Objective To investigate the frequency and dose of X-ray computed tomography (CT) medical exposure in Shantou City, and to evaluate the collective effective dose burden of residents caused by CT medical exposure. Methods The study subjects were selected using the stratified random sampling method from CT scanners in all medical institutions in Shantou City in 2020. CT application units were divided into the four tiers of municipal hospitals, district hospitals, subdistrict hospitals, and private hospitals, and 50% of the hospitals in each tier were randomly selected according to the number of hospitals in the tier. The study analyzed CT dose index results, CT scanning standard conditions, and the distribution of characteristic doses of medical exposure to evaluate the dose burden of residents in Shantou City caused by CT medical exposure. Results There were 51 CT scanners in medical institutions in Shantou City. By the end of 2020, the average number of CT scanners per million population was 9.30, and the frequency of CT medical exposure was 135.24 per 1000 population. Jinping District had the highest number of CT scanners per million population (23.2), while Chaoyang District had the lowest number of CT scanners per million population (3.6). The median and range of effective doses for different scan regions were 1.65 (0.76, 4.49) mSv in the head, 4.12 (1.90, 53.21) mSv in the chest, 5.96 (2.68, 10.25) mSv in the abdomen, and 10.30 (4.12, 12.67) mSv in the lumbar spine. By the end of 2020, the effective dose to the public in Shantou City was 6080.67 Sv·person, and the average annual effective dose per person was 1.10 mSv. Conclusion Medical exposure is the most important factor affecting resident dose burden, particularly the overuse of medical exposure examinations. CT examination is the most significant component of medical exposure causing resident dose burden. Reducing unnecessary medical exposure, ensuring the rational use of CT examination, and properly utilizing personal protective equipment are effective measures to minimize the dose burden on examinees.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To report a Charcot-Marie-Tooth disease type 2 (CMT2) patient with SORD gene mutations, aiming to enhance the understanding of SORD gene-associated peripheral neuropathy. Methods:A CMT2 patient with SORD gene mutations was identified through whole exome sequencing in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January 2024, and the patients′ clinical features were elaborated in detail. 31-Phosphorus magnetic resonance spectroscopy ( 31P-MRS) was employed to assess the phosphorus profile of the limbs, and real-time quantitative reverse transcription polymerase chain reaction was utilized to detect peripheral blood SORD gene mRNA expression levels in the patient, the family members, and the normal control. Additionally, the genetic and clinical characteristics of SORD gene mutation-related CMT2 and distal hereditary motor neuropathy (dHMN) were reviewed by searching the CNKI and PubMed databases. Results:The male CMT2 patient was 15 years old, presented with early-onset lower limb muscle weakness and atrophy, hypoesthesia, reduced tendon reflexes, and flat feet. 31P-MRS examination indicated that the pH of the patient′s leg was lower than that of the upper limb. Whole exome sequencing showed the patient carrying complex heterozygous mutations c.757delG (p.Ala253GlnfsTer27) and c.218C>T (P.Ser73Leu) in the SORD gene. The mRNA expression of the SORD gene of the patient′s mother [0.623(0.614, 0.645)] was lower than that of the patient′s father [0.961(0.888,1.020), H=13.330, P=0.007] and normal people [1.001(0.917, 1.092), H=14.830, P=0.002]. Through literature review, it is found that 31 SORD gene mutations have been reported worldwide, among which c.757delG (p.Ala253GlnfsTer27) was found to be a hotspot mutation, and all patients exhibited an autosomal recessive inheritance pattern. Conclusions:A patient with CMT2 caused by a compound heterozygous mutation c.757delG/c.218C>T in the SORD gene, with the main clinical symptoms of bilateral lower limb weakness, atrophy, sensory disturbance and reduced tendon reflexes is reported. Furthermore, 31P-MRS of the extremities is anticipated to both early and sensitively detect muscle lesions in patients with hereditary peripheral neuropathy.

Using conventional broth microdilution assays,the synthetic phenolic antioxidant 2,6-di-tert-butyl-4-methylphenol(butylated hydroxytoluene,BHT)was screened for synergistic antimi-crobial activity with β-lactam antibiotics.Further validation through checkerboard assays,growth curve analysis,and time-kill curve experiments confirmed the synergistic effect of BHT and β-lac-tams against methicillin-resistant Staphylococcus aureus(MRSA)(FICI≤0.5).To elucidate the underlying mechanism of synergy,this study evaluated changes in membrane permeability and pro-ton transmembrane gradients-key factors in biofilm functionality-along with critical indicators of bacterial energy metabolism,including ATP levels and the NAD+/NADH ratio.The results dem-onstrated that BHT disrupts the proton motive force(PMF),impairs membrane potential,and perturbs bacterial energy homeostasis,thereby significantly enhancing the antibacterial efficacy ofβ-lactams.Furthermore,a murine pneumonia infection model was established to assess the in vivo therapeutic efficacy of BHT combined with amoxicillin.The combination therapy alleviated pulmo-nary tissue damage,reduced bacterial loads in target organs(liver,spleen,and lungs),and decreased systemic inflammatory responses.This study elucidates the synergistic antimicrobial action and mechanistic basis of BHT combined with amoxicillin,offering a novel combinatorial therapeutic strategy to address MRSA resistance.The findings hold significant clinical potential and research value for overcoming antibiotic resistance in MRSA infections.

