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Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.
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Objective To investigate the vaccination status and vaccination willingness of novel coronavirus in HIV/AIDS population in Yunnan.Methods From October 2021 to June 2022,a questionnaire survey was conducted among 2180 HIV/AIDS patients in Kunming,Qujing,Yuxi,Zhaotong,Puer,Baoshan,Lincang,Honghe,Wenshan,Xishuangbanna,Dali,Dehong and Nujiang prefectures.The questionnaire included age,sex,education,nationality,education level,vaccination,adverse reactions within 7 days after the vaccination,safety of COVID-19 vaccine,awareness of effectiveness,vaccination willingness and so on.Results Among the subjects,2109 completed 3 injections,accounting for 96.74%,and 71 were not vaccinated,accounting for 3.26% .Within 7 days of inoculation,local adverse reactions occurred in 116 cases,accounting for 5.50%,and systemic adverse reactions occurred in 56 cases,accounting for 2.66% .Injection site pain,fatigue and muscle pain accounted for the highest proportion of adverse symptoms in different sex,age and the Han nationality,while the proportion of minority adverse reactions was very low,and there was no difference among the different sex and age(P>0.05).The main reasons for the reluctance of HIV/AIDS population to be vaccinated were(recommended by doctors)that HIV/AIDS patients could not be vaccinated(67.61%)and may have serious adverse reactions after the vaccination(19.72%).The factors affecting the vaccination were found by logistic regression analysis,whether they were worried about infecting novel coronavirus(OR = 0.121,95% CI = 0.083～0.640,P<0.001)and how much they knew about COVID-19 vaccine(OR = 28.932,95% CI = 15.469～54.115,P<0.001),safety of vaccination(OR = 13.953,95% CI = 4.819～40.404,P<0.001)and belief in the preventive effect of vaccine(OR = 14.017,95% CI = 4.752～41.348,P<0.001)were significant factors affecting vaccination.Among the 13 prefectures and cities,Dehong(20),Zhaotong(21)and Lincang(14)had the largest number of unvaccinated people.Conclusion After the mass vaccination,the rate of adverse reaction in HIV/AIDS population is low,the symptoms are mild,the correct and scientific advice and guidance from doctors and the full understanding of the harmfulness of the disease,the safety,prevention and effectiveness of the vaccine are the key to complete vaccination and put an end to vaccine hesitancy.
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OBJECTIVE: The aim of this study is to explore the safety and efficacy of iodine-125 seeds interstitial brachytherapy (PISI-BT) for patients aged 80 and above with early primary high-risk non-melanoma skin cancer (NMSC). METHODS: In this retrospective single-center study, we collected and analyzed data from patients ≥ 80 years of age with early primary high-risk NMSC treated with PISI-BT between December 2003 and May 2020. Survival status, efficacy, adverse effects (AEs), cosmetic outcomes, and treatment cost were analyzed (data cut-off: November 20th, 2021). RESULTS: Only 9 patients met the inclusion criteria (median age, 86 years (81-90)). Five patients had an Eastern Cooperative Oncology Group (ECOG) score of 1, and allthe patients had at least one comorbidity. Six patients showed complete responseand three showed partial response, while none had stable or progressive disease. No recurrences, disease persistence, or AEs were detected during the follow-up period. After a median follow-up of 29.3 months (3-99), only two patients were alive, but the cause of death in the remaining patients was not related to NMSC. The cosmetic outcomes were excellent and good in two and four patients, respectively, while they could not be evaluated in three patients. The cost (which was within the scope of medical insurance reimbursement) was acceptable. CONCLUSION: PISI-BT could be an alternative treatment option in patients above 80 years old with early primary high-risk NMSC and comorbidities.
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Pullulan possesses excellent film-forming properties and oxygen isolation capabilities. However, it exhibits limited antibacterial properties and poor water resistance, thereby hindering its application in the field of food preservation. In this study, we synthesized D-arginine-succinic anhydride-pullulan (Arg-SA-Pul) by carboxylating pullulan and subsequently grafting it with D-arginine. The antimicrobial test demonstrated that Arg-SA-Pul exhibited comparable antibacterial activity against Escherichia coli and Staphylococcus aureus. Using Arg-SA-Pul as the primary material and glycerol as the plasticizer, we fabricated an antibacterial film via the tape casting method. The film's light transmittance, water solubility, and water vapor permeability were evaluated. Compared to the natural pullulan film, the Arg-SA-Pul film exhibited lower vapor permeability. Additionally, we conducted preservation tests on cherries by coating them with the Arg-SA-Pul film. The results demonstrated that the Arg-SA-Pul film exhibited a significant preservation effect on cherries and effectively delayed their ripening and senescence. In the future, the Arg-SA-Pul film could be employed as a bacteriostatic preservation material to extend the shelf life of fruits.
