ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

ObjectiveTo investigate the relationship of physical activity (PA) and cognitive function to sleep quality in older adults with cognitive impairment based on resting electroencephalogram (EEG), and to explore the mediating role of specific EEG markers in the relationship between PA and sleep quality. MethodsFrom March to May, 2024, 137 older adults were recruited from Chenfu Jiayuan and Qiangwei Jiuli in Songjiang district, and Luyan communities in Jinshan district, Shanghai. The assessments included Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Pittsburgh Sleep Quality Index (PSQI), along with a five-minute EEG recording. ResultsThere was significant difference in sleep quality among older adults with different levels of cognitive impairment (t = -7.400, P < 0.001). The PSQI total score was negatively correlated with MoCA scores (r = -0.412, P < 0.001) and total physical activity level (PAL) (r = -0.363, P < 0.001). The θ power in the frontal areas (F3, F4) was significantly correlated with both PSQI scores and PAL (P < 0.01). The θ power in F3 + F4 exhibited a significant partial (effect size = -0.0004, 95%CI -0.0007 to -0.0002) mediating effect between PA and sleep quality in older adults with cognitive impairment. ConclusionOlder adults with more severe cognitive impairment tend to have poorer sleep quality, whereas higher PAL is associated with better sleep quality. PA can indirectly influence sleep quality in older adults with cognitive impairment by affecting θ power (F3 + F4).

Nasopharyngeal carcinoma is one of the most common head and neck tumors. At present, intensity modulated radiation therapy (IMRT) is the main radical treatment. In recent years, adaptive radiation therapy (ART) becomes the focus in the research field of precision radiotherapy. ART can reduce the target conformal and dose changes and increase the dose of exposed organs caused by factors such as weight loss, positioning error, systematic error, and anatomical changes of lesions and organs at risk, thus improving the effectiveness and safety of intensity modulated radiotherapy. This article focuses on and summarizes the recent progress in the application of ART in nasopharyngeal carcinoma, and puts forward the possible research direction in the future.

Objective:To explore the impact of tissue inhomogeneity correction on the accuracy of dose calculations in brachytherapy of cervical carcinoma by comparing the results of Monte Carlo (MC) dose simulation with those (TG43 algorithm) of treatment planning system (TPS).Methods:Firstly, the 192Ir source was modeled by using a MC code specially designed for brachytherapy, called egs_brachy. The accuracy of this model was verified by comparing it with the published data. Then, 8 brachytherapy plans of cervical carcinoma were selected which completed treatment at Sun Yat-sen University Cancer Center from January 2022 to May 2023, and their CT image data and treatment parameters were exported. Relevant plan information such as the source dwell positions and their corresponding dwell times were reconstructed on the patient's individualized CT images using a self-developed program. The MC dose distributions were calculated for each case and compared with the TPS calculations. When the anterior wall of the rectum was filled with gas, the differences between MC simulation and TPS calculation were compared. Additionally, 5 different calculation ranges were set for MC simulation, and the MC simulation results of different calculation ranges were compared with the TPS's, combining with the time of MC simulation, a reasonable MC calculation range was comfirmed. Then, the scipy.stats library of Python was utilized to perform independent sample t-test on dosimetric comparison results, including D 90% of high risk clinical target volume (HR-CTV) and D max, D mean, and D 2 cm3 of organs at risk (OAR). Results:The comparison between MC calculations and TPS results showed that the CTV's D 90%, the bladder's D mean and the small intestine's D mean were all within ± 1%, except for the D max difference of approximately 3% on the anterior wall of the rectum. The 2%/2 mm gamma pass rates were all>98%. When anterior wall of the rectum filled with gas, compared with MC, TPS overestimated the anterior wall of the rectum's D 2 cm3 and D mean by approximately 6.06% ( t=-6.80, P=0.002) and 5.35% ( t=-6.57, P=0.003), respectively. When the dose calculation range of MC was consistent with that of TPS, the MC calculation result underestimated the dose distribution in water by approximately 4%. When extending the MC dose calculation range by 2 cm beyond the TPS calculation range, the dose difference between MC and TPS in homogeneous water was approximately 1%, and the calculation time was saved by at least 8 h compared to MC dose calculation based on the whole CT. Conclusion:The existing TPS TG43 algorithm can ensure that the dose calculation of cervical carcinoma meets the basic accuracy requirements of clinical practice, but tissue inhomogeneity correction is recommended to improve the accuracy of dose calculation whenever possible.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To explore the characteristics of tongue microbiota in patients with pancreatic neuroendocrine neoplasms (pNENs).Methods:The tongue coating microbiota of 15 pathologically diagnosed pNENs patients from Nanjing First Hospital between November 2019 and July 2020 were selected, and 15 healthy volunteers were recruited as the healthy control group. Oral pharyngeal swab was used to scrape the tongue coating, and DNA extraction and detection of the tongue coating samples from two groups were performed, 16S rRNA gene high-volume sequencing was applied to analyze the differences on the microbiome. The α and β diversity differences were tested by Chao1 index, Shannon index and principal component analysis, respectively. The inter-group analysis of variances was used to compare the species composition of tongue coating microbiota at the phylum, genus, and species levels between two groups. Differences in dominant bacterial genera between two groups were analyzed by using linear discriminant analysis (LEfSe).Results:Compared with the healthy control group, the types and quantities of tongue coating microbiota in pNENs patients were similar, but the structural composition was significantly different. At the phylum level, Proteobacteria, Bacteroides, Firmicutes, Fusobacteria and Actinobacteria were mainly present in both two groups, but Firmicutes and Actinobacteria were relatively more in pNENs patients compared with healthy groupy with more Bacteroides. The dominant genera of tongue coating microbiota in pNENs patients and healthy individuals included Haemophilus, Neisseria, and Prevotella_7, Streptococcus, Fusobacterium, Alloprevotella and Veillonella. The relative abundance of Fusobacterium, Alloprevotella, Prevotella and Aggregatibacter in the healthy control group's tongue coating microbiota was higher, while Veillonella had a higher relative abundance in the tongue coating microbiota of pNENs patients. LEfSe results showed that the dominant microflora were Actinobacteria at phylum level and Roseburia at genera level in pNENs patients, which were Aggregatibacter at genera level in healthy group. Conclusions:The distribution of tongue coating microbiota in pNENs patients are different from those in healthy people. The increase in abundance of Actinobacteria and Roseburia, as well as the decrease in abundance of Aggregatibacter, may have potential implications for the diagnosis of pNENs.

