Objective:To prepare aldolylated hyaluronic acid-modified antimicrobial carbon dots (AHA-CDs) eye drops and evaluate its antibacterial activity against Staphylococcus aureus in vitro and in vivo. Methods:AHA-CDs eye drops were synthesized by modifying small particle size positively charged carbon dots and introducing aldehyde-based hyaluronic acid.The AHA-CDs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy.The antibacterial activity of AHA-CDs against Staphylococcus aureus was evaluated using the microdilution method, plate counting, and live-dead bacteria fluorescence staining in vitro.The mouse bacterial keratitis model was established by removing the corneal epithelium after ring drilling and inoculating Staphylococcus aureus.Eighteen conventional female C57BL/6 mice aged 6-8 weeks were selected and divided into a blank control group, an AHA-CDs-treated group and a tobramycin-treated group of 6 mice each using random number table method, and the mice were treated with phosphate buffer saline, 80 μg/ml AHA-CDs, and 80 μg/ml tobramycin eye drops three times daily for 5 consecutive days accordingly to assess antibacterial activity against Staphylococcus aureus in vivo.Another 12 mice were divided into an AHA-CDs group and a normal control group using the random number table method, with 6 mice in each group, which were treated with 80 μg/ml AHA-CDs and phosphate buffer saline for 7 days.The mice were then sacrificed.Their eyeballs were removed and stained with hematoxylin-eosin to observe and compare the morphology and integrity of the eyeballs between the two groups to evaluate the treatment's biosafety.The use and care of the animals complied with the principles of the ARRIVE guidelines.The study protocol was approved by the Ethics Committee of the Experimental Animal Care of Henan Eye Hospital (No.HNEECA-2022-17). Results:The successful preparation of AHA-CDs was demonstrated by transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. In vitro studies showed that the minimum inhibitory concentration of AHA-CDs against Staphylococcus aureus was approximately 8 μg/ml, which effectively inhibited bacterial growth at a lower concentration.Plate counting results showed that only 20% of the bacteria survived after 10 minutes of treatment with AHA-CDs.Fluorescence staining of live/dead bacteria showed obvious red fluorescence signals after 4 hours of treatment with AHA-CDs and SP-CDs. In vivo studies showed that, after 5 days of treatment with AHA-CDs eye drops, the corneas of mice with bacterial keratitis were obviously transparent, and the corneal epithelium was basically repaired.In contrast, the tobramycin-treated group exhibited incomplete epithelial repair and mild corneal edema. In vivo safety evaluation revealed that the eye tissue morphology remained intact and no structural abnormalities were observed after AHA-CDs treatment. Conclusions:AHA-CDs eye drops have superior antibacterial effects in vivo and in vitro, and inactivate bacteria rapidly and effectively.

Objective:To investigate the potential value of cerebral glucose metabolism characteristics in anti-leucine-rich glioma-inactivated protein 1 (LGI1) antibody-related encephalitic patients during acute phase as the clinical indicator of disease outcomes.Methods:From October 2019 to December 2023, 28 patients (18 males, 10 females; age (56.6±11.9) year) with anti-LGI1 antibody-related encephalitis diagnosed at Huashan Hospital, Fudan University were prospectively enrolled. All patients received baseline brain 18F-FDG PET imaging and were divided into different subgroups according to the prognosis (good prognosis and poor prognosis groups) and recurrence (recurrence and non-recurrence groups) after follow-up. The difference of Montreal Cognitive Assessment (MoCA) score between the two groups was compared by Mann-Whitney U test. Statistical parametric mapping (SPM) analysis was used to analyze the PET images of different groups by independent-sample t test, and the characteristics of cerebral glucose metabolism of patients with different outcomes were obtained. Results:MoCA scores between the recurrence group ( n=6) and the non-recurrence group ( n=22; 14.0(9.8, 20.5) vs 22.0(18.0, 24.0); Z=2.17, P=0.030), and between the poor prognosis group ( n=13) and the good prognosis group ( n=15; 14.0(10.0, 22.0) vs 22.0(19.8, 25.3); Z=2.47, P=0.013) were significantly different. Compared with the good prognosis group, the cerebral glucose metabolism in the poor prognosis group was decreased in the bilateral frontal lobe, lateral temporal lobe, inferior parietal lobule and cingulate gyrus, but increased in the brainstem, bilateral lentiform nucleus and bilateral paracentral lobule/postcentral gyrus (all t=1.71, all P<0.05). Compared with the non-recurrence group, the metabolism of bilateral medial frontal gyrus, anterior cingulate gyrus, bilateral insula, superior temporal gyrus and thalamus decreased in the recurrence group, while the metabolism of bilateral precentral gyrus, inferior frontal gyrus and bilateral lentiform nucleus increased (all t=1.71, all P<0.05). Conclusion:18F-FDG PET imaging reveals the differences in brain metabolism of anti-LGI1 antibody-related encephalitic patients at baseline with different outcomes (prognosis, recurrence or not), which can provide a new perspective for the clinical evaluation of the disease at baseline.

