ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.

Hymenoptera venom-sensitized patients may experience systemic reactions,and severe patients may even present life-threatening symptoms such as collapse and syncope.Here we report a case of anaphylaxis triggered by multiple sensitization with Hymenoptera venom.Clinical diagnosis and in vitro allergen testing showed that the patient developed anaphylaxis to wasp and/or fire ant venom.In clinical practice,allergen testing of patients with anaphylaxis to Hymenoptera venom aims to clarify the sensitizing proteins and lay a foundation for future research on immunotherapy for Hymenoptera venom in China.For Hymenoptera-allergic patients,daily outdoor protection is crucial,and an epinephrine syringe can be carried with them if necessary.
Anaphylaxis/etiology* ; Humans ; Animals ; Hymenoptera/immunology* ; Arthropod Venoms/adverse effects* ; Male ; Female ; Middle Aged ; Adult ; Wasp Venoms/adverse effects*

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ²=18.396,P<0.01;66.7% vs 16.7%,χ²=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ²=6.597,P<0.05;37.0% vs 7.4%,χ²=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were β-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ²=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.
Male ; Animals ; Cattle ; Female ; Child ; Humans ; Milk Hypersensitivity/diagnosis* ; Cross-Sectional Studies ; Food Hypersensitivity ; Allergens ; Immunoglobulin E

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ²=18.396,P<0.01;66.7% vs 16.7%,χ²=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ²=6.597,P<0.05;37.0% vs 7.4%,χ²=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were β-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ²=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.
Male ; Animals ; Cattle ; Female ; Child ; Humans ; Milk Hypersensitivity/diagnosis* ; Cross-Sectional Studies ; Food Hypersensitivity ; Allergens ; Immunoglobulin E

Sporotrichosis, a fungal infection caused by Sporothrix species, can greatly lead to chronic inflammation of the skin, mucosa, and lymphatic vessels and disseminate systemically sometimes, even threatening life. It is known that Sporothrix is distributed worldwide, while in China, most of the cases were reported in northeast China and parts of south China. Sporothrix globosa is the main source of infection, and other regions may lack relevant awareness and attention to the disease, making it a public health challenge in China. Thus, it is important to understand its epidemiology and public health risks to prevent and control the disease properly.

AIM: To compare the difference and consistency of corneal refractive power and astigmatism measured by CASIA2 and IOL Master 700 in patients with age-related cataract.METHODS: Retrospective study. A total of 153 patients(232 eyes)with age-related cataract admitted to Daping hospital from November to December 2021 were selected. The flat keratometry(Kf), steep keratometry(Ks), mean keratometry(Km), degree and axis of astigmatism(vector representation J0 and J45)of the anterior, posterior surfaces together with the total cornea from cataract patients were measured by CASIA2 and IOL Master 700, respectively. The difference, correlation and consistency of the two instruments were analyzed.RESULTS:There was no significant difference in J45 values of posterior corneal surface measured by CASIA2 and IOL Master 700(-0.006±0.038D vs. -0.005±0.044D, P>0.05), but there were significant differences in other parameters(all P<0.05). All parameters measured by the two instruments were significantly positive correlated(all r/rs>0.7, P<0.001); Bland-Altman analysis showed that the refractive power and astigmatism of the anterior cornea surface measured by the two facilities were in good consistency, while the refractive power of the posterior surface and the whole cornea showed poor consistency.CONCLUSION: CASIA2 and IOL Master 700 showed little differences and good consistency in the refractive power and astigmatism of the anterior, posterior and total corneal surface in cataract patients, which seems interchangeable. However, the refractive power of the posterior surface and the whole cornea has significant differences and poor consistency, which should not be interchange casually.

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*