AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degenerative disease characterized by yellow-white crystal deposits in the posterior pole, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroid. Mutations in the cytochrome P450 4V2 gene (CYP4V2) cause BCD, which is associated with lipid metabolic disruption. The use of gene-replacement therapy in BCD has been hampered by the lack of disease models. To advance CYP4V2 gene-replacement therapy, we generated BCD patient-specific induced pluripotent stem cell (iPSC)-RPE cells and Cyp4v3 knockout (KO) mice as disease models and AAV2/8-CAG-CYP4V2 as treatment vectors. We demonstrated that after adeno-associated virus (AAV)-mediated CYP4V2 gene-replacement therapy BCD-iPSC-RPE cells presented restored cell survival and reduced lipid droplets accumulation; restoration of vision in Cyp4v3 KO mice was revealed by elevated electroretinogram amplitude and ameliorated RPE degeneration. These results suggest that AAV-mediated gene-replacement therapy in BCD patients is a promising strategy.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice.

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.

Ribavirin inhibits peste des petits ruminants virus proliferation in vitro.

Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase (RdRp), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.

Developmental Trends in Postnatal Thyroid Hormones and Thyroid Dysfunction in Preterm Infants Born at less than 34 weeks Gestation.

OBJECTIVES: To analyse the trends in thyroid function tests (TFT) in preterm infants, evaluate the frequency of thyroid dysfunction, and identify the factors that influence thyroid function. METHODS: The TFT results and risk factors for thyroid dysfunction in preterm infants with gestational ages (GA) between 25 and 34 weeks were analysed. RESULTS: In total, 535 infants were enrolled in this study. Thyroid hormone levels vary with gestational and postnatal age, and the total frequency of thyroid dysfunction is 50.3%. Thirty-one infants (5.8%) had delayed TSH elevation. Transient hypothyroxinaemia of prematurity remained significantly associated with both lower birth weight and GA. Congenital hypothyroidism was significantly associated with lower birth weight, 5 min Apgar score, and dopamine use. CONCLUSIONS: Thyroid hormone levels in preterm infants are related to gestation and postnatal age, the frequency of thyroid dysfunction in premature infants is high, and is negatively correlated with GA and birth weight.

circNFATC3 sponges miR-548I acts as a ceRNA to protect NFATC3 itself and suppressed hepatocellular carcinoma progression.

Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. This study performed quantitative reverse-transcription polymerase chain reaction to determine if circNFATC3 was downregulated in 46 paired HCC tissues and cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptotic, and transwell assay proved that circNFATC3 can inhibit hepatoma cell proliferation, apoptosis, and migration/invasion in vitro. Mouse xenograft assay demonstrated that circNFATC3 suppressed tumor size and weight and reduced lung metastasis in vivo, and vice versa. The RNA-seq results showed that NFATC3 itself was the most significantly differentially expressed gene when circNFATC3 was manipulated, and bioinformatics and luciferase reporter assays verified circNFATC3 regulated the expression of NFATC3 by interacting with the hsa-miR-548I. Additionally, it was also indicated that the level of NFATC3 was downregulated in HCC patients also and was significantly correlated with the staging and prognosis of HCC. Moreover, both circNFATC3 and NFATC3 were shown to inhibit the phosphorylation of JNK, c-Jun, AKT, and mTOR signaling pathways. Overall, the circNFATC3 can sponge miR-548I to protect NFATC3 itself, then it regulates hepatoma cell function via the JNK, c-Jun, AKT, and mTOR signaling pathways, and the circNFATC3 can be a tumor-repressor on HCC.

Proteomic and Immunological Identification of Diagnostic Antigens from Spirometra erinaceieuropaei Plerocercoid.

Human sparganosis is a food-borne parasitic disease caused by the plerocercoids of Spirometra species. Clinical diagnosis of sparganosis is crucial for effective treatment, thus it is important to identify sensitive and specific antigens of plerocercoids. The aim of the current study was to identify and characterize the immunogenic proteins of Spirometra erinaceieuropaei plerocercoids that were recognized by patient sera. Crude soluble extract of the plerocercoids were separated using 2-dimensional gel electrophoresis coupled with immunoblot and mass spectrometry analysis. Based on immunoblotting patterns and mass spectrometry results, 8 antigenic proteins were identified from the plerocercoid. Among the proteins, cysteine protease protein might be developed as an antigen for diagnosis of sparganosis.

Human Cases of Fascioliasis in Fujian Province, China.

