Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm² in 2020 to 3 894.45 hm² in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm² in 2020 to a peak in 2023 (172.04 hm²), followed by a reduction to 132.36 hm² in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm² in 2020 to a peak in 2022 (78.43 hm²), followed by a reduction to 40.21 hm² in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m² in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m² in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m² in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ² = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ² = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ² = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ² = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ² = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m²] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m²] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.

Objective:To investigate the therapeutic effect of transcranial direct current stimulation (tDCS) for post-stroke aphasia (PSA) in acute phase.Methods:Patients with acute ischemic stroke who met the PSA diagnostic criteria and admitted to the Department of Neurology, the Third Affiliated Hospital of Anhui Medical University from June 2022 to November 2023 were prospectively included. They were randomly divided into a tDCS group and a control group using a random number table method. All patients received routine speech and language therapy, and the tDCS group received tDCS on this basis. The anode was the left Broca area, with a stimulation current intensity of 1.5 mA, 20 min per session, once a day, for 7 consecutive days. Before and after treatment, the Western Aphasia Battery (WAB) was used to assess spontaneous speech, comprehension, repetition and naming ability, and to calculate the Aphasia Quotient (AQ). National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological deficits. The effectiveness of treatment was evaluated based on changes in various speech function scores, and improvements in AQ and Boston Diagnostic Aphasia Examination (BDAE) severity grading scale scores.Results:A total of 56 patients with PSA were included, of which 42 (75.00%) were male and aged 66.95±11.07 years. The median baseline NIHSS score was 4.00 (interquartile range, 2.00-7.00). The median WAB-AQ score was 64.30 (interquartile range, 50.60-73.05). Thirty-one patients (55.36%) were mild aphasia, 20 (35.71%) were moderate aphasia, and 5 (8.92%) were severe aphasia. There were 28 patients in the tDCS group and 28 in the control group. There were no statistically significant differences in baseline data between the two groups. After treatment, spontaneous speech, comprehension, repetition and naming ability were significantly improved in both groups compared with before treatment (all P<0.001). The repetition ability score in the tDCS group was significantly higher than that in the control group after treatment ( P=0.049). In addition, the differences in spontaneous speech, comprehension, repetition and naming ability scores before and after treatment in the tDCS group were significantly higher than those in the control group (all P<0.05), with the most significant differences in spontaneous speech and naming ability scores before and after treatment (all P<0.05). However, there was no statistically significant difference in the effectiveness of AQ and BDAE grading improvement between the two groups, and the difference in NIHSS scores before and after treatment were also no statistically significance. Conclusion:tDCS has an improvement effect on the spontaneous speech, comprehension, repetition and naming ability in patients with PSA in acute phase, but the degree of improvement is relatively weaker.

Background: Antibiotic resistance is a significant public health concern around the globe.Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.

Post-stroke aphasia (PSA) is a common speech disorder after stroke, involving at least 1/3 of stroke patients, and causing serious adverse effects on their lives and work. The available intervention measures include speech and language rehabilitation therapy, drug therapy, and non-invasive brain stimulation technology. The latter mainly includes transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). tDCS can have a positive impact on PSA by promoting its self-repair, regulating the level of neurotransmitters, and inhibiting inflammation. This article reviews the effect of tDCS on the self-recovery mechanism of PSA and its treatment.

Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury caused by a variety of intrapulmonary and/or extrapulmonary factors such as infection and trauma. Uncontrolled inflammatory response is the main pathological feature. Different functional states of alveolar macrophages have different effects on inflammatory response. Transcription activating factor 3 (ATF3) is a fast response gene in the early stage of stress. In recent years, it has been found that ATF3 plays an important role in regulating the inflammatory response of ARDS by regulating the function of macrophages. This paper reviews the regulatory effects of ATF3 on alveolar macrophage polarization, autophagy and endoplasmic reticulum stress and its effects on the inflammatory process of ARDS, aiming to provide a new research direction for the prevention and treatment of ARDS.

OBJECTIVE: To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer. METHODS: TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed. RESULTS: The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05). CONCLUSION Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
Animals ; Humans ; Mice ; Apoptosis ; Dendritic Cells/immunology* ; Glycyrrhizic Acid/pharmacology* ; HMGB1 Protein ; Lung Neoplasms/immunology*

In order to reveal the intestinal absorption mechanism of saikosaponin d (SSd) in vitro and in vivo, the current research investigated the effects of different experimental conditions (time, concentration, temperature, pH, intestinal segments), transporter inhibitors, paracellular pathway enhancer, metabolic enzyme inhibitors on the intestinal absorption of SSd, in Caco-2 monolayers and a single pass perfusion model in rats.The results showed that the apparent permeability coefficient (Papp) and effective permeability coefficient (Peff) of SSd were 4.75 × 10-7 - 6.38 × 10-7 cm/s and 0.19 × 10-4- 0.27 × 10-4 cm/s, respectively, indicating that it was a low permeability compound, and that the transmembrane transport of SSd was concentration-dependent (0.5-5 μmol/L) and time-dependent (0-180 min).Ileum was the main absorption site for SSd. Experimental results based on Caco-2 monolayers showed that the P-gp inhibitor and paracellular permeability enhancer significantly increased the absorption of SSd (P < 0.05), which was consistent with the results obtained in rats. Inhibitors of OATPs and OCTs showed different results in vitro and in vivo, which may be related to the lower expression of them in jejunum.In summary, the intestinal absorption of SSd occurs through a carrier-mediated and energy-dependent transport, as well as passive diffusion, and P-glycoprotein plays an important role in the active transport of SSd.

