Objective To systematically analyze the medical radiation exposure levels in a district of Ningbo City and to provide a scientific basis for the reasonable and effective control of medical radiation exposure. Methods Based on the radiological diagnosis frequency and dose information system, basic medical radiation exposure data were collected, such as radiation doses received by patients in various X-ray diagnostic examinations, from all 13 public medical institutions in a district of Ningbo City from January 1 to December 31, 2020. The data were analyzed for the percentage and collective effective dose of various diagnostic examinations, the distribution of examinations by sex and age, and the number of patients undergoing two or more examinations and their cumulative doses within multiple time intervals. Results Among medical X-ray diagnostic examinations in the district, the percentages of CT examination and routine photography examination were 50.88% and 47.93%, respectively, and the collective effective dose of CT examination accounted for 97.75%. By age and sex, the frequency of examination was the highest in the age group of 45-54 years, and the frequency of examination in the male was higher than that in the female before age 55. The annual effective dose for two patients exceeded 100 mSv. Conclusion In this study, CT examination accounted for up to 50.88% of all medical X-ray diagnostic examinations, and contributed 97.75% of the collective effective dose, highlighting the need for particular attention to the justification of medical radiation exposure from CT.

Objective With the increase in pet-owning households in China, veterinary clinics have increased at an annual rate of 19.86%. However, the management blind area that may exist in multi-department supervision has led to a significantly worse working environment of radiation workers in veterinary clinics than that of medical institutions. The purpose of this study was to understand the levels of occupational external exposure of radiation workers in veterinary clinics in China, analyze the occupational risks faced by radiation workers in veterinary clinics, contribute to the protection of the occupational health of radiation workers, and provide data and scientific basis for the formulation of national relevant regulations and standards. Methods The individual dose monitoring data of radiation workers in selected veterinary clinics in 2022 were obtained from the National Individual Dose Registration System. Results This study involved 1868 radiation workers from 1216 veterinary clinics in 28 provinces and municipalities in China. The maximum annual effective dose was 8.93 mSv, the annual collective dose was 536.77 man·mSv, the average annual effective dose was 0.29 mSv, and the median was 0.15 mSv. The largest proportion of individuals (94.5%) received a dose of less than 1.0 mSv, while 5.4% had doses ranging from 1.0 mSv to less than 5.0 mSv. For radiation workers with an annual effective dose of 1.0 mSv and above, the individual distribution ratio of radiation workers in veterinary clinics was significantly higher compared with those in medical institutions and industrial applications (P < 0.05). Conclusion The levels of occupational external exposure of radiation workers in veterinary clinics meet the requirements of national standards. However, attention should still be paid to the radiation protection of radiation workers in veterinary clinics. This includes enhancing the responsibility awareness of veterinary clinic owners, strengthening protection training for radiation workers, protecting the occupational health of practitioners, and preventing the occurrence of occupational radiation diseases.

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.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To prepare water-soluble graphene-based itraconazole antifungal eye drops and evaluate its antifungal activity against Fusarium solani. Methods:By oxidative modification of graphene and modification of polymer materials, water-soluble graphene oxide-modified polyethylene glycol (GO-PEG) composites were prepared.The composites were characterized by scanning electron microscopy, zeta potential, and Raman spectroscopy.The antifungal drug itraconazole was loaded onto the GO-PEG vector by solvent evaporation method, and itraconazole eye drops were obtained.The drug loading of itraconazole eye drops was measured using a UV and visible spectrophotometer.The antifungal effect in vitro was assessed by the microdilution method and light microscopy. Results:Scanning electron microscopy showed that GO-PEG had a two-dimensional nanosheet structure and many wrinkles.The zeta potential of GO-PEG was -42.40 mV.Raman spectroscopy showed that the ID/ IG of GO-PEG was 1.003.Using the water-soluble GO-PEG vector, a maximum itraconazole concentration of 10 mg/ml was achieved with a 10 000-fold increase in apparent solubility (10 mg/ml vs 0.001 mg/ml). The antifungal results showed that the minimum inhibitory concentration of itraconazole eye drops against Fusarium solani was approximately 1.88 μg/ml, but the GO-PEG vector has no significant antifungal activity against Fusarium solani. Conclusions:GO-PEG achieves effective loading and solubilization of itraconazole, demonstrating an in vitro inhibitory effect on Fusarium solani.

