ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail fragment （α1ACT） signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups （n=12 per group）： Sham-operated group， model group， Tianma Goutengyin high-， medium-， and low-dose groups （5.13， 10.26， and 20.52 g·kg^-1）， and a nimodipine group （8.1 mg·kg^-1）. The vascular dementia model was established by permanent bilateral common carotid artery occlusion， followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test， and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 （IL-6） and C-C motif chemokine ligand 2 （CCL2） in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal neuronal morphology was observed by Nissl staining， and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and myelin basic protein （MBP）. Western blot analysis was performed to measure the protein expression levels of TNF-α， TNF receptor 1 （TNFR1）， phosphorylated STAT3 （p-STAT3）， α1ACT， IL-6， complement component 3 （C3）， BDNF， S100 calcium-binding protein A10 （S100A10）， and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group， the model group showed a significantly reduced relative recognition index in the novel object recognition test （P<0.01）， prolonged immobility time and increased immobility frequency in the forced swimming test （P<0.01）. Hippocampal IL-6 and CCL2 levels were significantly increased （P<0.01）. Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies （P<0.01）. MBP-positive expression was significantly decreased （P<0.01）， apoptosis was significantly increased （P<0.01）， BDNF-positive expression was significantly reduced （P<0.05）， and GFAP-positive expression was significantly increased （P<0.01）. In addition， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly elevated （P<0.01）， while BDNF and S100A10 expression levels were significantly decreased （P<0.01）. Compared with the model group， all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index （P<0.05）， shortened immobility time and reduced immobility frequency （P<0.05， P<0.01）. IL-6 and CCL2 levels were significantly decreased （P<0.01）， neuronal number was significantly increased （P<0.05， P<0.01）， and MBP-positive expression was significantly enhanced （P<0.01）. Apoptosis was significantly reduced （P<0.01）， BDNF-positive expression was significantly increased （P<0.05）， and GFAP-positive expression was significantly decreased （P<0.01）. Moreover， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly decreased （P<0.01）， while BDNF and S100A10 protein expression levels were significantly increased （P<0.01）. ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway， thereby reducing neuronal apoptosis and improving learning and memory function.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.

Objective Estimating the residual risk of transfusion-transmitted diseases in voluntary blood donors is crucial for monitoring blood safety.and to analyze the evolution trend over a five-year period in Yantai,Shandong Province.Methods This study retrospectively reviewed screening data from Yantai Central Blood Station between 2018 and 2022.We compared the positivity rates between first-time and repeat donors,calculated the prevalence of each virus,and estimated the residual risk using the prevalence-window period model.Meanwhile,the age characteristics of all positive donors were analyzed.Results Over the five-year period,a total of 320 016 individuals donated blood.The overall reaction rate of transfusion-transmitted diseases was 0.165%,with HBV(0.129%)being the most common.The positivity rate among first-time donors[P(FTDs)](0.310%)was significantly higher than that among repeat donors[P(RDs)](0.054%)(χ2=312.783,P<0.05).The serological residual risks for HBV,HCV,and HIV were 1∶188 090,1∶1 042 805,and 1∶392 995,respectively.During the five-year period,they decreased from 1∶129 495 to 1∶390 011,from 1∶697 002 to 1∶1 145 826,and from 1∶684 109 to 1∶1 067 317,respectively.The residual risks of HCV and HIV after NAT were 1∶22 369 329 and 1∶6 639 965,respectively,which were significantly reduced by 21.5-fold and 16.9-fold,and decreased steadily during the study period.Among the HBV-DNA(+)donors,61.8%(68/110)were RDs,and the residual risk was 1∶65 350.Conclusion This study demonstrates the remarkable effectiveness of introducing nucleic acid amplification technology(NAT)in reducing the residual risk of HBV,HCV,and HIV,particularly for HCV and HIV.The residual risk for HBV remains higher compared to HCV and HIV due to the discovery of occult HBV infections(OBI).Therefore,a crucial step toward further reducing this residual risk is the use of more sensitive reagents and detection platforms.Furthermore,implementing effective long-term incentive mechanisms and strategic planning to increase the proportion of repeat donors(RDs)is critical for enhancing transfusion safety.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.

