OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

OBJECTIVE To screen and quantitatively analyze the quality marker （Q-Marker） associated with anti-renal fibrosis in Shenqi shenshuai mixture （SQSS）， so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology， gene expression omnibus （GEO） and connectivity map （CMAP） databases， the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics，and 84 active ingredients with anti-renal fibrosis activity were further screened out， such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database， including berberine， quercetin， honokiol， nicotinamide， daidzein， coumarin， kaempferol， formononetin and amygdalin. The quantitative results showed that the average contents of the above components （excluding amygdalin） in 10 batches of SQSS were 2.523， 1.942， 26.848， 1.415， 0.692， 0.171， 0.374， 7.401 μg/mL， respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study， and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.

ObjectiveTo investigate the expression level of mammalian sterile 20-like kinase 1 （MST1） in prostate cancer （PCa） tissues， its biological functions， and its regulatory effects on androgen receptor （AR） and vascular endothelial growth factor （VEGF） expression. MethodsImmunohistochemistry was performed to detect MST1 expression in 77 prostate cancer tissues and 34 benign prostatic hyperplasia （BPH） tissues， and the relationship between MST1 expression and clinicopathological parameters was analyzed. MST1-overexpressing C4-2 and LNCaP cell lines were constructed. CCK-8 assay， Transwell migration assay， and angiogenesis assay were conducted to evaluate the effects of MST1 on cell proliferation， migration， and angiogenesis. The expression changes of AR and VEGF were detected by qRT-PCR and Western blot. ResultsMST1 expression was significantly lower in PCa tissues compared with BPH tissues （P=0.012）. Low MST1 expression was significantly associated with tumor metastasis （P=0.033）. MST1 overexpression inhibited C4-2 cell proliferation and migration， with transmembrane migrated cells reduced by 53.6% （P<0.01）. MST1 overexpression decreased the mRNA and protein expression levels of AR and VEGF （P<0.05）. Angiogenesis assay demonstrated that the length of new vessel structure was significantly reduced （P<0.05）. ConclusionMST1 shows a low expression level in PCa tissues and is associated with tumor metastasis. MST1 exerts tumor-suppressive effects in prostate cancer by inhibiting cell proliferation， migration， and angiogenesis， as well as downregulating the expression of AR and VEGF， indicating its potential as a therapeutic target for prostate cancer.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.

Objective:To compare the clinical efficacy and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

Objective To analyze the characteristics of brain functional networks in patients with post-stroke aphasia(PSA)during a Chinese word-picture matching task.Methods A total of 18 PSA patients in Dongzhimen Hospital from January,2018 to December,2021 were enrolled as PSA group,and nine healthy controls matched for sex,age and education were included as the control group.The Chinese Rehabilitation Research Center Aphasia Examination(CRRCAE)and task-state electroencephalogram(EEG)data based on a Chinese word-picture matching paradigm were collected.Source-space reconstruction was applied to EEG signals to construct functional connectivity matrices.Graph-theoretical analysis was used to com-pute global network properties,and network-based statistics were used to identify subnetwork differences be-tween groups.Correlations between global network properties and CRRCAE subscales were further analyzed.Results The global properties of each frequency band were higher in the control group(unmatched)than in PSA group and the control group(matched)(P<0.01).Subnetworks connections enhanced in the alpha band in the frontal,temporal,parietal,occipital lobes and limbic system(23 nodes,31 edges,P<0.05),and weakened connections in the frontal,temporal,limbic system and basal ganglia(20 nodes,26 edges,P<0.01)in PSA group;in the beta band,subnetwork connections enhanced in the frontal,temporal lobes,basal ganglia and limbic system(15 nodes,23 edges,P<0.01);in the theta band,subnetwork connections weakened in the left frontal and temporal lobes(10 nodes,11 edges,P<0.05),and enhanced in the right frontal and temporal lobes(7 nodes,7 edges,P<0.05).Under the matched condition,the global properties of the alpha and beta bands in PSA group were positive-ly correlated with reading(r=0.511 to 0.650,all P<0.05),and the local efficiency and average clustering coeffi-cient of the theta band were negatively correlated with repetition(r=-0.500 to-0.505,all P<0.05);under the unmatched condition,the local efficiency and average clustering coefficient of the alpha and beta bands in PSA group were positively correlated with reading(r=0.522 to 0.642,all P<0.05),and the global efficiency and lo-cal efficiency of the alpha band were positively correlated with auditory comprehension(r=0.486 to 0.496,all P<0.05).The comparison between the task state and the resting state further revealed that compensatory connec-tion enhanced in the alpha band in the frontal lobe and limbic system(6 nodes,5 edges,P<0.05)and in the beta band in the frontal,temporal,parietal,occipital lobes and limbic system(38 nodes,52 edges,P<0.01)in PSA pa-tients.Conclusion The core network damage characteristics of PSA patients are abnormally decreased global properties across multiple frequency bands and frequency-specific abnormal network reorganization,suggesting the overall brain network efficiency decline coexists with local compensation.This provides an objective basis for the neuroelec-trophysiological evaluation and targeted intervention of PSA.