Objective:To observe the effects of overexpression of polypyrimidine tract binding protein-associated splicing factor (PSF) on the endoplasmic reticulum (ER) oxidative stress damage of human retinal microvascular endothelial cells (hRMEC) under high concentration of 4-hydroxynonenal (4-HNE).Methods:The logarithmic growth phase hRMEC cultured in vitro was divided into normal group, simple 4-HNE treatment group (simple 4-HNE group), empty plasmid combined with 4-HNE treatment group (Vec+4-HNE group), and PSF high expression combined with 4-HNE treatment group (PSF+4-HNE group). In 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group cell culture medium, 10 μmol/L 4-HNE was added and stimulated for 12 hours. Subsequently, the Vec+4-HNE group and PSF+4-HNE group were transfected with transfection reagent liposome 2000 into pcDNA empty bodies and pcDNA-PSF eukaryotic expression plasmids, respectively, for 24 hours. Flow cytometry was used to detect the effects of 4-HNE and PSF on cell apoptosis. The effect of PSF overexpression on the expression of reactive oxygen species (ROS) in hRMEC was detected by 2', 7'-dichlorodihydrofluorescein double Acetate probe. Western blot was used to detect ER oxide protein 1 (Ero-1), protein disulfide isomerase (PDI), C/EBP homologous transcription factor (CHOP), glucose regulatory protein (GRP) 78, protein kinase R-like ER kinase (PERK)/phosphorylated PERK (p-PERK), and Eukaryotic initiation factor (eIF) 2α/the relative expression levels of phosphorylated eIF (peIF) and activated transcription factor 4 (ATF4) proteins in hRMEC of normal group, 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group. Single factor analysis of variance was performed for inter group comparison.Results:The apoptosis rates of the simple 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group were (22.50±0.58)%, (26.93±0.55)%, and (11.70±0.17)%, respectively. The intracellular ROS expression levels were 0.23±0.03, 1.60±0.06, and 0.50±0.06, respectively. The difference in cell apoptosis rate among the three groups was statistically significant ( F=24.531, P<0.05). The expression level of ROS in the Vec+4-HNE group was significantly higher than that in the simple 4-HNE group and the PSF+4-HNE group, with a statistically significant difference ( F=37.274, P<0.05). The relative expression levels of ER Ero-1 and PDI proteins in the normal group, simple 4-HNE group, Vec+4-HNE group, and PSF+4-HNE group were 1.25±0.03, 0.45±0.03, 0.63±0.03, 1.13±0.09, and 1.00±0.10, 0.27±0.10, 0.31±0.05, and 0.80±0.06, respectively. The relative expression levels of CHOP and GRP78 proteins were 0.55±0.06, 1.13±0.09, 0.90±0.06, 0.48±0.04 and 0.48±0.04, 1.25±0.03, 1.03±0.09, 0.50±0.06, respectively. The relative expression levels of Ero-1 ( F=43.164), PDI ( F=36.643), CHOP ( F=42.855), and GRP78 ( F=45.275) proteins in four groups were compared, and the differences were statistically significant ( P<0.05). Four groups of cells ER p-pERK/pERK ( F=35.755), peIF2 α/ The relative expression levels of eIF ( F=38.643) and ATF4 ( F=31.275) proteins were compared, and the differences were statistically significant ( P<0.05). Conclusion:PSF can inhibit cell apoptosis and ROS production induced by high concentration of 4-HNE, and its mechanism is closely related to restoring the homeostasis of ER and down-regulating the activation level of PERK/eIF2α/ATF4 pathway.

BACKGROUND: The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system. METHODS: From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed. RESULTS: A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively. CONCLUSION The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.
Male ; Humans ; Robotic Surgical Procedures/methods* ; Robotics ; Treatment Outcome ; Retrospective Studies ; Ureter/surgery* ; Urologic Surgical Procedures/methods* ; Laparoscopy/methods*

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

Object:To explore surgical treatments for duodenal fistula with intra-abdominal infection.Methods:The data of 19 patients with duodenal fistula treated at the Affiliated Tumor Hospital of Zhenzhou University between Jan 2015 and Dec 2021 were analyzed retrospectively. Surgery is performed with duodenostomy or modified duodenal shunt procedures.Result:All patients were accompanied by intra-abdominal infection, including 9 duodenal stump fistulas. All patients successfully completed the operation,11cases underwent duodenostomy, 8 case underwent modified duodenal shunt procedures. operating time was 110(60-140)min, postoperative hospitalization time was 29(9-103)d. Two patients died postoperatively. Fistula heals in other patients.Conclusion:Surgical intervention for duodenal fistula should focus on controlling the source of infection, strengthening intestinal and abdominal drainage, and reducing postoperative complications.