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.

ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） patients without liver cirrhosis， to clarify their association with outcomes， and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023， including prognostic scores and key biochemical indicators on Days 3， 7， 14， 21， and 28 of the disease course. According to the outcome of patients at 1 year， they were divided into death/liver transplantation group with 43 patients， liver cirrhosis group with 23 patients， and non-liver cirrhosis group with 88 patients， and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups； the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval （CI） were calculated for each indicator at difference time points； the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve； the 95%CI was visualized using the semi-transparent ribbon area， with the transparency parameter （α=0.2） optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes； likelihood ratio was used to evaluate the significance of the interaction effect between time and group， and in case of the significant interaction effect， the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy， MELD score， MELD-Na score， CLIF-C ACLF score， COSSH-ACLF Ⅱ score， total bilirubin （TBil）， international normalized ratio （INR）， alpha-fetoprotein， blood sodium， alanine aminotransferase， and procalcitonin at the baseline（all P0.05）. The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR （TBil400 μmol/L， INR2.5）， as well as a low level of platelet count （PLT） （100×10⁹/L）. The non-liver cirrhosis group had rapid improvements in indicators， with TBil200 μmol/L， INR1.5， and PLT100×10⁹/L by day 28， while the liver cirrhosis group showed a trend of recovery， with TBil200 μmol/L， INR2.0， and PLT 100×10⁹/L on day 28， with significant global heterogeneity in the temporal trends of the above indicators across the three groups （all P0.01）. ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year， individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5， TBil 200 μmol/L， and PLT 100×10⁹/L at day 28.

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 improve the understanding of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma complicated with hemophagocytic syndrome (HPS) in children.Methods:A retrospective analysis was conducted on the diagnosis and treatment of a case of EB virus-associated ALK-negative anaplastic large cell lymphoma in a child with HPS as the clinical manifestation at Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University in December 2019, and literature review was conducted.Results:The patient was an 8-year-old boy who was admitted with facial yellowing and recurrent fever. After comprehensive examination, he was diagnosed with HPS. After 2 weeks of chemotherapy according to the hemophagocytic lymphohistiocytosis (HLH)-1994 regimen, lymph node biopsy was performed. Immunohistochemistry showed that CD30, CD5, CD4, CD7, EMA, TIA-1, and VIM were positive, ALK, CD2, CD3, CD8, CD117, CD20, INI-1, CD68, MyoD1, Myogenin, Desmin, Langerin, SALL4, CD56, GramB, and CK were negative, LCA was weakly positive, TFE3 was partially weakly positive, and Ki-67 positivity index was 90%. The clonality assay for TCRD gene rearrangement was positive. The supplementary diagnosis was ALK-negative anaplastic large cell lymphoma, and the clinical risk stratification was classified as high-risk group. After 2 courses of chemotherapy with the South China Children's Cancer Group-non-Hodgkin lymphoma 2017 regimen (SCCCG-NHL-2017), he was evaluated as complete remission (CR), and after 6 courses, he was still evaluated as CR. The patient received autologous hematopoietic stem cell transplantation. The patient was followed up until May 2024, his survival status was good.Conclusions:EB virus-associated ALK-negative anaplastic large cell lymphoma complicated with HPS in children is rare, chemotherapy combined with autologous hematopoietic stem cell transplantation is a feasible treatment option.

Objective To observe the clinical efficacy of therapy of tonifying heart and spleen for the treatment of patients with postpartum depression of heart and spleen deficiency syndrome based on the theory of intestinal flora-neurotransmitter-brain axis(shortened as brain-intestine axis),and to explore its effect on the improvement of patients'depression and anxiety.Methods A total of 136 patients with postpartum depression of heart and spleen deficiency syndrome who admitted to The 908th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China from June 2021 to July 2023 were randomly divided into the conventional treatment group(control group)and the tonifying heart-spleen group(observation group)according to the random number table method,with 68 cases in each group.The control group was treated with conventional antidepressant drugs,and the observation group was treated with therapy of tonifying heart and spleen by utilization of Shen Qi Jieyu Prescription Granules)on the basis of treatment for the control group.Both groups were treated for six continuous weeks.Before and after the treatment,the two groups were observed in the changes of main symptom scores of traditional Chinese medicine(TCM)syndrome,Hamilton Depression Scale(HAMD)scores,7-Item Generalized Anxiety Disorder Scale(GAD-7)scores,and the levels of serum neurotransmitters of 5-hydroxytryptamine(5-HT),dopamine(DA),norepinephrine(NE),as well as microflora metabolites such as short-chain fatty acids(SCFAs),glutamic acid(GLU),gamma-aminobutyric acid(GABA).Moreover,the clinical efficacy and safety of the two groups of patients were evaluated.Results(1)After six weeks of treatment,the total effective rate of the observation group was 89.71%(61/68)and that of the control group was 73.53%(50/68),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of TCM syndrome main symptoms such as emotional upset,slow thinking,poor appetite,abdominal distension and loose stools in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the HAMD scores and GAD-7 scores in the two groups of patients were all decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the serum levels of neurotransmitters 5-HT,DA,and NE in the two groups of patients were all increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.01).(5)After treatment,the serum levels of microflora metabolites SCFAs,GLU and GABA in the two groups of patients were all increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.01).(6)The incidence of adverse reactions in the observation group was 8.82%(6/68)and that in the control group was 5.88%(4/68),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion The application of therapy of tonifying heart and spleen for the treatment of patients with postpartum depression of heart and spleen deficiency syndrome based on brain-intestine axis exerts certain efficacy and safety through correcting the imbalance of neurotransmitters and regulating the microflora metabolites of the patients,thus to alleviate depression and anxiety.