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Anti-Infective Agents , Food Packaging , Food Packaging/methods , Anti-Bacterial Agents/pharmacology , Glucans/pharmacology , Carboxylic AcidsABSTRACT
Objective To retrieve the relevant evidence of ICU nurse ventilator alarm management and summarize the best evidence to provide a reference for ICU nurse ventilator alarm management decision.Methods The clinical decision,guideline,systematic evaluation,expert consensus and all kinds of original studies related to the alarm management of ICU nurses in PubMed,CINAHL,Embase,Web of Science,VIP,CNKI and Wanfang were searched from database construction until April 22,2023.The literature quality evaluation and result extraction were performed independently by 2 investigators.Results 14 articles were finally involved,including 4 guidelines,2 international standards,2 national standards,2 expert consensuses,3 systematic evaluations and 1 randomized controlled trial;combined with professional judgment,27 pieces of the evidence were summarized,including multidisciplinary teamwork,alarm monitoring and processing,alarm setting,alarm management requirements,alarm education and training and ventilator maintenance.Conclusion This study summarizes the best evidence of ventilator alarm management for ICU nurses,which can provide evidence-based bases for clinical decisions,solve clinical ventilator alarm problems in a scientific management way,and improve the quality of management.
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Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.
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Objective:To retrospectively evaluate the effects of lung-protective ventilation strategies on postoperative pulmonary complications in the patients undergoing long-time neurosurgery.Methods:Based on the duration of anesthesia>8 h, the clinical data from patients underwent elective first craniotomy under general anesthesia from January 1, 2019 to December 31, 2021 were retrospectively collected. Patients were divided into lung-protective ventilation group (group L) and conventional mechanical ventilation group (group C) according to whether lung-protective ventilation was performed during operation. The baseline characteristics, intraoperative condition, postoperative pulmonary complications and hospitalization of patients in the two groups were recorded.Results:Compared with group C, the tidal volume was significantly decreased, positive end-expiratory pressure and respiratory rate were increased, the incidence of intraoperative hypoxemia was decreased, the number of patients with grade 1 according to the severity grade of postoperative pulmonary complications was significantly increased, and the length of hospital stay was shortened in group L ( P<0.05). There were no statistically significant differences in the baseline characteristics, incidence of postoperative pulmonary complications at 7 days after surgery and other parameters between group L and group C ( P>0.05). Conclusions:Lung-protective ventilation strategies can reduce the severity of postoperative pulmonary complications in the patients undergoing long-time neurosurgery.
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Objective:To investigate the influencing of high sodium donor liver transplan-tation from the death of a citizen′s organ donation (DCD) on the prognosis of recipients.Methods:The retrospective cohort study was constructed. The clinicopathological data of 125 pairs of donors and recipients who underwent DCD liver transplantation in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected. Of the 125 donors, there were 93 males and 32 females. Of the 125 recipients, there were 92 males and 33 females, aged 48(41,55)years. According to the last time of serum sodium level of donor liver in the 125 recipients, 9 donor livers with serum sodium level ≥170 mmol/L were divided into group 1 (extremely high sodium), 33 donor livers with serum sodium level ≥150 mmol/L and <170 mmol/L were divided into group 2 (moderate high sodium), and 83 donor livers with serum sodium level <150 mmol/L were divided into group 3 (normal sodium), respectively. Observation indicators: (1) postoperative recover situations; (2) follow-up and survival analysis. Measurement data with normal distribution were represented as Mean± SD. Repeated measures were analyzed by repeated measures ANOVA. