BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

Large language models (LLMs) offer a modern approach to help inherit traditional Chinese medicine (TCM). This article discussed the progress of LLM applications in TCM and proposed future development directions by reviewing the existing research. We have found that LLMs and related technologies have excellent applications and performance in the management of TCM knowledge and data. They are often applied in information extraction, knowledge graph construction, and data standardization processing. However, data quality and security issues need to be given more attention. In clinical diagnosis and treatment, LLMs can imitate the thinking of TCM by disassembling and reconstructing its diagnostic process and can achieve functions such as prescription recommendation and question and answer (Q&A). However, this approach involves LLMs making inferences and predictions based on existing corpora and thus may not flexibly handle complex environments and tasks. Moreover, the current evaluation criteria for TCM LLMs can be summarized into 3 categories: general evaluation metrics, technical framework evaluation, and evaluation criteria for the characteristics of TCM (such as consistency rates of prescriptions and diagnostic suggestions). However, the lack of a unified and standardized evaluation system hinders the clinical application of TCM LLMs. The future progress of TCM LLMs should focus on the 3 aforementioned critical aspects to achieve technological breakthroughs. In addition, we are promoting the research on vertical TCM LLMs and application terminals. We believe this will bring new ideas to the research on TCM LLMs.

Objective To comprehensively describe the epidemiology,clinical outcomes,and treatment modes of post-transplant cytomegalovirus(CMV)infection in solid organ transplant(SOT)recipients in China.Methods Relevant studies were retrieved from domestic and foreign databases from 2013 to 2023.Indicators such as CMV in-fection incidence were included.Random-effects model analysis was conducted using R software.Results A total of 29 studies were included in the analysis,with an overall CMV infection incidence of 22.51％.CMV infection inci-dence after liver and kidney transplant were 23.62％and 13.01％,respectively.CMV infection rates after thoracic organ transplant were 52.27％and 61.24％.When serological status of donors and recipients was D+/R-,the in-cidence of CMV infection in transplant recipients was higher(83.89％).The incidence of CMV disease in CMV in-fected patients was 46.22％.Ganciclovir and valganciclovir were commonly used agents,but both had high risks of bone marrow suppression.Conclusion In China,CMV infection is a common viral infection after SOT surgery.Agents with better treatment efficacy and tolerance is necessary in clinics.

Objective:To investigate the change trend in the burden of 5 common malignant tumors of digestive system (esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer) in the Chinese population from 1990 to 2021.Methods:The descriptive epidemio-logic method was conducted. The number of new cases, crude incidence rate, age-standardized incidence rate, the number of deaths, crude mortality rate and age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021 of the Global Burden of Disease were collected. The age-standardized rate was calculated based on the standardized demographics of the whole world in the Global Burden of Disease for the year 2021. Observation indicators: (1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (2) the mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (3) the change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (4) the change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The Joinpoint regression model was constructed for trend analysis, specifically to calculate the annual percentage change, average annual percentage change (AAPC), and their 95% confidence interval ( CI) for age-standardized incidence and mortality rates for each cancer type at different time periods. Results:(1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of new cases of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 207 495, 407 471, 158 389, 37 818 and 96 434 in 1990 to 320 805, 611 799, 658 321, 118 665 and 196 637 in 2021. The crude incidence rates of the above cancer types changed from 17.64/100 000, 34.64/100 000, 13.46/100 000, 3.21/100 000, 8.20/100 000 in 1990 to 22.55/100 000, 43.00/100 000, 46.27/100 000, 8.34/100 000, 13.82/100 000 in 2021. The new cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increasing trend, with absolute changes of 54.61%, 50.15%, 315.64%, 213.78%, and 103.91%, respectively. (2) The mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of deaths of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 210 821, 374 066, 119 303, 38 883 and 94 937 in 1990 to 296 443, 445 013, 275 129, 119 602 and 172 068 in 2021. The crude death rates of the above cancer types changed from 17.92/100 000, 31.80/100 000, 10.14/100 000, 3.31/100 000, 8.07/100 000 in 1990 to 20.84/100 000, 31.28/100 000, 19.34/100 000, 8.41/100 000, 12.09/100 000 in 2021. Death cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increa-sing trend, with absolute changes of 40.61%, 18.97%, 130.61%,207.59%, and 81.24%, respectively. (3) The change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trends of age-standardized incidence rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 5 periods, respectively, and the AAPCs of age-standardized incidence rates of the above cancer types were -1.60% (95% CI as -1.78% to -1.42%), -1.60% (95% CI as -1.78% to -1.43%), 1.66% (95% CI as 1.39% to 1.94%), 0.72% (95% CI as 0.36% to 1.08%), and -0.31% (95% CI as -0.39% to -0.23%). (4) The change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trend of age-standardized mortality rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 4 periods, respectively, and the AAPC of age-standardized mortality rates for each of the above mentioned cancer types were -1.96% (95% CI as -2.03% to -1.90%), -2.44% (95% CI as -2.50% to -2.38%), -0.49% (95% CI as -0.58% to -0.41%), 0.56% (95% CI as 0.48% to 0.63%), and -0.68% (95% CI as -0.89% to -0.52%). Conclusions:From 1990 to 2021, the disease burden of esophageal cancer, gastric cancer and liver cancer in the Chinese population show a downward trend. The standardized incidence of colorectal cancer shows an upward trend, and the standardized mortality rate shows a downward trend. The disease burden of pancreatic cancer shows an upward trend.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