Objective: To explore the gene transduction method of chimeric antigen receptor (CAR) mediated by novel cationic polymer nanocarrier mPEG-P (Asp-AED-g-HFB) (PAEF) and PigyBac transposon system to modify natural killer (NK) cells, providing a new strategy for immunotherapy of cancer cells. Methods: PAEF/DNA (transposase+transposon) complex were prepared. The particle size distribution and surface potential of PAEF/DNA complexes were measured with Nano-ZSE Dynamic Light Scattering System (Malvern Instruments). The DNA encapsulation rate, release and stability of PAEF were evaluated by DNA gel electrophoresis, and then by combiningwithparticlesizeandsurfacepotentialtodeterminethepreferentialN/PratiotoenterNKcells.Thecell cytotoxicity of PAEF/DNA complexes under different N/P ratios was analyzed by CCK-8 cytotoxicity test. Transduction efficiency of NK cells was evaluated by Fluorescence microscopy and Flow cytometry, and the feasibility of PAEF gene transfection vectors was assessed. Results: PAEF could encapsulate DNA to form nano-complexes with the diameter of 100-150 nm, which was suitable to mediate DNA entering into cells. PAEF could completely encapsulate DNA with N/P ratio of 20. In the presence of reducing agent dithiothreitol (DTT), PAEF had a good ability to release DNA. NK-92 cells transfected with PAEF/DNA complex, which was formed at the N/P ratio of 80, attained a significantly higher cell viability than cells of lipofectamine transfection group [(72.50±3.9)% vs (64.03±1.8)%, P<0.05]; Fluorescence microscopic observation showed more fluorescence and higher fluorescence intensity in cells of PAEF/DNA group; Flow cytometry showed the highest transfection efficiency of 83.4%. Conclusions: Nanocarrier PAEF can encapsulate DNA well by electrostatic adsorption, and has good biocompatibility and high efficiency for gene transduction. It provides a good experimental basis for adoptive immunotherapy.

Objective:To study the pharmacokinetics of the broad-spectrum antifungal drug butenafine nanomicelles (BTF-NM) after topical instillation.Methods:The self-assembly method was used to prepare BTF-NM.The particle size, Zeta potential, and polydispersity index (PDI) of BTF-NM were measured by a nano-particle size-Zeta potential analyzer, and the encapsulation efficiency was determined by high-performance liquid chromatography (HPLC). Forty-two healthy New Zealand white rabbits without eye disease were randomly divided into the BTF-NM group and the BTF suspension (BTF-S) group.The corresponding drugs were instilled in the conjunctival sac with a single instillation of 50 μl.The 7.5 mm filter paper was placed in the conjunctival sac of rabbit eye for 1 minute at 5, 15, 30, 60, 120, 180, 240 minutes after the administration.Then the rabbits were sacrificed by intravenous injection of 4% sodium pentobarbital solution through the ears of the rabbits.The aqueous humor was extracted and the corneal tissue was dissected.The drug concentration of BTF in different tissues was measured by HPLC.The study was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HNEECA-2019-01).Results:The particle size and PDI of BTF-NM were (15.65±0.04)nm and 0.11±0.01, respectively, the Zeta potential was (-0.29±0.36)mV, the encapsulation rate was (98.38±0.29)%.The peak time of the drug both in tears and corneal tissues after BTF-NM application was 5 minutes.The peak concentrations of the drug in tears and corneas of the BTF-NM group were (485.21±66.29) μg/g and (12.53±2.32) μg/g, which were 5.6 and 78 times than that of the BTF-S group, respectively.Within the observation time, the mass fractions of the drug in tears and corneas of the BTF-NM group at each time point were significantly higher than those of BTF-S group at corresponding time points (all at P<0.01), respectively.The area under the concentration-time curve (AUC) 0-240 minutes in tears and corneas of the BTF-NM group was 7 488.90 (μg/g)·minute and 829.01 (μg/g)·minute, which was 7.2 and 52 times than that of the BTF-S group, respectively.No drugs were detected in the aqueous humor of the BTF-NM group and the BTF-S group. Conclusions:BTF-NM is an ideal agent with a simple preparing process, high drug encapsulation efficiency and small particle size.Compared with BTF suspension, BTF-NM can significantly improve the bioavailability of BTF in rabbit corneas.