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Kruskal-Wallis test. Count data were described as absolute numbers, and Pearson chi-square test or Fisher exact probability were used for data test. The Kaplan-Meier method was used to draw survival curves and Log-rank test was used for survival analysis. Results:(1) Postoperative recover situations. The changes of alanine transaminase (AlT), aspartate aminotransferases (AST), total bilirubin (TBil), alkaline phosphatase (ALP), prothrombin time (PT), international normalized ratio (INR), albumin (Alb) and creatinine (Cr) from the first day to the 14th day after operation were (736±972)IU/L to (75±46)IU/L, (1 290±1 651)IU/L to (38±20)IU/L, (102±98)μmol/L to (33±11)μmol/L, (66±34)IU/L to (104±54)IU/L, (19.9±3.3)seconds to (11.3±1.0)seconds, 1.76±0.31 to 1.00±0.08, (34±5)g/L to (38±3)g/L and (91±41)μmol/L to (76±19)μmol/L, respectively, in the recipients of group 1. The above indicators were (505±377)IU/L to (48±46)IU/L, (855±727)IU/L to (24±17)IU/L, (64±42)μmol/L to (32±22)μmol/L, (68±51)IU/L to (91±46)IU/L, (16.8±3.5)seconds to (11.9±1.2)seconds, 1.47±0.30 to 1.04±0.09, (33±4 g/L) to (40±5)g/L and (106±32)μmol/L to (97±27)μmol/L in the recipients of group 2 and (637±525)IU/L to (65±60)IU/L, (929±1 193)IU/L to (33±27)IU/L, (66±48)μmol/L to (33±36)μmol/L, (64±28)IU/L to (125±64)IU/L, (17.2±4.7)seconds to (13.3±12.8)seconds, 1.51±0.42 to 1.05±0.13, (35±6)g/L to (39±4)g/L, (105±44)μmol/L to (94±40)μmol/L in the recipients of groups. Results of overall effect showed there were significant differ-ences in the change trend of TBil (time effect, inter-group effect, interaction effect) in recipients among the three groups after liver transplantation ( Fgroup=5.42, Ftime=22.78, Finteraction=3.85, P<0.05). There were significant differences in the time effect of ALT, AST, ALP, PT, INR, Alb, Cr in recipients among the three groups after liver transplantation ( Ftime=50.17, 36.24, 19.24, 10.55, 59.61, 41.94, 10.82, P<0.05). (2) Follow-up and survival analysis. All recipients were followed up. Cases with early postoperative liver dysfunction, cases with donor liver failure 1 year after operation, cases with biliary complica-tions 1 year after operation, cases with vascular complications 1 year after operation, cases with rejection 1 year after operation were 2, 1, 0, 0, 0 in the recipients of group 1. The above indicators were 2, 1, 3, 0, 1 in the recipients of group 2 and 10, 8,20, 1, 6 in the recipients of group 3. There was no significant difference in the above indicators among the three groups ( χ2=1.58, 0.60, 5.19, 1.62, 0.97, P>0.05). The 1-year and 3-year cumulative survival rates of the donor liver were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 94.74% and 77.16% in the recipients of group 2 and 91.57% and 89.30% in the recipients of group 3. There was no significant difference in the cumulative survival rate of donor liver among the three groups ( χ2=2.69, P>0.05). The 1-year and 3-year cumulative survival rates were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 93.74% and 77.16% in the recipients of group 2 and 89.40% and 86.00% in the recipients of group 3. There was no significant difference in the cumulative survival rate among the three groups ( χ2=1.94, P>0.05). Conclusion:Donor livers with high serum sodium level can be used in the DCD liver transplantation.
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OBJECTIVE To establish the quality control method of Flueggea suffruticosa. METHODS The microscopical identification and thin layer chromatography （TLC） of F. suffruticosa were carried out， and the mass fractions of moisture， total ash， acid-insoluble ash and alcohol-soluble extracts in F. suffruticosa were measured based on the 2020 version of Chinese Pharmacopoeia （part Ⅳ）. The content of securinine in medicinal materials was determined by high performance liquid chromatography. RESULTS The powder of F. suffruticosa was gray-green， with obvious microscopic characteristics such as pores， pollen grains， calcium oxalate cluster crystals， ducts. The results of TLC identification showed that in the chromatograms of 16 batches of medicinal samples， the same color spots were found on the corresponding positions of the chromatograms of securinine， rutin， quercetin and F. suffruticosa control. The average mass fractions of moisture， total ash， acid-insoluble ash and alcohol- soluble extracts in 16 batches of medicinal materials were 9.26%， 6.96%， 1.17% and 28.89%， respectively. The injection volume of securinine in the range of 0.052 4-0.524 0 µg had a good linear relationship with the peak area （R2＝0.999 8）. RSDs of precision， repeatability and stability （24 h） test were all less than 3% （n＝6 or 7）. The average recovery of sample was 97.47%， RSD was 1.63% （n＝6）. The content of securinine in 16 batches of medicinal materials was 1.003-6.872 mg/g. CONCLUSIONS The quality control method of F. suffruticosa is established， and the mass fractions of moisture， total ash and acid-insoluble ash should not exceed 12.0%， 9.0% and 2.0%， respectively； the alcohol-soluble extract should not be less than 20%， and the content of securinine should not be less than 1.00 mg/g.
