Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of severe fever with thrombocytopenia syndrome (SFTS) in Huai'an City, Jiangsu Province from 2011 to 2024, so as to provide a basis for optimizing local SFTS prevention and control strategies, and identifying high-risk areas and key populations. Methods: Data on SFTS incidence and deaths in Huai'an City from 2011 to 2024 were collected from the Infectious Disease Reporting Information System of the Chinese Disease Prevention and Control Information System. The reported incidence, mortality, and fatality rates were calculated. Descriptive analysis was performed on temporal, population, and regional distribution. The average annual percent change (AAPC) was used to analyze the trend in the reported incidence of SFTS. Global and local spatial autocorrelation analyses were employed to examine the spatial distribution patterns and spatial association patterns of SFTS incidence while spatio-temporal scanning analyses was used to assess the spatial-temporal clustering of SFTS. Results: A total of 337 SFTS cases were reported in Huai'an City from 2011 to 2024, with the reported incidence rising from 0.17/100 000 to 1.88/100 000. There were 20 deaths, with an average annual mortality of 0.03/100 000, and a fatality rate of 5.93%. The incidence showed obvious seasonality, with a peak in May and June (148 cases, accounting for 43.92%). Spring and summer accounted for 107 cases (31.75%) and 159 cases (47.18%), respectively. The reported SFTS cases were mainly male, farmers, and individuals aged ≥41 years, accounting for 56.38%, 79.23%, and 96.74%, respectively. The population distribution of death cases was basically consistent with that of incident cases. Xuyi County was a high-incidence area, with a total of 332 reported cases, accounting for 98.52%. All death cases were reported in this county. Spatial autocorrelation analyses revealed a positive spatial correlation in SFTS incidence from 2019 to 2024, with Moran's I values ranging from 0.214 to 0.336 (all P<0.05). Heqiao Town, Tianquanhu Town, and Guiwu Town in Xuyi County were identified as high-high clustering areas. Spatio-temporal scanning analyses showed that cluster 1 was consistent with the high-high clustering areas, with an aggregation time from the second quarter of 2019 to the second quarter of 2022. Conclusions From 2011 to 2024, the reported incidence of SFTS in Huai'an City showed an upward trend, with a high incidence in spring and summer. Males, farmers, and the middle-aged and elderly population were the key populations for prevention and control. Xuyi County was the key area for prevention and control.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To investigate the effect of abdominal circumference on intestinal radiation dose volume and acute intestinal toxicity in pelvic intensity modulated radiation therapy for rectal cancer.Methods:A total of 150 patients with locally advanced rectal cancer (LARC) who received adjuvant and neoadjuvant concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guizhou Medical University from March 2023 to January 2025 were enrolled, including 82 cases of adjuvant radiotherapy and 68 cases of neoadjuvant radiotherapy. All patients underwent radiotherapy CT simulation positioning in the standard mode of prone position with abdominal board padding and bladder filling. Intestinal toxicity was categorized as a binary variable based on the occurrence of ≥2 grade acute intestinal toxicity. Linear and logistic regression models were used to analyze the factors influencing intestinal radiation dose volumes (V 10, V 20, V 30, V 40) and acute intestinal toxicity in LARC patients. Generalized additive models and piecewise linear and logistic regression analyses were employed to examine the threshold effects of abdominal circumference on intestinal radiation dose volumes and acute intestinal toxicity. The threshold value for abdominal circumference was determined based on the upper limit of the 95% CI for the threshold. A difference test was used to validate the differences in intestinal radiation dose volume and acute intestinal toxicity between small and medium-to-large abdominal circumferences. Results:Univariate analysis showed that, gender, body mass, abdominal circumference, planning target volume (PTV), intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, abdominal