Male ; Humans ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Varicocele/diagnosis* ; Biomarkers

Objective To compare the value of the 2018 Chinese guideline prognostic score with that of the 2019 European Society of Cardiology(ESC)in the predicting efficiency for acute pulmonary embolism(APE)in 30-day all-cause mortality.Methods The data of the hospitalized patients with confirmed APE from January 2015 to December 2019 were retrospectively collected.According to death within 30 days,the patients were divided into a death group and a survival group.Subgroup analysis was performed according to gender,oxygen saturation and infection.The SPSS software was used to establish the receiver operating characteristic curve(ROC)for the two scores and calculated the area under the curve(AUC).The Delong's test was applied to compare the AUC differences.The net reclassification index(NRI)and integrated discrimination improvement(IDI)were calculated using the R software packages of survival,survIDINRI,and PredictABEL.Results 626 APE patients were enrolled,and 30-day death was predicted in those patients using two scores.In terms of overall discrimination,the 2018 Chinese guideline prognostic score was better than the 2019 ESC guideline prognostic score,with an AUC of 0.782 and 0.749,respectively;but there were no statistical differences between the two AUC(P＞0.05).In terms of prediction accuracy,the NRI of the 2019 ESC guideline prognostic score was 44.4%(95%CI:0.091～0.753),higher than that of the 2018 Chinese guidelines prognostic score,which increased by 58.6%(95%CI:0.161～0.917)in the correct reclassification to death group,while decreased by 14.2%(95%CI:-0.249～0.08)in the correct reclassification to survival group.IDI increased by 3.38%(P＜0.05).Subgroup analysis showed the prognostic scores of the 2018 Chinese guidelines and the 2019 ESC guidelines prognostic scores had predictive ability for patients with different gender and different oxygen saturation(P＜0.05),and the prognostic scores for co-infected population(AUC:0.749,0.772)(P＞0.05),non-coinfected population(AUC:0.652,0.833).Conclusions Both the 2018 Chinese guideline prognostic score and the 2019 ESC guideline prognostic score can predict 30-day mortality in APE patients,and have a better predictive ability for the co-infected population.However,the predictive accuracy of the former is higher than that of the latter in the survival group,and the score is more rapid and convenient for clinical application,while the latter has improved the prediction ability in the death group.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

italic>Sophora flavescens is a traditional Chinese medicine rich in flavonoids and has wide application potential in drug development and clinical practice. In this study, a total of 227 flavonoids were detected among five tissues of S. flavescens during anthesis using widely targeted metabolomics techniques. There were 137 flavonoids shared by five S. flavescens tissues and 18 root-specific flavonoids. There were 156, 155, 156 and 150 differentially accumulated metabolites identified in stem, leaf, flower, and young pod, respectively, compared with root. Forty-seven potentially active flavonoid components in S. flavescens were identified using the PubChem and SwissADME databases. The 58 potential target proteins for these potentially active components were predicted to be important in the treatment of type 2 diabetes mellitus (T2DM) based on the SwissTargetPrediction and GeneCards database. These 58 target proteins were used to construct a protein-protein interaction network through the STRING database, from which we performed GO and KEGG functional enrichment analysis. The mechanisms by which S. flavescens flavonoids may be useful in the treatment of T2DM was further explored in a multi-level and systematic way based on a "component-target-pathway" network. Finally, ten key potentially effective components were identified and found to be mainly distributed in the roots, flowers, and pods, and their content varied significantly between tissues. The results predict that the key targets of S. flavescens flavonoids in the treatment of T2DM are AKT1, ESR1, EGFR, PIK3R1, TNF and PTGS2, and that they play a hypoglycemic role through the regulation of endocrine resistance, AGE-RAGE, the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance and other signaling pathways. This analysis of the tissue distribution and network pharmacology of S. flavescens flavonoids provides a theoretical basis for further studies on S. flavescens metabolites, the rational development and utilization of the S. flavescens aboveground parts, and initiates a comprehensive exploration of the mechanisms by which S. flavescens can be used in the treatment of T2DM.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

ObjectiveTo analyze the disease and functioning characteristics of older adults with sarcopenia, the main exercise rehabilitation interventions, and its health benefits. MethodsLiterature related to exercise rehabilitation for older adults with sarcopenia was searched in PubMed, Medline, Embase, Cochrane Library and CNKI, from 2013 to 2023. The quality of included systematic reviews were evaluated. ICD-11 and ICF classification systems, and PICO framework from PRISMA guideline were used to report characteristics of the disease and functioning of the population, the exercise rehabilitation interventions, and its health benefits. ResultsFinally, seven systematic reviews from Netherlands, Spain, China, Brazil and Mexico were included, covering 98 related randomized controlled trials, involving 19 794 participants. These systematic reviews mainly came from the journals in the fields of aging, rehabilitation, nutrition, public health and physical exercise, and were published between 2018 and 2023. Exercise rehabilitation for sarcopenia were categorized into three types: exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Interventions primarily included aerobic training, resistance training, gait training, strength training, and balance and flexibility exercises. The intervention frequency was six to 150 minutes, one to five times a week, with intensities ranging from low to high, over a duration of six to 144 weeks. The health benefits for older adults with sarcopenia from exercise rehabilitation were reflected in improvement in physical function and structure, and enhancement in activity and participation. In terms of body function and structure, exercise rehabilitation improved muscle strength, control, coordination, gait, balance, leg extension, leg press, back strength and grip strength, and increased muscle quality. In terms of activity and participation, exercise rehabilitation improved physical activity performance, such as walking speed and time of five-repetition chair stand test. ConclusionExercise rehabilitation for sarcopenia includes exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Exercise rehabilitation can improve the physical function and structure, and enhance activity and participation.

