Humans ; Lung Transplantation/adverse effects* ; Risk Factors

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION This cell-based vascular graft is ready to undergo clinical trials for human patients.

The advantages of lymph node dissection through total laparoscopic total gastrectomy (TLTG) seem to be more and more accepted by the academic community. However, reconstruction of digestive tract is challenging and remains a focus of debate and research. Which way is better for esophagojejunostomy, circular stapler or linear stapler,remains to be answered. The authors believe that, under the conditions of existing anastomosis instruments, using of linear stapler for esophagojejunal side-to-side anastomosis may be the most common choice, but it must be used with strict indications, because there are still many problems to be solved. It is believed that with the breakthrough in the development of the circular stapler suitable for esophagojejunostomy in TLTG, the application of circular stapler for digestive tract reconstruction will become the mainstream again in future. Thus, the current routine clinical practice of TLTG should be cautious and the surgical indications should be strictly evaluated.
Humans ; Laparoscopy ; Stomach Neoplasms/pathology* ; Anastomosis, Surgical ; Esophagoplasty ; Gastrectomy ; Retrospective Studies

Hilar splenic lymph node metastasis is one of the risk factors for poor prognosis in patients with proximal gastric cancer. Laparoscopic spleen-preserving splenic hilar lymph node dissection (LSPSHLD) can effectively improve the survival benefits of patients at high risk of splenic hilar lymph node metastasis. However, LSPSHLD is still a challenging surgical difficulty in radical resection of proximal gastric cancer. Moreover, improper operation can easily lead to splenic vascular injury, spleen injury and pancreatic injury and other related complications, due to the deep anatomical location of the splenic hilar region and the intricate blood vessels.Therefore, in the prevention and treatment of LSPSHLD-related complications, we should first focus on prevention, clarify the indication of surgery, and select the benefit group of LSPSHLD individually, so as to avoid the risk caused by over-dissection. Meanwhile, during the perioperative period of LSPSHLD, it is necessary to improve the cognition of related risk factors, conduct standardized and accurate operations in good surgical field exposure and correct anatomical level to avoid surrounding tissues and organs injury, and master the surgical skills and effective measures to deal with related complications, so as to improve the surgical safety of LSPSHLD.
Humans ; Spleen/surgery* ; Lymphatic Metastasis/pathology* ; Stomach Neoplasms/pathology* ; Gastrectomy/adverse effects* ; Lymph Node Excision/adverse effects* ; Lymph Nodes/pathology* ; Laparoscopy/adverse effects* ; Retrospective Studies

A patient with fever, chills, and pancytopenia as major clinical manifestations was presented. To investigate the cause, the patient's peripheral blood was collected for pathogen screening using metagenomic next - generation sequencing (mNGS). The DNA sequence of Leishmania donovani was detected, and Leishmania amastigotes were found in bone marrow smears using microscopy. The case was therefore definitively diagnosed as visceral leishmaniasis, and was cured and discharged from hospital following treatment with liposomal amphotericin B for 14 days. This is the first imported case of visceral leishmaniasis since the founding of Shenzhen City in 1979.
Humans ; Fever ; High-Throughput Nucleotide Sequencing ; Leishmania donovani/genetics* ; Leishmaniasis, Visceral/drug therapy*

OBJECTIVE: To investigate the spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody, and to examine the correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, so as to provide insights into advanced schistosomiais control in the province. METHODS: The epidemiological data of schistosomiasis in Hunan Province in 2020 were collected, including number of permanent residents in survey villages, number of advanced schistosomiasis patients, number of residents receiving serological tests and number of residents seropositive for anti-Schistosoma antibody, and the prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were descriptively analyzed. Village-based spatial distribution characteristics of prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were identified in Hunan Province in 2020, and the correlation between the revalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody was examined using Spearman correlation analysis. RESULTS: The prevalence of advanced schistosomiasis was 0 to 2.72% and the seroprevalence of anti-Schistosoma antibody was 0 to 20.25% in 1 153 schistosomiasis-endemic villages in Hunan Province in 2020. Spatial clusters were identified in both the prevalence of advanced schistosomiasis (global Moran's I = 0.416, P < 0.01) and the seroprevalence of anti-Schistosoma antibody (global Moran's I = 0.711, P < 0.01) in Hunan Province. Local spatial autocorrelation analysis identified 98 schistosomiasis-endemic villages with high-high clusters of the prevalence of advanced schistosomiasis, 134 endemic villages with high-high clusters of the seroprevalence of anti-Schistosoma antibody and 36 endemic villages with high-high clusters of both the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province. In addition, spearman correlation analysis showed a positive correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody (r_s = 0.235, P < 0.05). CONCLUSIONS There were spatial clusters of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, which were predominantly located in areas neighboring the Dongting Lake. These clusters should be given a high priority in the schistosomiasis control programs.
Animals ; Humans ; Prevalence ; Seroepidemiologic Studies ; Schistosomiasis/epidemiology* ; Schistosoma ; Spatial Analysis ; Antibodies, Helminth ; China/epidemiology*