Objective:To investigate the pharmacokinetics of econazole solid lipid nanoparticles (E-SLNs) after administration of one single dose in rabbit eyes.Methods:E-SLNs with 0.2% econazole was prepared by microemulsion method.Its antifungal activity against Fusarium isolated from the eyes of patients with fungal keratitis was evaluated in vitro and was compared with natamycin eye drops.Four healthy New Zealand white rabbits were assigned to the blank control group without any drug interference during the experimental period, and other matched 21 rabbits were randomized into 7 groups according to the specimen-collected time, with 3 rabbits in each group.E-SLNs of 50 μl was singly applied to conjunctival sac in both eyes in the 21 rabbits, and tear was collected using a filter paper at 5, 15, 30, 60, 90, 120 and 180 minutes following administration of the drug.The cornea specimen was collected at above-mentioned time points respectively.The drug levels in each sample were assayed by high performance liquid chromatography.The accuracy, recovery rate, stability and antifungal activity of the drugs in tear fluid and cornea were detected.This study protocol was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HENNCA-2017-22). Results:For the tear samples and corneal tissue samples, the relative standard deviation ( RSD) of the accuracy of the drug was 2.34%-4.04%; the stability analysis result showed that the RSD of the drugs was less than 10%.The 50% minimum inhibitory concentration (MIC 50) and 90% minimum inhibit concentration (MIC 90) of E-SLNs were 0.37 μg/ml and 0.89 μg/ml, respectively.The MIC 50 and MIC 90 of natamycin were 1.15 μg/ml and 1.70 μg/ml, respectively.After one single dose application of E-SLNs eye drops, the peak time of the drug in tears fluids and cornea of rabbits were 5 minutes and maximum concentrations in tears and cornea were 597.64 μg/g and 33.15 μg/g, respectively. Conclusions:The drug levels in tears and cornea achieved are higher than MIC against Fusarium.

