Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

For Perihilar cholangiocarcinoma (pCCA), surgical resection is the only effective way to cure this disease. However, it has high postoperative mortality and high recurrence rate. Domestic and foreign scholars have constructed statistics-based evaluation methods to predict patients′ postoperative survival and complications, such as nomogram, scoring system and other prognostic models. Based on these methods, clinicians can better select patients who can benefit from surgery and choose the optimal? treatment for more severe patients. Through the adoption of other treatments or some ways to ameliorate some preoperative condition, to improve the patient′s mortality and survival. This article reviews the prognostic risk factors and prognostic models of pCCA in order to provide a reference for clinicians to predict the prognosis about the surgery.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Objective:To analyze the epidemiological characteristics of norovirus (NoV) acute gastroenteritis (AGE) outbreaks caused by GII.17[P17] variant in China, 2022.Methods:Information and specimens of AGE outbreaks between January and December 2022 were collected. NoV RNA was detected in all specimens by real-time RT-PCR. The viral genome of the positive specimens were amplified, sequenced and analyzed.Results:Between January and December 2022, 360 AGE outbreaks were reported cumulatively, of which 266 outbreaks successfully obtained genotype results. GII.17 [P17] was one of the main genotypes and detected in 34 outbreaks (12.78%, 34/266), with the highest number of outbreaks detected in spring (6 outbreaks in March and 7 outbreaks in May), mainly in childcare facilities and primary schools (61.76%, 21/34). According to the result of NoV genotype analysis in different age groups, 14 strains of GII.17 [P17] in this study belonged to Cluster III b and SC III branch of Cluster III (Kawasaki308) in the capsid region and polymerase region, respectively, and both belonged to the same cluster as the variant strain (GZ41621 strain) that caused the NoV AGE outbreaks in China during the 2014/15 season. Compared to reference strains of Cluster I, Cluster II and Cluster III a, Cluster III b was provided with 22 amino acid mutations in VP1. The main amino acid changes in the subgroup of Cluster III b including the virus strains isolated in this study were at T294I and Q299R of antigen epitope A, an insertion mutation occurred at antigen epitope D, H353Q at the site I of the human histo-blood group antigen receptor binding site. The selection pressure analysis detected a large number of negative selection sites, indicating that negative selection plays an important role in the evolution of VP1 genes.Conclusions:GII.17 [P17] was one of the primary genotypes responsible for NoV diarrhea outbreaks in China in 2022. Phylogenetic analysis had revealed that it still belonged to the same cluster as the novel GII.17 [P17] variant (strain GZ41621) that caused NoV epidemics in China during the 2014/15 season, exhibiting minor amino acid variations at the potential epitope.

Objective:To analyze the surveillance data of population in rabies exposure and post-exposure prophylaxis (PEP) clinics in Shandong province from 2019 to 2023, explore risk factors for exposure, and provide a basis for further standardizing PEP.Methods:Based on surveillance data from the rabies exposure treatment clinic vaccination information system, population, and spatial administrative division data in Shandong province from 2019 to 2023, descriptive epidemiological methods were applied to analyze using SPSS 18.0.Results:The number of individuals receiving post-exposure treatment at PEP clinics in Shandong province from 2019 to 2023 was over 1 million annually and showed an increasing trend year by year, with the highest number of visits occurring from May to August each year. The number of female patients is increasing year by year. The 15-year-old and younger age group accounted for 31.69%-36.86% of clinic visits. Grade Ⅲ exposures accounted for 53.40%, and limbs accounted for approximately 89.81% of exposed areas. Approximately 1.94% is multi site exposure. The main injuring animals were dogs, followed by cats, and the proportion of cats is increasing year by year. The proportion of doctor′s office visitors who self-treated wounds increased from 32.32% to 45.46%, while the proportion of outpatient wound treatment decreased from 76.07% to 66.24%. The whole course vaccination rate after initial exposure is 63.79%. The whole course vaccination rate for the 15-29-year-old age group was lower than that for other age groups. The usage rate of passive immune preparations among grade Ⅲ exposed individuals is 35.66%. From 2019 to 2023, 8 cases of rabies were reported, none of whom received standard post-exposure treatment.Conclusions:The epidemic characteristics and exposure risk of people exposed to suspected rabies animals in Shandong province have changed. It is necessary to pay attention to the female population, the population with low vaccination rate between 15 to 29 years of age, cat bitten people, and carry out continuous monitoring on the exposed population, and timely adjust the prevention and control strategies.

Objective:A recombinant adenoviral vector vaccine based on non-replicating human adenovirus type 5 (Ad5), encoding the conserved domain of respiratory syncytial virus G protein (RSV-G) was constructed. The immunogenicity and protective efficacy of this vaccine were subsequently evaluated in mice.Methods:The recombinant Ad5 vector plasmid (Ad5-Gbcc-Gacc) was constructed by inserted conserved domains of RSV A and RSV B. The recombinant adenovirus Ad5-Gbcc-Gacc was rescued in HEK293A cells. The genome of virus Ad5-Gbcc-Gacc was identified by multi-enzyme digestion, and the expression of Ad5-Gbcc-Gacc was verified by Western blot. Recombinant adenovirus was used to immunize BALB/c mice via intramuscular injection with signal dose, and then challenged with RSV Long strain at week 6. The levels of G specific IgG and antibody subtypes in serum were detected by enzyme-linked immunosorbent assay, the level of neutralizing antibodies was determined by micro-neutralization assay. After challenge, the mice′s weight was recorded daily, the copies of RSV virus in the lung and nasal tissues were detected. Pathological changes in lung tissue were also examined.Results:Western blot and multi-enzyme digestion identification confirmed the successful rescue of the recombinant adenovirus. Ad5-Gbcc-Gacc elicit high titers of specific IgG, robust neutralizing antibodies, and a balanced Th1/Th2 immune response in mice. In comparison to unimmunized controls, mice immunized with Ad5-Gbcc-Gacc reduced the viral copies in both lung and nasal tissue, and exhibited only minimal pathological damage of lung tissue following RSV challenge. In conclusion, Ad5-Gbcc-Gacc induced robust immunogenicity and offers protective effects against RSV infection in murine models.Conclusions:Ad5-Gbcc-Gacc induce robust immunogenicity and can protect mice from RSV challenge, which lays a foundation for further development of RSV vaccine based on G protein.

OBJECTIVE To obtain stronger cytotoxic activity of panaxadiol derivatives. METHODS The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480. RESULTS These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity. CONCLUSION These results show that 7 and 7j can be used as promising lead compounds for further research.

Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB)integrity through PI3K/Akt pathway after cerebral ischemia.Methods A permanent middle cerebral artery occlusion(MCAO)model was established in SPF adult male SD rats.Totally 48 rats were randomly divided into sham group(n=12),model group(n=12),MCAO+miR-199a-5p group(n=12),and MCAO+miR-199a-5p negative control group(n=12).The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats;The integrity of the BBB after ischemia stroke was detected through Evans blue staining;Immunofluorescent staining was used to determine apoptosis after cerebral ischemia;Western blotting technology was used to detect the protein expression of claudin-5,phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2),p-Akt,Akt,and vascular endothelial growth factor(VEGF)-A;Real-time PCR was used to investigate the expression levels of miR-199a-5p,claudin-5,and VEGF-A in the ischemic penumbra and infarcted area of the brain.Results The result showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats.MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke,activated the Akt signaling pathway,and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra.In addition,miR-199a-5p alleviated inflammation after cerebral ischemia.MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia.Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke,activate the Akt signaling pathway,reduce the expression of inflammatory cytokines,and alleviate the damage to the blood-brain barrier.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.