circumference, intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Body mass index (BMI), abdominal circumference, intestinal volume and individual intestinal radiation volumes (V 10, V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, BMI, abdominal circumference, multiple intestinal radiation dose volumes (V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Multivariate analysis showed that, abdominal circumference (V 10: β=-1.01, 95% CI: -1.68--0.33, P=0.004; V 20: β=-0.94, 95% CI: -1.28--0.60, P<0.001; V 30: β=-0.58, 95% CI: -0.82--0.34, P<0.001; V 40: β=-0.41, 95% CI: -0.60--0.23, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference (V 10: β=-0.92, 95% CI: -1.62--0.22, P=0.010; V 20: β=-0.84, 95% CI: -1.11--0.57, P<0.001; V 30: β=-0.42, 95% CI: -0.57--0.28, P<0.001; V 40: β=-0.30, 95% CI: -0.41--0.19, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy. Abdominal circumference ( OR=0.86, 95% CI: 0.78-0.95, P=0.002) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference ( OR=0.87, 95% CI: 0.79-0.96, P=0.004) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy. The generalized additive model revealed a nonlinear relationship between abdominal circumference and intestinal radiation dose volume and acute intestinal toxicity of adjuvant radiotherapy patients. Further segmented regression analysis results showed that there was a threshold effect between abdominal circumference and intestinal radiation dose volume (V 10, V 20, V 30, V 40) and acute intestinal toxicity. The inflection point values between abdominal circumference and intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing adjuvant radiotherapy were all 71.9 cm; the inflection point values between abdominal circumference and the intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing neoadjuvant radiotherapy were 69.0, 69.0, 69.0, 68.6 cm, respectively; The inflection point values between abdominal circumference and acute intestinal toxicity in LARC patients undergoing adjuvant radiotherapy and neoadjuvant radiotherapy were 71.9, 69.0 cm, respectively. Based on the upper limit of the 95% CI threshold, the cutoff values for small and medium-to-large abdominal circumferences for patients undergoing adjuvant and neoadjuvant radiotherapy were set at 76.1, 71.9 cm, respectively. In patients undergoing adjuvant radiotherapy, the levels of intestinal radiation dose volume V 10 [ (7.65±2.29) cm 3vs. (5.88±2.68) cm 3, t=2.76, P=0.007], V 20 [ (4.28±1.27) cm 3vs. (2.72±1.31) cm 3, t=4.81, P<0.001], V 30 [ (2.42±1.07) cm 3vs. (1.37±0.76) cm 3, t=4.95, P<0.001], V 40 [ (1.69±0.74) cm 3vs. (0.92±0.58) cm 3, t=4.93, P<0.001] in the small abdominal circumference group ( n=22) were significantly higher than those in patients with medium-to-large abdominal circumferences ( n=60) ; In patients undergoing neoadjuvant radiotherapy, patients with small abdominal circumferences ( n=11) had significantly higher V 20 [ (3.09±0.84) cm 3vs. (2.28±1.17) cm 3, t=2.17, P=0.033], V 30 [1.44 (1.22, 1.53) cm 3vs. 0.91 (0.56, 1.22) cm 3, Z=-3.04, P=0.002], V 40 [0.93 (0.84, 1.09) cm 3vs. 0.44 (0.30, 0.81) cm 3, Z=-3.19, P=0.001] than patients with medium-to-large abdominal circumferences ( n=57). In patients receiving adjuvant radiotherapy and neoadjuvant radiotherapy, there were statistically significant differences in acute intestinal toxicity between patients with small abdominal circumferences and with medium-to-large abdominal circumferences ( χ2=10.46, P=0.001; χ2=8.13, P=0.004) . Conclusions:In the standard mode (prone position with abdominal board padding and bladder filling), abdominal circumference is an independent factor influencing the intestinal radiation dose volume and acute intestinal toxicity in rectal cancer radiotherapy patients. There is a significant non-linear threshold effect between abdominal circumference and different levels of intestinal radiation dose volume and acute intestinal toxicity. The impact of abdominal circumference on intestinal radiation dose volume and toxicity differs significantly before and after the inflection point value. Patients with smaller abdominal circumferences not only fail to achieve the expected benefits under the current standard radiotherapy regimen but also face higher risks of intestinal radiation dose volume and toxicity.

