Objective To analyze and verify the role of senescent genes in the treatment,prognosis,and tumor microenvironment(TME)characteristics of osteoblastic osteosarcoma,bioinformatic methods were employed.Methods Senescent genes were obtained from the China National Genome Science database(https://ngdc.cncb.ac.cn/aging/index).The gene expression profile and clinical information of osteosarcoma patients were sourced from the TARGET database(https://ocg.cancer.gov/programs/target),while single-cell RNA-sequencing(scRNA-seq)data was collected from GSE162454 on the Gene Expression Omnibus(GEO)for downstream analysis.Osteosarcoma cells were classified based on scRNA-seq,and differential expression analysis between osteoblasts/chondroblasts and other cell types was conducted to identify differently expressed genes(DEGs).After matching with the senescent genes,prognostic senescent DEGs were identified through univariable and multivariable Cox regression analysis.Subsequently,the osteosarcoma senescent-related model(OSRM)was constructed,and the risk score was calculated.The role of OSRM in treatment,prognosis,and TME of osteosarcoma was further investigated.Results The analysis revealed that GSE162454 contained 6 osteosarcoma samples,with 19933 cells identified after filtering,quality control,and normalization.Seventeen cellular subtypes were identified using uniform manifold approximation and projection(UMAP)methods.A total of 4821 DEGs were found between osteoblasts/chondroblasts and other subtypes,with 132 senescent DEGs obtained after matching with the senescent gene set.In the TARGET database,4 prognostic senescent DEGs[ADH5(alcohol dehydrogenase 5),ARHGAP1(Rho GTPase activating protein 1),APOE(apolipoprotein E),and ATF4(activating transcription factor 4)]were identified through univariable and multivariable Cox analyses to construct OSRM.Based on risk score,patients were stratified into high-and low-risk groups,with the latter showing better prognosis(HR=0.13,95%CI 0.06-0.28,P<0.001)and higher sensitivity to immune checkpoint inhibitors.qRT-PCR and Western blotting confirmed the high expression of senescent genes ADH5(P<0.01),APOE(P<0.01),and ATF4(P<0.05)in the K7M2 osteosarcoma cell line,suggesting the potential for predicting the response to anti-PD-1 immunotherapy for osteosarcoma.Conclusions scRNA-seq facilitated the division of osteosarcoma into 17 cell subtypes.ADH5,ARHGAP1,APOE,and ATF4 emerged as potential cancer-promoting or suppressing senescent genes in osteosarcoma.OSRM was found to be associated with treatment response,prognosis,and TME characteristics,thereby promoting the molecular pathological diagnosis of osteoblastic osteosarcoma and prediction for anti-PD-1 immunotherapy.

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

OBJECTIVE: To evaluate the feasibility of S₂ alar iliac screw insertion in Chinese children using computerized three-dimension reconstruction and simulated screw placement technique, and to optimize the measurement of screw parameters. METHODS: A total of 83 pelvic CT data of children who underwent pelvic CT scan December 2018 to December 2020 were retrospectively analyzed, excluding fractures, deformities, and tumors. There were 44 boys and 39 girls, with an average age of (10.66±3.52) years, and were divided into 4 groups based on age (group A:5 to 7 years old;group B:8 to 10 years old;group C:11-13 years old;group D:14 to 16 years old). The original CT data obtained were imported into Mimics software, and the bony structure of the pelvis was reconstructed, and the maximum and minimum cranial angles of the screws were simulated in the three-dimensional view with the placement of 6.5 mm diameter S2 alar iliac screws. Subsequently, the coronal angle, sagittal angle, transverse angle, total length of the screw, length of the screw in the sacrum, width of the iliac, and distance of the entry point from the skin were measured in 3-Matic software at the maximum and minimum head tilt angles, respectively. The differences among the screw parameters of S₂ alar iliac screws in children of different ages and the differences between gender and side were compared and analyzed. RESULTS: In all 83 children, 6.5 mm diameter S₂ iliac screws could be placed. There was no significant difference between the side of each screw placement parameter. The 5 to 7 years old children had a significantly smaller screw coronal angle than other age groups, but in the screw sagittal angle, the difference was more mixed. The 5 to 7 years old children could obtain a larger angle at the maximum head tilt angle of the screw, but at the minimum cranial angle, the larger angle was obtained in the age group of 11 to 13 years old. There were no significant differences among the age groups. The coronal angle and sagittal angle under maximum cephalic angle and minimum cranial angle of 5 to 7 years old male were (40.91±2.91)° and (51.85±3.75)° respectively, which were significantly greater than in female. The coronal angle under minimum cranial angle was significantly greater in girls aged 8-10 years old than in boys. For the remaining screw placement angle parameters, there were no significant differences between gender. The differences in the minimum iliac width, the screw length, and the length of the sacral screws showed an increasing trend with age in all age groups. The distance from the screw entry point to the skin in boys were significantly smaller than that of girls. The minimum width of the iliac in boys at 14 to 16 years of age were significantly wider than that in girls at the same stage. In contrast, in girls aged 5 to 7 years and 11 to 13 years, the screw length was significantly longer than that of boys at the same stage. CONCLUSION The pelvis of children aged 5 to 16 years can safely accommodate the placement of 6.5 mm diameter S₂ alar iliac screws, but the bony structures of the pelvis are developing and growing in children, precise assessment is needed to plan a reasonable screw trajectory and select the appropriate screw length.
Humans ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Ilium/surgery* ; Retrospective Studies ; Feasibility Studies ; Bone Screws ; Pelvis ; Sacrum/surgery* ; Spinal Fusion/methods*

