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.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.
3.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.
4.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.
5.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.
6.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.
7.Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland.
Gang LU ; Yun LING ; Minghao JIANG ; Yun TAN ; Dong WEI ; Lu JIANG ; Shuting YU ; Fangying JIANG ; Shuai WANG ; Yao DAI ; Jinzeng WANG ; Geng WU ; Xinxin ZHANG ; Guoyu MENG ; Shengyue WANG ; Feng LIU ; Xiaohong FAN ; Saijuan CHEN
Frontiers of Medicine 2023;17(4):758-767
With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.
8. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
9.Treatment of spinal burst fractures with pedicle screw fixation at high altitude area.
Jun YUAN ; Xin-Jun ZHANG ; Xiao-Gang HUANG ; Lei DAI ; Chao LIU
China Journal of Orthopaedics and Traumatology 2023;36(5):450-453
OBJECTIVE:
According to the characteristics of spinal burst fractures in high-altitude areas and the local medical conditions, to explore the clinical efficacy of short-segment fixation with pedicle screws combined with screw placement in injured vertebrae in the treatment of thoracolumbar burst fractures.
METHODS:
From August 2018 to December 2021, 12 patients with single-vertebral thoracolumbar burst fractures without neurological symptoms were treated with injured vertebral screw placement technique, including 7 males and 5 females;aged 29 to 54 years old, with an average of(42.50±7.95) years old;6 cases of traffic accident injury, 4 cases of high fall injury, 2 cases of heavy object injury;2 cases of T11, 4 cases of T12, 3 cases of L1, 2 cases of L2, and 1 case of L3. In the operation, screws were first placed in the upper and lower vertebrae of the fracture, pedicle screws were placed in the injured vertebra, and connecting rods were installed, and the fractured vertebral body was reset by positioning and distraction. Visual analogue scale (VAS) and Japanese Orthopedic Association (JOA) scoring were used to evaluate the changes in pain and quality of life of patients, and the kyphotic correction rate and correction loss rate of the injured segment were measured by X-ray.
RESULTS:
All operations were successful without significant intraoperative complications. All 12 patients were followed up, the duration ranged from 9 to 27 months, with an mean of (17.75±5.79) months. VAS at 3 days after operation was significantly higher than that at admission (t=6.701, P=0.000). There was significant difference in JOA score between 9 months after operation and at admission (t=5.085, P=0.000). Three days after operation, Cobb angle was (4.42±1.16)°, and the correction rate was (82±5)% compared with (25.67±5.71)° at admission. Cobb angle was (5.08±1.24) °at 9 months after operation, with a corrected loss rate of (16±13)%. No loosening or breakage of internal fixation was found.
CONCLUSION
Under the high-altitude hypobaric and hypoxic environment, the effect of the operation should be ensured while reducing the trauma. The application of the technique of placing screws on the injured vertebra can effectively restore and maintain the height of the injured vertebra, with less bleeding and shorter fixed segments, which is an effective method.
Male
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Female
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Humans
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Adult
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Middle Aged
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Pedicle Screws
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Altitude
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Quality of Life
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Lumbar Vertebrae/injuries*
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Thoracic Vertebrae/injuries*
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Spinal Fractures/surgery*
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Fracture Fixation, Internal/methods*
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Fractures, Compression
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Treatment Outcome
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Fractures, Comminuted
10.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.

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