Objective To observe the reliability of regional 4D flow and whole heart 4D flow cardiac MRI(CMRI)for measuring hemodynamic parameters of left ventricle.Methods Heart ultrasonography and CMRI were prospectively obtained in 31 healthy subjects.Hemodynamic parameters of left ventricle were measured using heart ultrasound,3-chamber 4D flow CMRI(based on inflow and outflow channel of left ventricle)and whole heart 4D flow CMRI,respectively.Intra-class correlation coefficient(ICC)was performed to evaluate the consistencies of the measured left ventricle hemodynamic parameters among the above 3 methods.Results Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,E peak diastolic velocity of mitral valve,supravalvular/subvalvular aortic pressure and aortic valve pressure gradient(all ICC＞0.75),while moderate consistency of A peak diastolic velocity of mitral valve(ICC=0.718)were found between heart ultrasound and 3-chamber 4D flow CMRI.Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,A peak diastolic velocity of mitral valve and supravalvular/subvalvular aortic pressure(all ICC＞0.75),while moderate consistencies of E peak diastolic velocity of mitral valve and aortic valve pressure gradient(ICC=0.600,0.628)were found between heart ultrasound and whole heart 4D flow CMRI.Meanwhile,good consistencies of the above parameters were found between 3-chamber 4D flow CMRI and whole heart 4D flow CMRI(all ICC＞0.75).Conclusion Measuring left ventricular hemodynamic parameters using local regional 4D flow and whole heart 4D flow CMRI were reliable,with good consistency with cardiac ultrasound.

Objective:We genetically modified our non-replicating vaccinia virus NTV to improve its immunogenicity.Methods:We constructed NTV-modified strain NTV-ΔF1L-C7L by homologous recombination of vaccinia virus based on CRISPR-Cas9 technology by inserting the C7L gene while deleting the F1L gene. The recombinant virus NTV-ΔF1L-C7L was then immunized with 10 7 PFU in BALB/c mice, and the levels of humoral and cellular immunity induced by NTV-ΔF1L-C7L were detected by ELISA and ELISpot method, respectively, and the levels of neutralizing antibodies were determined by the phage-reduced neutralization assay. Results:The PCR and western- blot identification proved that the F1L gene of the constructed NTV-modified strain NTV-ΔF1L-C7L was missing, while the C7L gene was inserted back in the region, and the C7L gene could be expressed normally, indicating that the recombinant virus was constructed correctly. After immunization of mice with NTV-ΔF1L-C7L, ELISA result showed that the recombinant virus NTV-ΔF1L-C7L induced a higher level of IgG antibody than NTV; ELISpot result also showed that the recombinant virus was able to induce a higher level of IFN-γ; and the result of plaque reduction neutralization test showed that the recombinant virus was able to induce a higher level of IFN-γ antibody than that of NTV.Conclusions:We correctly constructed the NTV gene-modified strain NTV-ΔF1L-C7L, which induced stronger humoral and cellular immunity compared with NTV, and provided reference data for the research and development of replacement products for smallpox or monkeypox vaccines.

OBJECTIVE To investigate the value of magnetic resonance imaging(MRI)parameters in differentiation between olfactory neuroblastoma(ONB)and sinonasal diffusion large B cell lymphoma(DLBCL).METHODS Pathology-proven 34 ONB patients and 29 DLBCL patients with MRI examinations before treatment were included.The conventional MRI features and semi-quantitative parameters of two groups were documented and analysis.Statistical analysis between the two groups were performed.The independent sample t-test and was used for continuous variables in normal distribution,Mann-Whitney U test was used for non-normal distribution.The frequency of categorical variables were compared by Chi-square test.Logistic regression analysis was done to identify the most predictive MRI features for differentiation.RESULTS ONB often located in the nasal cavity olfactory recess and ethmoid sinus,characterized by intracranial extension through the cribriform plate,forming a'dumbbell'shape mass(P=0.004).DLBCL more often located in paranasal sinus,orbits(P<0.001,P=0.024).T2WI signal intensity of ONB were higher than DLBCL(P<0.001).ONB showed more signs of outward turbinate and lobulation(P=0.001,P=0.004).ADCave of ONB was obviously higher than DLBCL(P<0.001).On DCE-MRI,ONB showed higher CImax,WR(P<0.001,P=0.011),lower TTP than DLBCL(P=0.003).ONB presented more wash-out type TIC curve(P=0.022).Logistic regression analysis demonstrated that tumor location(olfactory cleft or maxillary sinus),T2WI intensity,ADCave with cutoff value of 0.82×10-3mm2/s and TTP with cut off value of 52 seconds were the most predictive MRI features for differentiation.CONCLUSION The multiple MRI conventional and functional parameters are helpful in differentiating ONB from DLBCL.