Objective To evaluate the effects of ketamine combined with sufentanil on postoperative analgesia and depression in patients undergoing hip arthroplasty.Methods A total of 60 patients who underwent elective hip arthroplasty were selected and divided into the S group,the SK1 group and the SK2 group according to the patient-controlled intravenous analgesia regimen,with 20 cases in each group.Patients in the S group were received 2 μg/kg of sufentanil for postoperative analgesia,patients in the SK1 group were received 1 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia,and patients in the SK2 group were received 2 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia.At 1,4,24,and 48 hours after surgery,the analgesic effect of patients was evaluated using the numeric rating scale(NRS),and the sedation effect of patients was evaluated using the Ramsay sedation score.Depression of patients before and 48 hours after surgery was assessed by self-rating depression scale(SDS).The adverse reactions such as nausea and vomiting,dizziness and headache,respiratory depression,and mental symptoms within 48 hours after surgery of patients were recorded.Results The NRS scores 1,4,and 24 hours after surgery of patients in the SK1 group and the SK2 group were lower than those in the S group(P<0.05);there was no statistically significant difference in the NRS scores 48 hours after surgery of patients among the three groups(P>0.05);there was no statistically significant difference in the NRS scores at different postoperative points of patients between the SK1 and SK2 groups(P>0.05).The SDS scores 48 hours after surgery of patients in each group were lower than those before surgery(P<0.05).There was no statistically significant difference in the Ramsay scores at different postoperative points of patients among the three groups(P>0.05).The incidence of adverse reactions 48 hours after surgery in the SK2 group was higher than those in the S group and the SK1 group(P<0.05).Conclusion Using 1 mg/kg of esketamine combined with 2 μg/kg of sufentanil after hip arthroplasty has a good analgesic effect without obvious increase of adverse reactions or significant effect on improving depression of patients.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.
Acoustic Stimulation/methods* ; Neurons/physiology* ; Auditory Cortex/physiology* ; Auditory Perception ; Pyramidal Cells

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

Clostridium perfringens can produce many kinds of toxins and hydrolase, causing gas gangrene, enteritis and enterotoxemia in both human and animals. It is known that C. perfringens can produce more than 20 toxins and hydrolases. The different toxin types are associated with specific disease types. At present, molecular toxin-typing method by PCR has replaced the traditional serological typing method. In this study, we systematically summarize the types, basic characteristics, pathogenic mechanism and the relationship with disease of C. perfringens toxins to provide evidence for the establishment of rapid detection method, immune antigen screening, antibody preparation and research of related pathogenic mechanism.
Animals ; Humans ; Clostridium perfringens ; Antibodies ; Polymerase Chain Reaction

Vascular calcification is an important pathophysiological basis of cardiovascular disease with its underlying mechanism unclear. In recent years, studies have shown that aging is one of the risk factors for vascular calcification. The purpose of this study was to investigate the microenvironmental characteristics of vascular calcification, identify aging/senescence-induced genes (ASIGs) closely related to calcified plaques, and explore the evolution trajectory of vascular calcification cell subsets. Based on the bioinformatics method, the single cell transcriptome sequencing data (Gene Expression Omnibus: GSE159677) of carotid artery samples from 3 patients undergoing carotid endarterectomy were grouped and annotated. Vascular calcification-related aging genes were identified by ASIGs data set. The pseudotime trend of ASIGs in cell subsets was analyzed by Monocle 3, and the evolution of vascular calcification cells was revealed. After quality control, all cells were divided into 8 cell types, including B cells, T cells, smooth muscle cells, macrophages, endothelial cells, fibroblasts, mast cells, and progenitor cells. Ten ASIGs related to vascular calcification were screened from the data set of ASIGs, which include genes encoding complement C1qA (C1QA), superoxide dismutase 3 (SOD3), lysozyme (LYZ), insulin-like growth factor binding protein-7 (IGFBP7), complement C1qB (C1QB), complement C1qC (C1QC), Caveolin 1 (CAV1), von Willebrand factor (vWF), clusterin (CLU), and αB-crystallin (CRYAB). Pseudotime analysis showed that all cell subsets were involved in the progression of vascular calcification, and these ASIGs may play an important role in cell evolution. In summary, AGIS plays an important role in the progression of vascular calcification, and these high expression genes may provide ideas for early diagnosis and treatment of vascular calcification.
Humans ; Endothelial Cells ; Muscle, Smooth, Vascular ; Aging ; Vascular Calcification/metabolism* ; Computational Biology ; Myocytes, Smooth Muscle/metabolism*

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Bone Neoplasms/immunology* ; Computational Biology/methods* ; Gene Expression Profiling/methods* ; Humans ; Osteosarcoma/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor-Associated Macrophages/immunology*