Using conventional broth microdilution assays,the synthetic phenolic antioxidant 2,6-di-tert-butyl-4-methylphenol(butylated hydroxytoluene,BHT)was screened for synergistic antimi-crobial activity with β-lactam antibiotics.Further validation through checkerboard assays,growth curve analysis,and time-kill curve experiments confirmed the synergistic effect of BHT and β-lac-tams against methicillin-resistant Staphylococcus aureus(MRSA)(FICI≤0.5).To elucidate the underlying mechanism of synergy,this study evaluated changes in membrane permeability and pro-ton transmembrane gradients-key factors in biofilm functionality-along with critical indicators of bacterial energy metabolism,including ATP levels and the NAD+/NADH ratio.The results dem-onstrated that BHT disrupts the proton motive force(PMF),impairs membrane potential,and perturbs bacterial energy homeostasis,thereby significantly enhancing the antibacterial efficacy ofβ-lactams.Furthermore,a murine pneumonia infection model was established to assess the in vivo therapeutic efficacy of BHT combined with amoxicillin.The combination therapy alleviated pulmo-nary tissue damage,reduced bacterial loads in target organs(liver,spleen,and lungs),and decreased systemic inflammatory responses.This study elucidates the synergistic antimicrobial action and mechanistic basis of BHT combined with amoxicillin,offering a novel combinatorial therapeutic strategy to address MRSA resistance.The findings hold significant clinical potential and research value for overcoming antibiotic resistance in MRSA infections.

Objective:To report a Charcot-Marie-Tooth disease type 2 (CMT2) patient with SORD gene mutations, aiming to enhance the understanding of SORD gene-associated peripheral neuropathy. Methods:A CMT2 patient with SORD gene mutations was identified through whole exome sequencing in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January 2024, and the patients′ clinical features were elaborated in detail. 31-Phosphorus magnetic resonance spectroscopy ( 31P-MRS) was employed to assess the phosphorus profile of the limbs, and real-time quantitative reverse transcription polymerase chain reaction was utilized to detect peripheral blood SORD gene mRNA expression levels in the patient, the family members, and the normal control. Additionally, the genetic and clinical characteristics of SORD gene mutation-related CMT2 and distal hereditary motor neuropathy (dHMN) were reviewed by searching the CNKI and PubMed databases. Results:The male CMT2 patient was 15 years old, presented with early-onset lower limb muscle weakness and atrophy, hypoesthesia, reduced tendon reflexes, and flat feet. 31P-MRS examination indicated that the pH of the patient′s leg was lower than that of the upper limb. Whole exome sequencing showed the patient carrying complex heterozygous mutations c.757delG (p.Ala253GlnfsTer27) and c.218C>T (P.Ser73Leu) in the SORD gene. The mRNA expression of the SORD gene of the patient′s mother [0.623(0.614, 0.645)] was lower than that of the patient′s father [0.961(0.888,1.020), H=13.330, P=0.007] and normal people [1.001(0.917, 1.092), H=14.830, P=0.002]. Through literature review, it is found that 31 SORD gene mutations have been reported worldwide, among which c.757delG (p.Ala253GlnfsTer27) was found to be a hotspot mutation, and all patients exhibited an autosomal recessive inheritance pattern. Conclusions:A patient with CMT2 caused by a compound heterozygous mutation c.757delG/c.218C>T in the SORD gene, with the main clinical symptoms of bilateral lower limb weakness, atrophy, sensory disturbance and reduced tendon reflexes is reported. Furthermore, 31P-MRS of the extremities is anticipated to both early and sensitively detect muscle lesions in patients with hereditary peripheral neuropathy.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Particle size and surface properties are crucial for lymphatic drainage (LN), dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation induced by nanovaccine injection, which lead to an effective cell-mediated immune response. However, the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) affect this immune response is unknown. We prepared 50, 100, and 200 nm of MSNs that adsorbed ovalbumin antigen (OVA) while modifying β-glucan to enhance immunogenicity. The results revealed that these MSNs with different particle sizes were just as efficient in vitro, and MSNs with β-glucan modification demonstrated higher efficacy. However, the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs. The results also indicate that β-glucan-modified MSN, with a particle size of ∼100 nm, has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Objective:To provide references on evaluating autonomic nervous stability training effect of military flying personnel by studying the evaluation index of heart rate variability (HRV).Methods:The ECG signals of 98 military flying personnel before and after three-stage autonomic nervous stability training were collected, and the ratio of 0.1Hz power (R) of HRV was calculated. The R value before and after personal training was marked as R 1 and R 2 respectively, and the D value was used to represent the difference value between R 2 and R 1. The feasibility of using R 2 and D to evaluate the training effect was analyzed to formulate evaluation standards. In order to more intuitively display an individual′s autonomic nervous stability training level, the Z value was used to convert the original score of R 2 and D, and the evaluation criteria were formulated. Results:The R value after autonomic nervous stability training (R 2=0.473±0.248) was significantly higher than that before (R 1=0.197±0.092, P<0.01), and the individuals with lower R value before training have more obvious growth trend of R value after training. Conclusions:"0.1Hz index" is suitable to be the evaluation index of autonomic nervous stability training effect. The evaluation of autonomic nervous stability training effect of flying personnel should comprehensively consider the grade evaluation results of R 2 and D.