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OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.
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Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
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Animals , Mice , Lipid Droplets , Autophagy , Autophagosomes , Homeostasis , TriglyceridesABSTRACT
ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.
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Sialyllactose is one of the most abundant sialylated oligosaccharides in human milk oligosaccharides (HMOs), which plays an important role in the healthy development of infants and young children. However, its efficient and cheap production technology is still lacking presently. This study developed a two-step process employing multiple-strains for the production of sialyllactose. In the first step, two engineered strains, E. coli JM109(DE3)/ pET28a-BT0453 and JM109(DE3)/pET28a-nanA, were constructed to synthesize the intermediate N-acetylneuraminic acid. When the ratio of the biomass of the two engineered strains was 1:1 and the reaction time was 32 hours, the maximum yield of N-acetylneuraminic acid was 20.4 g/L. In the second step, E. coli JM109(DE3)/ pET28a-neuA, JM109(DE3)/ pET28a-nst and Baker's yeast were added to the above fermentation broth to synthesize 3'-sialyllactose (3'-SL). Using optimal conditions including 200 mmol/L N-acetyl-glucosamine and lactose, 150 g/L Baker's yeast, 20 mmol/L Mg2+, the maximum yield of 3'-SL in the fermentation broth reached 55.04 g/L after 24 hours of fermentation and the conversion rate of the substrate N-acetyl-glucosamine was 43.47%. This research provides an alternative technical route for economical production of 3'-SL.
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Child , Humans , Child, Preschool , N-Acetylneuraminic Acid , Escherichia coli/genetics , Lactose , Fermentation , Saccharomyces cerevisiae , Oligosaccharides , GlucosamineABSTRACT
OBJECTIVE@#To investigate the effect of hydrogen gas on NOD-like receptor protein 3 (NLRP3) inflammasomes in the cerebral cortex of rats with traumatic brain injury (TBI).@*METHODS@#120 adult male Sprague-Dawley (SD) rates were randomly divided into 5 groups (n = 24): sham operation group (S group), TBI model group (T group), TBI+NLRP3 inhibitor MCC950 group (T+M group), TBI+hydrogen gas group (T+H group), TBI+hydrogen gas+MCC950 group (T+H+M group). TBI model was established by controlled cortical impact. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected for 14 consecutive days before TBI operation in T+M and T+H+M groups. 2% hydrogen inhalation was given for 1 hour at 1 hour and 3 hours after TBI operation in T+H and T+H+M groups. At 6 hours after TBI operation, the pericontusional cortex tissues were obtained, the content of Evans blue (EB) was detected to evaluate the permeability of the blood-brain barrier. Water content in brain tissue was detected. The cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) and the neuronal apoptosis index was calculated. The expressions of Bcl-2, Bax, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 p20 were detected by Western blotting. The levels of interleukins (IL-1β, IL-18) were detected by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#Compared with the S group, the content of EB in cerebral cortex, water content in brain tissue, apoptosis index and the expressions of Bax, NLRP3, ASC, caspase-1 p20 in T group were significantly increased, the expression of Bcl-2 was down-regulated, the levels of IL-1β and IL-18 were increased [the content of EB (μg/g): 87.57±6.89 vs. 10.54±1.15, water content in brain tissues: (83.79±2.74)% vs. (74.50±1.19)%, apoptotic index: (62.66±5.33)% vs. (4.61±0.96)%, Bax/β-actin: 4.20±0.44 vs. 1, NLRP3/β-actin: 3.55±0.31 vs. 1, ASC/β-actin: 3.10±0.26 vs. 1, caspase-1 p20/β-actin: 3.28±0.24 vs. 1, Bcl-2/β-actin: 0.23±0.03 vs. 1, IL-1β (ng/g): 221.58±19.15 vs. 27.15±3.27, IL-18 (ng/g): 