Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective:To explore the effect of combining hand-brain perception training with hand-brain motor training based on mirror neuron theory on the recovery of upper limb function after a stroke.Methods:A group of 105 stroke survivors with upper limb dysfunction were randomly divided into a hand-brain perception (HP) group, a hand-brain motor (HM) group, and a combination (C) group, each of 35. In addition to conventional rehabilitation treatment (including exercise therapy, occupational therapy and physical factor therapy), the HP and HM groups were given hand-brain perception training and hand-brain motor training respectively, while group C was provided with both. Before the intervention and after 4 weeks, the upper limb motor functioning of all of the participants was assessed using the simplified version of the Fugl-Meyer upper limb motor function scale (FMA-UE). Sensory functioning was quantified using the tactile Semmes Weinstein monofilament examination (SWME), and the modified Barthel index (MBI) was used to quantify the participants′ ability in the activities of daily living.Results:After the intervention the average FMA-UE, MBI and SWME scores of all three groups had improved significantly, with group C′s average FMA-UE and MBI scores significantly better than the other two groups′ averages. The average SWME score of group C was then significantly better than that of group HM.Conclusions:Hand-brain perception combined with hand-brain motor training based on mirror neuron theory can further promote the recovery of upper limb sensory and motor functioning of stroke survivors., Such therapy is worthy of clinical promotion and application.

Objective:To explore the diagnostic value of improved 18F-prostate specific membrane antigen (PSMA)-1007 PET-CT score (referred to as PSMA score) and multi parameter magnetic resonance imaging (mpMRI) prostate imaging reporting and data system (PI-RADS) score (referred to as PI-RADS score) for primary prostate cancer (PCa). Methods:A retrospective case series study was conducted. The imaging and clinical data of 134 suspected PCa patients underwent 18F-PSMA-1007 PET-CT and mpMRI examinations at Shanxi Province Cancer Hospital from July 2018 to May 2023 were collected. Pathological diagnosis showed 92 cases of PCa and 42 cases of benign prostatic lesions. The clinical and imaging parameters, as well as the distribution of patients with two scores, were compared between the two groups. The blind diagnosis of benign and malignant lesions was made based on the improved PSMA score (dividing 1 point into 1a and 1b points, 1b, 2 and 3 points were diagnosed as PCa), PI-RADS score (3, 4 and 5 points were diagnosed as PCa) and the combination of the two (diagnosed as PCa when either PSMA score ≥ 1b point or PI-RADS score ≥ 4 points was met). The indicators of the diagnostic efficiency of PSMA score, PI-RADS score and the combination of the two for PCa were calculated. Using pathological results as the gold standard, the receiver operating characteristic (ROC) curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa was drawn, and the diagnostic efficiency of the 3 methods was analyzed. Results:The age, serum prostate-specific antigen, and maximum standard uptake value of PET-CT in the PCa group were higher than those in the benign prostatic lesion group, and the differences were statistically significant (all P < 0.05). The sensitivity, specificity, accuracy, false negative rate, false positive rate, positive predictive value, and negative predictive value of PSMA score for diagnosing PCa were 91.30% (84/92), 80.95% (34/42), 88.06% (118/134), 8.70% (8/92), 19.05% (8/42), 91.30% (84/92), and 80.95% (34/42), respectively; those of PI-RADS score were 93.48% (86/92), 61.90% (26/42), 83.58% (112/134), 61.90% (26/42), 38.10% (16/42), 84.31% (86/102), and 81.25% (26/32), respectively; those of the combination of the two were 97.83% (90/92), 88.10% (37/42), 94.78% (127/134), 2.17% (2/92), 11.90% (5/42), 94.74% (90/95), and 94.87% (37/39), respectively. The differences in specificity, accuracy, false negative rate, and false positive rate among the 3 methods were statistically significant (all P < 0.05). ROC curve analysis showed that the area under the curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa were 0.930 (95% CI: 0.872-0.967), 0.935 (95% CI: 0.826-0.939) and 0.959 (95% CI: 0.910-0.986), respectively, and the differences between each two methods were statistically significant (all P < 0.05); the sensitivity of PSMA score, PI-RADS score and the combination of the two was 90.11%, 89.13% and 98.09%, and the specificity was 90.48%, 90.48% and 92.09%. Conclusions:Compared with the PI-RADS score, the improved PSMA score can improve the specificity and accuracy of PCa diagnosis, and decrease the false negative and false positive rates; the diagnostic efficiency of the combination of the two is superior.

Objective:To explore the clinical application value of multimodal"one-stop"CT in assessing acute ischemic stroke(AIS).Methods:A total of 98 patients who were diagnosed as AIS and underwent the treatment of intravenous thrombolysis in Department of Neurology of Huainan Chaoyang Hospital from December 2019 to July 2023 were selected.In them,the degree of vascular stenosis of 49 patients was<30%(mild stenosis),and that of 39 patients was 30%～69%(moderate stenosis),and that of 10 patients was 70%～99%(severe stenosis)and 100%occlusion(severe group).All subjects underwent multimodal"one-stop"CT scan,and the changes of perfusion parameters included time to peak(TTP),mean transit time(MTT),cerebral blood flow(rCBF)and cerebral blood volume(rCBV)of them were analyzed.Results:All 98 patients existed stenosis at different locations and degrees,and CT examination showed existed respectively 5 cases of suspicious low density foci in frontal lobe and parietal lobe.Post-processing pseudo-color map showed that all 98 cases had abnormal hypoperfusion.The responsible vessel of 25 cases with occlusion and 20 cases with stenosis was the cerebral middle artery,and that of 3 cases with occlusion and 7 cases with stenosis was posterior artery,and that of 7 cases was internal carotid artery,and that of 3 cases with occlusion and 5 cases with stenosis was basilar artery,and that of 7 cases with occlusion and 18 cases with stenosis was vertebrobasilar artery.In addition,3 cases existed arteriosclerosis.There were significant differences in the average levels of rCBF,rCBV,MTT and TTP among patients with different degrees of stenosis,and the differences were all statistically significant(F=66.689,46.751,3.401,41.565,P<0.05),respectively.The area under curve(AUC)values of the receiver operating characteristic(ROC)curves of rCBF,rCBV,MTT and TTP were all>0.5 in assessing AIS,and the AUC value of the combined examination of above indicators was higher than the AUC value of each single indicator of the above indicators.Conclusion:Brilliance iCT multimodal"one-stop"CT scan can comprehensively understand the vascular morphology and stenosis location of the head and neck,and effectively assess responsible vessels,and provide perfusion parameters of whole brain.This technique can improve the accuracy of diagnosis and treatment decision,which has important impact in improving the efficacy of cerebral stroke.It can provide the basis for the selection of subsequent treatment plan and the prognosis judgment.

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.
Mice ; Animals ; Mice, Obese ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Network Pharmacology ; RNA, Ribosomal, 16S ; Diabetes Mellitus, Type 2/complications* ; Obesity/genetics* ; Body Weight ; Lipids ; Insulin ; Transcription Factors ; Dyslipidemias/genetics* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal