ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

ObjectiveThis study proposes a novel single-cell protein localization method based on a class perception graph convolutional network (CP-GCN) to overcome several critical challenges in protein microscopic image analysis, including the scarcity of cell-level annotations, inadequate feature extraction, and the difficulty in achieving precise protein localization within individual cells. The methodology involves multiple innovative components designed to enhance both feature extraction and localization accuracy. MethodsFirst, a class perception module (CPM) is developed to effectively capture and distinguish semantic features across different subcellular categories, enabling more discriminative feature representation. Building upon this, the CP-GCN network is designed to explore global features of subcellular proteins in multicellular environments. This network incorporates a category feature-aware module to extract protein semantic features aligned with label dimensions and establishes a subcellular relationship mining module to model correlations between different subcellular structures. By doing so, it generates co-occurrence embedding features that encode spatial and contextual relationships among subcellular locations, thereby improving feature representation. To further refine localization, a multi-scale feature analysis approach is employed using the K-means clustering algorithm, which classifies multi-scale features within each subcellular category and generates multi-cell class activation maps (CAMs). These CAMs highlight discriminative regions associated with specific subcellular locations, facilitating more accurate protein localization. Additionally, a pseudo-label generation strategy is introduced to address the lack of annotated single-cell data. This strategy segments multicellular images into single-cell images and assigns reliable pseudo-labels based on the CAM-predicted regions, ensuring high-quality training data for single-cell analysis. Under a transfer learning framework, the model is trained to achieve precise single-cell-level protein localization, leveraging both the extracted features and pseudo-labels for robust performance. ResultsExperimental validation on multiple single-cell test datasets demonstrates that the proposed method significantly outperforms existing approaches in terms of robustness and localization accuracy. Specifically, on the Kaggle 2021 dataset, the method achieves superior mean average precision (mAP) metrics across 18 subcellular categories, highlighting its effectiveness in diverse protein localization tasks. Visualization of the generated CAM results further confirms the model’s capability to accurately localize subcellular proteins within individual cells, even in complex multicellular environments. ConclusionThe integration of the CP-GCN network with a pseudo-labeling strategy enables the proposed method to effectively capture heterogeneous cellular features in protein images and achieve precise single-cell protein localization. This advancement not only addresses key limitations in current protein image analysis but also provides a scalable and accurate solution for subcellular protein studies, with potential applications in biomedical research and diagnostic imaging. The success of this method underscores the importance of combining advanced deep learning architectures with innovative training strategies to overcome data scarcity and improve localization performance in biological image analysis. Future work could explore the extension of this framework to other types of microscopic imaging and its application in large-scale protein interaction studies.

Objective:To investigate the effects of ATG5 and ATG7 genes on the sensitivity of multiple myeloma(MM)cell line RPMI-8226 cells to ferroptosis.Methods:CRISPR/Cas9 technology was used to knock out the autophagy key genes ATG5 and ATG7 in RPMI-8226 cells.Western blot was used to identify gene knockout cells,and detect the expression changes of autophagy-related proteins P62 and LC3B.Flow cytometry was used to detect the change of sensitivity of gene knockout cells to RSL3.The content of intracellular ferrous ions and reactive oxygen species(ROS)level in gene knockout cells were detected.Results:Western blot result confirmed that ATG5 and ATG7 genes were knocked out successfully in RPMI-8226 cells.The result of flow cytometry showed that the cell viability of RPMI-8226 cells was dose-dependent on different concentrations of RSL3(r=-0.969).RSL3(10 μmol/L)was used to induce ferroptosis in cells of control group and gene knockout groups,then the cell viability in gene knockout groups were both higher than control group after 48 hours(both P＜0.001).After knocking out the ATG5 and ATG7 genes,the content of intracellular Fe2+decreased significantly compared with control group(both P＜0.01),and the ROS level also decreased(both P＜0.001).Conclusion:Knockout of ATG5 and ATG7 genes can inhibit the ferroptosis of MM cells,and LAP pathway may be involved in the regulation.