Objective:To compare the clinical efficacy and analyze the surgical approach differences using CT parameters between mini-open transforaminal lumbar interbody fusion (MO-TLIF) and minimally invasive surgery of transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar diseases.Methods:A total of 68 consecutive patients with degenerative lumbar diseases undergoing surgery at the Second Affiliated Hospital of Soochow University from January 2022 to January 2023 were randomized into the MO-TLIF group (34 cases, percutaneous screw-assisted posterior midline MO-TLIF) and the MIS-TLIF group (34 cases, Wiltse approach MIS-TLIF using the Quadrant channel). Perioperative indicators (operative time, incision length, intraoperative blood loss, fluoroscopy frequency, postoperative bedrest duration, and hospital stay) and complications were compared. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed preoperatively and at 3 days, 3 months, and 1 year postoperatively. Effective cross-sectional area (eCSA) of paraspinal muscles was evaluated on MRI preoperatively and 1 year postoperatively. CT parameters of surgical approaches, including spinous process-midline distance (SM), Wiltse-midline distance (WM), surgical approach angle, depth, and multifidus muscle displacement were compared. Pearson correlation and multivariate linear regression analyses were performed to explore associations between CT parameters, operative time, blood loss, and eCSA atrophy.Results:Baseline characteristics showed no significant differences between groups ( P>0.05). The MO-TLIF group exhibited shorter operative time (109.85±7.82 min vs. 133.82±20.22 min), reduced blood loss (77.21±21.83 ml vs. 141.18±31.44 ml), smaller incision length (6.09±0.22 cm vs. 7.00±0.43 cm), shorter bedrest duration (1.59±0.49 d vs. 2.38±0.50 d), and shorter hospital stay (8.93±1.44 d vs. 10.35±1.45 d), but higher fluoroscopy frequency (19.53±1.92 times vs. 16.29±1.78 times) compared to the MIS-TLIF group ( P<0.05). Complications included fat liquefaction (5 cases) and dural tears (2 cases). Both groups showed improved VAS and ODI postoperatively ( P<0.05). At 3 d postoperatively, the MO-TLIF group had lower VAS (2.74±0.47 points vs. 3.35±0.48 points) and ODI (27.46%±2.16% vs. 30.42%±2.52%) than the MIS-TLIF group ( P<0.05). Postoperative eCSA decreased significantly in the MIS-TLIF group ( P<0.05) but remained stable in the MO-TLIF group ( P>0.05). The MO-TLIF group demonstrated smaller SM (8.43±1.81 mm vs. 31.15±6.53 mm), approach angle, depth, and muscle displacement ( P<0.05). CT parameters in the MO-TLIF group showed no correlation with operative time, blood loss, or eCSA atrophy ( r<0.3, P>0.05), whereas parameters in the MIS-TLIF group correlated positively with these outcomes (0.3< r<0.6, P<0.05). Multivariate regression revealed a significant association between CT parameters and eCSA atrophy in the MIS-TLIF group ( R 2=0.474, P<0.05). Conclusion:Compared to MIS-TLIF, MO-TLIF reduces intraoperative blood loss, accelerates recovery, and minimizes paraspinal muscle trauma.

Objective To analyze the characteristics of brain functional networks in patients with post-stroke aphasia(PSA)during a Chinese word-picture matching task.Methods A total of 18 PSA patients in Dongzhimen Hospital from January,2018 to December,2021 were enrolled as PSA group,and nine healthy controls matched for sex,age and education were included as the control group.The Chinese Rehabilitation Research Center Aphasia Examination(CRRCAE)and task-state electroencephalogram(EEG)data based on a Chinese word-picture matching paradigm were collected.Source-space reconstruction was applied to EEG signals to construct functional connectivity matrices.Graph-theoretical analysis was used to com-pute global network properties,and network-based statistics were used to identify subnetwork differences be-tween groups.Correlations between global network properties and CRRCAE subscales were further analyzed.Results The global properties of each frequency band were higher in the control group(unmatched)than in PSA group and the control group(matched)(P<0.01).Subnetworks connections enhanced in the alpha band in the frontal,temporal,parietal,occipital lobes and limbic system(23 nodes,31 edges,P<0.05),and weakened connections in the frontal,temporal,limbic system and basal ganglia(20 nodes,26 edges,P<0.01)in PSA group;in the beta band,subnetwork connections enhanced in the frontal,temporal lobes,basal ganglia and limbic system(15 nodes,23 edges,P<0.01);in the theta band,subnetwork connections weakened in the left frontal and temporal lobes(10 nodes,11 edges,P<0.05),and enhanced in the right frontal and temporal lobes(7 nodes,7 edges,P<0.05).Under the matched condition,the global properties of the alpha and beta bands in PSA group were positive-ly correlated with reading(r=0.511 to 0.650,all P<0.05),and the local efficiency and average clustering coeffi-cient of the theta band were negatively correlated with repetition(r=-0.500 to-0.505,all P<0.05);under the unmatched condition,the local efficiency and average clustering coefficient of the alpha and beta bands in PSA group were positively correlated with reading(r=0.522 to 0.642,all P<0.05),and the global efficiency and lo-cal efficiency of the alpha band were positively correlated with auditory comprehension(r=0.486 to 0.496,all P<0.05).The comparison between the task state and the resting state further revealed that compensatory connec-tion enhanced in the alpha band in the frontal lobe and limbic system(6 nodes,5 edges,P<0.05)and in the beta band in the frontal,temporal,parietal,occipital lobes and limbic system(38 nodes,52 edges,P<0.01)in PSA pa-tients.Conclusion The core network damage characteristics of PSA patients are abnormally decreased global properties across multiple frequency bands and frequency-specific abnormal network reorganization,suggesting the overall brain network efficiency decline coexists with local compensation.This provides an objective basis for the neuroelec-trophysiological evaluation and targeted intervention of PSA.