei XU ; Fangfang XIA ; Xinglin XIANG ; Jian LI
Chinese Journal of Radiological Medicine and Protection 2024;44(8):693-698
Objective:To explore the clinical application value of single pass scanning using muti-slice spiral CT for polytrauma patients.Methods:Totally 60 polytrauma patients treated from January to November in 2023 were randomly enrolled in this study. They were categorized into an experimental group and a control group using a random number table, with 30 patients in each group. The patients in the experimental group underwent single pass scaning for the head, neck, chest, and abdomen, whereas those in the control group receiving separate scanning for various parts. Then, the noise, signal-to-noise ratio (SNR), and contrast-to-noise (CNR) of the CT images of both groups were recorded. Furthermore, the objective and subjective evaluation, volume CT dose index (CTDI vol), effective dose ( E), scanning time, and scan ranges of the images were compared between both groups. Results:Compared to the control group, the test group exhibited lower SNR of the head ( t = -5.47, P < 0.05) and higher SNR and CNR of the chest scans ( t = -5.95, -6.15, P < 0.05). Furthermore, the test group demonstrated decreased ED, CTDIvol, scanning time, and scan range, which dropped from 18.53 mSv to 13.81 mSv ( t = 3.29, P < 0.001), from 15.77 mGy to 10.59 mGy ( t = 4.48, P< 0.001), from 31.68 s to 10.97 s ( t = 6.95, P < 0.001), and from 64.92 cm to 45.21 cm ( t = 9.05, P < 0.001), respectively compared to the control group. Conclusions:Single pass CT scanning can reduce E, scanning time, and scan range in the treatment of polytrauma patients while ensuring the high quality of CT images, thus warranting wide clinical applications.
7.Association of community built environment with obesity among elderly residents
Yuhua ZHAO ; Tao FANG ; Miao DU ; Gang CHEN ; Mengqi ZHANG ; Xuchao DAI ; Hong HUANG ; Kun MEI
Journal of Environmental and Occupational Medicine 2023;40(2):176-183
Background In the context of improving urban environment for healthy aging, it is necessary to rationally plan and provide community living space and public service facilities suitable for the elderly, and constantly optimize the built environment towards an age-friendly city. Objective To understand the relationship between community built environment and obesity in the elderly in Longgang City, and to provide a reference basis for improving the health of the elderly. Methods Elderly adults aged 60-90 years (n=6527) who completed a physical examination during the period from October 2020 to January 2021 in Longgang City were surveyed, and data on height and weight, waist circumference (WC), and other sociological demographic characteristics were obtained. Overweight was determined by 24 kg·m−2 ≤ body mass index (BMI) < 28 kg·m−2 and obesity by BMI ≥ 28 kg·m−2. Men with WC ≥ 85 cm and women with WC ≥ 80 cm were considered central obesity. Based on the participants' residential addresses, geocoding was performed using a geographic information system, and built environment indicators such as restaurants, convenience stores, and basic medical facilities were obtained using Gaode Map. A binary logistic regression model with adjusted individual-level covariates was used to evaluate the relationship between obesity and built environment indicators among elderly adults by gender and age. Results Among the 6527 community elderly, 46.93% were male and 53.07% were female, with a mean age of (73.69±0.07) years, a mean BMI of (24.32±2.84) kg·m−2, and 51.92% of the elderly were overweight or obese. The regression results showed that for elderly men, the more convenience stores and the higher mixed land use in residential areas, the higher risk of central obesity; however, the increases in street connectivity and accessibility to parks and recreational areas were associated a decreased risk of central obesity. The prevalence of overweight/obesity was higher among elderly women with more convenience stores in residential areas, while increased street connectivity was associated with a lower prevalence of central obesity among elderly women. Accessibility to primary health care facilities was negatively associated with the risk of central obesity among the 60- to 70-year-olds. For elderly residents aged 71−80 years, higher mixed land use and better accessibility to transit stations were associated with a higher prevalence of overweight/obesity, while street connectivity was negatively associated with the central obesity. Proximity to parks and recreational areas was associated with a reduced risk of overweight/obesity among the 81- to 90-year-olds. Conclusion Among the variables of a 500-m neighborhood built environment, the number of convenience stores, mixed land use, street connectivity, accessibility to primary health care facilities, accessibility to public transit stations, and accessibility to parks and recreational areas are correlated with obesity among elderly residents, and the degree of influence varies by gender and age.
8.Relationship Between p53, EGFR and Radiotherapy Resistance of Head and Neck Squamous Cell Carcinoma
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(4):596-600
Head and neck cancers are the seventh most common type of cancer in the world, among which more than 90% are squamous cell carcinomas(HNSCC). Radiotherapy is one of the important treatments for HNSCC, and the sensitivity of tumor cells to the therapy is a key factor influencing the efficacy of treatment. p53 is one of the most common mutated genes in HNSCC, and epidermal growth factor receptor(EGFR) is overexpressed in many HNSCC. Both of these genes could enhance cellular DNA repair, which may be related to the radiotherapy resistance of HNSCC. This review focuses on the mechanisms by which tumor cells escape radiation-mediated apoptosis through p53 and EGFR-mediated DNA repair.
9.Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis.
Bing-Ying WAN ; Dong-Wei CAO ; Yi-Gang WAN ; Dai CHEN ; Wei WU ; Qi-Jun FANG ; Si-Yi LIU ; Yue TU ; Yu WANG ; Zi-Yue WAN
China Journal of Chinese Materia Medica 2023;48(10):2657-2666
Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
Rats
;
Animals
;
Abelmoschus
;
Reactive Oxygen Species/metabolism*
;
Flavones/pharmacology*
;
Endoplasmic Reticulum Stress
;
Diabetic Nephropathies/drug therapy*
;
Apoptosis
;
Diabetes Mellitus
10.Clinical effect of Kirschner wire intramedullary fixation in the treatment of pediatric both-bone forearm fractures at high altitude area.
Dunzhu PUBU ; Pingcuo ZHAXI ; Ouzhu DANZENG ; Sang GE ; Jie LUO ; Duo MEI ; Jun YUAN ; Xin-Jun ZHANG ; Xiao-Gang HUANG ; Lei DAI ; Chao LIU
China Journal of Orthopaedics and Traumatology 2023;36(7):619-622
OBJECTIVE:
To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area.
METHODS:
From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard.
RESULTS:
The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up.
CONCLUSION
Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.
Male
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Female
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Humans
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Child
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Child, Preschool
;
Adolescent
;
Bone Wires
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Forearm
;
Altitude
;
Treatment Outcome
;
Fractures, Bone/surgery*
;
Fracture Fixation, Internal/methods*
;
Radius Fractures/surgery*
;
Fracture Fixation, Intramedullary/methods*

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