Objective:To investigate the correlation between total MRI burden and serum uric acid level in patients with cerebral small vessel disease(CSVD) and its gender differences.Methods:A total of 217 patients with CSVD were retrospectively included as the research objects, and the clinical data such as serum uric acid value were collected.The imaging findings of patients with CSVD were evaluated by MRI, and the total MRI burden score of CSVD was calculated.According to the total MRI burden score of CSVD, patients with CSVD were divided into mild-to-moderate burden group ( n=133) and severe burden group ( n=84). SPSS 20.0 software was used for data analysis and processing.Logistic regression was used to analyze the relationship between uric acid and the total MRI burden score of CSVD. Results:The serum uric acid of severe burden group was higher than that of mild-to-moderate burden group((326.94±70.95)μmol/L, (293.42±80.52)μmol/L, P=0.002). The multivariate logistic regression analysis showed that the elevated level of serum uric acid was an independent risk factors for total MRI burden of CSVD ( β=0.005, OR=1.005, 95% CI=1.001-1.009, P=0.019). The patients with CSVD were equally divided into four group based on the serum uric acid concentration.After controlling the confounding factors, with the increase of uric acid level, the risk of aggravating total MRI burden score of CSVD increased, and the difference was statistically significant( P=0.001). Serum uric acid(for each quartile increase)was an independent risk factor for total MRI burden in male patients with CSVD( β=0.482, OR=1.619, 95% CI=1.125-2.330, P=0.010), while there was no significant difference in female patients( P=0.070). Conclusion:Serum uric acid level is a risk factor for increasing the total MRI burden in male patients with CSVD, but this effect is not found in female patients with CSVD.

Objective: To study the immune regulation function of high expressing interleukin-10 (IL-10) in B cells on CD4⁺T-cells in periodontitis mouse model. Methods: Twenty-four 7-weeks-old female C57BL/6 mice were randomly and equally assigned into 4 groups: the healthy control group (HC group, n=6), the ligation combined Porphyromonasgingivalis (Pg) infection group (P group, n=6), the ligation combined Pg infection with non-stimulated B cell transfer group (P+NSB group, n=6) and the ligation combined Pg infection with stimulated B cell transfer group (P+SB group, n=6). Ligation combined Pg infection of the maxillary second molar was used to induce periodontitis of mice. The exogenous non-stimulated B cells or stimulated B cells were injected into the palate gingivalat the 5th day after ligation, and all mice were sacrificed at the 14th day. HE stain was used to detect the histological of periodontal tissues, toluidine blue stain was used to analysis the alveolar bone loss, immunofluorescence stain was used to detect the expression of CD4⁺T-cell and IL-10, immunohistochemical was used to detect the expression of receptor activator of NF-κB ligand (RANKL) and IL-1β. Results: Results of HE staining showed that more hyperplasia of gingival epithelium and the alveolar bone resorption in P group, P+NSB group and P+SB group compared with HC group. Results of toluidine blue staining showed that the alveolar bone losses in P group [(0.668±0.041) mm²], P+NSB group [(0.750±0.039) mm²] and P+SB group [(0.517±0.038) mm²] were significantly increased compared with that in HC group [(0.336±0.029) mm²](F=146.051, P<0.01), and the alveolar bone resorption was significantly increased in P+NSB group compared with that in P group (F=146.051, P<0.01). However, compared with P+NSB group and P group, the alveolar bone loss in P+SB groupwas significantly decreased (F=146.051, P<0.01). Results of immunofluorescence staining showed that CD4⁺T-cells expressed in P group [(287.5±37.9) cell/mm²], P+NSB group [(314.6±53.3) cell/mm²] and P+SB group [(185.4±42.9) cell/mm²] were higher than that in HC group [(12.5±13.7) cell/mm²)(F=71.284, P<0.01). Compared with P group and P+NSB group, CD4⁺T-cells expression in group P+SB was decreased (F=71.284, P<0.01). IL-10 levels were increased in P group [(111.7±20.4) cell/mm²], P+NSB group [(126.7±15.1) cell/mm²] and P+SB group [(191.0±22.6) cell/mm²] compared with that in HC group [(22.7±4.3) cell/mm²] (F=98.516, P<0.01), and the IL-10 expressed in P+SB group was significantly higher than those in P+NSB group and P group. Results of immunohistochemical tests showed that RANKL expressions in gingival tissues among P group [(674.0±71.5) cell/mm²], P+NSB group [(831.0±97.5) cell/mm²] and P+SB group [(420.1±40.8) cell/mm²] were significantly higher than that in HC group [(69.3±29.1) cell/mm²] (F=154.886, P<0.01). However, it dramatically decreased in P+SB group compared with those in P group and P+NSB group.The IL-1βexpression in P group [(447.8±40.8) cell/mm²], P+NSB group [(512.5±38.2) cell/mm²] and P+SB group [(281.6±32.4) cell/mm²] were significantly higher than that in HC group [(50.8±20.9) cell/mm²], and it also higher in P+NSB group compared with in P group. However, it decreased in P+SB group compared with those in P group and P+NSB group (F=221.185, P<0.01). Conclusions High expression IL-10 in B cell smight inhibit alveolar bone loss, RANKL and IL-1β expressions and CD4⁺T-cell infiltration through IL-10.