Objective:To explore whether Ph+acute lymphoblastic leukemia (ALL)cell line SUP-B15 treated with imatinib occurs a tolerant status charactered by cell proliferation suppression but apoptotic resistance,then evaluate whether IGF1-R inhibitor AEW541 can break this tolerance,and further explain its mechanisms.Methods:SUP-B15 cells were treated with different concentrations of imatinib or AEW541.Cell proliferation was assayed by Deep Blue,and apoptotic cells were determined by Annexin V/7-AAD staining.Apoptotic rate was measured by flow cytometry after co-treatment of imatinib and AEW541.Western blot was used to evaluate ABL downstream signals,including the phosphorylation of STAT5,ERK1/2,and AKT,as well as to detect cleaved caspase-3 and PARP1,the molecular signatures of apoptosis.Furthermore,an inhibitor of STAT5 or MEK-ERK1/2 was used to confirm the key mechanism of the combination of imatinib and AEW541 induced SUP-B15 cell apoptosis.Results:Imatinib monotherapy effectively suppressed the proliferation of SUP-B15 cells,but did not induce significant increase of apoptotic rate,leading to occurrence of tolerant status.AEW541 monotherapy did not dramatically affect the proliferation and apoptosis of SUP-B15 cells,but significantly increased apoptotic rate of SUP-B15 cells and cleavage of caspase-3 and PARP1 when combined with imatinib simultaneously. A combination of imatinib and AEW541 reduced STAT5 and ERK1/2 phosphorylation as compared with imatinib monotherapy in SUP-B15 cells,but had no impact on AKT phosphorylation.Apoptosis could be induced by STAT5 inhibitor AC-4-130,but not by MEK-ERK1/2 inhibitor trametinib in SUP-B15 cells.Conclusion:SUP-B15 cells treated with imatinib can establish drug tolerance.IGF1-R inhibitor AEW541 can further reduce STAT5 activation,thereby boosting the effect of apoptotic induction of imatinib on SUP-B15 cells.This research may provide a new idear to overcome imatinib tolerance.

Objective:To compare the effects of transurethral resection of the prostate(TURP)and transurethral columnar bal-loon dilatation of the prostate(TUCBDP)in the treatment of BPH.Methods:This study included 218 BPH patients treated in Qin-huangdao Workers'Hospital from July 2021 to November 2022,109 by TURP and the other 109 by TUCBDP.We followed up the patients for 12 months,observed their postoperative recovery,complications,serum pain,inflammatory index,cytokine level,urodynamic index,symptom improvement and quality of life(QOL)and compared the data obtained between the two groups of patients.Results:At 12 months after surgery,the total effectiveness rate was significantly higher in the TUCBDP than in the TURP group(93.58%vs 84.40%,P<0.05),and the postoperative recovery was better in the former than in the latter(P<0.05).Compared with the baseline,the lev-els of serum prostaglandin E2(PGE2),substance P,tumor necrosis factor-alpha(TNF-α)and high sensitive C-reactive protein(hs-CRP)were remarkably increased in both of the groups on the first day after surgery(P<0.05),more significantly in the TURP than in the TUCBDP group(P<0.05),while the levels of serum PSA and E2 decreased and the T level elevated in all the patients at 3 months postoperatively(P<0.05),more significantly in the TUCBDP than in the TURP group(P<0.05).Before and at 3 and 12 months af-ter operation,the postvoid residual urine volume(PVR)and NIH-CPSI,IPSS and QOL scores showed a decreasing trend,while the maximum urinary flow rate(Qmax),maximum cystometric capacity(MCC)and maximum urethral closure pressure(MUCP)exhibited an increasing trend in both of the two groups,even more significantly in the TUCBDP than in the TURP group(P<0.05).Conclu-sion:TUCBDP is advantageous over TURP in promoting postoperative recovery,improving QOL,reducing postoperative pain,inflamma-tion and complications,regulating the levels of serum cytokines,and improving urodynamics and clinical symptoms in BPH patients.However,with the extension of postoperative time,the two strategies are basically comparable in improving the urodynamics,symptoms and QOL of the patients.

Objective:To assess the usage of the robot-assisted core-needle biopsy for the bone tumors, moreover to compare its outcomes with the manual technique.Methods:A retrospective study was conducted from February 2019 to February 2021, the medical records of the patients with bone lesions that had received core-needle biopsy were collected. There were 57 males and 45 females, the age was 45.9 (10~79) years. Eight patients received robot-assisted biopsy, whereas 94 patients underwent C-arm/ CT guided biopsy, the recorded data included operational duration, aspirational direction adjustment, etc. The pathological diagnosis reports of the biopsy specimens and the operational specimens were compared.Results:The diagnosis outcomes included metastases (33 cases), osteosarcoma (12 cases), chondrosarcoma (12 cases), giant cell tumor of bone (12 cases), fibrous dysplasia (7 cases), chronic osteomyelitis (7 cases), lymphoma (4 cases), multiple myeloma (4 cases), chronic fracture (3 cases), chondroblastoma (2 cases), pleomorphic undifferentiated sarcoma (2 cases), leiomyosarcoma (1 case), and Langerhans cell histiocytosis (1 case). Eighty-seven cases (85.29 %) lesions were found in the limbs, whereas 15 cases (14.71%) were in the axial locations. Compared with the manual group, the robot-assisted group had more axial locations: 7/8 vs. 11.70%(11/94), P<0.01; fewer aspirational direction adjustment: (0.4 ± 0.1) times vs. (3.1 ± 1.5) times, P<0.01 ; longer operational duration: (48.8 ± 8.8) min vs. (29.6 ± 6.0) min, P<0.01. There were no statistical differences between the two groups regarding the sex, age, pathological fracture, diagnostic accuracy, open biopsy rate and complications ( P>0.05). Conclusions:The robot-assisted core-needle biopsy is a reliable technique, it helps decrease the operational difficulty. The usage of this technique is recommendable for the bone lesions with great difficulty for biopsy, such as the minimal bone tumors and the lesions in the spine and the pelvis.