Fascioliasis is a foodborne zoonotic parasitic disease. We report 4 cases occurring in the same family, in whom diagnosis of acute fascioliasis was established after series of tests. One case was hospitalized with fever, eosinophilia, and hepatic lesions. MRI showed hypodense changes in both liver lobes. The remaining 3 cases presented with the symptom of stomachache only. Stool analysis was positive for Fasciola eggs in 2 adult patients. The immunological test and molecular identification of eggs were confirmed at the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China. The results of serological detection were positive in all the 4 patients. DNA sequencing of PCR products of the eggs demonstrated 100% homology with ITS and cox1 of Fasciola hepatica. The conditions of the patients were not improved by broad-spectrum anti-parasitic drugs until administration of triclabendazole.

Four Human Cases of Diphyllobothrium nihonkaiense (Eucestoda: Diphyllobothriidae) in China with a Brief Review of Chinese Cases.

We described 4 human infection cases of zoonotic fish-tapeworm, Diphyllobothrium nihonkaiense, identified with morphological and molecular characters and briefly reviewed Chinese cases in consideration of it as an emerging parasitic disease in China. The scolex and mature and gravid proglottids of some cases were seen, a rosette-shaped uterus was observed in the middle of the mature and gravid proglottids, and the diphyllobothriid eggs were yellowish-brown in color and displayed a small knob or abopercular protuberance on the opposite end of a lid-like opening. The average size of the eggs was recorded as 62-67×42-45 µm. The parasitic materials gathered from 4 human cases were morphologically identified as belonging to the genera Diphyllobothrium and Adenocephalus. The phylogenetic analysis based on the nucleotide sequences of cytochrome c oxidase subunit 1 gene of the etiologic agents confirmed that the 4 cases were D. nihonkaiense infection. The finding of 4 additional D. nihonkaiense cases suggests that D. nihonkaiense might be a major causative species of human diphyllobothriasis in China. A combined morphological and molecular analysis is the main method to confirm D. nihonkaiense infection.

Development of Lateral Flow Immunoassay for Antigen Detection in Human Angiostrongylus cantonensis Infection.

Angiostrongyliasis is difficult to be diagnosed for the reason that no ideal method can be used. Serologic tests require specific equipment and are not always available in poverty-stricken zone and are time-consuming. A lateral flow immunoassay (LFIA) may be useful for angiostrongyliasis control. We established a LFIA for the diagnosis of angiostrongyliasis based on 2 monoclonal antibodies (mAbs) against antigens of Angiostrongylus cantonensis adults. The sensitivity and specificity were 91.1% and 100% in LFIA, while those of commercial ELISA kit was 97.8% and 86.3%, respectively. Youden index was 0.91 in LFIA and 0.84 in commercial ELISA kit. LFIA showed detection limit of 1 ng/ml of A. cantonensis ES antigens. This LFIA was simple, rapid, highly sensitive and specific, which opened an alternative approach for the diagnosis of human angiostrongyliasis.

[Digital Description and Identification of 11 Kinds of Principal Parasite Eggs].

Objective: To facilitate the identification of parasite eggs using computer technology, establish the automation-based applications, and propose an algorithm for egg classification. Methods: Eggs of 11 parasites, Clonorchis sinensis, Taenia solium, Enterobius vermicularis, Ascaris lumbricoides, Trichuris trichiura, Spirometra mansoni, Diphyllobothrium latum, Ancylostoma duodenale, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski, were selected and divided into two groups, the training group and the testing group, and were microphotographed. The eigenvalue was extracted using the VC++-based method. The eigenvalue database was constructed, and the training data set was tested with a variety of classification algorithms. The classifier was constructed using algorithm with the highest efficiency and an identification method was established by multi-feature fusion. Results: After removal of images with invalid values, the training group received 19 844 egg images, and the testing group, 3 721 images. Based on the 14 eigenvalues, there were significant differences in the size and color among the eggs of 11 parasite species. For example, the length, width, area and brightness of the smallest parasite egg of Clonorchis sinensis were 292.24 µm, 192.64 µm, 43 416.61 µm2 and 53.84, respectively, while those of the largest parasite egg of Fasciolopsis buski were 945.31 µm, 610.88 µm, 536 002.60 µm2 and 100.54, respectively. When using dynamic weights to construct the classifier, the discrimination rate on the training data set was 88.89%（17 641/19 844）, and that on the verification data set was 91.83%（3 004/3 271）, with an average modeling time of 0.01 s. Conclusion: The algorithm for egg classification has been established, which pravides a basis for further study on its feasibility.