Objective:To investigate the potential value of cerebral glucose metabolism characteristics in anti-leucine-rich glioma-inactivated protein 1 (LGI1) antibody-related encephalitic patients during acute phase as the clinical indicator of disease outcomes.Methods:From October 2019 to December 2023, 28 patients (18 males, 10 females; age (56.6±11.9) year) with anti-LGI1 antibody-related encephalitis diagnosed at Huashan Hospital, Fudan University were prospectively enrolled. All patients received baseline brain 18F-FDG PET imaging and were divided into different subgroups according to the prognosis (good prognosis and poor prognosis groups) and recurrence (recurrence and non-recurrence groups) after follow-up. The difference of Montreal Cognitive Assessment (MoCA) score between the two groups was compared by Mann-Whitney U test. Statistical parametric mapping (SPM) analysis was used to analyze the PET images of different groups by independent-sample t test, and the characteristics of cerebral glucose metabolism of patients with different outcomes were obtained. Results:MoCA scores between the recurrence group ( n=6) and the non-recurrence group ( n=22; 14.0(9.8, 20.5) vs 22.0(18.0, 24.0); Z=2.17, P=0.030), and between the poor prognosis group ( n=13) and the good prognosis group ( n=15; 14.0(10.0, 22.0) vs 22.0(19.8, 25.3); Z=2.47, P=0.013) were significantly different. Compared with the good prognosis group, the cerebral glucose metabolism in the poor prognosis group was decreased in the bilateral frontal lobe, lateral temporal lobe, inferior parietal lobule and cingulate gyrus, but increased in the brainstem, bilateral lentiform nucleus and bilateral paracentral lobule/postcentral gyrus (all t=1.71, all P<0.05). Compared with the non-recurrence group, the metabolism of bilateral medial frontal gyrus, anterior cingulate gyrus, bilateral insula, superior temporal gyrus and thalamus decreased in the recurrence group, while the metabolism of bilateral precentral gyrus, inferior frontal gyrus and bilateral lentiform nucleus increased (all t=1.71, all P<0.05). Conclusion:18F-FDG PET imaging reveals the differences in brain metabolism of anti-LGI1 antibody-related encephalitic patients at baseline with different outcomes (prognosis, recurrence or not), which can provide a new perspective for the clinical evaluation of the disease at baseline.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Objective:To prepare aldolylated hyaluronic acid-modified antimicrobial carbon dots (AHA-CDs) eye drops and evaluate its antibacterial activity against Staphylococcus aureus in vitro and in vivo. Methods:AHA-CDs eye drops were synthesized by modifying small particle size positively charged carbon dots and introducing aldehyde-based hyaluronic acid.The AHA-CDs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy.The antibacterial activity of AHA-CDs against Staphylococcus aureus was evaluated using the microdilution method, plate counting, and live-dead bacteria fluorescence staining in vitro.The mouse bacterial keratitis model was established by removing the corneal epithelium after ring drilling and inoculating Staphylococcus aureus.Eighteen conventional female C57BL/6 mice aged 6-8 weeks were selected and divided into a blank control group, an AHA-CDs-treated group and a tobramycin-treated group of 6 mice each using random number table method, and the mice were treated with phosphate buffer saline, 80 μg/ml AHA-CDs, and 80 μg/ml tobramycin eye drops three times daily for 5 consecutive days accordingly to assess antibacterial activity against Staphylococcus aureus in vivo.Another 12 mice were divided into an AHA-CDs group and a normal control group using the random number table method, with 6 mice in each group, which were treated with 80 μg/ml AHA-CDs and phosphate buffer saline for 7 days.The mice were then sacrificed.Their eyeballs were removed and stained with hematoxylin-eosin to observe and compare the morphology and integrity of the eyeballs between the two groups to evaluate the treatment's biosafety.The use and care of the animals complied with the principles of the ARRIVE guidelines.The study protocol was approved by the Ethics Committee of the Experimental Animal Care of Henan Eye Hospital (No.HNEECA-2022-17). Results:The successful preparation of AHA-CDs was demonstrated by transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. In vitro studies showed that the minimum inhibitory concentration of AHA-CDs against Staphylococcus aureus was approximately 8 μg/ml, which effectively inhibited bacterial growth at a lower concentration.Plate counting results showed that only 20% of the bacteria survived after 10 minutes of treatment with AHA-CDs.Fluorescence staining of live/dead bacteria showed obvious red fluorescence signals after 4 hours of treatment with AHA-CDs and SP-CDs. In vivo studies showed that, after 5 days of treatment with AHA-CDs eye drops, the corneas of mice with bacterial keratitis were obviously transparent, and the corneal epithelium was basically repaired.In contrast, the tobramycin-treated group exhibited incomplete epithelial repair and mild corneal edema. In vivo safety evaluation revealed that the eye tissue morphology remained intact and no structural abnormalities were observed after AHA-CDs treatment. Conclusions:AHA-CDs eye drops have superior antibacterial effects in vivo and in vitro, and inactivate bacteria rapidly and effectively.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Recent studies have demonstrated that bitter taste receptors are distributed not only in oral cavity but also in non-gustatory systems,such as the respiratory,digestive,reproductive and cardiovascular systems.The physiological role of bitter taste receptors is to recognize bitter substances or bacterial secretions,to trigger the immune response and to maintain the internal environmental homeosta-sis.In addition,oral bitter taste receptors are expressed not only in taste buds,perceiving bitter taste,but also in many other parts of periodontal tissues,which is the potential treatment target for oral infectious diseases.This review summarized the expression and distri-bution of oral bitter taste receptors which was off the taste buds and their roles in regulating oral inflammation and oral bacteria,dis-cussed the effects of genetic polymorphism of bitter taste receptor 38 subtype(TAS2R38)on innate immunity and its relationship with the susceptibility of dental caries and periodontal,aimed to provide novel ideas for the better prevention and treatment of dental caries and periodontal diseases.