Abstract: Objective　To study severe fever with thrombocytopenia syndrome virus (SFTSV) in tick samples from different species and genera in Suizhou City, Hubei Province, China, and to explore the phylogenetic relationship between ticks and patients sources of viruses at the molecular evolutionary level. Methods In 2016 and 2017, over a continuous two-year period, 1 158 ticks were collected from Suizhou, Hubei, and their species and genera were identified. Meanwhile, 86 serum samples were collected to detect SFTSV RNA by real-time quantitative reverse transcription-PCR. All viral RNA-positive supernatants of tick homogenates were inoculated into Vero cells for viral isolation, and full genome sequencing of isolated strains was conducted. Phylogenetic tree research on SFTSV strains from ticks and cases was performed using the bootstrapped maximum-likelihood (1 000 iterations) method with Molecular Evolutionary Genetics Analysis (MEGA) software, ver. 11.0 to provide confidence estimates. Results Haemaphysalis longicornis, Ixodes sinensis, and Rhipicephalus microplus were the dominant species (95.34%) in Suizhou City, Hubei Province, China. Tick samples were pooled according to their species and developmental stage, yielding 832 pools, of which 4 were positive for SFTSV by qRT-PCR. The overall minimum infection rate (MIR) in the region was 0.35%. One SFTSV strain named HB 2016-P35, was successfully isolated from Haemaphysalis longicornis and demonstrated high homology to 16 previously reported patient-derived viruses in Hubei Province, especially to the human strain HB 2017-49 from the same region, with a genome similarity of 99.9%. In addition, the molecular phylogenetic analysis revealed five distinct SFTSV genotypes in Hubei, covering almost all currently known SFTSV genotypes. Conclusions Some areas of Suizhou City, Hubei Province, demonstrate a relatively low level of SFTSV carrying and transmission by ticks. The new SFTSV strain isolated from ticks exhibits similar genotype characteristics and high sequence homology with viruses carried by cases in surrounding cases. The study suggests that tick-to-human transmission is most likely the pathway for human infection with SFTSV, highlighting the need for continual and long-term monitoring of tick carriage of SFTSV in endemic areas.

Objective To explore the value of 11C-methionine(MET)PET/CT radiomics model for evaluating isocitrate dehydrogenase1(IDH1)status of glioblastoma.Methods Data of 157 patients with glioblastoma who underwent 11C-MET PET/CT examination,including 68 cases of IDH1 mutation and 89 cases of IDH1 wild-type were retrospectively analyzed.The patients were divided into training set(n=125)and validation set(n=32)at the ratio of 8:2.Based on PET/CT images,lesions ROI were delineated and radiomics features were extracted and screened to establish radiomics models with logistic regression(LR),support vector machine(SVM)and decision trees(DT),respectively.Meanwhile,the nomogram based on patients'age and radiomics features was drawn.The efficacy of radiomics models and clinical-radiomics nomogram for evaluating IDH1 status were comparatively observed.Results The area under the curve(AUC)of DT radiomics model for evaluating IDH1 status of glioblastoma in training set was 0.910,higher than that of LR(0.697)and SVM(0.698)models(both P＜0.05).In validation set,the AUC of DT model for evaluating IDH1 status of glioblastoma was 0.805,which was higher than that of LR model(0.740)and clinical-radiomics nomogram(0.704)(both P＜0.05).Conclusion 11C-MET PET/CT radiomics model based on DT was helpful for evaluating IDH1 status of glioblastoma.

Gastroesophageal reflux related cough is located in the lung and stomach.The basic pathogenesis is the inversion of stomach qi and the lung loss propagating and descending.In view of the above,based on the theory of"relevance of lung and stomach",this article analyzed the modern mechanism of"relevance of lung and stomach"in gastroesophageal reflux related cough,which included"microinhalation"theory,"esophagus-bronchial reflex"theory,and"airway neurogenic inflammation"theory.This article also put forward the TCM disease name of"gastric cough",and the treatment methods of"simultaneous treatment of lung and stomach"and"treatment of cough from stomach",which would provide new ideas for the theoretical and mechanism research of TCM treatment of gastroesophageal reflux related cough.

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G^-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G^- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.