Neurological impairment in the form of stroke,cognitive dysfunction and delirium is a common complication after cardiac surgery and a major cause of postoperative death and long-term disability in patients undergoing cardiac surgery.There have been many studies attempting to identify intervention and treatment strategies,but no standardized protocols for neurological protection have been developed.The purpose of this article is to discuss the risk factors,mechanisms and neuroprotective measures to improve patient prognosis of neurological injury after cardiac surgery,and to review the recent research progress from three aspects:preoperative assessment and intervention,intraoperative management and monitoring,and postoperative diagnosis and treatment,emphasizing that the focus of perioperative prevention and treatment should be on the prevention of ischemic-hypoxic injury.Future research directions should focus on translational research of preclinical experiments and the development of novel imaging techniques to reduce the incidence of neurological complications and improve clinical outcome.

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; Case-Control Studies ; Colorectal Neoplasms/drug therapy* ; Fluorouracil/therapeutic use* ; Humans ; Leucovorin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Prognosis ; Retrospective Studies

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective To understand the main serotypes, antibiotic resistance profiles and molecular typing characteristics of Listeria monocytogenes（LM) isolated from foods in Shandong Province from 2013 to 2016. Methods The antibiotic sensitivity of LM was tested by broth microdilution method. The serotypes were determined by slide agglutination and PCR, and the molecular typing was carried out by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing(MLST) . Results Most of 191 LM strains were sensitive to the eight antibiotics tested. Tetracycline resistance was most prevalent (15/191, 7.85%). There was no significant difference in the 8 antibiotic resistance monitored for 4 years (P=1.000). The serotype 1/2a, 1/2b and 1/2c accounted for 38.82% (66/170), 18.82% (32/170), and 42.36% (72/170), respectively. The patterns of SDSRZXDZ016, S2014L031 and SDSRZX030, totally accounted for 33.78%, were the dominant types. The main ST types were ST9, ST8 and ST121, which accounted for 81.18% (69/85). The clinical common types, ST3, ST7 and ST87 accounted for 8.23% (7/85), mainwhile new ST type was not found. Conclusion The LM strains isolated in Shandong Province from 2013 to 2016 were sensitive to most antibiotics, but some strains were resistant to tetracycline and erythromycin. The dominant serotypes were 1/2c and 1/2a. Serotype 4b, prone to outbreaks of listeriosis, was not found. The main PFGE types were SDSRZXDZ016, S2014L031 and SDSRZX030, which were continuously found from 2013 to 2016. The main ST types were ST8, ST9 and ST121. The clinical types, ST3, ST7 and ST87 were isolated from food and should be paid seriously attention to.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

OBJECTIVE To investigate the protective effect and mechanisms of luteolin-7-O-β-d-glucuronide (LGU) on oxygen glucose deprivation (OGD)-induced H9C2 cardiomyocytes injury. METH-ODS The protective effect of LGU on OGD-induced H9C2 cardiomyocytes death were investigated by MTT assay. The microfilament change of H9C2 cardiomyocytes was detected by phalloidin staining and the lactate dehydrogenase (LDH) leakage rate was also detected by LDH kit. In order to explore the possible mechanisms of LGU, ATP content, intracellular Ca2+fluorescent intensity and concentra-tion, mitochondrial membrane potential (MMP)and the expressions of apoptosis-related proteins were detected by ATP kit,CLSM(Fluo-3/AM probe),Ca2+kit,CLSM(JC-1 probe)and western blotting meth-od, respectively. RESULTS The inhibition of H9C2 cardiomyocyte survival rate inducedby OGD was improvedby pretreated with LGU in a concentrationdependent manner. The microfilaments injury as well as the increase of LDH leakage rate were also improvedby pretreated with LGU.The ATP content was significantly decreased,intracellular Ca2+fluorescent intensity and concentration were significantly increased and the MMP was significantly decreased 4 hafter OGD. LGU significantly reversed the de-crease of intracellular ATP content,the increase of Ca2+fluorescent intensity and concentration and the decrease of MMP.The release of cytochrome C,the expressionsof caspase-9 and caspase-3 in H9C2 cardiomyocytes were increased 16 h after OGD.LGUsignificantly inhibited the changes of these apop-tosis-related proteins. CONCLUSION LGU has a significant protective effect against OGD-induced H9C2 cardiomyocytes injury through inhibiting calcium overload,increasing ATP content,improving mi-tochondrial function and inhibiting apoptosis.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use