Objective To investigate the effect of microRNA-223(miR-223)on prostate cancer cell damage by regulating the Kelch-like epichlorohydrin related protein 1(Keap1)/nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods The prostate cancer cell line PC3 was cultured and randomly divided into control,down-regulated miR-223,and up-regulated miR-223 groups.Changes in miR-223 expression,cell proliferation rate,cell migration number,cell invasion number,apoptosis rate,and expression level of Keap1/Nrf2/ARE signaling pathway were explored.Results Compared with the control group,the cell invasion number,cell migration number,cell proliferation rate,Nrf2 and ARE expression increased at 24,48 and 72 h in down-regulated miR-223 group,while the expressions of miR-223,Keap1 and apoptosis rate decreased(P<0.05).Compared with the down-regulated miR-223 group,24,48 and 72 h cell proliferation rate,cell invasion number,cell migration number,ARE and Nrf2 expression decreased in the up-regulated miR-223 group,while miR-223,apoptosis rate and Keap1 expression increased(P<0.05).Conclusion Regulation of miR-223 effectively ameliorates prostate cell injury,and the mechanism may be related to the Keap1/Nrf2/ARE signaling pathway.

Objective To explore the expression and significance of miR-21 in patients with primary gout. Methods The patients were divided into 4 groups: 35 acute gout patients (AG), 50 intermittent gout patients (IG), 25 chronic gout patients (CG) and 39 healthy patients. Their peripheral blood were collected and laboratory indexes were recorded. The expression of miR-21 and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) mRNA in the peripheral blood mononuclear cells (PBMCs) was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The blood and clinical data of another 5 healthy volunteers were collected, their peripheral blood was stimulated with 100 μg/ml monosodium urate (MSU) for 1 hour, pho-sphate buffer (PBS) was used as controls, then the expression of microRNA (miR)-21, NLRP3, interleukin (IL)-1β mRNA was detected by RT-qPCR. Rank sum test and spearman correlation analysis were used for data analysis. Results In primary gout patients, the expression of miR-21 in AG [12 ×10-4 (8.0 ×10-4)], IG [9.4 ×10-4 (6.9 ×10-4)], CG [7.3 ×10-4 (5.6 ×10-4)] was significantly higher than that in healthy control group [1.0×10-4(2.0×10-4)] (Z=9.83, P=0.02], while the expression of NLRP3 in AG[0.0444(0.0233)], IG[0.0581(0.0326)], CG[0.0314(0.0198)] was significantly lower than that in healthy control group [0.0886(0.0359)] (Z=13.82, P<0.01). In the primary gout of IG group, the expression of miR-21 was positively correlated with NLRP3 mRNA (r=0.449, P=0.016). After stimulated by 100 μg/ml MSU, the expression of miR-21 of the stimulated group [8.78×10-4(14×10-4)] was higher than that in the control group [6.25×10-4(6×10-4)](Z=-2.203, P<0.05), and the expression of IL-1βin stimulated group [3.06(2.00)] was higher than that in the control group [2.64 (1.22] (Z=-2.203, P<0.05). The level of miR-21 in patients with primary gout was positively correlated with the level of uric acid (UA), glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) (r=0.473, 0.639, 0.487, P<0.05). Conclusion The increase of miR-21 in patients with primary gout may be involved in the inflammatory reaction of gout.

Objective To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China.Methods Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results (1)The ratio of male to female in patients with gout was 14.7:1.The mean age of onset was(48.8 ± 15.1)years old.Mean serum urate level was(526.7 ± 132.3)μmol/L.Patients'education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity[51.9%(3 536/6 814)];(3)Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia.Most patients had the disease less than 5 years,and the longer the course,the more flares in the previous year of entry;(4)Febuxostat was the mostly used urate-lowering medication.20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration,and 18.9%(267/1 412),29.1%(215/739)and 38.1%(101/265)of them reached the control target of serum urate levels,respectively.After treatment,patients'liver function was not affected,but serum creatinine levels decreased significantly. Conclusions The proportion of gout patients who reach target serum urate level is very low.Further steps including education and survey need to be carried on.