Objective:To investigate the effects of different connection schemes of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) on arterial pressure (PA), venous pressure (PV), and transmembrane pressure (TMP), and to provide a theoretical basis for choosing a suitable connection scheme.Methods:① In vitro study: the different connection schemes of CRRT and ECMO were simulated and divided into 6 schemes according to the connection between CRRT and ECMO circuits at different positions. Scheme A: connected to the front and back points of the oxygenator; scheme B: connected to the points behind and in front of the oxygenator; scheme C: connected to the points in front of the oxygenator and in front of the centrifugal pump; scheme D: connected to the points behind the oxygenator and in front of the centrifugal pump; scheme E: connected to the points in front of the oxygenator and the return catheter; scheme F: connected to the points after the oxygenator and the return catheter. Each set of ECMO circuits was measured 5 times under each connection scheme and different flow rates (2, 3, 4, 5, 5.5 L/min). Six ECMO circuits for a total of 30 measurements, and the PA, PV, and TMP of the 6 schemes were compared. ② In vivo study: the patients who were treated with ECMO combined with CRRT in the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from August 2017 to August 2021 changed the connection scheme due to high PA or PV (from scheme A or B to scheme E or F) were retrospectively analyzed. The changes of PA and PV before and after changing the scheme were compared. Results:① In vitro study results: there was no significant difference in PA between schemes A and B, C and D, E and F under different ECMO blood flow (2-5.5 L/min). The PA of schemes C and D was the lowest, followed by schemes E and F. PV of scheme B was higher than that of scheme A under different ECMO blood flow (2-5.5 L/min). There was no significant difference in PV between schemes C and D, E and F under high ECMO blood flow (3-5.5 L/min), and the absolute value of PV was lowest in schemes E and F. Compared with schemes A and B [partial PA > 300 mmHg (1 mmHg≈0.133 kPa) at high flow rate], C and D (partial PV > 350 mmHg at high flow rate), schemes E and F were more reasonable connection schemes. TMP was negative in schemes C and D at ECMO blood flow of 5 L/min and 5.5 L/min (mmHg; 5 L/min: scheme C was -29.14±11.42, scheme D was -42.45±15.70; 5.5 L/min: scheme C was -35.75±13.21, scheme D was -41.58±15.42), which indicated the presence of dialysate reverse filtration. Most of the differences in TMP among schemes A, B, E, and F under different ECMO blood flow (2-5.5 L/min) were statistically significant, and the absolute value of mean fluctuation was 9.89-49.55 mmHg, all within the normal range. ② In vivo study results: a total of 10 patients who changed the connection scheme (from scheme A or B to E or F) due to high PA or PV were enrolled, including 8 males and 2 females; 7 cases of venous-arterial ECMO (VA-ECMO) and 3 cases of venous-venous ECMO (VV-ECMO), all used continuous veno-venous hemodiafiltration (CVVHDF) mode. After changing the scheme, both PA and PV decreased significantly as compared with those before changing [PA (mmHg): 244.00±22.58 vs. 257.20±21.92, PV (mmHg): 257.20±18.43 vs. 326.40±15.41, both P < 0.01], and PV decreased more significantly than PA [difference (mmHg): 69.20±6.55 vs. 13.20±5.45, P < 0.01]. Conclusion:For patients treated with ECMO in combination with CRRT, the scheme of connecting the access line of CRRT to the pre-oxygenator or post-oxygenator and connecting the return line to the point of the return catheter can significantly reduce PA and PV and maintains normal CRRT operation even running high-flow ECMO.

Objective:To investigate the effect of SCN1A gene polymorphism (SCN1A-rs3812718) on the alterations of spontaneous brain activity using amplitude of low-frequency fluctuations (ALFF) of MR in patients with temporal lobe epilepsy (TLE).Methods:A total of 37 TLE patients (TLE group) admitted to the Epilepsy Center of the 900th Hospital of Joint Logistic Team from March 2018 to August 2019 were retrospectively analyzed, and another 28 healthy volunteers matched for gender, age, and years of education with the TLE group were selected as the healthy control group (HC group). Sixty-five subjects were divided into four groups by genotype and diagnosis: 34 cases in AA/AG-TLE subgroup, 3 cases in GG-TLE subgroup, 20 cases in AA/AG-HC subgroup and 8 cases in GG-HC subgroup. All subjects underwent sagittal 3D-T 1WI and resting-state functional MRI using a Siemens 3.0 T Trio Tim MR scanner. Then ALFF values of the four groups were calculated using DPABI by the MATLAB 2010 platform. The ALFF values between two groups were compared by independent samples t-test. The ALFF values of different genotypes at rs3812718 locus in TLE and HC group were analyzed by multivariate analysis of variance to find out the corresponding brain regions with interaction, and then post hoc simple effect analysis was performed. Results:The ALFF values in TLE group significantly increased in left marginal lobe, left parahippocampal gyrus, left fusiform gyrus, left hippocampus, right insular lobe and right inferior temporal gyrus (Alphasim corrected P<0.001) and decreased in the left superior frontal gyrus, left middle frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right precuneus, left precuneus, bilateral cingulate gyrus and right angular gyrus (Alphasim correction P<0.05) compared with HC group. Subjects carrying the non-risk G allele had higher ALFF values in the right inferior temporal gyrus, right fusiform gyrus, and right cerebellum than subjects carrying the risk A allele ( t=3.30, Alphasim corrected P=0.002). There was a significant interaction effect on posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus, left superior parietal lobule and right precuneus of TLE patients with SCN1A-rs3812718 genotype. Post-hoc simple effect analysis showed that ALFF significantly increased in the left posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus and left fusiform gyrus in GG-TLE subgroup ( t=5.97, P<0.001), but significantly decreased in the right superior parietal lobule, right precuneus, right posterior cerebellar lobe in AA/AG-TLE subgroup compared to the HC group. Compared with GG-TLE subgroup, ALFF in left posterior cerebellar lobe, left fusiform gyrus and left inferior temporal gyrus decreased in AA/AG-TLE subgroup. Conclusion:SCN1A gene polymorphism in the rs3812718 locus affects spontaneous neural activity in resting state, which may be one of the pathophysiological mechanisms of TLE.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*