[Sequencing and Phylogenetic Tree Construction of 18S Ribosomal DNA from Five Species of Plasmodium from Yunnan Border between China and Myanmar and Other Areas].

Objective: To analyze sequence variation and construct phylogenetic tree based on 18S ribosomal DNA among five species of Plasmodium in Yunnan border between China and Myanmar and other areas. Methods: Blood samples (or DNA samples)from malaria patients were collected from 2000 to 2015 in Yunnan border and Myanmar and other areas. DNA was extracted from blood samples, and the 18S rDNA fragment was amplified, sequenced and aligned with relevant sequences available in the GenBank. The phylogenetic tree was constructed by methods of neighbor joining (NJ), maximum likelihood (ML), and maximum parsimony (MP), respectively. Results: A total of 94 blood samples or DNA from malaria patients were collected. The 18S rDNA was successfully amplified from all the samples. Sequence alignment revealed variations of 0-0.2%, 0-0.1%, 0-0.1%, 0-0.1% and 0 for 18S rDNA sequence among Plasmodium falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi, respectively. The phylogenetic tree constructed with the three method showed consistency. Phylogenic analysis revealed that there were five big branches of Plasmodium spp. studied. The P. falciparum branch clustered with the isolates from Cameroon（KC428741, KC428742）, Brazil（KC906718）, and Malaysia（HQ283221） in GenBank. The P. vivax branch clustered with isolates from Cameroon（HF945443）, India （HM014361, JQ627158）, and Colombia （U83877）. However, the samples Pv11, Pv18 and Pv21 formed a small branch that showed closer phylogenetic relationship with P. cynomolgi（L07559）, an isolate from Macaca fascicularis. Moreover, P. malariae samples from Yunnan Province including Pm1, Pm3 and Pm4 clustered to form a small branch, and then clustered with samples from Hainan Province, showing geographical diversity. All the isolates of P. ovale clustered with isolates from Vietnam（EU935736 and AF387038）. All the isolates of P. knowlesi clustered into a branch, and showed close relationship with those from Myanmar (GU816250 and GU816246). Conclusion: There is no significant difference in 18S rDNA gene of the five species of Plasmodium from Yunnan border between China and Myanmar and other areas. The phylogenetic tree constructed with the NJ, MP and ML methods shows consistency.

[Efficacy analysis and theoretical study on Chinese herbal properties of Açaí (Euterpe oleracea)].

Açaí (Euterpe oleracea) emerged as a source of herb has a long history in South America, which was approved by the Ministry of Health used in China and it has been introduced planting in Guangdong and Taiwan. This article summarized applied history of Açaí and its present status in China. Did theoretical study on the Chinese herbal properties of Açaí based on the Chinese traditional philosophical culture to analysis the function and symptom preliminary, combining with used for medical recordation, chemical component, biological activity. It is aiming at establishing the theoretical foundation for the application under the guidance of TCM theory.

[Advanced glycation end products inhibit testosterone production in rat Leydig cells].

OBJECTIVE: To study the expression of the receptor for advanced glycation end products (RAGE) and the inhibitory effect of advanced glycation end products (AGEs) on testosterone production in rat Leydig cells. METHODS: Rat Leydig cells were primarily cultured and the expression of RAGE in the Leydig cells was detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively, and the testosterone content was determined by ELISA. RESULTS: RT-PCR and immunofluorescence staining exhibited the expression of RAGE in the rat Leydig cells. AGEs remarkably suppressed hCG-induced testosterone production in the Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml groups as compared with the control (P < 0.01). CONCLUSION: RAGE exists in rat Leydig cells and AGEs can significantly inhibit the secretion of testosterone in primarily cultured rat Leydig cells.

[Analysis on parasitic infection of clinical samples from hospitals in Shanghai during 2011-2013].