OBJECTIVE: To evaluate the performance of recombinase-aided amplification (RAA) assay in detection of Clonorchis sinensis metacercariae in freshwater fish samples, so as to provide insights into standardization and field application of this assay. METHODS: Wild freshwater fish samples were collected in the rivers of administrative villages where C. sinensis-infected residents lived in Jiangyan District, Xinghua County and Taixing County of Taizhou City, Jiangsu Province from June to September 2022. Genomic DNA was extracted from six freshwater fish specimens (5 g each) containing 0, 1, 2, 4, 8 and 16 C. sinensis metacercariae for fluorescent RAA assay, and the diagnostic sensitivity was evaluated. Fluorescent RAA assay was performed with genomic DNA from C. sinensis, Metorchis orientalis, Haplorchis pumilio and Centrocestus formosanus metacercariae as templates to evaluate its cross-reactions. In addition, the detection of fluorescent RAA assay and direct compression method for C. sinensis metacercariae was compared in field-collected freshwater fish samples. RESULTS: Positive amplification was found in fresh-water fish specimens containing different numbers of C. sinensis metacercariae, and fluorescent RAA assay was effective to detect one C. sinensis metacercaria in 5 g freshwater fish specimens within 20 min. Fluorescent RAA assay tested negative for DNA from M. orientalis, H. pumilio and C. formosanus metacercariae. Fluorescent RAA assay and direct compression method showed 5.36% (93/1 735) and 2.88% (50/1 735) detection rates for C. sinensis metacercariae in 1 735 field-collected freshwater fish samples, with a statistically significant difference seen (χ² = 478.150, P < 0.001). There was a significant difference in the detection of C. sinensis metacercariae in different species of freshwater fish by both the direct compression method (χ² = 11.20, P < 0.05) and fluorescent RAA assay (χ² = 20.26, P < 0.001), and the detection of C. sinensis metacercariae was higher in Pseudorasbora parva than in other fish species by both the direct compression method and fluorescent RAA assay (both P values < 0.05). CONCLUSIONS Fluorescent RAA assay has a high sensitivity for detection of C. sinensis metacercariae in freshwater fish samples, and has no cross-reactions with M. orientalis, H. pumilio or C. formosanus metacercariae. Fluorescent RAA assay shows a higher accuracy for detection of C. sinensis infections in field-collected freshwater fish than the direct compression method.
Animals ; Clonorchis sinensis/genetics* ; Metacercariae/genetics* ; Recombinases ; Fresh Water ; Fishes ; DNA ; Fish Diseases/diagnosis*