87.26±7.17 vs. 12.10±1.85, all P < 0.05]. Compared with the T group, the T+M, T+H and T+H+M groups had significant reductions in the content of EB and water content in brain tissue, apoptotic index of the cerebral cortex, the expressions of Bax, NLRP3, and caspase-1 p20 in the brain tissue and the levels of IL-1β and IL-18, significant increases in the expression of Bcl-2. However, there was no significant difference in ASC expression. Compared with the T+H group, the content of EB in the cerebral cortex, water content in brain tissue, and apoptotic index, and the expressions of Bax, NLRP3 and caspase-1 p20 were further down-regulated in T+H+M group, the expression of Bcl-2 was further up-regulated, the levels of IL-1β and IL-18 were further decreased [the content of EB (μg/g): 40.49±3.15 vs. 51.96±4.69, water content in brain tissue: (76.58±1.04)% vs. (78.76±1.16)%, apoptotic index: (32.22±3.44)% vs. (38.54±3.89)%, Bax/β-actin: 1.92±0.16 vs. 2.56±0.21, NLRP3/β-actin: 1.94±0.14 vs. 2.37±0.24, caspase-1 p20/β-actin: 1.97±0.17 vs. 2.31±0.19, Bcl-2/β-actin: 0.82±0.07 vs. 0.52±0.04, IL-1β (ng/g): 86.23±7.09 vs. 110.44±10.48, IL-18 (ng/g): 40.18±3.22 vs. 46.23±4.02, all P < 0.05], but there were no statistical significance in all the indicators between T+M group and T+H group.@*CONCLUSIONS@#The mechanism by which hydrogen gas alleviates TBI may be related to inhibiting NLRP3 inflammasomes in the cerebral cortex of rats.
Subject(s)
Male , Animals , Rats , Rats, Sprague-Dawley , Actins , Interleukin-18 , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , bcl-2-Associated X Protein , Brain Injuries, Traumatic , Cerebral Cortex , CaspasesABSTRACT
Background and Purpose: This study aimed to investigate the arterial disease risk factors for the progression of intraplaque hemorrhage (IPH) in patients with carotid atherosclerosis using serial high-resolution magnetic resonance (MR) imaging. Methods: Consecutive symptomatic patients who had MRI evidence of intraplaque hemorrhage present in the ipsilateral carotid artery with respect to the side of the brain affected by stroke or TIA were recruited in the study. All the patients underwent follow-up MR imaging at least 6 months after baseline. The annual change in IPH and other carotid plaque morphology was calculated, and a tertile method was used to classify the plaques as progressed or not with respect to IPH volume using the software CASCADE. Logistic regression and receiver operating characteristic (ROC) curve were conducted to evaluate the risk factors for the progression of IPH. Results: A total of thirty-four symptomatic patients (mean age: 67.1 years, standard deviation [SD]: 9.8 years, 27 men) were eligible for the final analysis, and contralateral plaques containing IPH were seen in 11 of these patients (making 45 plaques with IPH in total). During mean 16.6-month (SD: 11.0 months) follow-up, the overall annual change in IPH volume in 45 plaques with IPH was mean -10.9 mm3 (SD: 49.1 mm3). Carotid plaques were significantly more likely to be classified in progressed IPH group if the patient was taking antiplatelet agent at baseline (OR: 9.76; 95%CI: 1.05 to 90.56; p = 0.045), had a baseline history of current or past smoking (OR: 9.28; 95%CI: 1.26 to 68.31; p = 0.029), or had a larger baseline carotid plaque-containing vessel wall volume (OR: 1.36 per 10 mm3; 95%CI: 1.02 to 1.81; p = 0.032) after adjustments for confounding factors. ROC analysis indicated that the combination of these three risk factors in the final model produced good discriminatory value for the progressed IPH group (area under the curve: 0.887). Conclusions: Taking an antiplatelet agent at baseline, a baseline history of current or past smoking and larger baseline carotid plaque-containing vessel wall volume were independently predictive of plaques being in the progressed IPH group. Our findings indicate that awareness and management of such risk factors may reduce the risk of intraplaque hemorrhage progression.