OBJECTIVE: To analyze the results of parasitic pathogen detection on clinical samples from Shanghai hospitals during 2011-2013. METHODS: Samples of serum, stool, sputum, body fluid and biopsy were collected from hospitals. The etiological, serological and molecular biology methods were used to detect parasitic infection cases. RESULTS: During 2011-2013, a total of 16,151 clinical samples were collected. 855 parasitic infection were found from 5939 samples by pathogen detection, belonging to 32 species, with a detection rate of 14.4%. The positive rate of Blastocystis hominis and Entamoeba histolytica was 8.3% (494/5939) and 3.1% (186/5939), respectively. The rate of intestinal protozoa infection in under 20-year-old age group was higher than other age groups (P<0.05). No significant difference was found between males and females (P>0.05). Totally 10,212 serum samples were examined, the total antibody-positive rate was 7.1% (730/10,212). In the 730 positive samples, 173 (23.7%), 143 (19.6%), 139 (19.0%), 132 (18.1%), and 128 (17.5%) showed positive for the antibodies against Cysticercus cellulosae, Schistosoma japonicum, Paragonimus westermani, Toxoplasma gondii and Sparganum mansoni, respectively. The main source regions of protozoal infection were Shanghai (269 cases), Jiangsu (142 cases), Anhui (106 cases) and Zhejiang (82 cases). 89 cases were worm infection, the main source were Zhejiang (24 cases), Shanghai (18 cases), Jiangxi (11 cases). CONCLUSION: Among the samples from hospitals, the major intestinal protozoans are Blastocystis hominis and Entamoeba histolytica, and the sero-positive cases are mainly Cysticercus cellulosae and Schistosoma japonicum infection.

[Effect of Gansui Banxia Tang plus-minus Gansui and Gancao anti-drug combination that preferred dose close to clinical application on diuretic effect in malignant ascites rats].

OBJECTIVE: To observe the effect of Gansui Banxia Tang plus-minus Gansui and Gancao anti-drug combination on hepatic and renal functions in malignant ascites rats to explore whether the efficacy or toxicity associated with the anti-drug combination. METHOD: The male wistar rats were randomly divided into a blank group, model group, furosemide group, Gansui Banxia Tang group, Gansui Banxia Tang removed Zhigancao group, Gansui Banxia Tang removed Cugansui group, Gansui Banxia Tang removed Zhigancao and Cugansui group. In addition to normal feeding, every morning except for the blank group and model group, the rest of the group was given drugs, the control group and the model group was given distilled water, the volume is 10 mL x kg(-1). Administered five days, all rats were fasted but except water for 24 hours to collect urine. Administered nine days all rats were fasted but except water for 12 hours, we need to weigh weight of rats. When we remove the ascites, we also need to weigh weight of rats. We use the weight before removing ascites minus weight after removing ascites to indirectly measure the amount of ascites. When we remove the ascites, we need to abdominal aortic blood, centrifuge testing renin, angiotensin II, aldosterone, antidiuretic hormone and other indicators. RESULT: The effect of Gansui Banixa Tang on increasing the net weight, lowering abdominal circumference and body weight ratio, lowering renin, angiotensin, aldosterone, antidiuretic hormone is better than the other treatment group. CONCLUSION: In diuresis party, the group of Gansui Banxia Tang is better than the group of Gansui Banxia Tang remove Zhigancao or Cugansui or Zhigancao and Cugansui, renin-angiotensin-aldosterone system may play a diuretic effect of its one way.

Implementation of the Observational Medical Outcomes Partnership Model in Electronic Medical Record Systems: Evaluation Study Using Factor Analysis and Decision-Making Trial and Evaluation Laboratory-Best-Worst Methods.

BACKGROUND: Electronic medical record (EMR) systems are essential in health care for collecting and storing patient medical data. They provide critical information to doctors and caregivers, facilitating improved decision-making and patient care. Despite their significance, optimizing EMR systems is crucial for enhancing health care quality. Implementing the Observational Medical Outcomes Partnership (OMOP) shared data model represents a promising approach to improve EMR performance and overall health care outcomes. OBJECTIVE: This study aims to evaluate the effects of implementing the OMOP shared data model in EMR systems and to assess its impact on enhancing health care quality. METHODS: In this study, 3 distinct methodologies are used to explore various aspects of health care information systems. First, factor analysis is utilized to investigate the correlations between EMR systems and attitudes toward OMOP. Second, the best-worst method (BWM) is applied to determine the weights of criteria and subcriteria. Lastly, the decision-making trial and evaluation laboratory technique is used to illustrate the interactions and interdependencies among the identified criteria. RESULTS: In this research, we evaluated the AliHealth EMR system by surveying 98 users and practitioners to assess its effectiveness and user satisfaction. The study reveals that among all components, "EMR resolution" holds the highest importance with a weight of 0.31007783, highlighting its significant role in the evaluation. Conversely, "EMR ease of use" has the lowest weight of 0.1860467, indicating that stakeholders prioritize the resolution aspect over ease of use in their assessment of EMR systems. CONCLUSIONS: The findings highlight that stakeholders prioritize certain aspects of EMR systems, with "EMR resolution" being the most valued component.

