Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Objective To investigate the effects and mechanism of circTRIM33-12 on proliferation,apoptosis and epithelial-mesenchymal transition(EMT)of brain glioma cells by miR-191/DAB2 axis.Methods The expressions of circTRIM33-12,miR-191 and DAB2 in brain glioma cell CHG-5 and human normal brain glial epithelial cells HEB were detected by RT-PCR.The cultured CHG-5 cells were divided into the siRNA NC group,the circTRIM33-12 siRNA group,the DAB2 siRNA group;the mimics NC group,the miR-191 mimics group;the circTRIM33-12 WT+mimics NC group,the circTRIM33-12 WT+miR-191 mimics group,the circTRIM33-12 MUT+ mimics NC group,the circTRIM33-12 MUT+miR-191 mimics group;the inhibitor NC group,the miR-191 inhibitor group;the pcDNA+ mimics NC group,the pcDNA-TRIM33-12+mimics NC group,the pcDNA+miR-191 mimics group,the pcDNA-TRIM33-12+miR-191 mimics group;the DAB2 WT+mimics NC group,the DAB2 WT+miR-191mimis group,the DAB2 MUT+mimics NC group,the DAB2 MUT+ miR-191 mimis group.CCK-8 assay was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on the prolifera-tion ability of CHG-5 cells;flow cytometry was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on the apoptosis of CHG-5 cells;Western blot was used to detect the effects of the expressions of circTRIM33-12,miR-191 and DAB2 on EMT of CHG-5 cells.TargetScan database was used to analyze the correlations among miR-191,circTRIM33-12 and DAB2,and dual luciferase reporter gene assay was used to verify their relationships;RT-qPCR was used to detect the effect of circTRIM33-12 on DAB2 expression through miR-191.Results Compared with HEB cells,the expression of circTRIM33-12 in CHG-5 cells was down-regulated(P<0.01),the expression of miR-191 was up-regulated(P<0.01),and the expression of DAB2 was down-regulated(P<0.01).Compared with the siRNA NC group,the proliferation activity and N-cadherin expression of CHG-5 cells in the circTRIM33-12 siRNA group and the DAB2 siRNA group were significantly increased(P<0.01),while the apoptosis rate and E-cadherin expression were decreased(P<0.01).circTRIM33-12 targeted miR-191,and miR-191 targeted DAB2.Compared with the inhibitor NC group,the proliferation activity and N-cadherin expression of CHG-5 cells in the miR-191 inhibitor group were significantly decreased(P<0.01),while the apoptosis rate and E-cadherin expression were increased(P<0.01).circTRIM33-12 overexpression inhibited CHG-5 cell proliferation and EMT through miR-191.Conclusion circTRIM33-12 may regulate the proliferation,apoptosis and EMT of brain glioma cells through the miR-191/DAB2 axis.

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock. METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created. RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fluid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identified prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001). CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

Objective: To examine the modalities of treatment and clinical outcomes of emphysematous pyelonephritis (EPN), in order to improve the survival rate of EPN patients. Methods: Totally 14 patients diagnosed as EPN between October 2011 and November 2020 at Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were included in this article. Data collection including patient demographics, clinical manifestations, management and clinical outcomes were conducted by retrospective charts review, after receiving the institutional review board's approval. There were 11 females and 3 males with a median age of 59 years (range: 52 to 73 years). The lesions were located on the left side in 10 patients and right side in 4 patients. All the 14 patients suffered from fever, and present with severe sepsis or septic shock. The median time from symptom onset to admission to hospital was 3 days(range: 2 to 5 days). All cases had diabetes mellitus. Escherichia coli was the most common organism been cultured (11 cases), while Klebsiella pneumonia was the second (3 cases). CT scan showed bubbly or located gas in the renal parenchyma in 5 cases and presence of steaky or mottled gas in the renal parenchyma in 9 cases. All patients had been admitted to ICU for anti-septic shock therapy. Three patients had undergone percutaneous catheter drainage along with broad-spectrum antibiotics therapy while 3 patients had immediate nephrectomy, the other 8 cases had a combination of an initial percutaneous catheter drainage and second stage nephrectomy. Results: In this case series, 3 patients were died from EPN while the other 11 were survived. The median ICU stay time was 6 days (range: 3 to 11 days). Of the 3 patients died from EPN, 2 had undergone percutaneous catheter drainage along and 1 had received immediate nephrectomy. Among the 11 patients who were survived, only 1 had received percutaneous catheter drainage while the other 10 received nephrectomy (8 patients had staged nephrectomy). Follow-up was performed 6 months after discharge. Of the 11 surviving patients, 2 were lost to follow-up, and the remaining 9 patients had an creatine level of (118.4±29.4) μmol/L (range: 89 to 176 μmol/L). Conclusions: For patients coupled with diabetes who were initially diagnosed as acute pyelonephritis, the possibility of EPN should be considered when the disease progressed rapidly especially septic shock occurred. On the basis of empirical broad-spectrum antibiotics therapy and standardized anti-septic shock treatment, a combination of an initial percutaneous catheter drainage and second stage nephrectomy could be efficacious.
Aged ; Emphysema/therapy* ; Escherichia coli Infections ; Female ; Humans ; Male ; Middle Aged ; Pyelonephritis/therapy* ; Retrospective Studies ; Treatment Outcome