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BACKGROUND: Prognostic indicators based on the initial prostate-specific antigen (PSA) levels, nadir PSA, and time to PSA nadir were calculated to evaluate prognosis after primary androgen deprivation therapy (PADT), as these have been reported in very few studies. We attempted to evaluate the prognostic role of the slope associated with nadir PSA in patients treated with PADT. METHODS: A total of 107 patients who were treated with PADT from 2015 to 2019 were reviewed. The Kaplan-Meier method and Cox regression model were used to analyze the prognostic significance of the slope associated with nadir PSA in predicting progression-free survival (PFS) and overall survival (OS). RESULTS: After PADT, the median follow-up duration was 40.1 months; 66 patients (61.7%) had disease progression, and 33 patients (30.8%) died. In the univariate analysis, T stage, N stage, nadir PSA, time to PSA nadir, nadir PSA declining slope (nPSA-DS), nadir PSA percentage declining slope (nPSA-PDS), and nadir PSA line slope (nPSA-LS) were significant predictors for PFS and OS. The multivariate analysis showed that a higher nPSA-DS (> - 0.74) and lower PSA nadir (≤0.16 ng/ml) were independent predictors for prolonged survival. The significance of nPSA-DS and nPSA was supported by the analysis of nPSA-DS and nPSA as time-dependent covariates. The combined analyses demonstrated that patients with a higher nPSA-DS and lower PSA nadir had the best PFS and OS. CONCLUSIONS: The slope associated with the nadir PSA of nPSA-DS was a significant independent predictor for patients treated with PADT. Nadir PSA and nPSA-DS have a synergistic effect on prognosis.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Androgen Antagonists/therapeutic use , Androgens , Humans , Male , Prognosis , Retrospective StudiesABSTRACT
Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy. .
Subject(s)
Humans , B7-H1 Antigen , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy , Lung Neoplasms/therapyABSTRACT
Objective:To compare the clinical efficacy between 3D printing-assisted percutaneous balloon dilatation calcaneal plasty (3D-PCP) and conventional open reduction and internal fixation (ORIF) via the extended lateral L-shaped approach in the treatment of osteoporotic calcaneal fractures of Sanders type Ⅱ or Ⅲ in the elderly patients.Methods:Retrospectively analyzed were the data of 36 elderly patients with osteoporotic calcaneal fracture of Sanders type Ⅱ or Ⅲ who had been surgically treated at Department of Orthopaedics, Yixing People's Hospital from June 2012 to June 2018. According to their treatment methods, the patients were divided into a 3D-PCP group [16 cases, 9 males and 7 females with an age of (73.0 ± 3.4) years] and an ORIF group [20 cases, 8 females and 12 females with an age of (71.4 ± 2.6) years]. The 2 groups were compared in terms of hospital stay, operation time, intraoperative fluoroscopy frequency, suture removal time, weight bearing time, fracture healing time, visual analogue scale (VAS) for the surgical site 2 days and one year after surgery, American Foot and Ankle Surgery Association (AOFAS) ankle-hindfoot score, calcaneal imaging parameters (B?hler angle, Gissane angle, and length, width and height of the calcaneus axis) at 2 days and one year after surgery, and postoperative complications.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P > 0.05). All patients were followed up for 14 to 18 months (mean, 15.6 months). Compared with the ORIF group, the 3D-PCP group had significantly shorter hospital stay, significantly shorter operation time, significantly earlier suture removal, significantly earlier weight-bearing, significantly lower VAS scores at 2 days after surgery, significantly higher AOFAS ankle-hindfoot scores at one month after surgery, but significantly more times of intraoperative fluoroscopy (all P < 0.05). In all patients, the VAS scores at 2 days after surgery were significantly lower than those before surgery, and those at one year after surgery significantly lower than those at 2 days after surgery ( P < 0.05). In all patients, the AOFAS ankle-hindfoot scores at one month after surgery were significantly higher than those before surgery ( P < 0.001). In the ORIF group, the AOFAS ankle-hindfoot scores at one year after surgery were significantly higher than those at one month after surgery ( P < 0.05), but in the 3D-PCP group there was no such a significant difference between one year and one month after surgery ( P > 0.05). There was no significant difference in VAS score, AOFAS score, fracture healing time or postoperative imaging parameters between the 2 groups at one year after surgery ( P > 0.05). There was no significant difference either in the incidence of complications between the 2 groups ( P > 0.05). Conclusion:In the treatment of osteoporotic calcaneal fractures of Sanders type Ⅱ or Ⅲ in the elderly patients, compared with conventional ORIF, 3D-PCP shows advantages of shorter operation time, minimal invasion, quicker incision healing, shorter hospital stay, earlier weight-bearing exercise, and better functional recovery but a disadvantage of increased times of intraoperative fluoroscopy.