Objective:To investigate the factors influencing the persistence of prostate specific antigen(PSA) following radical prostatectomy, and to develop and validate a predictive model for PSA persistence.Methods:Clinical data from 1 828 patients who underwent radical prostatectomy at Shanghai Changhai Hospital between January 2015 and December 2023 were retrospectively analyzed. Of these, 1 295 patients from January 2015 to April 2021 comprised the modeling group, while 533 patients from May 2021 to December 2023 formed the validation group. Additionally, 109 patients who underwent radical surgery at the Third Affiliated Hospital of Naval Medical University between March and December 2023 were included as an external validation group. Patients with incomplete clinical information, serum PSA levels exceeding 100 ng/ml, or those who received preoperative neoadjuvant therapy were excluded. Ultimately, 1 003, 369, and 86 patients were included in the modeling, validation, and external validation groups, respectively. The modeling group had serum PSA of 19.29 (8.43, 23.73) ng/ml; the clinical stages were distributed as T 1, T 2, T 3, and T 4 in 191, 673, 123, and 16 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 460, 466, and 77 patients, respectively; and the secondary Gleason scores were 3, 4, and 5 in 363, 486, and 154 patients, respectively. The validation group had serum PSA of 12.80 (6.82, 14.40) ng/ml; the clinical stages were distributed as T 1, T 2, T 3, and T 4 in 40, 289, 37, and 3 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 218, 145, and 6 patients, respectively; and the secondary Gleason scores were 3, 4, and 5 in 140, 184, and 45 patients, respectively. The external validation group had serum PSA of 12.84 (7.11, 12.97) ng/ml; the clinical stages were distributed as T 1, T 2 and T 3 in 9, 68, and 9 patients, respectively; the primary Gleason scores of biopsy were 3, 4, and 5 in 58, 27, and 1 patient, respectively; and the secondary Gleason scores were 3, 4, and 5 in 28, 50, and 8 patients, respectively. Logistic regression analysis was used to identify independent risk factors for PSA persistence after radical prostatectomy in the modeling group and a prediction model was constructed. The predictive performance of the model was analyzed using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve, the calibration curve, and the clinical decision curve. The predictive performance of the model was verified by the ROC curve in the validation group and the external validation group. Results:The incidence of persistent PSA after surgery in the modeling group, validation group, and external validation group was 8.97% (90/1 003), 7.32% (27/369), and 17.4% (15/86), respectively. In the modeling group, univariate and multivariate logistic regression analysis revealed that serum PSA, percentage of positive needle cores, primary Gleason score on biopsy, and secondary Gleason score on biopsy were independent risk factors for PSA persistence ( P<0.05), and a prediction model was constructed based on these factors. The AUC value of this model was 0.790 (95% CI 0.745-0.835). Calibration curve and clinical decision curve analyses showed that the model's predicted probabilities aligned well with actual risks within the 0-40% prediction interval, providing clinical benefit. The AUC values of the ROC curves in the validation group and external validation group were 0.808 (95% CI 0.719-0.897) and 0.822 (95% CI 0.714-0.929), respectively, indicating that the model had good predictive performance. Conclusions:The predictive model for PSA persistence, constructed based on serum PSA, percentage of positive needle cores, primary and secondary Gleason score on biopsy, demonstrated good clinical predictive performance, exhibiting high accuracy in both internal and cross-center validation.

Objective:To evaluate the diagnostic value of image enhancement endoscopy (IEE) for sinonasal malignant tumors.Methods:Patients with nasal neoplasms at the Department of Otorhinolaryngology Head and Neck Surgery at Beijing Tongren Hospital from January 2019 to December 2021 were examined using white light endoscopy (WLE) and IEE. Targeted biopsy was performed after image collection, and the images were analyzed by two blinded observers. Pathological diagnosis was compared with endoscopic findings. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and P<0.05 was statistically significant. Kappa(k) was employed to assess consistency between endoscopic and histopathological diagnoses. The vascular patterns of sinonasal malignancy were compared with Ni endoscopic classification.Results:This study ultimately included 193 patients with nasal tumors, and 41 cases (21.24%, 41/193) were comfirmed histopathologically with sinonasal malignancies. WLE correctly diagnosed 18 cases (43.90%, 18/41), while IEE diagnosed 28 cases (68.29%, 28/41). Among the 41 malignancies, 28 cases (68.29%, 28/41) showed patchy/punctate patterns and tortuous vessels (Ni type Ⅴ). All 14 squamous epithelium-derived malignancies (34.15%, 14/41) had Ni type Ⅴ vessels. Of 27 non-squamous malignancies, 14 cases (34.15%, 14/41) were Ni type Ⅴ, 7 cases (17.07%, 7/41) were false negatives, 6 cases (14.63%, 6/41) that their vessels were obscured by necrotic tissue. Compared to WLE, IEE had higher sensitivity (80.00% vs 51.42%), specificity (98.68% vs 96.69%), PPV (93.33% vs 78.26%), NPV (95.51% vs 89.57%), diagnostic consistency (95.16% vs 88.17%), and κ value (0.832 vs 0.554). Conclusions:IEE improves the endoscopic diagnosis of sinonasal malignancies. Ni type Ⅴ is suitable for the diagnosis of malignant tumors of squamous epithelial malignant tumors.

Objective:To analyze two families with inherited dysfibrinogenemia,and explore the molecular pathogenic mechanisms.Methods:The coagulation indexes of the probands and their family members were detected.The FGA,FGB,and FGG exons and their flanking sequences were amplified by PCR,and the mutation sites were identified by sequencing.SIFT,PolyPhen2,LRT,ReVe,MutationTaster,phyloP,and phastCons bioinformatics software were used to predict the functional impact of the mutation sites.Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software.Results:The thrombin time(TT)of the proband in family 1 was prolonged to 37.00 s,and Fg:C decreased to 0.52 g/L.The TT of the proband in family 2 was 20.30 s,and Fg:C was 1.00 g/L,which was lower than the normal range.Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T＞C in FGA,resulting in the substitution of phenylalanine 27 with serine(Phe27Ser).The proband in family 2 had a heterozygous mutation c.1007T＞A in FGG,resulting in the substitution of methionine 336 with lysine(Met336Lys).Bioinformatics software prediction analysis indicated that both mutations were deleterious variants.PyMOL mutation models revealed that the Aα chain mutation(Phe27Ser)in family 1 and y chain mutation(Met336Lys)in family 2 resulted in alterations in spatial structure and reduced protein stability.Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species.Conclusion:Heterozygous mutations of FGA gene c.80T＞C and FGG gene c.1007T＞A are both pathogenic variants,causing inherited dysfibrinogenemia.