BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Objective:To investigation the situation of water improvement projects in villages affected by drinking water-type endemic fluorosis in Qinghai Province and the prevalence of dental fluorosis among children, in order to provide a basis for consolidating the achievements in prevention and control of drinking water-type endemic fluorosis and adjusting prevention and control measures.Methods:The monitoring data on drinking water-type endemic fluorosis were collected from the disease prevention and control centers in various counties of Qinghai Province from 2021 to 2023, the situation of water improvement projects, the fluorine content of domestic drinking water and the prevalence of dental fluorosis in children aged 8 to 12 years old were retrospectively analyzed.Results:From 2021 to 2023, the numbers of villages affected by drinking water-type endemic fluorosis in Qinghai Province were 338, 335, and 328, respectively. The numbers of water improvement projects were 125, 127 and 124, respectively. The normal operation rates were 100%, 100% and 99.19% (123/124), respectively. The qualified rates of water fluoride level were 100%, 99.21% (126/127) and 99.19% (123/124), respectively. The detection rates of dental fluorosis among children aged 8 to 12 were 4.34% (515/11 877), 5.70% (646/11 331) and 4.48% (490/10 943), respectively. There was a statistically significant difference in the detection rate of dental fluorosis among children in different years (χ 2 = 22.79, P < 0.001). Conclusions:The overall operation status of water improvement project in villages affected by drinking water-type endemic fluorosis in Qinghai Province is generally good, but there has been some relaxation in management and maintenance in the later stage, and there is a phenomenon of project intermittency. The detection rate of dental fluorosis among children aged 8 to 12 remains low, and endemic fluorosis caused by drinking water is under continuous control.

Objective:To investigation the situation of water improvement projects in villages affected by drinking water-type endemic fluorosis in Qinghai Province and the prevalence of dental fluorosis among children, in order to provide a basis for consolidating the achievements in prevention and control of drinking water-type endemic fluorosis and adjusting prevention and control measures.Methods:The monitoring data on drinking water-type endemic fluorosis were collected from the disease prevention and control centers in various counties of Qinghai Province from 2021 to 2023, the situation of water improvement projects, the fluorine content of domestic drinking water and the prevalence of dental fluorosis in children aged 8 to 12 years old were retrospectively analyzed.Results:From 2021 to 2023, the numbers of villages affected by drinking water-type endemic fluorosis in Qinghai Province were 338, 335, and 328, respectively. The numbers of water improvement projects were 125, 127 and 124, respectively. The normal operation rates were 100%, 100% and 99.19% (123/124), respectively. The qualified rates of water fluoride level were 100%, 99.21% (126/127) and 99.19% (123/124), respectively. The detection rates of dental fluorosis among children aged 8 to 12 were 4.34% (515/11 877), 5.70% (646/11 331) and 4.48% (490/10 943), respectively. There was a statistically significant difference in the detection rate of dental fluorosis among children in different years (χ 2 = 22.79, P < 0.001). Conclusions:The overall operation status of water improvement project in villages affected by drinking water-type endemic fluorosis in Qinghai Province is generally good, but there has been some relaxation in management and maintenance in the later stage, and there is a phenomenon of project intermittency. The detection rate of dental fluorosis among children aged 8 to 12 remains low, and endemic fluorosis caused by drinking water is under continuous control.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Objective:To find out the variety, producing area, fluorine content of brick tea in Qinghai Province, and the drinking situation of brick tea among people, so as to provide basis for preventing and curing endemic fluorosis of drinking tea type.Methods:From April to November 2019, according to historical data, in 3 066 administrative villages in 39 counties (cities, districts, hereinafter referred to as counties) in Qinghai Province that had the habit of drinking brick tea, 10 families were randomly selected from each village to investigate the demographic data of each family and the drinking situation of brick tea, to collect brick tea samples to determine the fluorine content, and to calculate the daily average brick tea fluorine intake of the population > 16 years old.Results:A total of 31 067 brick tea samples were collected. The main brick tea consumed by the residents in the whole province was Fu brick tea, accounting for 89.97% (27 952/31 067), followed by Kang brick tea [5.12% (1 592/31 067)], Green brick tea [2.29% (710/31 067)], Black brick tea [1.85% (574/31 067)], and golden tip, mosaic, black wool and other brick tea [0.77% (239/31 067)]. There were 523 brands of brick tea in circulation in the province, among which there were 410 brands produced in Hunan Province, 26 brands in Sichuan Province, 11 brands in Hubei Province, and 76 brands in Henan Province and other provinces. The average content of fluorine in brick tea was 646.1 mg/kg, which ranged from 40.0 to 2 295.0 mg/kg. Brick tea with fluorine content ≤300 mg/kg accounted for 7.80% (2 422/31 067) of all samples. The annual average consumption of brick tea by population > 16 years old was 1.09 (0.35 - 7.40) kg, and the daily average brick tea fluorine intake was 1.93 (0.39 - 18.64) mg. There were 15 counties and 486 administrative villages in which the daily average brick tea fluorine intake exceeded the national standard (3.5 mg).Conclusion:The main brick tea in circulation in Qinghai Province is Fu brick tea, which has high fluorine content and is harmful to people, and prevention and control measures should be taken as soon as possible.

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic

Objective:To observe and evaluate the effect of health education on drinking brick-tea type fluorosis in Zhiduo County, Qinghai Province, so as to provide basis for further formulating health education strategies.Methods:From April 2019 to April 2020, according to the historical prevalence of drinking brick-tea type fluorosis in Zhiduo County, Qinghai Province, 3 townships (towns) were selected to carry out the health education activities on drinking brick-tea type fluorosis for students of grade 4 - 6, village doctors, adults and monks in each township (town). We carried out a one-year publicity on the prevention and treatment of drinking brick-tea type fluorosis, distributed health education materials and organized health education activities. Before and after the intervention, we conducted a questionnaire survey on health education among the target population (grade 4 - 6 students, village doctors, adults and monks), to evaluate the awareness rate and behavior formation rate of fluorosis prevention and control, and to evaluate the intervention effect.Results:A total of 86 students of grade 4 - 6, 40 village doctors, 42 adults and 20 monks were investigated, after the intervention, the awareness rates of prevention and treatment of drinking brick-tea type fluorosis in grade 4 - 6 students, village doctors, adults and monks were 87.98% (227/258), 96.67% (116/120), 81.75% (103/126), 83.33% (50/60), respectively, which were significantly higher than those before the intervention [38.38% (76/198), 83.33% (100/120), 15.45% (19/123), 28.89% (13/45), P < 0.05]. After the intervention, the behavior formation rates of prevention and treatment of the drinking brick-tea type fluorosis in grade 4 - 6 students, village doctors, adults and monks were 74.42% (128/172), 72.50% (58/80), 52.38% (44/84), 60.00% (24/40), respectively, which were significantly higher than those before the intervention [14.39% (19/132), 38.75% (31/80), 3.66% (3/82), 0(0/28), P < 0.05]. Conclusion:The comprehensive intervention measures based on health education can significantly improve the knowledge of local residents, and improve their bad drinking habits of drinking tea, which is of great significance to the prevention and treatment of drinking brick-tea type fluorosis.

Objective:To study the epidemic status of drinking tea type endemic fluorosis in Qinghai Province.Methods:In 2019, in counties (cities, districts, referred to as counties) that had the habit of drinking brick tea in 8 cities (prefectures) of Qinghai Province, epidemiological investigation of drinking tea type endemic fluorosis was carried out in villages. Ten households were randomly selected from each village, to investigate the demographic data of each household and the drinking situation of brick tea, residents' drinking water and brick tea samples were collected to determine the fluorine content, and calculate the daily per capita tea fluorine intake. At the same time, skeletal fluorosis was examined in all adults over 25 years old, and dental fluorosis was examined in all children aged 8 to 12 years old in survey sites. The content of fluorine in tea and water was detected by ion selective electrode method; the diagnosis of skeletal fluorosis was based on "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the diagnosis of dental fluorosis was based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011).Results:The mean (range) of fluorine of the 3 602 water samples was 0.31 (0.20 - 1.00) mg/L. The geometric mean (range) of fluorine of the 31 067 brick tea samples was 646 (40 - 2 295) mg/kg, the fluorine content of the brick tea ≤300 mg/kg accounted for 7.80% (2 422/31 067) of the total samples. The proportion of drinking Fu brick-tea was 89.97% (27 952/31 067); and the daily per capita tea fluorine intake was 1.93 mg, the daily per capita tea fluorine intake in Guoluo, Yushu and Hainan prefectures were higher than the health standard (3.50 mg). The detection rate of skeletal fluorosis in adults was 0.16% (2 357/1 484 907), Yushu Prefecture was the highest [29.23% (592/2 025)], followed by Guoluo Prefecture, which was 8.21% (771/9 393). The detection rate of dental fluorosis in children was 4.79% (8 076/168 623), Yushu Prefecture was the highest [32.61% (1 562/4 790)].Conclusion:Drinking tea type endemic fluorosis is prevalent in Qinghai Province, with obvious regional characteristics, covering a large population. The disease is relatively popular in Yushu Prefecture and Guoluo Prefecture.