Objective To investigate the corneal permeability of cyclosprin A (CsA) loaded on polymeric vector after topical application.Methods The grafted copolymer chitosan-graft-cyclodextrin (CS-g-CD) was synthesized,and the physicochemical structures of the polymer were investigated using nuclear magnetic resonance spectroscopy (NMR) and fourier transform infrared spectroscopy (FT-IR).A novel CsA eye drop was prepared using the grafted copolymer as carrier material.The physicochemical properties of eye drop,including drug-loading content,osmotic pressure and viscosity were investigated by high performance liquid chromatography-mass spectrometry (HPLC-MS),osmotic pressure gauge and viscometer,respectively.New Zealand albino rabbits were randomly divided into intact cornea CsA group,epithelium debrided CsA group and epithelium debrided control group.The corneal epithelia of the left eyes was debrided in the cornea epithelium debrided group.Cornea irritation test was performed on New Zealand albino rabbits.The aqueous humor was taken and the corneas were collected at 0.5 hour and 1 hour after instilled.The concentration of CsA was measured by HPLC-MS.Cy5 labeled vector loaded with Coumarin 6 served as model copolymers system,the penetration capabilities of the double fluorescent labeling copolymers system were monitored in vivo using two-photon scanning fluorescence microscopy on murine corneas after topical application.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The polymer of CS-g-CD was successfully synthesized and confirmed using NMR and FT-IR.The drug loading of CsA in eye drop solution was 0.06 ％;the osmotic pressure was 305 mOsmol/kg and the viscosity was 36.5 cP.The CsA drug delivery system had a reversible temperature-sensitive drug release behavior and had no obvious irritation on the eyes of New Zealand rabbits.One hour after treatment,the concentration of CsA in the cornea and aqueous humor of epithelium debrided CsA group was (5.88 ± 1.46) μg/g and (149.19 ± 3.93) ng/ml,respectively,which was significantly higher than (3.98 ±0.95) μg/g and (30.25± 11.43) ng/ml in epithelium debrided control group (both at P＜0.05);the concentration of CsA in the aqueous humor of intact cornea CsA group was (7.23 ± 1.31)ng/ml,which was significantly lower than that in epithelium debrided CsA group (P＜0.05).Polymer vectors were mainly retained in the corneal epithelium,and coumarin 6 gradually diffused into the deep corneal stroma with time.Conclusions The grafted copolymer can load CsA,and the eye drop can effectively overcome the corneal barrier and increase the corneal permeability of CsA.

Objective To investigate the corneal permeability of cyclosprin A (CsA) loaded on polymeric vector after topical application. Methods The grafted copolymer chitosan.graft.cyclodextrin ( CS.g.CD ) was synthesized, and the physicochemical structures of the polymer were investigated using nuclear magnetic resonance spectroscopy ( NMR) and fourier transform infrared spectroscopy ( FT.IR) . A novel CsA eye drop was prepared using the grafted copolymer as carrier material. The physicochemical properties of eye drop,including drug.loading content, osmotic pressure and viscosity were investigated by high performance liquid chromatography.mass spectrometry ( HPLC.MS) ,osmotic pressure gauge and viscometer,respectively. New Zealand albino rabbits were randomly divided into intact cornea CsA group, epithelium debrided CsA group and epithelium debrided control group. The corneal epithelia of the left eyes was debrided in the cornea epithelium debrided group. Cornea irritation test was performed on New Zealand albino rabbits. The aqueous humor was taken and the corneas were collected at 0. 5 hour and 1 hour after instilled. The concentration of CsA was measured by HPLC.MS. Cy5 labeled vector loaded with Coumarin 6 served as model copolymers system, the penetration capabilities of the double fluorescent labeling copolymers system were monitored in vivo using two.photon scanning fluorescence microscopy on murine corneas after topical application. The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results The polymer of CS.g.CD was successfully synthesized and confirmed using NMR and FT.IR. The drug loading of CsA in eye drop solution was 0. 06 ％;the osmotic pressure was 305 mOsmol/kg and the viscosity was 36. 5 cP. The CsA drug delivery system had a reversible temperature.sensitive drug release behavior and had no obvious irritation on the eyes of New Zealand rabbits. One hour after treatment,the concentration of CsA in the cornea and aqueous humor of epithelium debrided CsA group was (5. 88±1. 46)μg/g and (149. 19±3. 93)ng/ml,respectively,which was significantly higher than (3. 98±0. 95)μg/g and (30. 25±11. 43)ng/ml in epithelium debrided control group (both at P<0. 05);the concentration of CsA in the aqueous humor of intact cornea CsA group was ( 7. 23 ± 1. 31 ) ng/ml, which was significantly lower than that in epithelium debrided CsA group ( P<0. 05 ) . Polymer vectors were mainly retained in the corneal epithelium, and coumarin 6 gradually diffused into the deep corneal stroma with time. Conclusions The grafted copolymer can load CsA,and the eye drop can effectively overcome the corneal barrier and increase the corneal permeability of CsA.