OBJECTIVE: To measure the burden of hepatitis B-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2030. METHODS: The age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALY) rate of hepatitis B-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in burdens of hepatitis B-associated diseases were evaluated from 1990 to 2019 using estimated annual percentage change (EAPC) and annual percent change (APC). In addition, the changes in the burden of hepatitis B-associated diseases were predicted in China from 2020 to 2023 using the Bayesian model. RESULTS: The overall incidence of hepatitis B-associated diseases reduced from 2 725.98/10⁵ in 1990 to 1 397.31/10⁵ in 2019 in China [estimated annual percentage change (EAPC) = -2.35%, 95% confidential interval (CI): (-2.58%, -2.13%)], with a reduction in the prevalence from 12 239.53/10⁵ in 1990 to 6 566.12/10⁵ in 2019 [EAPC = -2.34%, 95% CI: (-2.54%, -2.14%)], a reduction in the mortality from 24.67/10⁵ in 1990 to 8.07/10⁵ in 2019 [EAPC = -4.92%, 95% CI: (-5.37%, -4.47%)], and a reduction in the DALY rate from 793.38/10⁵ in 1990 to 247.71/10⁵ in 2019 [(EAPC = -5.15%, 95% CI: (-5.64%, -4.66%)]. The DALY rate of hepatitis B-associated diseases were mainly attributed to liver cancer, and the DALY rate of hepatitis B-associated diseases appeared a tendency towards a rise in China from 2012 to 2019 [APC = 1.30%, 95% CI: (0.16%, 2.45%)]. The overall burden of hepatitis Bassociated diseases was higher in males than in females, and the DALY rate of hepatitis B-associated diseases increased with age, with the greatest DALY rate seen among patients at ages of 50 to 69 years. The overall incidence of hepatitis B-associated diseases was projected to be 866.79/10⁵ in China in 2030, with the greatest incidence seen in acute hepatitis B (854.87/10⁵), and the burden of hepatitis B-associated diseases was predicted to decline in China from 2020 to 2030; however, the burden of liver disease was projected to appear a tendency towards a rise. CONCLUSIONS The burden of hepatitis B-associated diseases appears an overall tendency towards a decline in China from 1990 to 2030; however, the burden of liver cancer appears a tendency towards aggravation. Early diagnosis and treatment of liver cancer should be given a high priority.
Male ; Female ; Humans ; Middle Aged ; Aged ; Bayes Theorem ; Quality-Adjusted Life Years ; Hepatitis B/epidemiology* ; Liver Neoplasms/epidemiology* ; China/epidemiology* ; Incidence

OBJECTIVE: To measure the burden of hepatitis C-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2044, so as to provide insights into formulation of the targeted hepatitis C control strategy. METHODS: The total burden due to hepatitis C-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALYs) rate of hepatitis C-associated acute hepatitis C (AHC), chronic liver diseases (CLD) and liver cancer in China from 1990 to 2019 were evaluated in China from 1990 to 2019 using estimated annual percentage change (EAPC). In addition, the changes in the burden of hepatitis C-associated diseases were predicted in China from 2020 to 2044 using a Bayesian model. RESULTS: The prevalence, incidence, mortality and DALY rate of hepatitis C-associated diseases all appeared an overall tendency towards a decline in China from 1990 to 2019 (EAPC = -2.64%, -2.24%, -3.81% and -3.90%, respectively); however, there was a minor rise in the incidence and prevalence of hepatitis C-associated diseases from 2015 to 2019. The overall prevalence of hepatitis C-associated diseases reduced from 2 152.7/10⁵ in 1990 to 1 254.1/10⁵ in 2019 in China, with a reduction of 41.7%. The overall incidence reduced from 87.9/10⁵ in 1990 to 55.0/10⁵ in 2019 in China, with a reduction of 37.4%, and the highest incidence was seen for AHC, followed by CLD and liver cancer. The overall mortality and DALY rate of hepatitis C-associated diseases was 4.0/10⁵ and 100.8/10⁵ in China from 1990 to 2019, with CLD showing the largest contributions to the gross mortality and DALY. The mortality and DALY rate of hepatitis C-associated diseases were 5.5/10⁵ and 142.4/10⁵ among men in China in 2019, which were both much higher than among women (2.8/10⁵ and 60.3/10⁵, respectively), and the overall prevalence (1 604.9/10⁵), mortality (30.2/10⁵) and DALYs (437.1/10⁵) of hepatitis C-associated diseases were all highest among patients at ages of 70 years and older, and the highest incidence was seen among patients at ages of 0 to 9 years (167.3/10⁵). The incidence of hepatitis C-associated diseases was predicted to rise in China from 2020 to 2044; however, the DALY rate was projected to appear a tendency towards a decline. CONCLUSIONS Although the burden of hepatitis C-associated diseases showed a tendency towards a decline in China from 1990 to 2019, the burden remained high, and was predicted to slightly rise from 2020 to 2044. High attention should be paid to screening of hepatitis C among infants and treatment among adults.
Male ; Adult ; Infant ; Humans ; Female ; Bayes Theorem ; Quality-Adjusted Life Years ; Hepatitis C/epidemiology* ; Liver Neoplasms/epidemiology* ; China/epidemiology* ; Incidence