[Purpose]To analyze the trends of disease burden for lung cancer worldwide and in China from 1990 to 2021.[Methods]Data of the disease burden of lung cancer and population demographics in 1990 and 2021 stratified by sex and age groups for global,five SDI quintiles re-gions,and eight countries including China,Japan,Republic of Korea,United Kingdom,France,United States,Canada,and Australia were extracted from the Global Burden of Disease Study 2021(GBD 2021)database.The age-standardized mortality rate(ASMR)and age-standard-ized disability-adjusted life year rate(ASDR)of lung cancer attributable to 7 level-3 risk factors in China for 1990 and 2021 were also extracted.Counterfactual analysis was used to decompose changes in lung cancer deaths and DALY from 1990 to 2021 into four contributing factors:popu-lation size,population structure,age-standardized incidence or prevalence,and lung cancer case fatality or disease severity.The percentage changes in lung cancer deaths and DALY attributed to these four factors were calculated respectively.[Results]In 2021,there were 934 704 new cases and 814 364 deaths of lung cancer in China.From 1990 to 2021,the incidence,preva-lence,mortality,and DALY rates of lung cancer in China increased faster than those worldwide and in high-middle SDI regions,which was similar to Japan and Republic of Korea.In contrast,the mortality rates of lung cancer decreased in United States and United Kingdom;and the DALY rates of lung cancer decreased in United States,United Kingdom,Canada and Australia.From 1990 to 2021,the age-related lung cancer deaths and DALY in China increased by 193.91％and 146.20％,respectively.The primary contributor to the increase in lung cancer deaths was population aging(102.82％)among men and rising age-standardized incidence(119.00％)among women,while the primary contributor to the increase in DALY was rising age-standardized prevalence for both men(153.12％)and women(218.77％).In 2021,the top three risk factors contributing to lung cancer ASMR and ASDR in China were smoking,particulate matter pollution and occupational carcinogen exposure.Compared with 1990,the ASMR of lung cancer and its proportion at-tributable to particulate matter pollution and low dietary fruits were decreased,while the propor-tions in ASDR of lung cancer attributable to smoking and secondhand smoke increased.[Conclu-sion]Lung cancer is a major public health challenge in China.Compared with worldwide,high-middle SDI regions and certain developed countries,China has experienced faster growth in the incidence,prevalence,mortality and DALY of lung cancer,especially among women.To reduce disease burden,sustained efforts on lung cancer prevention and control are urgently required in China.

[Purpose]To analyze the epidemiological characteristics of esophageal cancer world-wide and in China.[Methods]Data were extracted from the GLOBOCAN 2022 database.The in-cidence and mortality of esophageal cancer worldwide and in China were analyzed,stratified by sex,age group,and human development index(HDI).Spearman correlation analysis was conducted to evaluate the association between the HDI and the mortality-to-incidence ratio(MIR)of esophageal cancer.[Results]In 2022,there were an estimated 511 054 new cases and 445 391 deaths from esophageal cancer globally,with age-standardized incidence and mortality rates(ASIR and ASMR)of 5.0/105 and 4.3/105,respectively.In China,there were an estimated 224 012 new cases and 187 467 deaths accounting for 43.8％and 42.1％of global totals,respectively.Both the new cases and deaths of esophageal cancer in China ranked the first worldwide.The ASIR and ASMR in China were 8.3/105 and 6.7/105,both were as twice as the global average.The ASIR and ASMR for males were higher than those for females.The incidence and mortality of esophageal cancer increased with age,and more than 50％of global cases and deaths in individuals aged over 70 years old occurred in China.Additionally,a significantly negative correlation was ob-served between HDI and MIR of esophageal cancer(ρ=-0.67,P＜0.001),and MIR in China(0.81)was comparable to that of countries or regions with a very high HDI.[Conclusion]The burden of esophageal cancer remains significant worldwide and in China,particularly among males and the elderly.The MIR of esophageal cancer in China is still relatively high.The primary and secondary prevention measures should be strengthened to reduce the incidence and mortality of esophageal cancer.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

[Purpose]To analyze the epidemiological characteristics of esophageal cancer world-wide and in China.[Methods]Data were extracted from the GLOBOCAN 2022 database.The in-cidence and mortality of esophageal cancer worldwide and in China were analyzed,stratified by sex,age group,and human development index(HDI).Spearman correlation analysis was conducted to evaluate the association between the HDI and the mortality-to-incidence ratio(MIR)of esophageal cancer.[Results]In 2022,there were an estimated 511 054 new cases and 445 391 deaths from esophageal cancer globally,with age-standardized incidence and mortality rates(ASIR and ASMR)of 5.0/105 and 4.3/105,respectively.In China,there were an estimated 224 012 new cases and 187 467 deaths accounting for 43.8％and 42.1％of global totals,respectively.Both the new cases and deaths of esophageal cancer in China ranked the first worldwide.The ASIR and ASMR in China were 8.3/105 and 6.7/105,both were as twice as the global average.The ASIR and ASMR for males were higher than those for females.The incidence and mortality of esophageal cancer increased with age,and more than 50％of global cases and deaths in individuals aged over 70 years old occurred in China.Additionally,a significantly negative correlation was ob-served between HDI and MIR of esophageal cancer(ρ=-0.67,P＜0.001),and MIR in China(0.81)was comparable to that of countries or regions with a very high HDI.[Conclusion]The burden of esophageal cancer remains significant worldwide and in China,particularly among males and the elderly.The MIR of esophageal cancer in China is still relatively high.The primary and secondary prevention measures should be strengthened to reduce the incidence and mortality of esophageal cancer.