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Objective:To evaluate the effects of hydrogen-rich saline on acute lung injury in rats with traumatic brain injury (TBI) and the role of nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods:Forty-eight adult male Sprague-Dawley rats, weighing 220-250 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), TBI group (T group), TBI plus hydrogen-rich saline group (T+ H group), and TBI plus hydrogen-rich saline plus brusatol group (T+ H+ B group). TBI model was developed by controlled cortical impact.Nrf2 inhibitor brusatol 0.4 mg/kg was intraperitoneally injected every other day starting from 10 days before development of TBI model in T+ H+ B group.Hydrogen-rich fluid 10 ml/kg was intraperitoneally injected at 1 and 6 h after development of TBI model in T+ H group and T+ H+ B group.At 24 h after development of TBI model, the bronchoalveolar lavage fluid (BALF) was collected to detect the concentration of protein, blood samples from the right common carotid artery were collected and lung tissues were obtained for determination of the levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10) and high-mobility group box 1 protein (HMGB1) in serum and lung tissues (by enzyme-linked immunosorbent assay), wet to dry lung weight ratio (W/D ratio), expression of nuclear-Nrf2, total-Nrf2 and HO-1 in lung tissues (by Western blot), and expression of HO-1 mRNA (by real-time polymerase chain reaction) and for microscopic examination of histopathologic changes (by haematoxylin and eosin staining) which were scored. Results:Compared with S group, the concentrations of protein in BALF, W/D ratio of lung tissues and lung injury score were significantly increased, the levels of TNF-α, HMGB1 and IL-10 in serum and lung tissues were increased, and the expression of nuclear Nrf2, total Nrf2 and HO-1 protein and mRNA in lung tissues was up-regulated in T and T+ H groups ( P<0.05). Compared with T group, the concentrations of protein in BALF, W/D ratio of lung tissues and lung injury score were significantly decreased, the levels of TNF-α and HMGB1 in serum and lung tissues were decreased, the level of IL-10 in serum and lung tissues was increased, and the expression of nuclear Nrf2, total Nrf2 and HO-1 protein and mRNA in lung tissues was up-regulated in T+ H group ( P<0.05), and no significant changes were found in the parameters mentioned above in T+ H+ B group ( P>0.05). Compared with T+ H group, the concentrations of protein in BALF, W/D ratio of lung tissues and lung injury score were significantly increased, the levels of TNF-α and HMGB1 in serum and lung tissues were increased, the level of IL-10 in serum and lung tissues was decreased, and the expression of nuclear Nrf2, total Nrf2 and HO-1 protein and mRNA in lung tissues was down-regulated in T+ H+ B group ( P<0.05). Conclusions:Hydrogen-rich solution can alleviate acute lung injury in rats with traumatic brain injury, and the mechanism is related to activation of Nrf2/HO-1 signaling pathway and inhibition of the inflammatory responses.
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Objective:To investigate the relationship between dosimetric parameters and tumor volume change after 125I implantation for thyroid cancer and obtain better dosimetric parameters that predict the curative effect more accurately. Methods:A total of 22 consecutive patients with thyroid cancer (23 targets) who received 125I interstitial brachytherapy in Department of Oncology, Hebei General Hospital were retrospectively analyzed. All the patients received post-operative dose verification, and the D 90 (Minimum dose received by 90% target volume) was calculated. After a regular follow-up, the tumor volume reduction ratio after t months (R t) , actual absorbed dose (D 1m) , efficacy corrected absorbed dose (D 1e) , and sensitivity corrected absorbed dose (D 1s) of the first month were calculated according to the actual follow-up CT images. The statistical test was carried out by SPSS21.0. The Spearman linear analysis was applied to analyze the relationship between D 90, D 1m, D 1e, D 1s and R t, and the curve fitting was also completed. Results:The post-operative D 90, D 1m, D 1e, D 1s and R t were (129.73±14.22) Gy, (36.95±7.35) Gy, (43.45±11.32) Gy, (41.78±13.39) Gy, and (32.00±19.00) %, respectively. And the correlation coefficient were 0.692, 0.551, 0.728, and 0.858, respectively, which showed significant positive relevance between dosimetric parameters and tumor volume change ( P<0.01) , the curve fitting presented cubic function. Conclusion:The post-operative D 90, D 1m, D 1e, and D 1s can be predictors for curative effect, and D 1s is the best predictor.