Design and clinical application of a risk prediction model for diabetic foot.

OBJECTIVE: To construct and evaluate a nomogram prediction model for the risk of diabetic foot in patients with type 2 diabetes based on their clinical data, and to assist clinical healthcare professionals in identifying high-risk factors and developing targeted intervention measures. METHODS: We retrospectively collected clinical data from 478 hospitalized patients with type 2 diabetes at the First Affiliated Hospital of Shantou University Medical College from January 2019 to December 2021. The patients were divided into a diabetic foot group (n=312) and a non-diabetic foot group (n=166) based on whether they had diabetic foot. The baseline data of both groups were collected. Univariate and multivariate analyses as well as logistic regression analysis were conducted to explore the risk factors for diabetic foot. A nomogram prediction model was established using the package "rms" version 4.3. The model was internally validated using the area under the receiver operating characteristic curve (AUC). Additionally, the decision curve analysis (DCA) was performed to evaluate the performance of the nomogram model. RESULTS: The results from the logistic regression analysis revealed that being male, smoking, duration of diabetes, glycated hemoglobin, hyperlipidemia, and atherosclerosis were influencing factors for diabetic foot (all P<0.05). The AUC of the model in predicting diabetic foot was 0.804, with a sensitivity of 75.3% and specificity of 74.4%. Harrell's C-index of the nomogram prediction model for diabetic foot was 0.804 (95% CI: 0.762-0.844), with a threshold value of >0.675. The DCA findings demonstrated that the nomogram model provided a net clinical benefit. CONCLUSION: The nomogram prediction model constructed in this study showed good predictive performance and can provide a basis for clinical workers to prevent and intervene in diabetic foot, thereby improving the overall diagnosis and treatment.

Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways.

BACKGROUND: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. OBJECTIVES: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. METHODS: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. RESULTS: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly down-regulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. CONCLUSIONS: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Gansui Banxia decoction modulates immune-inflammatory homeostasis to ameliorate malignant ascites in rats.

BACKGROUND: "Gansui Banxia decoction" (GBD) is a classical traditional Chinese medicine formula for treating abnormal accumulation of fluid, such as malignant ascites (MA). Although GBD has shown definite water-expelling effects, its exact underlying mechanism has not been elucidated. PURPOSE: This study aimed to investigate the drug effects of GBD on MA rats and its underlying mechanisms. METHODS: The main chemical composition was determined by ultra-high performance liquid chromatography. The drug effects of GBD was evaluated in the established cancer cell-induced MA rat model. The symptoms were analyzed, and biological samples were collected for detecting immune and inflammation-related indicators by enzyme-linked immunosorbent assays, western blot, and flow cytometry. RESULTS: GBD increased urine discharge, decreased ascites production, and alleviated cachexia. After GBD treatment, the expression of TLR4, MyD88, and NF-кB and the release of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were reduced. In addition, GBD increased G1 phase arrest and inhibit excessive proliferation of cells in bone marrow while alleviating G1 phase arrest and increasing proliferation of cells in the thymus. Correspondingly, the development and maturation of T cells also changed. GBD increased the proportion of mature T-cells (CD4+CD8- and CD4-CD8+ single-positive (SP) T-cells), and decrease the proportion of immature cells (CD4+CD8+ double-positive (DP) T-cells and CD4-CD8- double-negative (DN) T-cells) in the blood or tumor microenvironment (TME, the ascites microenvironment). Finally, we further analysis of immune cell subsets, GBD decreased the proportion of immunosuppressive T-cells in the blood (CD4+CD25+Foxp3+T-cells) and TME (CD8+CD25+Foxp3+T-cells), and increased the proportion of anti-tumor immune cells (CD8+CD28+T-cells and NK cells) in the TME. CONCLUSION: These findings indicated that the drug effects of GBD were attributed to regulating the immune-inflammatory homeostasis, thereby mitigating the destruction of cancer cells and reducing the generation of ascites, which provided theoretical support for the clinical rational application and extended the scientific connotation of "water-expelling" of GBD.

Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters.

Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and Ghead (residues 182-602, FeNP-Ghead) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-Ghead, respectively) through Spycatcher/Spytag technology. Compared with sG and Ghead alone, FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group. These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 µg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.