Objective:To study the impact of different scattering correction algorithms in the reconstruction of PET/CT images on image artifacts and the precision of quantitative parameters.Methods:The phantom as described in the National Electrical Manufacturers Association (NEMA) NU2 standard was filled with 18F. The background activity was fixed, and the activity of the solution in the spheres was adjusted to obtain several configurations, including the normal ratio group (4.08∶1) and the extreme ratio group (200∶1). The surface contamination group with the same ratio as the extreme ratio group contained a small radioactive source with different doses of 18F (74, 37, 3.7 and 0.37 MBq) placed at the surface of the phantom. PET/CT images of 30 patients (21 males, 9 females, age: (44.5±10.2) years) from Peking University Cancer Hospital & Institute between July 2012 and December 2021 were retrospectively analyzed, including 10 with normal images ( 18F-FDG) and 20 with abnormal images (10 with dislocation during acquisition, 10 with surface contamination). The images were reconstructed with relative and absolute scattering correction. The phantom was evaluated using the target to background ratio (TBR) and the artifact classification. CV as well as the artifact classification were used to compare the clinical image quality. Mann-Whitney U test and χ2 test were used to analyze data. Results:In the normal ratio group and the extreme ratio group, the TBRs of phantom images reconstructed with relative correction were significantly higher than those with absolute correction (normal ratio group: 3.30(1.94, 4.53) vs 2.72(1.56, 3.56); z=-2.20, P=0.028; extreme ratio group: 105.47(45.62, 162.82) vs 101.36(43.96, 155.57); z=-1.99, P=0.046). In the surface contamination group, with the increase of the activity of the small source, the artifact became more obvious, and the artifact classification score of absolute correction was significantly better than that of relative correction (1.5(1.0, 2.0) vs 2.5(2.0, 3.0); z=-2.00, P=0.046). In the 10 normal 18F-FDG PET/CT patients, the CVliver of the relative correction (9.67%(8.00%, 11.00%)) was significantly lower than that of absolute correction (11.00%(9.00%, 12.00%); z=-2.57, P=0.010), indicating the higher image quality of images with relative correction. In abnormal images, the image quality of absolute correction was significantly higher than that of relative correction with fewer and less severe artifacts (dislocation cases: 9/10 vs 4/10; χ2=5.50, P=0.019; surface contamination cases: 9/10 vs 4/10; χ2=5.50, P=0.019). Conclusions:The relative scattering correction is suitable for normal situations in clinical PET acquisition. However, with dislocation or surface contamination, the absolute scattering correction helps to reduce the artifacts and improve the image quality.

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ² test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ² test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ²=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m², P<0.01; mean difference=2.429 kg/m², P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m², P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ²=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ²=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.
Aged ; Albumins ; Esophagitis, Peptic/surgery* ; Female ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective To study stress distributions of lower dentition distally moved with miniscrews in external oblique line area when the traction hooks with different lengths were placed at different positions by the three-dimensional (3D) finite element method. Methods Based on cone beam computed tomography (CBCT) data from a patient, traction hooks with the heights of 2 mm and 7 mm were constructed and fixed between the lateral incisors and the canine brackets, as well as between the canines and the first premolar brackets. Four kinds of 3D finite element models of full dentition distally moved with miniscrews were constructed. The 3 N traction force was loaded between the traction hook and the miniscrews. The maximum von Mises stress and initial displacement of the mandibular teeth and dentition under four working conditions were analyzed. ResultsWhen the traction hook with 7 mm-height was placed between the lateral incisor and the canine, the lower central incisor rotated clockwisely, with the crown moving labially and the root moving lingually. But under the other three working conditions, the central incisor rotated counterclockwisely, and the crown and root moved lingually. When the traction hook with 7 mm-height was placed between the canine and the first premolar, the lower canine crown moved proximally. But under the other three working conditions, both the crown and root moved distally. Under four working conditions, the mandibular molars all rotated counterclockwisely,with the crown and root moving distally. Conclusions Through 3D finite element analysis, biomechanical mechanism of the effect of different traction hooks on mandibular tooth movement during distalization of the lower dentition was elucidated.With full understanding of the biomechanical mechanism, proper selection for length and placement of the traction hook can achieve distal movement of the entire mandibular dentition more efficiently.

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.
Anastomosis, Surgical/methods* ; Esophagogastric Junction/surgery* ; Gastrectomy/methods* ; Gastroesophageal Reflux/surgery* ; Humans ; Quality of Life ; Stomach Neoplasms/surgery*