1.Epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome in Zhejiang Province
LÜ ; Jing ; XU Xinying ; QIAO Yingyi ; SHI Xinglong ; YUE Fang ; LIU Ying ; CHENG Chuanlong ; ZHANG Yuqi ; SUN Jimin ; LI Xiujun
Journal of Preventive Medicine 2026;38(1):10-14
Objective:
To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control.
Methods:
Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence.
Results:
A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk.
Conclusions
SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.
2.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
3.Hemophilia treatment and transfusion medicine
Yunhai FANG ; Yan CHENG ; Xinsheng ZHANG
Chinese Journal of Blood Transfusion 2025;38(2):168-171
The improvement of hemophilia treatment is attributed to the development of transfusion medicine, and the discovery of cryoprecipitate has opened up a new era of hemophilia treatment, laying the foundation for the development of modern hemophilia therapies. But with the further improvement of hemophilia treatment and the emergence of new treatment methods, transfusion medicine no longer plays a dominant role in hemophilia treatment. The new technologies and methods for hemophilia treatment can provide reference for the development of transfusion medicine, thereby better serving clinical practice and patients.
4.Active Components of Salviae Miltiorrhizae Radix et Rhizoma and Its Compound in Treatment of Nervous System Diseases: A Review
Weining SONG ; Shuxiang ZHANG ; Fang LU ; Zhize WANG ; Ruyang CHENG ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):303-313
Nervous system diseases, also known as neuropathies, encompass a wide range of conditions, primarily including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and other neurodegenerative disorders, as well as depression, subarachnoid hemorrhage, cerebral ischemia-reperfusion injury, vascular dementia, and other neurological diseases. These diseases pose serious threats to the health and lives of patients, bringing heavy burdens to society and families. The pathogenesis of nervous system diseases is highly complex, involving mechanisms such as neuroinflammation, oxidative stress, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, brain-derived neurotrophic factor deficiency, reduced cholinergic activity, axonal injury, and demyelination. In recent years, the incidence and mortality of nervous system diseases have been rising annually. Currently, western medicine primarily focuses on symptomatic treatment, often accompanied by many adverse reactions, including lethargy, excessive sedation, dizziness, headaches, tachycardia, liver function damage, metabolic disorders, and incomplete recovery after surgery. As a traditional Chinese medicine, Salviae Miltiorrhizae Radix et Rhizoma has effects such as promoting blood circulation, removing blood stasis, cooling the blood, clearing the heart, nourishing the blood, and calming the nerves. It can play a role in the treatment and protection against nervous system diseases through multiple targets, pathways, and mechanisms. Studies have found that the water-soluble phenolic acids and fat-soluble diterpenoid quinones in Salviae Miltiorrhizae Radix et Rhizoma are the main active ingredients for the treatment of nervous system diseases. This paper summarized the effects of the active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma on nervous system diseases over the past ten years, aiming to provide a theoretical basis and research ideas for the development and application of active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma in nervous system diseases.
5.Urban-rural difference in adverse outcomes of pulmonary tuberculosis in patients with pulmonary tuberculosis-diabetes mellitus comorbidity
FANG Zijian ; LI Qingchun ; XIE Li ; SONG Xu ; DAI Ruoqi ; WU Yifei ; JIA Qingjun ; CHENG Qinglin
Journal of Preventive Medicine 2025;37(1):7-11
Objective:
To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM.
Methods:
Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model.
Results:
A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM.
Conclusions
There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.
6.Naoqingtong Decoction Ameliorates Kidney Damage in Spontaneously Hypertensive Rats via NLRP3 Inflammasomes
Jiaxin JU ; Caocao CHENG ; Teng GE ; Yalong KANG ; Fang GUAN ; Haifang WANG ; Juanjuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):125-131
ObjectiveTo investigate the effect of Naoqingtong decoction (NQT) on the kidney damage and the inflammatory factors NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in spontaneously hypertensive rats (SHRs). MethodsTwenty-four SHRs were randomized into a model group, a low-dose (12.9 g·kg-1·d-1) NQT (NQT-L) group, a high-dose (25.8 g·kg-1·d-1) NQT group (NQT-H), and a captopril (CTP, 20 mg·kg-1·d-1) group, with 6 rats in each group. In addition, 6 homozygous male Wistar-Kyoto rats were used as the control group. The control and model groups were administrated with the same amount of normal saline by gavage for 8 weeks. General behaviors of rats were observed during the intervention period, and the blood pressure was measured periodically. At the end of intervention, the body mass was weighed, and both kidneys were collected and weighed for the calculation of the renal index. Hematoxylin-eosin staining was performed to observe the pathological changes in the kidney tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the expression levels of NLRP3, ASC, Caspase-1, IL-6, and TNF-α in the kidney tissue. ResultsDuring the experiment period, the control group had normal mental status, food intake, and activity, while the model group showed thinning of hair, loss of luster, reduced activity, loss of appetite, fecal adhesion, and irritability, and some of the skin had scratches or blood scabs. The above symptoms were alleviated to different degrees after 8 weeks of NQT administration. An intelligent non-invasive sphygmomanometer was used to measure the tail artery pressure of rats, which showed that the systolic and diastolic blood pressure of rats in the model group was higher than that in the control group (P<0.01). Compared with the model group, drug interventions lowered the systolic and diastolic blood pressure (P<0.05, P<0.01). Compared with the control group, the model group showed severe pathological damage in the kidney tissue, which was alleviated in each drug intervention group. Compared with the control group, the model group showed up-regulated expression levels of NLRP3, ASC, Caspase-1, IL-6, and TNF-α in the kidney tissue (P<0.05, P<0.01). Compared with the model group, the drug intervention groups showed down-regulated expression levels of NLRP3, ASC, Caspase-1, IL-6, and TNF-α in the kidney tissue (P<0.05, P<0.01). ConclusionNQT can lower the blood pressure in SHRs by inhibiting the activation of NLRP3 inflammasomes, suppressing renal inflammation, and ameliorating hypertensive kidney damage.
7.Controllability Analysis of Structural Brain Networks in Young Smokers
Jing-Jing DING ; Fang DONG ; Hong-De WANG ; Kai YUAN ; Yong-Xin CHENG ; Juan WANG ; Yu-Xin MA ; Ting XUE ; Da-Hua YU
Progress in Biochemistry and Biophysics 2025;52(1):182-193
ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.
8.Effect of Tuina at "Weizhong (BL 40)" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury
Tianwei ZHANG ; Xiangqian LYU ; Yani XING ; Liuchen ZHU ; Qingguang ZHU ; Lingjun KONG ; Yanbin CHENG ; Zhen YAN ; Wuquan SUN ; Min FANG ; Zhiwei WU
Journal of Traditional Chinese Medicine 2025;66(7):734-740
ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong (BL 40)" on neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups (8 rats in each group), sham-operated group, model group, Tuina group, and blockade group. The CCI model was established in the model group, Tuina group, and the blockade group by ligating the sciatic nerve with catgut, while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14, rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong (BL 40)" using a dynamic pressure distribution measurement system (5 N pressure, 2 Hz frequency, 10 min per session, once daily). The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline (10 mg/kg) once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were measured before surgery and on day 3, 7, 10, and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair, measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 (Iba-1), CD206, CD68, interleukin-10 (IL-10), and β-endorphin (β-EP) precursor pro-opiomelanocortin (POMC) in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group, the model group showed significantly reduced MWT and PWL on day 3, 7, 10, and 14 (P<0.01). Compared with the model group, the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 (P<0.05). Compared with the Tuina group, the blockade group exhibited higher MWT on day 7, 10, and 14, and higher PWL on day 10 (P<0.05). Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group, while the model group exhibited myelin collapse, distortion, and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse, whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group, the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn (P<0.05 or P<0.01). Compared with the model group, the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally, the Tuina group showed elevated levels of CD206, IL-10, and POMC, whereas the blockade group had decreased CD206 levels (P<0.05). ConclusionTuina at "Weizhong (BL 40)" alleviates neuropathic pain in CCI rats, potentially by regulating microglial activation in the spinal cord, inhibiting M1 polarization while promoting M2 polarization, and activating the IL-10/β-EP pathway to exert analgesic effects.
9.Herbal Textual Research on Picrorhizae Rhizoma in Famous Classical Formulas
Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Xiaoqin ZHAO ; Kaizhi WU ; Cheng FENG ; Wenyue LI ; Wei ZHANG ; Wentao FANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):228-239
This article systematically analyzes the historical evolution of the name, origin, quality evaluation, harvesting, processing and other aspects of Picrorhizae Rhizoma by referring to the medical books, prescription books, and other documents of the past dynasties, combined with relevant modern research materials, in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history, Huhuanglian has been used as its official name, and there are also aliases such as Gehu Luze, Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times, Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions, and also produced in China, mainly in Xizang. In ancient times, it was harvested and dried in early August of the lunar calendar, while in modern times, it is mostly harvested from July to September, with the best quality being those with thick and crispy rhizomes without impurities, and bitter taste. Throughout history, Picrorhizae Rhizoma was collected, washed, sliced, and dried before being used as a raw material for medicine, it has a bitter and cold taste, mainly used to treat bone steaming, hot flashes, infantile chancre fever, and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results, it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia, or the rhizomes of P. kurrooa, can be used in famous classical formulas containing this medicinal herb, which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements, the dried raw products are used as medicine.
10.Therapeutic Study on The Inhibition of Neuroinflammation in Ischemic Stroke by Induced Regulatory T Cells
Tian-Fang KANG ; Ai-Qing MA ; Li-Qi CHEN ; Han GONG ; Jia-Cheng OUYANG ; Fan PAN ; Hong PAN ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2025;52(4):946-956
ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4+ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.


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